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Internal medicine: cardiology
Educational book
Recommended by the Ministry of Education and Science of Ukraine
[pic]
Sumy
Sumy State University
2013
УДК 616.12(075.8)
ББК 54.10я73
І-73
Composite author:
V. F. Orlovskyi, Doctor of Medical Sciences, professor of Sumy State University;
L. N. Prystupa, Doctor of Medical Sciences, professor of Sumy State University;
N. M. Kyrychenko, Candidate of Medical Sciences, assosiate professor of Sumy State University;
O. S. Pogorelova, Candidate of Medical Sciences, assistant of Sumy State University;
Yu. O. Ataman, Doctor of Medical Sciences, assosiate professor of Sumy State University
Reviewers:
G. P. Pobedonna – Doctor of Medical Sciences, professor of Lugansk State Medical University;
I. P. Katerentchuk – Doctor of Medical Sciences, professor of Ukrainian Medical Stomatological Academy;
I. M. Fushtey – Doctor of Medical Sciences, professor of Zaporozhye Medical Academy of Postgraduate Education
Recommended by the Ministry of Education and Science of Ukraine for the English-speaking students of higher medical educational institutions
of III–IV levels accreditation
(letter № 1/11-13145 of 19.08.2013)
| |Internal medicine: cardiology : educational book / V. F. Orlovskyi, L. N. Prystupa, |
|I-73 |N. M. Kyrychenko et al. – Sumy : Sumy State University, 2013. – 243 р. |
| |ISBN 978-966-657-489-6 |
This manual is intended for the students of medical higher educational institutions of IV accreditation level, who study cardiology in English language.
Посібник рекомендований для студентів вищих медичних навчальних закладів IV рівня акредитації, які вивчають кардіологію англійською мовою.
УДК 616.12(075.8) ББК 54.10я73
© Orlovskyi V. F., Prystupa L. N., Kyrychenko N. M., Pogorelova O. S., Ataman Yu. O., 2013
ISBN 978-966-657-489-6 © Sumy State University, 2013
INTRODUCTION
The manual sets out the main issues of etiology, pathogenesis, clinical symptoms, diagnostics and treatment of the most common diseases of the circulatory system. It is recommended for the students of the higher medical educational establishments of the IV-th accreditation level.
Despite the considerable success of modern cardiology, the number of patients with heart and blood vessels pathology increases every year. It can be explained by the increase in life expectancy (aging of the world's population), sedentary lifestyle, obesity, addictions.
The manual presents the new classifications of diseases, modern etiology, pathogenesis, diagnostics, treatment and prevention of the heart and blood vessel diseases. The manual reflects extensive material in the condensed statement.
We hope that this manual will help students, medical interns to study the topic “Cardiology” and will be useful in the work of medical practitioners.
ARTERIAL HYPERTENSION
Arterial hypertension (AH) is frustration of cardiovascular systems owing to primary dysfunction of vasoregulation centres and subsequent neurohormonal and kidney mechanisms and is characterized by arterial hypertension, functional and organic disorder of kidneys, heart and central neurological system.
Table 1 – Classification of hypertension of blood pressure (BP) levels (mmHg) (2003 ESH/ESC)
|Category |Systolic | |Diastolic |
|Optimal |< 120 |and |< 80 |
|Normal |120–129 |and/or |80–84 |
|High normal |130–139 |and/or |85–89 |
|Grade 1 hypertension |140–159 |and/or |90–99 |
|Grade 2 hypertension |160–179 |and/or |100–109 |
|Grade 3 hypertension |≥ 180 |and/or |≥ 110 |
|Isolated systolic hypertension |≥ 140 |and |< 90 |
Total cardiovascular risk (factors influencing prognosis)
Risk factors (RF):
– levels of pulse pressure (in the elderly);
– age (M > 55 years; W > 65 years);
– smoking;
– dyslipidaemia: TC > 5.0 mmol/l (190 mg/dl) or LDL-C > 3.0 mmol/l (115 mg/dl) or HDL-C: M < 1.0 mmol/l (40 mg/dl), W < 1.2 mmol/l (46 mg/dl) or TG > 1.7 mmol/l (150 mg/dl);
– fasting plasma glucose 5.6–6.9 mmol/L (102–125 mg/dl);
– abnormal glucose tolerance test;
– abdominal obesity (waist circumference > 102 cm (M), > 88 cm (W));
– family history of premature cardiovascular (CV) disease (M < 55 years; W < 65 years).
Table 2 – Classification of arterial hypertension (1996)
|St. |BP, mmHg |Organ damage |
|1 |≥ 140/90 |Are absent |
|2 |≥ 140/90 |Heart: ECG LVH (Sokolow-Lyon > 38 mm); Cornell > 2440 mm/ms) or |
| | |echocardiographic LVH (LVMI: M ≥ 125 g/m2, W ≥ 110 g/m2). |
| | |Retinal: stenosis of vessels. |
| | |Kidney: microalbuminuria 30–300 mg/24 h or increase in plasma |
| | |creatinine: M: 115– 133 mmol/l (1.3–1.5 mg/dl); W: 107–124 mmol/l |
| | |(1.2–1.4 mg/dl); low estimated glomerular filtration rate (< 60 |
| | |ml/min). |
| | |Vessels: atherosclerosis (carotid wall thickening (IMT > 0.9 mm) or |
| | |plaque; carotid-femoral pulse wave velocity > 12 m/s). |
| | |NS: encephalopathy. |
|3 |≥ 140/90 |NS: cerebrovascular disease: ischaemic stroke; cerebral haemorrhage; |
| | |transient ischaemic attack. Heart disease: myocardial infarction; |
| | |angina; coronary revascularization; heart failure. |
| | |Renal disease: diabetic nephropathy; renal impair-ment (serum |
| | |creatinine M > 133, W > 1.24 mmol/l); proteinuria (> 300 mg/24 h). |
| | |Peripheral artery disease. |
| | |Advanced retinopathy: haemorrhages or exudates, papilloedema |
Note:
– the cluster of three out of 5 risk factors among abdominal obesity, altered fasting plasma glucose, BP > 130/85 mmHg, low HDL- cholesterol and high TG (as defined above) indicates the presence of metabolic syndrome;
– St. – stage; M – men; W – women; CV – cardiovascular disease; IMT – intima-media thickness; BP – blood pressure; TG – triglycerides; C – cholesterol; risk maximal for concentric LVH (left ventricular hypertrophy) increased LVMI (left ventricular hypertrophy) increased LVMI (left ventricular mass index) with a wall thickness/radius ratio > 0.42.
High/very high risk subjects
1. BP ≥ 180 mmHg systolic and/or ≥ 110 mmHg diastolic.
2. Systolic BP > 160 mmHg with low diastolic BP (< 70 mmHg).
3. Diabetes mellitus.
4. Metabolic syndrome.
5. ≥ 3 cardiovascular risk factors.
6. One or more of the following subclinical organ damages:
– electrocardiographic (particularly with strain) or echocardiographic (particularly concentric) left ventricular hypertrophy;
– ultrasound evidence of carotid artery wall thickening or plague;
– increased arterial stiffness;
– moderate increase in serum creatinine;
– reduced estimated glomerular filtration rate or creatinine clearance;
– microalbuminuria or proteinuria;
Established cardiovascular or renal disease.
Table 3 – Degree of risk of complications development
|Presence of risk factors (RF), organ damage and/or |Degree of AH (mmHg) (2003ESH/ESC) |
|other pathology | |
| |1 |2 |3 |
|RF are absent | (1)| (2) | (3) |
|1-2 of RF, except for | (2) | (4) |
|Diabetes mellitus (DM) | | |
|≥ 3 of FR or organ damage or DM |(3) | (4) |
|Other pathology | (4) |
|Note: |
|(1) – low risk; (2) – moderate risk; (3) – high risk; (4) – very high risk. |
The total 10-year risk of complications of AH (IHD, IM, insultus, sudden heart death, etc.) is estimated as follows:
– low risk – less than 15% in the next 10 years;
– moderate risk – 15–20%;
– high risk – 20–30%;
– very high risk – more than 30% in the next 10 years.
Pathophysiology
The level of BP is determined by three homodynamic parameters:
1. The level of cardiac output (CO) (minute volume).
2. Total peripheral vascular resistance (TPR).
3. Volume of blood circulations:
– abnormal Na transport;
– sympathetic stimulation of nervous system;
– renin-angiotensin-aldosterone system: renin catalyzes conversion of angiotensinogen to angiotensin I. This inactive product is cleaved by ACE to angiotensin II, a potent vasoconstrictor that also stimulates autonomic centres in the brain to increase sympathetic discharge and stimulates release of aldosterone and ADH that causes Na and water retention, BP elevation. Aldosterone also enhances K excretion; low plasma K (< 3.5 mEq/L) increases vasoconstriction through closure of K channels;
– vasodilator deficiency: (bradykinin, nitric oxide). Vasodilators and vasoconstrictors (mainly endothelin) are also produced in endothelial cells. Therefore, endothelial dysfunction greatly affects BP.
Diagnostic evaluation
Diagnostic procedures aim at:
– blood pressure levels establishing;
– identifying of secondary causes of hypertension;
– overall cardiovascular risk evaluating by searching for other risk factors, target organ damage and concomitant diseases or accompanying clinical conditions.
Diagnostic procedures comprise:
– repeated blood pressure measurements;
– medical history;
– physical examination;
– laboratory and instrumental investigations.
Blood pressure (BP) measurement
When measuring BP, care should be taken to:
– allow the patients to sit for several minutes in a quiet room before beginning of BP measurements;
– take at least two measurements spaced by 1–2 minutes, and additional measurements if the first two are quite different;
– use a standard bladder (12–13 cm long and 35 cm wide) but have a larger and a smaller bladder available for fat and thin arms, respectively. Use the smaller bladder in children;
– have the cuff at the heart level, whatever the position of the patient;
– use phase I and V (disappearance) of Korotkoff sounds to identify systolic and diastolic BP, respectively;
– measure BP in both arms at first visit to detect possible differences due to peripheral vascular disease. In this instance, take the higher value as the reference one;
– measure BP 1 and 5 min after assumption of the standing position in elderly subjects, diabetic patients, and in other conditions in which postural hypotension be frequent or suspected;
– measure heart rate by pulse palpation (at least 30 sec) after the second measurement in the sitting position.
Clinical signs of AH
– headache;
– discirculatory encephalopathy;
– cardiac pain;
– dyspnoea;
– oedema;
– vision disorder;
– kidney disorder.
Discirculatory encephalopathy: dizziness, infringements of memory, noise in the head, irritability, fast fatigue, disorder of mood.
Cardiac pain: is located in the apex of the heart or in the left side of the chest; arises at rest, at emotional pressure or BP increase; usually is not provoked by physical activity; in some cases lasts long enough (minute, hours); is not stopped by nitroglycerine.
Dyspnoea is a reason of HF of LV and diastolic dysfunction of LV.
Oedema on legs may be at biventricular HF, with a delayed Na+ and water, hyperactivity of rennin-angiotensin system.
Vision disorder: functional – fog, flickering of “flies” before eyes. Organic changes of the retina (trombosis of vessels, haemorrhages, degenerative changes or amotio of retina) are accompanied by significant decrease of sight, diplopia and even by complete loss of sight.
Kidney disorder is a reason of KF.
Physical examination of the heart
– stage 1 of AH: borders are in norm;
– stage 2 of AH: concentric hypotrophy of LV will result in amplification of apex push; eccentric hypotrophy of LV will result in dilatation of LV.
Auscultation of the heart: I sound at the stages 1–2 of AH – strengthening; at the stage 3 – weakening; II sound is aortic accent (the reasons are increase of BP and sclerosis of Ao wall); occurrence of IV sound at diastolic dysfunction of LV (at presence of concentric hypotrophy of LV); III sound at eccentric hypotropfy of LV and presence of volumetric overload of LV.
Cardiac murmurs: functional systolic murmur in the aorta (II intercostal to the right of sternum). Its reasons are: aortectasia; sclerosis of aorta. If systolic murmur at the apex, will be conducted in the left axillary area and is combined with weakening of I sound and increase of the sizes LA, it is mitral valve incompetence.
Pulse at AH: full pulse, tachycardia and arrhythmia are frequent.
Registration a HELL by Korotkoff method
Systolic BP register at occurrence of the first sound above radial artery (phase 1), and diastolic BP – at the moment of complete disappearance of Korotkoff sounds (phase 5).
Investigations
Routine tests:
– fasting plasma glucose;
– serum total cholesterol;
– serum LDL-cholesterol;
– serum HDL-cholesterol;
– fasting serum triglycerides;
– serum potassium;
– serum uric acid;
– serum creatinine;
– estimated creatinine clearance (Cockroft-Gault formula) or glomerular filtration rate (MDRD formula);
– haemoglobin and haematocrit;
– urinalysis (complemented by microalbuminuria via dipstick test and microscopic examination);
– electrocardiogram.
Recommended tests: echocardiogram, carotid ultrasound, quantitative proteinuria (if dipstick test is positive), ankle-brachial BP index, fundoscopy, glucose tolerance test (if fasting plasma glucose is > 5.6 mol/L (100 mg/dL), home and 24 h ambulatory BP monitoring, pulse wave velocity measurement (if available).
Extended evaluation (domain of the specialist)
Further search for cerebral, cardiac, renal and vascular damage. Mandatory in complicated hypertension.
Search for secondary hypertension when suggested by history, physical examination or routine tests: measurement of renin, aldosterone, corticosteroids, catecholamines in plasma and/or urine; arteriographies; renal and adrenal ultrasound; computer-assisted tomography; magnetic resonance imaging.
Position statement: searching for subclinical organ damage. Due to the importance of subclinical organ damage as an intermediate stage in the continuum of vascular disease and as a determinant of total cardiovascular risk, signs of organ involvement should be sought carefully by appropriate techniques:
1. Heart – electrocardiography should be a part of all routine assessments of patients with high BP in order to detect left ventricular hypertrophy, patterns of “strain”, ischaemia and arrhythmias. Echocardiography is recommended when a more sensitive detection of left ventricular hypertrophy is considered useful. Geometric patterns can be defined echocardiographically, of which concentric hypertrophy carries the worse prognosis. Diastolic dysfunction can be evaluated by transmitral Doppler.
2. Blood vessels – ultrasound scanning of carotid arteries is recommended when detection of vascular hypertrophy or asymptomatic atherosclerosis is deemed useful. Large artery stiffening (leading to isolated systolic hypertension in the elderly) can be measured by pulse wave velocity. It might be more widely recommended if its availability were greater. A low ankle-brachial BP index signals advanced peripheral.
3. Kidney – diagnosis of hypertension-related renal damage is based on a reduced renal function or an elevated urinary excretion of albumin. Estimation from serum creatinine of glomerular filtration rate (MDRD formula, requiring age, gender, race) or creatinine clearance (Cockroft-Gault formula, requiring also body weight) should be routine procedure. Urinary protein should be sought in all hypertensives by dipstick. In dipstick negative patients low grade albuminuria (microalbuminuria) should be determined in spot urine and related to urinary creatinine excretion.
4. Fundoscopy – examination of eye grounds is recommended in severe hypertensives only. Mild retinal changes are largely nonspecific except in young patients. Haemorrhages, exudates and papilloedema, only present in severe hypertension, are associated with increased CV risk
5. Brain – silent brain infarctions, lacunar infarctions, white matter lesions and microbleeds are not infrequent in hypertensives, and can be detected by MRI or CT. Availability and costs do not allow indiscriminate use of these techniques. In elderly hypertensives, cognitive tests may help to detect initial brain deterioration.
ECG: at ECG hypotrophy of LV, postinfarction cardiosclerosis, signs of coronary insufficiency, disorders of rhythm and conductivity can be revealed.
Roentgenological signs of LV hypertrophy: moderate dilatation of LV (lengthening of an arch LV and its displacement downwards); expressed of dilatation of LV (“aortic configuration” of heart). Roentgenological signs of LV increase in the left anterior slanting projection in – (circuit on I. H. Rabkin: I, II and III of a degree). The arrow shows a back contour of heart shadow and disappearance of retrocardial space.
Echocardiography: left parasternum access. Increase of intraventriculus septum and posterior wall of LV, increase of LV cavity.
Ophthalmoscope: degrees of retina vessels disorder:
I degree – minimal narrowing of arterioles and non-uniformity of their gleam. The signs of hypertensions retinopathy are absent.
II degree – expressed narrowing of arterioles with sites spasm and expansion of venules at their chiasm with arteries (Salus`s and Gvist`s symptoms). The signs of retinopathy are absent.
III degree – on a background of sharp spasm of arterioles and the expansions of venules are determined by signs of hypertensive retinopathy: oedema and moderate turbidity of the retina; multiple haemorrhage in the retina; “floccular” exudates on the retina.
IV degree – any of set forth above signs + oedema of disk of a visual nerve.
Complications of AH
Hypertensive crisis, impairment of cerebral circulation (haemorrhagic or ischaemic insult), myocardial infarction, nefrosclerosis (contracted kidney), heart failure, dissecting aortic aneurysm, etc.
Treatment of AH
Positive lifestyle changes
The lifestyle measures that are widely recognized to lower BP or cardiovascular risk, and that should be considered are: smoking cessation, weight reduction (and weight stabilization), reduction of excessive alcohol intake, physical exercise, reduction of salt intake, increase in fruit and vegetable intake and decrease in saturated and total fat intake.
Drugs treatment of AH
Groups of antihypertensive preparations: ACE inhibitors; angiotensin receptor antagonists; b-blockers, Ca channel blockers, α-blockers, diuretics.
Table 4 – ACE inhibitors and angiotensin II receptor blockers
|ACE inhibitors |Angiotensin II receptor blockers |
|Benazepril 5–40 mg once/day |Candesartan 8–32 mg once/day |
|Captopril12.5–150 mg tid |Eprosartan 400–1200 mg once/day |
|Fosinopril 10–80 mg once/day |Irbesartan 75–300 mg once/day |
|Quinapril 5–80 mg once/day |Losartan 25–100 mg once/day |
|Ramipril 1.25–20 mg once/day |Olmesartan 20–40 mg once/day |
| |Telmisartan 20–80 mg once/day |
| |Valsartan 80–320 mg once/day |
β-blockers
|Atenolol 25–100 mg once/day |Metoprolol 50–400 mg once/day |
|Betaxolol 5–20 mg once/day |Nadolol 40–320 mg once/day |
|Bisoprolol 2.5–20 mg once/day |Penbutolol 10–20 mg once/day |
|Carvedilol 6.25–25 mg tid |Pindolol 5–30 mg tid |
|Carvedilol 20–80 mg once/day |Propranolol 20–160 mg tid |
|Labetalol 100–900 mg tid |Propranolol 60–320 mg once/day |
|Metoprolol 25–150 mg tid |Timolol 10–30 mg tid |
Goals of the treatment:
– the primary goal of treatment is to achieve maximum reduction in the long-term total risk of cardiovascular disease;
– BP should be reduced to at least below 140/90 mmHg (systolic/diastolic) in all hypertensive patients;
– target BP should be at least < 130/80 mmHg in diabetics and in high or very high risk patients, such as those with associated clinical conditions (stroke, myocardial infarction, renal dysfunction, proteinuria);
– in order to more easily achieve goal BP, antihypertensive treatment should be initiated before significant cardiovascular damage develops.
Ca channel blockers
Benzodiazepine derivatives:
Diltiazem, sustained release (60–180 mg tid); diltiazem, extended release (120–360 mg once/day); selected adverse effects: headache, dizziness, asthenia, flushing, oedema, negative inotropic effect; possibly liver dysfunction; comments: contraindicated in heart failure due to systolic dysfunction, in sick sinus syndrome, or in greater than 1st degree atrioventricular block.
Diphenylalkylamine derivatives:
Verapamil (40–120 mg tid); verapamil, sustained release (120–480 mg once/day); selected adverse effects: same as for benzodiazepine derivatives, plus constipation; comments: same as for benzodiazepine derivatives.
Dihydropyridines:
Amlodipine (2.5–10 mg once/day), isradipine (2.5–10 mg tid), felodipine (2.5–20 mg once/day), nifedipine, extended release (30–90 mg once/day).
Selected adverse effects: dizziness, flushing, headache, weakness, nausea, heartburn, pedal oedema, tachycardia; comments: contraindicated in heart failure, possibly except for amlodipine. Use of short acting nifedipine is possibly associated with higher MI rate.
Diuretics
Thiazide type diuretics: chlorothiazide 62.5–500 mg tid (max.:1000), chlorthalidone 12.5–50 mg once/day, indapamide 1.25–5 mg once/day.
K-sparing diuretics: amiloride 5–20 mg once/day, spironolactone 25–100 mg once/day, triamterene 25–100 mg once/day.
Adrenergic modifiers
α2-Agonists (central acting): clonidine 0.05–0.3 mg tid, guanabenz 2–16 mg tid, guanfacine 0.5–3 mg once/day, methyldopa 250–1000 mg tid;
α-Blockers: doxazosin 1–16 mg once/day, prazosin 1–10 mg tid, terazosin 1–20 mg once/day; peripheral-acting adrenergic blockers: guanethidine 10–50 mg once/day, rauwolfia alkaloids 50–100 mg once/day, reserpine 0.05–0.25 once/day.
Combination of drugs used for hypertension (mg/mg)
Diuretic/diuretic:
– triamterene/hydrochlorothiazide 37.5/25, 50/25, 75/50;
– spironolactone/hydrochlorothiazide 25/25, 50/50.
β-Blocker/diuretic:
– nadolol/bendroflumethiazide 40/5, 80/5;
– timolol/hydrochlorothiazide 10/25;
– bisoprolol/hydrochlorothiazide 2.5/6.25, 5/6.25, 10/6.25.
Adrenergic inhibitor/diuretic:
– guanethidine/hydrochlorothiazide 10/25;
– methyldopa/hydrochlorothiazide 250/15, 250/25, 500/30, 500/50.
ACE inhibitor/diuretic:
– enalapril/hydrochlorothiazide 5/12.5, 10/25;
– lisinopril/hydrochlorothiazide 10/12.5, 20/12.5, 20/25.
Angiotensin II receptor blocker/diuretic:
– valsartan/hydrochlorothiazide 80/12.5, 160/12.5;
– irbesartan/hydrochlorothiazide 75/12.5, 150/12.5, 300/12.5.
Ca channel blocker/ACE inhibitor:
– amlodipine/benazepril 2.5/10, 5/10, 5/20, 10/20;
– felodipine (extended-release)/enalapril 5/5.
Conditions favouring the use of some antihypertensive drugs versus others
Thiazide diuretics: isolated systolic hypertension (elderly), heart failure, hypertension in blacks.
Beta-blockers: angina pectoris, postmyocardial infarction, heart failure, tachyarrhythmias, glaucoma, pregnancy.
Calcium antagonists (dihydropyridines): isolated systolic hypertension (elderly), angina pectoris, LV hypertrophy, carotid/coronary atherosclerosis, pregnancy, hypertension in blacks.
Calcium antagonists (verapamil/diltiazem): angina pectoris, carotid atherosclerosis, supraventricular tachycardia.
ACE inhibitors: heart failure, LV dysfunction, postmyocardial infarction, diabetic nephropathy, non-diabetic nephropathy, LV hypertrophy, carotid atherosclerosis, proteinuria/microalbuminuria, atrial fibrillation, metabolic syndrome.
Angiotensin receptor antagonists: heart failure, postmyocardial infarction, diabetic nephropathy, proteinuria/microalbuminuria, atrial fibrillation, metabolic syndrome, ACEI-induced cough, LV hypertrophy.
Diuretics (antialdosterone): heart failure, postmyocardial infarction.
Loop diuretics: end stage renal disease, heart failure.
Table 5 – Antihypertensive treatment: preferred drugs
|Clinical signs |Drugs |
|Subclinical organ damage |
|LVH |ACEI, CA, ARB |
|Asymptomatic atherosclerosis |CA, ACEI |
|Microalbuminuria |ACEI, ARB |
|Renal dysfunction |ACEI, ARB |
|Clinical event |
|Previous stroke |any BP lowering agent |
|Previous MI |BB, ACEI, ARB |
|Angina pectoris |BB, CA |
|Heart failure |diuretics, BB, ACEI, ARB, |
| |antialdosterone agents |
|Atrial fibrillation |
|Recurrent |ARB, ACEI |
|Permanent |BB, non-dihydropiridine CA |
|ESRD/proteinuria |ACEI, ARB, loop diuretics |
|Peripheral artery disease |CA |
|Condition |
|ISH (elderly) |diuretics, CA |
|Metabolic syndrome |ACEI, ARB, CA |
|Diabetes mellitus |ACEI, ARB |
|Pregnancy |CA, methyldopa, BB |
|Blacks |diuretics, CA |
|Abbreviations: LVH: left ventricular hypertrophy; ISH: isolated systolic hypertension; |
|ESRD: renal failure; ACEI: ACE inhibitors; ARB: angiotensin receptor |
|antagonists; CA: calcium antagonists; BB: β-blockers |
Table 6 – Compelling and possible contraindications to antihypertensive drugs use
|Drugs |Compelling |Possible |
|Thiazide diuretics |Gout |Metabolic syndrome, |
| | |glucose intolerance, |
| | |pregnancy |
|Beta-blockers |Asthma |Peripheral artery disease, |
| |A-V block (grade 2 or 3) |metabolic syndrome, |
| | |glucose intolerance, |
| | |athletes and physically active |
| | |patients, chronic obstructive |
| | |pulmonary disease |
|CA dihydropiridines | |Tachyarrhythmias, |
| | |heart failure |
|CA (verapamil, |A-V block (grade 2 or 3), heart | |
|diltiazem) |failure | |
|ACE inhibitors |Pregnancy, angioneurotic oedema, | |
| |hyperkalaemia, | |
| |bilateral renal artery stenosis | |
|Angiotensin receptor |Pregnancy, hyperkalaemia, | |
|antagonists |bilateral renal artery stenosis | |
|Diuretics |Renal failure, hyperkalaemia | |
|(antialdosterone) | | |
Causes of resistant hypertension
Poor adherence to therapeutic plan, failure to modify lifestyle including weight gain heavy alcohol intake (NB: binge drinking). Continued intake of drugs that raise blood pressure (licorice, cocaine, glucocorticoids, non-steroid anti-inflammatory drugs, etc.). Obstructive sleep apnoea. Unsuspected secondary cause. Irreversible or scarcely reversible organ damage. Volume overload due to inadequate diuretic therapy, progressive renal insufficiency, high sodium intake, hyperaldosteronism. Causes of spurious resistant hypertension: isolated office (white-coat) hypertension, failure to use large cuff on large arm, pseudohypertension.
Treatment of associated risk factors
Lipid lowering agents
All hypertensive patients with established cardiovascular disease or with type 2 diabetes should be considered for statin therapy aiming at serum total and LDL cholesterol levels of, respectively, < 4.5 mmol/l (175 mg/dl) and < 2.5 mmol/l (100 mg/dl), and lower, if possible.
Hypertensive patients without overt cardiovascular disease but with high cardiovascular risk (≥ 20% risk of events in 10 years) should also be considered for statin treatment even if their baseline total and LDL serum cholesterol levels are not elevated.
Antiplatelet therapy
Antiplatelet therapy, in particular low-dose aspirin, should be prescribed to hypertensive patients with previous cardiovascular events, provided that there is no excessive risk of bleeding.
Low-dose aspirin should also be considered in hypertensive patients without a history of cardiovascular disease if older than 50 years, with a moderate increase in serum creatinine or with a high cardiovascular risk. In all these conditions, the benefit-to-risk ratio of this intervention (reduction in myocardial infarction greater than the risk of bleeding) has been proven favourable.
To minimize the risk of haemorrhagic stroke, antiplatelet treatment should be started after achievement of BP control.
Glycaemic control
Effective glycaemic control is of great importance in patients with hypertension and diabetes.
In these patients dietary and drug treatment of diabetes should aim at lowering plasma fasting glucose to values ≤ 6 mmol/l (108 mg/dl) and glycated haemoglobin of < 6.5%.
Hypertensive crisis
Hypertensive crisis (HC) is a sudden sharp increase in BP. If it is not treated promptly, it can lead to stroke, coma and even death.
Causes of hypertensive crisis
Chronic hypertension with acute exacerbation (most common):
1. Renovascular hypertension.
2. Parenchymal renal disease:
– acute glomerulonephritis,
– renal infarction,
– vasculitis.
3. Sclerodermatous renal crisis.
4. Drug ingestion:
– tricyclic antidepressants,
– monoamine oxidase inhibitors,
– cocaine,
– amphetamines.
5. Antihypertensive drug withdrawal or failed compliance:
– centrally acting antihypertensives (e.g., clonidine),
– peripheral alpha blockers (e.g., prazosin),
– β-blocker acute withdrawal.
6. Preeclampsia and eclampsia.
7. Autonomic hyperactivity:
– Guillain-Barre syndrome,
– spinal cord injury.
8. Pheochromocytoma.
Signs of HC: sudden acute onset, high level of BP increase, blood vessels and organs damage. HC depending on presence or absence of the organ affection is divided into complicated and uncomplicated.
Features of complicated hypertensive crisis:
1. With acute progress of organ damage: heart attack and myocardial infarction, transitory ischaemic attack and stroke, aortic dissecting, unstable stenocardia, acute LV insufficiency (cardiac asthma, pulmonale oedema), arrhythmia, eclampsia, bleeding, acute hypertensive encephalopathy.
2. HC severe and potentially life-threatening increase in blood pressure. These conditions require immediate in the course of the 1 hour BP reduction.
3. Treatment in ward of intensive therapy with the use of parental drugs is necessary.
Parental therapy of complicated hypertensive crisis
Nitroglycerin
Highly effective in setting of coronary ischaemia, acute coronary syndromes. The dose is 5–100 µg/min as IV infusion. Start 5–10 µg/min, then may be up to > 200 µg/min parenteral especially in patients where Na nitroprusside is relatively contraindicated and in patients with ischaemic heart disease, impaired renal or hepatic function. Onset: immediate. Duration: 1–5 min. May cause headache, tachycardia, vomiting, methemoglobinemia. Excellent for titrating blood pressure in setting of coronary ischaemia.
Labetalol (trandate)
Mixed alpha/beta blocker, excellent for most hypertensive emergencies. The dose is 20–80 mg IV bolus every 10 minutes or 0.5–2 mg/min infusion IV. Start 20 mg IV, then 20–80 mg q10 min parenteral, or start with 0.5 mg/min infusion, then 1–2 mg/min (may be up to 4 mg/min) IV infusion up to 300 mg/d max. Onset: 5–10 min. Duration: 1–5 min. May cause headache, tachycardia, vomiting, methemoglobinemia. Excellent for titrating blood pressure in setting of coronary ischaemia.
Avoid in patients with heart block, bradycardia, CHF, severe asthma or bronchospasm. First or second line for eclampsia; excellent in catecholamine surges.
Enalaprilat
Intravenous formulation of enalapril (ACE inhibitor). The dose is 1.25–5.0 mg q6 hour IV (duration of action is 6 hours). Onset of action: in 15–30 minutes. Duration: 6 hours or more. Highly variable response; precipitous BP drop in high-renin states, rarely angioedema, hyperkalemia, or acute renal failure.
May be most useful in acute cardiogenic pulmonary oedema. Avoid in acute myocardial infarction.
Sodium nitroprusside
Standard rapidly acting agent is effective in many cases. The dose is 0.25–8 µg/kg/minute as IV infusion, start with 0.3–0.5 µg/kg/min (about 20–50 µg/min), then 1–3 µg/kg/min IV (max:< 10 µg/kg/min) (50 mg in 250 ml D5W). Onset: 0.5–1 min. Duration: 2–5 min. Adverse effects: hypotension, N and V, apprehension, cyanide (thiocyanate level > 10 mg/dl is toxic; > 20 mg/dl may be fatal) toxicity convulsion, twitching, psychosis, dizziness, etc.
Nitroprusside has decreased efficacy in renal failure. Toxic levels of cyanide build up rapidly in patients with renal failure. Nausea, vomiting, muscle twitching and sweating can occur.
Diltiazem (cardizem)
Initial dose is 0.25 mg/kg over 2 min, followed by infusion of 0.35 mg/kg at an initial rate of 10 mg/hour. Onset: 3–30 min. Adverse effects: excessive hypotension, flushing, rarely amblyopia.
Hydralazine (apresoline)
Indicated primarily for eclampsia. The dose is 10–50 mg IV or IM titrate to effect (onset < 20 minutes, duration 3–8 hours). Onset: 10–20 min. Duration: 3–8 h. Adverse effects: tachycardia, flushing, contraindicated in angina or aortic dissection. Can be given in IM as well, 10–50 mg (onset: 20–30 minutes). Tachycardia, flushing, headache, vomiting, increased angina may occur.
Nicardipine (cardene)
IV formulation is available, though not commonly used. The dose is 5–15 mg/hr IV. Onset: 5–10 minutes. Duration: 1–4 hours. Do not use in acute CHF or with coronary ischaemia. May be most useful for hypertension in setting of subarachnoid haemorrhage.
Esmololol (breviblock)
Very half life (2–4 minutes) nonselective ß-blockade. The dose is 250–500 µg/kg/min for 1 minute, then 50–100 µg/kg for 4 minutes. Sequence may be repeated, and continuous drip may be maintained. Onset of action is 1–2 minutes; 10–20 minute duration. Mainly for acute aortic dissection, perioperatively, acute coronary ischaemia. May be used with caution in acute MI with depressed LV to modulate heart rate. Very close monitoring is required, and fluid load is large with this agent.
Phentolamine
Mainly for catecholamine surges (pure alpha-adrenergic blockade). The dose is 5–15 mg IV. Onset: in 1–2 minutes. Duration: 3–10 minutes. Tachycardia, flushing and headache may occur.
Features of uncomplicated hypertensive crisis:
1. Without progress of organ damage.
2. HC with potentially life-threatening increase in BP. Reduction of BP is necessary in several hours. Symptoms of HC include: severe chest pain, severe headache, stiff or sore neck, enlarged pupils, fast or slow heartbeat, increased sensitivity of eyes to light, increased sweating (possibly with fever or cold, clammy skin), nausea and vomiting.
3. Hospitalization is not obligatory with the use of per os PO and intramuscular drugs.
Therapy of uncomplicated hypertensive crisis
Nifedipine
The dose is 10–20 mg may be under tongue. Adverse effects: headache, tachycardia, angina pectoris, reddening of skin.
Clonidine (catapres)
PO 0.2 mg, followed by 0.1 mg/hr to total of 0.8 mg until the diastolic BP is 9 mm), which may result in a clinically remarkable left-to-right shunt, blood will shunt from the left atrium to the right atrium. This extra blood from the left atrium may cause a volume overload of both the right atrium and the right ventricle. If untreated, this condition can result in enlargement of the right side of the heart and ultimately heart failure.
Any process that increases the pressure in the left ventricle can cause worsening of the left-to-right shunt. This includes hypertension, which increases the pressure that the left ventricle has to generate in order to open the aortic valve during ventricular systole, and coronary artery disease which increases the stiffness of the left ventricle, thereby increasing the filling pressure of the left ventricle during ventricular diastole.
The right ventricle will have to push out more blood than the left ventricle due to the left-to-right shunt. This constant overload of the right side of the heart will cause an overload of the entire pulmonary vasculature. Eventually pulmonary hypertension may develop.
Pulmonary hypertension will cause the right ventricle to face increased afterload in addition to the increased preload that the shunted blood from the left atrium to the right atrium caused. The right ventricle will be forced to generate higher pressures to try to overcome pulmonary hypertension. This may lead to right ventricular failure (dilatation and decreased systolic function of the right ventricle) or elevations of the right sided pressures relative to left sided pressures.
When the pressure in the right atrium rises to the level in the left atrium, there will no longer be a pressure gradient between these heart chambers, and the left-to-right shunt will diminish or cease.
If left uncorrected, the pressure in the right side of the heart will be greater than the left side of the heart. This will cause the pressure in the right atrium to be higher than the pressure in the left atrium. This will reverse the pressure gradient across the ASD, and the shunt will reverse; a right-to-left shunt will exist. This phenomenon is known as Eisenmenger's syndrome.
ASDs can be classified by location: ostium secundum (defect in the fossa ovalis – in the central (or middle) part of the atrial septum), sinus venosus (defect in the posterior aspect of the septum, near the superior vena cava or inferior vena cava), or ostium primum (defect in the anteroinferior aspect of the septum, a form of endocardial cushion defect).
In ASD, shunting is left to right initially. Most small ASDs close spontaneously during the 1st few years of life. However, persistent, large shunts result in right atrial and ventricular volume overload, pulmonary artery hypertension, elevated pulmonary vascular resistance, and right ventricular hypertrophy. Atrial fibrillation may occur later. Ultimately, the increase in right-sided pressure may result in a bidirectional atrial shunt with cyanosis during adulthood.
Symptoms
Most small ASDs are asymptomatic. Symptoms: exercise intolerance, dyspnoea during exertion, fatigue, atrial arrhythmias sometimes with palpitations, cerebral or systemic thromboembolic disorders.
Rarely, when an ASD is undiagnosed or untreated, Eisenmenger's syndrome develops.
Physical examination: (ejection systolic) murmur at the upper left sternal border; split, fixed S2 at the upper left sternal border; a low-pitched diastolic murmur (due to increased tricuspid flow) at the left lower sternal border.
Diagnosis
Diagnosis is suggested by cardiac examination, chest X-rays, and ECG and confirmed by 2-dimensional echocardiography with colour flow and Doppler studies.
ECG: may show right axis deviation, right ventricular hypertrophy, or right bundle branch block (with rSR′ pattern in V1).
Chest X-rays: show cardiomegaly with dilation of the right atrium and right ventricle, prominent main pulmonary artery segment, and increased pulmonary vascular markings.
Treatment
Most small ostium secundum ASDs (< 3 mm) close spontaneously; about 80% of those between 3 mm and 8 mm close spontaneously by age 18 mo. However, ostium primum and sinus venosus ASDs do not close spontaneously.
Asymptomatic children with a small shunt require annual echocardiography. Because these children are at risk of paradoxical systemic embolization, some centres recommend a catheter-delivered closure device even for small ASDs. However, these devices are not suitable for primum or sinus venosus defects because these defects are near important structures.
Patients with moderate to large defects (e.g., pulmonary to systemic flow ratio > 1.5:1) should have ASD closed, typically between age 2 to 6 yr. Before repair, patients with large shunts and heart failure should be treated with diuretics, digoxin, and ACEI.
Patients with primum ASD require endocarditis prophylaxis; those with secundum or sinus venosus ASD do not.
Ventricular Septal Defect
A ventricular septal defect is one or more openings in the interventricular septum, producing a shunt between ventricles.
VSDs are classified by location: membranous (perimembranous), trabecular muscular, outlet (supracristal or subpulmonary), or inlet defects.
Pathophysiology
During ventricular contraction, or systole, some of the blood from the left ventricle leaks into the right ventricle, passes through the lungs and reenters the left ventricle via the pulmonary veins and left atrium. This has two net effects. First, the circuitous refluxing of blood causes volume overload on the left ventricle. Second, because the left ventricle normally has a much higher systolic pressure (~120 mm Hg) than the right ventricle (~20 mm Hg), the leakage of blood into the right ventricle therefore elevates right ventricular pressure and volume, causing pulmonary hypertension with its associated symptoms (elevated pulmonary artery vascular resistance, right ventricular pressure overload, and right ventricular hypertrophy). Ultimately, the increased pulmonary vascular resistance causes shunt direction to reverse (from the right to the left ventricle), leading to Eisenmenger's syndrome.
Small defects produce a relatively small left-to-right shunt; the pulmonary artery pressure is normal or only slightly increased. Heart failure (HF) and Eisenmenger's syndrome do not develop.
Symptoms
Symptoms depend on defect size and magnitude of the left-to-right shunt. Children with a small VSD are typically asymptomatic and grow and develop normally.
In those with a larger defect, symptoms of HF: poor weight gain, fatigue after feeding, tachypnoea, dyspnoea with feeding. Eventually, untreated patients may develop symptoms of Eisenmenger's syndrome.
Physical examination: holosystolic murmur (with or without thrill) at the lower left sternal border; it is audible shortly after birth. S2 is usually narrowly split with an accentuated pulmonary component; gallop; crackles; hepatomegaly.
Diagnosis
Diagnosis is suggested by clinical examination, supported by chest X-ray and ECG, and established by echocardiography.
Chest X-ray: shows cardiomegaly and increased pulmonary vascular markings.
ECG: shows left ventricular hypertrophy or combined ventricular hypertrophy and, occasionally, left atrial hypertrophy. ECG and chest X-ray are typically normal if the VSD is small.
Echocardiography: reveals pulmonary arterial and RV and RA dilatation with abnormal (paradoxical) ventricular septal motion in the presence of a significant right heart volume overload. The atrial septal defect may be visualized directly by two-dimensional imaging, colour flow imaging, or echocontrast.
Treatment
Small VSDs, particularly muscular septal defects, often close spontaneously during the 1st few years of life. A small defect that remains open does not require medical or surgical therapy.
Moderate-sized defects are less likely to close spontaneously. Diuretics, digoxin, and ACE inhibitors are indicated before surgery if HF develops. If infants do not respond to medical treatment or have large shunts (with pulmonary to systemic flow ratio ≥ 2:1), surgical repair may be done during the 1st few months of life.
All patients with a VSD, regardless of size, should be given endocarditis prophylaxis with antibiotics before dental or surgical procedures that are likely to produce bacteraemia.
Patent Ductus Arteriosus
Patent ductus arteriosus (PDA) is a persistence of the foetal connection (ductus arteriosus) between the aorta and pulmonary artery after birth, resulting in a left-to-right shunt.
Patent ductus arteriosus (PDA) accounts for 5 to 10% of congenital heart anomalies; the male:female ratio is 1:3.
Pathophysiology
In the developing fetus, the ductus arteriosus (DA) is the vascular connection between the pulmonary artery and the aortic arch that allows most of the blood from the right ventricle to bypass the fetus' fluid-filled compressed lungs. During foetal development, this shunt protects the right ventricle from pumping against the high resistance in the lungs, which can lead to right ventricular failure if the DA closes inutero.
When the newborn takes its first breath, the lungs open and pulmonary vascular resistance decreases. After birth, the lungs release bradykinin to constrict the smooth muscle wall of the DA and reduce bloodflow through the DA as it narrows and completely closes, usually within the first few weeks of life.
In normal newborns, the DA is substantially closed within 12–24 hours after birth, and is completely sealed after three weeks. The primary stimulus for the closure of the ductus is the increase in neonatal blood oxygen content. Withdrawal from maternal circulating prostaglandins also contributes to ductal closure. The residual scar tissue from the fibrotic remnants of DA, called the ligamentum arteriosum, remains in the normal adult heart.
The ductus arteriosus is a normal foetal blood vessel that closes soon after birth. In a patent ductus arteriosus (PDA) the vessel does not close and remains “patent” resulting in irregular transmission of blood between two of the most important arteries close to the heart, the aorta and the pulmonary artery. In patent ductus arteriosus, pulmonary blood flow, LA and LV volumes, and ascending AO volume are increased.
Physiologic consequences depend on ductal size. A small ductus rarely produces symptoms. A large (and short) ductus causes a large left-to-right shunt. Over time, a large shunt results in pulmonary artery hypertension and elevated pulmonary vascular resistance, ultimately leading to Eisenmenger's syndrome.
Symptoms
Clinical presentation depends on PDA size and gestational age at delivery. Infants and children with a small PDA are generally asymptomatic; infants with a large PDA present with signs of HF.
Physical examination:
1. Most children with a small PDA have normal heart sounds and peripheral pulses.
2. A grade 1 to 3/6 continuous machinery murmur is heard best in the upper left sternal border.
3. A gallop rhythm may be audible if HF develops.
4. Left subclavicular thrill.
Diagnosis
Diagnosis is suggested by clinical examination, supported by chest X-rays and ECG, and established by 2-dimensional echocardiography with colour flow and Doppler studies.
Chest X-ray and ECG are typically normal if the PDA is small. If the shunt is significant it show prominence of the left atrium, left ventricle, and ascending aorta and increased pulmonary vascular markings. ECG may show left ventricular hypertrophy.
Treatment
In premature infants with compromised respiratory status, the PDA can sometimes be closed by using a prostaglandin synthesis inhibitor (e.g., indomethacin IV q 12 h for 3 doses; or ibuprofen 10 mg/kg po followed by 2 doses of 5 mg/kg at 24-h intervals) with or without fluid restriction. If this treatment is ineffective, surgical ligation is indicated.
In full-term infants, indomethacin is usually ineffective. For a large PDA, surgical ligation and division are typically done electively at age 6 mo to 3 yr. If HF develops, surgery can be done earlier after medical management for HF.
Coarctation of Aorta
Coarctation of aorta is localized narrowing of the aortic lumen. Coarctation of aorta accounts for 8 to 10% of congenital heart anomalies. It occurs in 10 to 20% of patients with Turner's syndrome. The male:female ratio is 2:1.
Pathophysiology
There are three types:
Preductal coarctation. The narrowing is proximal to the ductus arteriosus. Blood flow to the aorta that is distal to the narrowing is dependent on the ductus arteriosus; therefore severe coarctation can be life-threatening. Preductal coarctation results when an intracardiac anomaly during foetal life decreases blood flow through the left side of the heart, leading to hypoplastic development of the aorta. This is the type seen in approximately 5% of infants with Turner’s syndrome.
Ductal coarctation. The narrowing occurs at the insertion of the ductus arteriosus. This kind usually appears when the ductus arteriosus closes.
Postductal coarctation. The narrowing is distal to the insertion of the ductus arteriosus. Even with an open ductus arteriosus blood flow to the lower body can be impaired. This type is most common in adults. It is associated with notching of the ribs (because of collateral circulation), hypertension in the upper extremities, and weak pulses in the lower extremities.
Postductal coarctation is most likely the result of the extension of a muscular artery (ductus arteriosus) into an elastic artery (aorta) during foetal life, where the contraction and fibrosis of the ductus arteriosus upon birth subsequently narrows the aortic lumen.
Physiologic consequences include increased left ventricular pressure overload, left ventricular hypertrophy, overperfusion of the upper part of the body including the brain, and malperfusion of the abdominal organs and lower extremities.
Symptoms
If coarctation is significant, circulatory shock with renal insufficiency (oliguria or anuria) and metabolic acidosis may develop during the neonatal period and may mimic findings of other systemic disorders such as sepsis.
Less severe coarctation may be asymptomatic during infancy. Patients may have such symptoms:
– headache;
– chest pain;
– fatigue;
– leg claudication during physical activities.
Physical examination: hypertension in the upper extremities, diminished or delayed femoral pulses, low or unobtainable arterial BP in the lower extremities; a grade 2 to 3/6 ejection systolic murmur is best heard in the left interscapular area.
Diagnosis
Diagnosis is suggested by clinical examination (including BP measurement in all 4 extremities), supported by chest X-rays and ECG, and established by 2-dimensional echocardiography with colour flow and Doppler studies or with CT or MR angiography.
Chest X-ray: shows coarctation as a “3” sign in the upper left mediastinal shadow. Heart size is normal unless HF supervenes. Dilated intercostal collateral arteries may erode the 3rd to 8th ribs, making the ribs notched, but notching is seldom seen before age 5 yr.
ECG: shows left ventricular hypertrophy but may be normal. ECG usually shows right ventricular hypertrophy or right bundle branch block rather than left ventricular hypertrophy.
Treatment
Symptomatic neonates require cardiopulmonary stabilization with infusion of prostaglandin E1 (0.05 to 0.10 μg/kg/min – may titrate up to 0.4 μg/kg/min, then back down to lowest effective dose) to reopen the constricted ductus arteriosus. Then, pulmonary artery blood can perfuse the descending aorta through the ductus, improving systemic perfusion and reversing metabolic acidosis. Short-acting inotropic drugs (e.g., dopamine, dobutamine), diuretics, and O2 are used to treat HF.
Before surgery, hypertension may be treated with β-blockers; ACE inhibitors should be avoided. After surgery, hypertension can be treated with β-blockers, ACE inhibitors, or angiotensin II receptor blockers.
The preferred definitive treatment is controversial. Some centres prefer balloon angioplasty with or without stent placement, but others prefer surgical correction and reserve the balloon procedure for recoarctation after surgical correction.
Surgical options include resection and end-to-end anastomosis, patch aortoplasty, and left subclavian flap aortoplasty. Choice depends on anatomy and centre preference. All patients should be given endocarditis prophylaxis before dental or surgical procedures that are likely to produce bacteraemia, regardless of whether surgical correction has been done.
HEART VALVULAR DISEASE
Aortic Regurgitation
Aortic regurgitation is incompetency of the aortic valve causing flow from the aorta into the left ventricle during diastole. Causes include idiopathic valvular degeneration, rheumatic fever, endocarditis, myxomatous degeneration, congenital bicuspid aortic valve, aortic root dilatation or dissection, and connective tissue or rheumatologic disorders.
Aetiology: aortic regurgitation (AR) may be acute or chronic. The primary causes of acute AR are: infective endocarditis and dissection of the ascending aorta; idiopathic degeneration of the aortic valves or root, rheumatic fever, infective endocarditis, myxomatous degeneration (in patients with Marfan’s or Ehlers-Danlos’ syndromes); trauma. In children, the most common cause is a ventricular septal defect with aortic valve prolapse.
Symptoms: acute AR causes symptoms of HF and cardiogenic shock. Chronic AR is typically asymptomatic for years.
Signs: progressive exertional dyspnoea, orthopnoea, paroxysmal nocturnal dyspnoea, palpitations. Chest pain (angina pectoris) affects only about 5% of patients.
Physical examination:
– large-volume pulse with rapid rise and fall (slapping, water-hammer, or collapsing pulse);
– systolic apical or carotid thrill;
– LV impalce displaced downward and laterally, with systolic depression of the entire left parasternal area;
– systolic BP increases while diastolic BP decreases.
Auscultatory findings: normal 1st heart sound (S1); nonsplit, loud, sharp or slapping 2nd heart sound (S2); diastolic murmur is blowing, high-pitched, and decrescendo, beginning soon after the aortic component of S2 (A2). The murmur is heard best when the patient is leaning forward, with breath held at end-expiration. Diastolic murmur heard near the axilla or mid left thorax (Cole-Cecil murmur); mid-to-late diastolic rumble heard at the apex (Austin Flint murmur); sharp sound heard over the femoral pulse (pistol-shot sound, or Traube's sign); femoral systolic bruit distal and a diastolic bruit proximal to arterial compression (Duroziez's murmur).
Visible signs include:
– head bobbing (Musset's sign);
– pulsation of the fingernail capillaries (Quincke's sign, best seen with slight pressure) or uvula (Müller's sign);
– pulsation of the carotid arteries (Corrigan's sign);
– pulsation of the retinal arteries (Becker's sign);
– pulsation of the liver (Rosenbach's sign);
– pulsation of the spleen (Gerhard's sign).
Diagnosis is suspected based on history and physical examination and confirmed by echocardiography.
Doppler echocardiography: is the test of choice to detect and quantify the magnitude of regurgitant blood flow. Two-dimensional echocardiography can quantify aortic root size and anatomy and LV function.
Echocardiography: can also assess severity of pulmonary hypertension secondary to LV failure, detect vegetations or pericardial effusions (e.g., in aortic dissection), and provide information about prognosis.
Radionuclide imaging: may be used to determine LVEF if echocardiographic results are borderline abnormal or if echocardiography is technically difficult.
An ECG: may show repolarization abnormalities with or without QRS voltage criteria of LV hypertrophy, left atrial enlargement, and T-wave inversion with ST-segment depression in precordial leads.
Chest X-ray: may show cardiomegaly and a prominent aortic root in patients with chronic progressive AR. If AR is severe, signs of pulmonary oedema and HF may also be present. Exercise testing may help assess functional capacity and symptoms in patients with documented AR and equivocal symptoms.
Coronary angiography: should be considered before surgery, even if no angina is present, because about 20% of patients with severe AR have significant CAD, which may need concomitant coronary artery bypass graft surgery.
Treatment
Treatment of chronic AR varies by symptoms and degree of LV dysfunction. Patients with symptoms precipitated by normal daily activity or during exercise testing require aortic valve replacement; patients who prefer to avoid surgery may be treated with vasodilators (e.g., long-acting nifedipine 30 to 90 mg po once/day or ACE inhibitors). Also, diuretics or nitrates to reduce preload may be beneficial for severe AR. Patients who do not meet these criteria should be reevaluated by physical examination, echocardiography, and possibly rest-exercise radionuclide cineangiography to measure LV contractility q 6 to 12 mo.
Antibiotic prophylaxis against endocarditis is indicated before procedures that can result in bacteraemia.
Nitroprusside and inotropic agents (dopamine or dobutamine) may be used before surgery in patients with poorly tolerated acute AR to stabilize their clinical condition. In patients with chronic severe AR and heart failure, ACE-inhibitors are the treatment of choice when surgery is contraindicated or in cases with persistent postoperative LV dysfunction. In asymptomatic patients with high blood pressure, the indication for antihypertensive treatment with vasodilators such as ACE-inhibitors or dihydropyridine calcium channel blockers is warranted.
The role of vasodilators in the asymptomatic patients without high blood pressure in order to delay surgery is unproved.
In patients with Marfan’s syndrome, beta-blockers slow the progression of the aortic dilatation and should also be given after operation. In patients with severe AR, the use of beta-blockers should be very cautious because the lengthening of diastole increases the regurgitant volume. However, they can be used in patients with severe LV dysfunction. Recently, enalapril has also been used to delay aortic dilatation in patients with Marfan’s syndrome. Whether the same beneficial effect occurs in patients with bicuspid aortic valves is not known. Patients with AR should be educated on endocarditis prevention and antibiotic prophylaxis.
Indications for surgery
In symptomatic acute AR, urgent intervention is indicated (aortic valve replacement).
In chronic AR, the goals of the operation are to improve outcome, to diminish symptoms, to prevent the development of postoperative heart failure and cardiac death, and to avoid aortic complications in patients who present with aortic aneurysm. Surgery should be considered in asymptomatic patients with severe AR and impaired LV function at rest (resting EF 50% and/or LV end-diastolic diameter 70 mm and/or end-systolic diameter 50 mm (or 25 mm/m² BSA)) since the likelihood of early development of symptoms is high, perioperative mortality is low, and postoperative results are excellent.
Indications for surgery in aortic regurgitation: severe AR; symptomatic patients (dyspnoea, NYHA class II, III, IV or angina) (IB); asymptomatic patients with resting LVEF ≤ 50% (IB); patients undergoing CABG or surgery of ascending aorta, or on another valve (IC); asymptomatic patients with resting LVEF > 50% with severe LV dilatation; end-diastolic dimension > 70 mm or (IIa, C); ESD > 50 mm (or > 25 mm/m2 BSA) (IIa, C); whatever the severity of AR; patients who have aortic root disease with maximal aortic diameter: ≥ 45 mm for patients with Marfan's syndrome (IC); ≥ 50 mm for patients with bicuspid valves (IIa, C); ≥ 55 mm for other patients (IIa, C).
Aortic Stenosis
Aortic stenosis (AS) is narrowing of the aortic valve obstructing blood flow from the left ventricle to the ascending aorta during systole. Causes include a congenital bicuspid valve, idiopathic degenerative sclerosis with calcification, and rheumatic fever.
Aetiology and pathophysiology
The most common cause of AS in patients < 70 yr is a congenital bicuspid aortic valve. Congenital AS affects more males.
Causes include: congenital bicuspid valve, idiopathic degenerative sclerosis with calcification, rheumatic fever.
The left ventricle (LV) gradually hypertrophies in response to AS. Significant LV hypertrophy causes diastolic dysfunction and, with progression, may lead to decreased contractility, ischaemia, or fibrosis, any of which may cause systolic dysfunction and heart failure (HF). LV chamber enlargement is a late finding unless there is coexisting MI. Patients with AS have a higher incidence of GI bleeding (called Heyde's syndrome) because the high shear stress of stenotic valves makes multimeric von Willebrand's factor more susceptible to cleavage by a plasma metalloprotease and may increase platelet clearance. GI bleeding may also be due to angiodysplasia.
Symptoms
Congenital AS is usually asymptomatic until at least age 10 or 20 yr, when symptoms may begin to develop insidiously: exertional syncope, angina, dyspnoea (SAD triad); ventricular fibrillation leading to sudden death, exertional or nonexertional syncope, exertional angina pectoris.
Physical examination: carotid and peripheral pulses that are reduced in amplitude and slow rising (pulsus parvus, mollus et tardus); the LV impulse may become displaced; systolic BP may be high with mild or moderate AS and falls as AS becomes more severe; systolic thrill, which felt best at the left upper sternal border; S1 is normal and S2 is single because aortic valve closing is delayed and merges with the pulmonic (P2) component of S2. Ejection murmur, heard best at the right and left upper sternal border when a patient who is sitting upright leans forward. The murmur typically radiates to the right clavicle and both carotid arteries
But in elderly patients, vibration of the unfused cusps of calcified aortic valve leaflets may transmit a louder, more high-pitched, “cooing” or musical sound to the cardiac apex, with softening or absence of the murmur parasternally (Gallavardin's phenomenon), thereby mimicking mitral regurgitation.
Diagnosis: diagnosis is suspected clinically and confirmed by echocardiography.
Two-dimensional transthoracic echocardiography: is used to identify a stenotic aortic valve and possible causes, to quantify LV hypertrophy and degree of diastolic or systolic dysfunction, and to detect coexisting valvular heart disorders (aortic regurgitation, mitral valve disorders) and complications (e.g., endocarditis).
Doppler echocardiography is used to quantify degree of stenosis by measuring aortic valve area, jet velocity, and transvalvular systolic pressure gradient. A valve area of 0.5 to 1.0 cm² or a mean gradient > 45 to 50 mm Hg represents severe stenosis.
Cardiac catheterization is necessary to determine whether coronary artery disease (CAD) is the cause of angina and, occasionally, to resolve differences between clinical and echocardiographic findings.
An ECG is obtained. ECG typically shows changes of LV hypertrophy with or without an ischaemic ST- and T-wave pattern.
Chest X-ray findings may include calcification of the aortic cusps (seen on the lateral projection or on fluoroscopy) and evidence of HF. Heart size may be normal or only mildly enlarged.
Treatment
Asymptomatic patients with gradients of 25 to 50 mm Hg or valve area < 1.0 cm² are at higher risk of developing symptoms in the next 2 yr, but generally elective valve replacement is not required in the absence of symptoms. Valve replacement is indicated for patients who have moderate or severe AS and primarily require CABG. Surgery may be indicated for patients who become hypotensive during exercise treadmill testing and for those with LV ejection fraction < 50%. Patients with ventricular arrhythmias and severe LV hypertrophy are also often referred for surgery, but benefits are less clear. Recommendations for patients without any of these qualifying conditions include more frequent monitoring for progression of symptoms, LV hypertrophy, gradients, and valve area with medical management as needed. It is unclear whether statins reduce the progression of AS. Other drugs may be detrimental, especially those that can cause hypotension. Small studies suggest that perhexilene maleate may decrease symptoms. Nitroprusside has been used as a temporizing measure to reduce afterload in patients with decompensated HF in the hours before valve replacement, but because this drug can have the same effect as rapid-acting nitrates, it must be used cautiously and monitoring is required.
Symptomatic patients should undergo valve replacement or balloon valvotomy. Valve replacement is indicated for virtually all who can tolerate surgery. In younger patients, the patient's own pulmonic valve can be used, providing good durability; a bioprosthesis is then used to replace the pulmonic valve (Ross procedure). Most often, the aortic valve is replaced with a mechanical or bioprosthetic valve. Preoperative evaluation for CAD is indicated so that CABG and valve replacement, if indicated, can be done during the same procedure.
Balloon valvotomy is used primarily in children and very young adults with congenital AS. In older patients who are unfit for surgery, balloon valvuloplasty can provide temporary relief of symptoms, perhaps for 6 to 12 mo, and can be repeated in selected patients.
Although several retrospective reports have shown beneficial effects of statins and ACE-inhibitors, data are still conflicting and the only randomized trial assessing the effect of statin therapy is negative. It is, therefore, too early for treatment recommendations. Symptomatic patients require early surgery, as no medical therapy for AS is able to delay the inevitability of surgery. However, patients who are unsuitable candidates for surgery may be treated with digitalis, diuretics, ACE-inhibitors, or angiotensin receptor blockers if they are experiencing heart failure. Beta-blockers should be avoided in these circumstances. In selected patients with pulmonary oedema, nitroprusside can be used under haemodynamic monitoring.
Indications for aortic valve replacement in aortic stenosis: patients with severe AS and any symptoms IB; patients with severe AS undergoing coronary artery bypass surgery, surgery of the ascending aorta, or on another valve (IC); asymptomatic patients with severe AS and systolic LV dysfunction (LVEF < 50%) unless due to other cause (IC); asymptomatic patients with severe AS and abnormal exercise test showing symptoms on exercise (IC); asymptomatic patients with severe AS and abnormal exercise test showing fall in blood pressure below baseline (IIa, C); patients with moderate AS undergoing coronary artery bypass surgery, surgery of the ascending aorta or another valve (IIa, C); asymptomatic patients with severe AS and moderate-to-severe valve calcification, and a rate of peak velocity progression ≥ 0.3 m/s per year (IIa, C); AS with low gradient (< 40 mmHg) and LV dysfunction with contractile reserve (IIa, C); asymptomatic patients with severe AS and excessive LV hypertrophy ( ≥ 15 mm) unless this is due to hypertension (IIb, C); AS with low gradient (< 40 mmHg) and LV dysfunction without contractile reserve (IIb, C); asymptomatic patients with severe AS and abnormal exercise test showing complex ventricular arrhythmias (IIb, C).
Mitral Regurgitation
Mitral regurgitation (MR) is incompetency of the mitral valve causing flow from the left ventricle (LV) into the left atrium during systole.
Aetiology and pathophysiology
MR may be acute or chronic. Causes of acute MR include: ischaemic papillary muscle dysfunction or rupture; infective endocarditis; acute rheumatic fever; spontaneous, traumatic, or ischaemic tears or rupture of the mitral valve leaflets or subvalvular apparatus; acute dilation of the LV due to myocarditis or ischaemia; mechanical failure of a prosthetic mitral valve.
Common causes of chronic MR include: those of acute MR; myxomatous degeneration of the mitral leaflets or chordae tendineae; mitral valve prolapse (MVP); mitral annular enlargement; nonischemic papillary muscle dysfunction; calcification of the mitral annulus (mainly in elderly women).
Acute MR may cause acute pulmonary oedema and biventricular failure with cardiogenic shock or sudden cardiac death.
Symptoms: acute MR causes the same symptoms and signs as acute heart failure and cardiogenic shock.
Most patients with chronic MR have dyspnoea, fatigue (due to heart failure), orthopnoea, and palpitations (often due to AF).
Physical examination: LV impulse that is sustained, enlarged, and displaced downward and to the left; diffuse precordial lift occurs with severe MR because the LA enlarges, causing anterior cardiac displacement; diffuse precordial lift; regurgitant murmur (or thrill) may also be palpable in severe cases.
On auscultation: the 1st heart sound (S1) may be soft (or occasionally loud). The 3rd heart sound (S3) is at the apex; (pansystolic) murmur, heard best at the apex when the patient is in the left lateral decubitus position. The murmur radiates toward the left axilla.
Diagnosis is suspected clinically and confirmed by echocardiography.
Doppler echocardiography is used to detect regurgitant flow and help quantify its severity; 2-dimensional echocardiography is used to determine the cause of MR and to detect pulmonary hypertension.
If endocarditis or valvular thrombi are suspected, transoesophageal echocardiography (TEE) can provide a more detailed view of the mitral valve and LA. TEE is also indicated when mitral valve repair instead of replacement is being considered to confirm the anatomy in more detail.
An ECG shows LA enlargement and LV hypertrophy with or without ischaemia. Sinus rhythm is usually present when MR is acute because the atria have not had time to stretch and remodel.
Chest X-ray in acute MR may show pulmonary oedema; abnormalities in cardiac silhouette are not evident unless an underlying chronic disorder is also present. Chest X-ray in chronic MR may show LA and LV enlargement. It may also show pulmonary vascular congestion and pulmonary oedema with heart failure.
Cardiac catheterization is done before surgery, mainly to determine whether coronary artery disease (CAD) is present. A prominent systolic c-v wave is seen on pulmonary artery occlusion pressure (pulmonary capillary wedge pressure) tracings during ventricular systole. Ventriculography can be used to quantify MR.
Treatment
Acute MR requires emergency mitral valve repair or replacement; patients with ischaemic papillary muscle rupture may also require coronary revascularization. Pending surgery, nitroprusside or nitroglycerin infusion may be used to reduce afterload, thus improving forward stroke volume and reducing ventricular and regurgitant volume.
Indications for surgery in severe chronic organic mitral regurgitation: symptomatic patients with LVEF > 30% and ESD < 55 mm (IB); asymptomatic patients with LV dysfunction (ESD > 45 mm and/or LVEF ≤ 60%) (IC); asymptomatic patients with preserved LV function and atrial fibrillation or pulmonary hypertension (systolic pulmonary artery pressure > 50 mm Hg at rest) (IIa, C); patients with severe LV dysfunction (LVEF < 30% and/or ESD > 55 mm) refractory to medical therapy with high likelihood of durable repair, and low comorbidity (IIa, C); asymptomatic patients with preserved LV function, high likelihood of durable repair, and low risk for surgery (IIb, B); patients with severe LV dysfunction (LVEF < 30% and/or ESD > 55 mm) refractory to medical therapy with low likelihood of repair and low comorbidity (IIb, C).
Definitive treatment of chronic MR is also mitral valve repair or replacement, but patients with asymptomatic or mild chronic MR and no pulmonary hypertension or AF may do well with periodic monitoring. ACE inhibitors or angiotensin receptor blockers are used to decrease left ventricular preload and afterload. They are used in patients with moderate mitral insufficiency to delay dilation of the LV. Loop diuretics such as furosemide are helpful in patients with exertional or nocturnal dyspnoea. Digoxin may reduce symptoms in patients with atrial fibrillation or those in whom valve surgery is not appropriate. The ideal timing for surgery is uncertain, but intervention before ventricular decompensation (defined as echocardiographic end-diastolic dimension > 70 mm, end-systolic dimension > 45 mm, and ejection fraction < 60%) improves outcomes and decreases the chance of worsening LV function. After decompensation, ventricular function becomes dependent on the afterload reduction of MR, and in about 50% of decompensated patients, valve replacement causes a markedly depressed ejection fraction. Antibiotic prophylaxis is indicated before procedures that can cause bacteraemia.
Mitral Stenosis
Mitral stenosis (MS) is narrowing of the mitral orifice impeding blood flow from the left atrium to the left ventricle.
Aetiology and pathophysiology
Rheumatic fever, less common causes include bacterial endocarditis, SLE, atrial myxoma, RA malignant carcinoid syndrome with an atrial right-to-left shunt.
Occasionally, MS is congenital.
The normal area of the mitral valve orifice is 4 to 5 cm². An area of 1 to 1.5 cm² reflects moderate MS and often causes exertional symptoms. An area < 1 cm² represents severe stenosis and may cause symptoms during rest. However, the relationship between the area of the valve orifice and symptoms is not always reliable. Left atrial (LA) size and pressure increase progressively to compensate for MS; pulmonary venous and capillary pressures also increase and may cause secondary pulmonary hypertension, leading to right ventricular (RV) heart failure and tricuspid and pulmonic regurgitation. Rate of progression varies.
LA enlargement predisposes to atrial fibrillation (AF), a risk factor for thromboembolism. The faster heart rate and loss of atrial contraction with onset of AF often leads to sudden worsening of symptoms.
Symptoms: symptoms correlate poorly with disease severity because the disease often progresses insidiously and patients reduce their activity without being aware of it. Many patients are asymptomatic until they become pregnant or AF develops.
Initial symptoms are usually those of heart failure. They typically do not appear until 15 to 40 yr after an episode of rheumatic fever. Less common symptoms include haemoptysis due to rupture of small pulmonary vessels and pulmonary oedema.
Physical examination: classic mitral facies, a plum-coloured malar flush; palpable 1st and 2nd heart sounds (S1 and S2). S1 is best palpated at the apex, and S2 at the upper left sternal border; evident pulmonic component of S2 (P2); RV impulse (heave) palpable at the left sternal border; auscultatory findings include: loud S1, it is heard best at the apex; diastolic murmur, heard best with the bell of the stethoscope at the apex (or over the palpable apex beat) at end-expiration when the patient is in the left lateral decubitus position. Austin Flint murmur (a low-pitched mid-diastolic murmur heard at the apex due to AR); Graham Steell's murmur (a soft decrescendo diastolic murmur heard best along the left sternal border and caused by pulmonic regurgitation secondary to severe pulmonary hypertension).
Diagnosis is suspected clinically and confirmed by echocardiography.
Two-dimensional echocardiography provides information about the degree of valvular calcification and stenosis and LA size.
Doppler echocardiography provides information about the transvalvular gradient and pulmonary artery pressure.
Transoesophageal echocardiography can be used to detect or exclude small LA thrombi, especially those in the LA appendage.
ECG show LA enlargement, right axis QRS deviation, and tall R waves in V1 suggest RV hypertrophy.
Chest X-ray shows straightening of the left cardiac border due to a dilated LA appendage, and widening of the carina. With barium in the oesophagus, the lateral chest X-ray will show the dilated LA displacing the oesophagus posteriorly. The main pulmonary artery (trunk) may be prominent; the descending right pulmonary artery diameter is ≥ 16 mm if pulmonary hypertension is significant. The upper lobe pulmonary veins may be dilated. A double shadow of an enlarged LA may be seen along the right cardiac border. Horizontal lines in the lower posterior lung fields (Kerley B lines) indicate interstitial oedema associated with high LA pressure.
Cardiac catheterization indicated only for perioperative assessment of coronary artery disease (CAD) before surgical repair, can confirm elevated LA and pulmonary artery pressures, mitral gradient and valve area.
Treatment
Asymptomatic patients require only prophylaxis against recurrent rheumatic fever (e.g., with IM injections of benzathine penicillin G 1.2 million units q 3 or 4 wk) until age 25 to 30 and prophylaxis against endocarditis before high-risk procedures.
Mildly symptomatic patients usually respond to diuretics and, if sinus tachycardia or AF is present, to β-blockers or Ca channel blockers, which can control ventricular rate. Anticoagulants are indicated to prevent thromboembolism. All patients should be encouraged to continue at least low levels of physical exercise despite exertional dyspnoea.
Indications for percutaneous mitral commissurotomy in mitral stenosis with valve area < 1.5 cm2: symptomatic patients with favourable characteristics for PMC (IB); symptomatic patients with contraindication or high risk for surgery (IC); as initial treatment in symptomatic patients with unfavourable anatomy but otherwise favourable clinical characteristics (IIa, C); asymptomatic patients with favourable characteristics and high thromboembolic risk or high risk of haemodynamic decompensation; previous history of embolism (IIa, C); dense spontaneous contrast in the left atrium (IIa, C); recent or paroxysmal atrial fibrillation (IIa, C); systolic pulmonary pressure > 50 mmHg at rest (IIa, C); need for major non-cardiac surgery (IIa, C); desire of pregnancy (IIa, C).
More severely symptomatic patients and patients with evidence of pulmonary hypertension require valvotomy, commissurotomy, or valve replacement.
Patients with severe subvalvular disease, valvular calcification, or LA thrombi may be candidates for surgical commissurotomy, in which fused mitral valve leaflets are separated using a dilator passed through the LV (closed commissurotomy) via thoracotomy, or by direct vision (open commissurotomy) via sternotomy. Choice of procedure is based on surgeon's experience and the morphology of the valve, although closed valvotomy is now performed less frequently in Western countries.
Valve replacement is confined to those with severe morphologic changes that make the valve unsuitable for balloon or surgical valvotomy.
Common complications are pulmonary hypertension, atrial fibrillation, and thromboembolism.
Tricuspid Regurgitation
Tricuspid regurgitation (TR) is insufficiency of the tricuspid valve causing blood flow from the right ventricle to the right atrium during systole.
Aetiology: TR is most commonly caused by dilation of the right ventricle (RV) with malfunction of a normal valve, as occurs in pulmonary hypertension, RV dysfunction induced heart failure (HF), and pulmonary outflow tract obstruction. Less commonly from infective endocarditis in IV drug abusers, carcinoid syndrome, chest or abdominal injury, rheumatic fever, idiopathic myxomatous degeneration, ischaemic papillary muscle dysfunction, congenital defects (e.g., cleft tricuspid valve, endocardial cushion defects), Ebstein's anomaly, Marfan syndrome, use of certain drugs (e.g., ergotamine, fenfluramine, phentermine).
Symptoms and signs: TR usually causes no symptoms, but some patients experience neck pulsations due to elevated jugular pressures. Acute or severe TR may cause symptoms of RV dysfunction induced HF. Patients may also develop symptoms of AF or atrial flutter.
Physical examination: jugular venous distention, pedal oedema; ascites; hepatomegaly; systolic hepatic pulsation and an RV impulse at the left lower sternal border.
On auscultation: the 2nd heart sound (S2) may be split; holosystolic murmur heard best at the left middle or lower sternal border or at the epigastrium when the patient is sitting upright or standing. The murmur varies with respiration, becoming louder with inspiration (Carvallo's sign).
Diagnosis
Mild TR is most often detected on echocardiography done for other reasons. Doppler echocardiography. ECG is usually normal but, in advanced cases, may show tall peaked P waves caused by right atrial enlargement, a tall R or QR wave in V1 characteristic of RV hypertrophy, or AF.
Chest X-ray is usually normal but, in advanced cases with RV hypertrophy or RV dysfunction-induced HF, may show an enlarged superior vena cava, an enlarged right atrial or RV silhouette (behind the upper sternum in the lateral projection), or pleural effusion.
Treatment
Surgical options include: annuloplasty, valve repair, and valve replacement. If endocarditis has damaged the tricuspid valve and cannot be cured with antibiotics, the valve may be totally excised and not replaced until 6 to 9 mo later; this procedure is well tolerated.
Tricuspid Stenosis
Tricuspid stenosis (TS) is narrowing of the tricuspid orifice that obstructs blood flow from the right atrium to the right ventricle.
Aetiology: TS is almost always due to rheumatic fever; rare causes of TS include SLE, right atrial (RA) myxoma, congenital malformations, metastatic tumours.
The RA becomes hypertrophied and distended, and sequelae of right heart disease-induced heart failure develop but without right ventricular (RV) dysfunction; the RV remains underfilled and small. Uncommonly, atrial fibrillation occurs.
Symptoms: fluttering discomfort in the neck (due to giant a waves in the jugular pulse), fatigue and cold skin (due to low cardiac output), right upper quadrant abdominal discomfort (due to an enlarged liver), peripheral oedema, ascites.
On auscultation: TS may produce a soft opening snap and a mid-diastolic rumble with presystolic accentuation. The murmur becomes louder and longer with maneuvers that increase during inspiration.
Diagnosis is suspected based on history and physical examination and confirmed by Doppler echocardiography.
Two-dimensional echocardiography shows thickened leaflets with reduced movement and RA enlargement.
ECG and chest X-ray are often obtained. ECG may show RA enlargement out of proportion to RV hypertrophy and tall, peaked P waves in inferior leads and V1.
Chest X-ray shows a dilated superior vena cava and RA enlargement, indicated by an enlarged right heart border.
Liver enzymes are elevated because of passive hepatic congestion.
Cardiac catheterization is rarely indicated for evaluation of TS. When catheterization is indicated (e.g., to evaluate coronary anatomy), findings include elevated RA pressure with a slow fall in early diastole and a diastolic pressure gradient across the TV.
Treatment
Evidence to guide treatment is scarce. For all symptomatic patients, treatment should include a low-salt diet, diuretics, and aldosterone antagonists. Patients with hepatic congestion leading to cirrhosis or severe systemic venous congestion and effort limitation may benefit from interventions such as balloon valvotomy or valve repair or replacement.
Indications for intervention in tricuspid valve disease: severe TR in a patient undergoing left-sided valve surgery (IC); severe primary TR and symptoms despite medical therapy without severe right ventricular dysfunction (IC); severe TS (±TR), with symptoms despite medical therapy (IC); severe TS (±TR) in a patient undergoing left-sided valve intervention (IC); moderate organic TR in a patient undergoing left-sided valve surgery (IIa, C); moderate secondary TR with dilated annulus (> 40 mm) in a patient undergoing left-sided valve surgery (IIa, C); severe TR and symptoms, after left-sided valve surgery, in the absence of left-sided myocardial, valve, or right ventricular dysfunction and without severe pulmonary hypertension (systolic pulmonary artery pressure > 60 mmHg) (IIa, C); severe isolated TR with mild or no symptoms and progessive dilation or deterioration of right ventricular function (IIb, C).
INFECTIVE ENDOCARDITIS
Infective endocarditis (IE). If not to treat it, it is a fatal disease. The achievements of last years in diagnostics and treatment have improved that the prognosis of the patients with IE is poor. The reason of high mortality in IE is later establishment of the diagnosis or later treatment. Therefore it is very important that: 1) the opportunity of IE occurrence was considered (examined) at early stages of inspection of each patient having a fever or septicemia and cardiac murmur; 2) urgently carried out cardiography to each patient with suspicion on IE; 3) to ensure (supply) cooperation of cardiologists, microbiologists and cardiosurgeons at suspicion on IE or at establishment of this diagnosis.
Densities of IE in structure of the acquired defects have increased 8 times for last ten years. The reason of such increase is the growth of narcomania. At those who introduce drugs intravenously, IE arises 30 times more often, than in people in general and 4 times is more often, than in patients with rheumatic heart defects. In 1–4% of the patients with prosthetic valves IE arises in the first year after the operation. At 10% IE arises after the realization of diagnostic and medical manipulations.
The men are sick for IE 2–3 times more often, than the women. In the industrialized countries the tendency to “aging” IE is marked for last 30 years. The average age of such patients is 50 years and 25% of the patients are older than 60 years.
Definitions. IE is an endovascular, microbial infection of intracardiac structures facing the blood including infections of the large intrathoracic vessels and of intracardiac foreign bodies. The early characteristic lesion is a variably sized vegetation, although destruction, ulceration or abscess formation may be seen earlier by echocardiography.
Aetiology and pathophysiology
The normal heart is relatively resistant to infection. Bacteria and fungi do not easily adhere to the endocardial surface, and constant blood flow helps prevent them from settling on endocardial structures. Thus, 2 factors are generally required for endocarditis: predisposing abnormality of the endocardium and microorganisms in the bloodstream (bacteraemia). Rarely, massive bacteraemia or particularly virulent microorganisms cause endocarditis on normal valves.
Endocardial factors:
– Endocarditis usually involves the heart valves. Major predisposing factors are congenital heart defects, rheumatic valvular disease, bicuspid or calcific aortic valves, mitral valve prolapse, and hypertrophic cardiomyopathy. Prosthetic valves are a particular risk. Occasionally, mural thrombi, ventricular-septal defects, and patent ductus arteriosus sites become infected. The actual nidus for infection is usually a sterile fibrin-platelet vegetation formed when damaged endothelial cells release tissue factor.
– Infective endocarditis occurs most often on the left side (mitral or aortic valve). About 10 to 20% of cases are right-sided (tricuspid or pulmonic valve). IVDA have a much higher incidence of right-sided endocarditis (about 30 to 70%).
Microorganisms:
– Microorganisms that infect the endocardium may originate from distant infected sites (cutaneous abscess, inflamed or infected gums) or have obvious portals of entry such as a central venous catheter or a drug injection site. Almost any implanted foreign material (ventricular or peritoneal shunt, prosthetic device) is at risk of bacterial colonization, thus becoming a source of bacteraemia and hence endocarditis. Endocarditis also may result from asymptomatic bacteraemia, such as typically occurs during invasive dental, medical, or surgical procedures. Even toothbrushing and chewing can cause bacteraemia (usually due to streptococci viridans) in patients with gingivitis.
– Causative microorganisms vary by site of infection, source of bacteraemia, and host risk factors (IVDA), but overall, streptococci and Staphylococcus aureus cause 80 to 90% of cases. Enterococci, gram-negative bacilli, HACEK organisms (Cardiobacterium hominis, Kingella kingae, Actinobacillus actinomycetemcomitans, Eikenella corrodens, Haemophilus sp. are included in the group), and fungi cause most of the rest. Why streptococci and staphylococci frequently adhere to vegetations and why gram-negative aerobic bacilli seldom adhere are unclear. However, the ability of S. aureus to adhere to fibronectin may play a role, as may dextran production by streptococci viridans.
Table 16 – Terminology for infective endocarditis
| |
Examples: Active mitral valve IE due to Enterococcus faecalis; healed recurrent prosthetic aortic valve endocarditis due to Staphylococcus epidermidis; suspected culture-negative late prosthetic mitral valve endocarditis.
Pathophysiology:
– damage of endothelia and formation of micro blood clots;
– colonization of micro thrombus by microorganisms;
– repeated deposit of thrombocytes and fibrin on a surface;
– formation of vegetation;
– formation of vegetation on cusp of the valve.
Table 17 – Frequency of revealing aetiology agents of IE in the USA, Canada and advanced countries of Europe (by W. М. Sheld, М. А. Sand, 1995)
|Activators of disease |Frequency of revealing, % |
|- Streptococcus: Streptococcus viridans, |60–80: 30–40, 5–18, 15–25; |
|Enterococcus and others Streptococcus; | |
|- Staphylococcus: St. aureus and others St.; | |
|- gram-negative bacilli; |20–35: 10–27, 1–3; |
|- HACEK organisms; | |
|- fungi; |13–15; |
|- infection of polymicroorganism |less than 5; |
| |2–4; |
| |1–2 |
Consequences: endocarditis has local and systemic consequences.
Local consequences include:
– formation of myocardial abscesses;
– severe valvular regurgitation may develop suddenly, causing heart failure and death (usually due to mitral or aortic valve lesions);
– aortitis may result from contiguous spread of infection;
– prosthetic valve infections are particularly likely to involve valve ring abscesses, obstructing vegetations, myocardial abscesses, and mycotic aneurysms manifested by valve obstruction, dehiscence, and conduction disturbances.
Systemic consequences include:
1. Immunological change as cellular and humoral infringements of immunity and not specific system of protection:
– an oppression of Т-system lymphocytes and hyperactivation of B-system (high IgМ and IgG titre);
– high autoantibody titre (cryoglobulins, rheumatoid factor, anti-myocardial antibodies, etc.);
– decrease of the contents compliment;
– formation of circulating immune complexes (CIC).
2. Immunopathological reaction of basal membranes in internal organs on antibodies and CIC:
– glomerulonephritis;
– myocarditis;
– arthritis;
– vasculitis, etc.
3. Occurrence of thromboembolic complication in arterial vessels of lungs, heart, brain, intestine, spleen, and other organs.
4. The combination of these pathological changes determines a clinical picture of IE.
Classification
Infective endocarditis may have an indolent, subacute course or a more acute, fulminant course with greater potential for rapid decompensation.
– Subacute bacterial endocarditis (SBE), although aggressive, usually develops insidiously and progresses slowly (i.e., over weeks to months). Often, no source of infection or portal of entry is evident. SBE is caused most commonly by streptococci (especially viridans, microaerophilic, anaerobic, and nonenterococcal group D streptococci and enterococci) and less commonly by S. aureus, Staphylococcus epidermidis, Gemella morbillorum, Abiotrophia defectiva, Granulicatella sp, and fastidious Haemophilus sp. SBE often develops on abnormal valves after asymptomatic bacteraemia due to periodontal, GI, or GU infections.
– Acute bacterial endocarditis (ABE) usually develops abruptly and progresses rapidly (i.e., over days). A source of infection or portal of entry is often evident. When bacteria are virulent or bacterial exposure is massive, ABE can affect normal valves. It is usually caused by S. aureus, group A haemolytic streptococci, pneumococci, or gonococci.
– Prosthetic valvular endocarditis (PVE) develops in 2 to 3% of patients within 1 yr after valve replacement and in 0.5%/yr thereafter. It is more common after aortic than after mitral valve replacement and affects mechanical and bioprosthetic valves equally. Early-onset infections (< 2 mo after surgery) are caused mainly by contamination during surgery with antimicrobial-resistant bacteria (e.g., S. epidermidis, diphtheroids, coliform bacilli, Candida sp, Aspergillus sp). Late-onset infections are caused mainly by contamination with low-virulence organisms during surgery or by transient asymptomatic bacteraemias, most often with streptococci; S. epidermidis; diphtheroids; and the fastidious gram-negative bacilli, Haemophilus sp, Actinobacillus actinomycetemcomitans, and Cardiobacterium hominis.
Criteria that should raise suspicion of IE:
1. High clinical suspicion (urgent indication for echocardiographic screening and possibly hospital admission):
– new valve lesion/(regurgitant) murmur;
– embolic event(s) of unknown origin (esp. cerebral and renal infarction);
– sepsis of unknown origin;
– haematuria, glomerulonephritis, and suspected renal infarction;
– “fever” plus: prosthetic material inside the heart, other high predispositions for IE, newly developed ventricular arrhythmias or conduction disturbances, first manifestation of CHF, positive BCs (if the organism identified is typical for NVE/PVE), cutaneous (Osler, Janeway) or ophthalmic (Roth) manifestations, multifocal/rapid changing pulmonic infiltrations (right heart IE), peripheral abscesses (renal, splenic, spine) of unknown origin predisposition and recent diagnostic/therapeutic interventions known to result in significant bacteraemia.
2. Low clinical suspicion:
– fever plus none of the above.
Revised Duke clinical diagnostic criteria for IE
Major criteria:
– two positive blood cultures for organisms typical of endocarditis;
– three positive blood cultures for organisms consistent with endocarditis;
– serologic evidence of Coxiella burneti;
– echocardiographic evidence of endocardial involvement: oscillating intracardiac mass on a heart valve, on supporting structures, in the path of regurgitant jets, or on implanted material without another anatomic explanation; cardiac abscess; new dehiscence of prosthetic valve; or new valvular regurgitation.
Minor criteria:
– predisposing heart disorder;
– IV drug abuse;
– fever ≥ 38° C;
– vascular phenomena: arterial embolism, septic pulmonary embolism, mycotic aneurysm, intracranial haemorrhage, conjunctival petechiae or Janeway lesions;
– immunologic phenomena: glomerulonephritis, Osler's nodes, Roth's spots, or rheumatoid factor;
– microbiologic evidence of infection consistent with but not meeting major criteria;
– serologic evidence of infection with organisms consistent with endocarditis.
For definite clinical diagnosis: 2 major criteria or 1 major and 3 minor criteria or 5 minor criteria.
For possible clinical diagnosis: 1 major and 1 minor criteria or 3 minor criteria.
For disconfirmation of diagnosis:
Firm alternative diagnosis explaining the findings of infective endocarditis, resolution of symptoms and signs after antimicrobial therapy for ≤ 4 days, no pathologic evidence of infective endocarditis found during surgery or autopsy, or failure to meet the clinical criteria for possible endocarditis.
Symptoms and signs
SBE. Initially, symptoms are vague: low-grade fever (< 39° C), night sweats, fatigability, malaise, and weight loss. Chills and arthralgias may occur. Symptoms and signs of valvular insufficiency may be the first clue. Initially, ≤ 15% of patients have fever or murmur, but eventually almost all develop both. Physical examination may be normal or include pallor, fever, change in a preexisting murmur or development of a new regurgitant murmur, and tachycardia.
Retinal emboli can cause round or oval haemorrhagic retinal lesions with small white centres (Roth's spots). Cutaneous manifestations include petechiae (on the upper trunk, conjunctivae, mucous membranes, and distal extremities), painful erythematous subcutaneous nodules on the tips of digits (Osler's nodes), nontender haemorrhagic macules on the palms or soles (Janeway lesions), and splinter haemorrhages under the nails. About 35% of patients have CNS effects, including transient ischaemic attacks, stroke, toxic encephalopathy, and, if a mycotic CNS aneurysm ruptures, brain abscess and subarachnoid haemorrhage. Renal emboli may cause flank pain, and, rarely, gross haematuria. Splenic emboli may cause left upper quadrant pain. Prolonged infection may cause splenomegaly or clubbing of fingers and toes.
ABE and PVE. Symptoms and signs are similar to those of SBE, but the course is more rapid. Fever is almost always present initially, and patients appear toxic; sometimes septic shock develops. Heart murmur is present initially in about 50 to 80% and eventually in > 90%. Rarely, purulent meningitis occurs.
Right-sided endocarditis. Septic pulmonary emboli may cause cough, pleuritic chest pain, and sometimes haemoptysis. A murmur of tricuspid regurgitation is typical.
Palpation and percussion of heart:
1. Conducting in a clinical picture of IE, alongside with fever and intoxication symptom, are the diseases of heart caused by formation of heart defect, myocarditis and (sometimes) by defeat of coronary vessels (embolism, vasculitis).
2. At acute course of IE, sudden break of tendinous ailment of MV or ТV develops acute LV or RV insufficiency.
3. АV lesion is more often (in 55–65% of the patients), МV insufficiency is less often (in 15–40% of the patients). Combined АV and МV defeat comes to light in 13% of cases. Isolated ТV insufficiency meets in 1–5% of cases, though at narcomaniac this localization of a defeat (in 45–50% of the patients) prevails.
4. The data palpation and percussion of heart are determined by localization of an infectious lesion (АV, МV, ТV), and also presence of an accompanying pathology, on which background IE was developed.
5. The signs of LV expansion and its hypertrophy are observed in most cases: displacement to the left of apical push and left border of relative dullness of heart, amplification of apical push.
Аuscultation of heart:
1. Аuscultation signs of formed heart defect usually begin to be shown in 2–3 months of the feverish period. At affected АV I and II heart tones are weaken. Silent diastolic murmur after II tone occurs in II intercostal to the right sternum and in Botkin point. The murmur has decrescendo character and will be carried over the apex of the heart. At affected МV there is an easing of I heart tone and rough systolic murmur occurs on the apex, which will be carried over the left axillary area.
2. ТV defeat is characterized by systolic murmur TV insufficiency, which is maximum located in V intercostal to the left of sternum.
Аrterial pulse and arterial pressure (AP):
1. It is important always to compare auscultation data with the research of properties of arterial pulse and changes in AP. Diastolic murmur occurs at formation of АV insufficiency, which associates with the changes of pulse for a type pulsus celer, altus et magnus, and also with decrease of diastolic AP and tendency to increase systolic AP.
2. At MV insufficiency there is a poorly expressed tendency to decrease systolic and diastolic AP.
Laboratory data
Сlinical blood examination: normochromic anaemia; increase of erythrocyte sedimentation rate; displacement of leukogram to the left.
Biochemical blood examination: increase of alanine aminotranspherase, lactate dehydrogenase, creatine phosphokinase, α2- and γ-globulin, cialic acid, fibrinogen, seromucoid, haptoglobin, C-reactive protein, rheumatoid factor.
Immunologic examination: increase of titre of circulating immune complex, C3 and C4 complements.
Standard blood culture techniques:
1. Three or more blood cultures (BC) should be taken irrespective of body temperature at least 1 h apart. If the patient has been on short-term antibiotics, one should wait, if possible, at least for 3 days after discontinuing of antibiotic treatment before new BCs are taken. Blood cultures after long-term antibiotic treatment may not become positive after treatment has been discontinued for 6–7 days.
2. One BC consists of one aerobic and one anaerobic bottle, each containing approximately 50 ml of medium (less in pediatric BC bottles). Venous blood, minimally 5 ml and better 10 ml in adults and 1–5 ml in children should be added to each bottle. Minimum inhibitory concentrations should be determined for the drugs of choice.
Culture-negative endocarditis (CNE):
1. The most frequent cause of CNE is previous antimicrobial treatment. If traditional (non-automatic) BC systems are used, longer incubation periods (> 6 days) are required when organisms of the HACEK group, Propionibacterium spp., Neisseria spp., Brucella, Abiotrophia spp., or Campylobacter spp. are suspected. Especially in CNE all material excised during cardiac surgery for active IE should also be cultured and examined.
2. The value of serology has been proven for IE due to Bartonella, Legionella, Chlamydia (immunofluorescence) and Coxiella burnetii.
3. The use of broad-spectrum polymerase chain reaction (PCR) provides a significant improvement in the capability to detect difficult-to-culture organisms and even dead bacteria.
[pic]
Figure 4 – Algorithm for the use of transthoracic (TTE) and transoesophageal echocardiography (TEE) in suspected IE. N.B. TTE “positive” indicates finding of typical IE (e.g., fresh vegetation or abscess formation)
Echocardiography
Any patient suspected of having NVE by clinical criteria should be screened by transthoracic echocardiography (TTE). When images are of good quality and prove to be negative and there is only a low clinical suspicion of IE, endocarditis is unlikely and other diagnoses are to be considered. If there is high suspicion of IE, TEE should be performed in all TTE-negative cases, in suspected PVE, and if TTE is positive but complications are suspected or likely and before cardiac surgery during active IE. If TEE remains negative and there is still suspicion, it should be repeated within one week. A repeatedly negative study should virtually exclude the diagnosis.
[pic]
Figure 5 – Echocardiographic sings of vegetation on cusp of the MV
a) One-dimensional echocardiogram (circuit);
b) Two-dimensional echocardiogram (fragment);
c) Two-dimensional echocardiogram from apical position of four-chamber heart
Three echocardiographic findings are considered to be major criteria in the diagnosis of IE:
1. Mobile, echodense mass attached to the valvular or the mural endocardium or to implanted prosthetic material.
2. Demonstration of abscesses or fistulas.
3. New dehiscence of a valve prosthesis, especially when occurring late after implantation.
ECG: decrease of T wave or ST segments, downward T wave, upward ST segments, atrioventricular block, extrasystole, auricular fibrillation or flutter.
Treatment
Table 18 – Decision making for antibiotic treatment of native (NVE) and prosthetic valve endocarditis (PVE) due to streptococci
|Regimen (A) NVE; full susceptibility to penicillin (MIC 0.1mg/l) |
|Patient, 65 years, normal serum |Penicillin G 12–20 million units/24 h IV, divided |
|creatinine levels |into 4–6 doses for 4 weeks plus gentamicin 3 |
| |mg/kg/24 h IV (maximum 240 mg/day), divided into 2–3|
| |doses for 2 weeks |
|The same conditions as above with |Penicillin G 12–20 million units/24 h IV, divided |
|uncomplicated courses and rapid |into 4–6 doses for 2 or 4 weeks with ambulatory |
|clinical response to therapy |treatment after 7 days treatment in hospital |
|Patient, 65 years, and/or elevated |Penicillin G adapted to renal function for 4 weeks |
|serum creatinine levels or allergy to|or ceftriaxone 2 g/24 h IV single dose for 4 weeks |
|penicillin | |
|Patients allergic to penicillin and |Vancomycin 30 mg/kg/24 h IV divided into two doses |
|cephalosporins |for 4 weeks |
|Regimen (B) susceptibility to penicillin (MIC 0.1 mg/l–0.5 mg/l) or PVE |
|penicillin G 20–24 million units/24h IV divided into 4–6 doses or ceftriaxone 2 g/24 h IV |
|as single dose both for 4 weeks plus gentamicin 3 mg/kg/24 h IV, divided into 2–3 doses |
|for 2 weeks, followed by ceftriaxone 2 g/24 h IV for additional 2 weeks; |
|vancomycin as single drug treatment for 4 weeks (dosage see above) |
|Regimen (C) resistance to penicillin; MIC > 0.5 mg/ld |
Table 19 – Decision making for antibiotic treatment of IE due to staphylococci
|Regimen (A) native valve endocarditis |
|Methicillin-susceptible S. |Oxacillin 8–12 g/24 h IV, divided into 3–4 doses|
|aureus, no allergy to |for at least 4 weeks plus gentamicin 3 mg/kg/24 h IV |
|penicillin |(maximum 240 mg/day), divided into 2–3 doses for the first|
| |3–5 days of treatment |
|Methicillin-susceptible |Vancomycin 30 mg/kg/24 h IV divided into two doses for 4–6|
|S. aureus, allergy to |weeks, plus gentamicin 3 mg/kg/24 h IV (maximum 240 |
|penicillin |mg/day) divided into 2–3 doses for the first 3–5 days of |
| |treatment |
|Methicillin-resistant S. |Vancomycin 30 mg/kg/24 h IV divided into two doses for 6 |
|Aureus |weeks |
|Regimen (B) Endocarditis involving prosthetic material/cardiac valve prostheses |
|Methicillin-susceptible |Oxacillinb 8–12 g/24 h IV, divided into 3–4 doses |
|S. aureus |plus rifampicin 900 mg/24 h IV divided into three doses, |
| |both for 6–8 weeks, plus gentamicin 3 mg/kg/24 h IV |
| |(maximum 240 mg/day) divided into 2–3 doses for the first |
| |2 weeks of treatment |
|Methicillin-resistant S. |Vancomycin 30 mg/kg/24 h IV divided into two doses for 6 |
|aureus. Coagulase-negative |weeks, plus rifampicin 900 mg/24 h IV divided into|
|staphylo-cocci. In |three doses, plus gentamicin 3 mg/kg/24 h IV (maximum |
|oxacillin-susceptible CONS |240 mg/day) divided into 2–3 doses, all for 6–8 weeks |
|vancomycin should be replaced | |
|by oxacillin. For resistant | |
|staphylo-cocci treatment with | |
|oxazolidinone may be an option | |
|but should be initiated only | |
|after advice from a reference | |
|centre has been taken. | |
Table 20 – Decision making for antibiotic treatment of IE due to enterococci and penicillin-resistant streptococci
|Penicillin MIC 8 mg/l and for gentamicin |Penicillin G, 16–20 million units in 4–6 divided|
|MIC < 500 mg/l |doses plus gentamicin 3 mg/kg, IV, divided in|
| |two doses for 4 weeks |
|Penicillin-allergic patients with |Vancomycin 30 mg/kg/day IV in two divided doses |
|penicillin/gentamicin susceptible |plus gentamicin (dosage as above) for 6 weeks |
|enterococcal isolates | |
|Penicillin-resistant strains, MIC > 8 |Vancomycin plus gentamicin (dosage as above) for|
|mg/l |6 weeks |
|Vancomycin-resistant strains including |Assistance of an experienced microbiologist is |
|strains with low resistance to vancomycin|mandatory. If antimicrobial therapy fails, valve|
|(MIC 4–16 mg/l) or high resistance to |replacement should be considered early |
|gentamicina | |
Table 21 – Antimicrobial treatment in CNE or if therapy is urgent and the causative organism unidentified
|NVE |PVE |
|Vancomycin 15 mg/kg i.v. every 12 h 4–6 weeks|Vancomycin 15 mg/kg i.v. every 12 h 4–6 |
|+ gentamicin 1.0 mg/kg i.v. every 8 h 2 weeks|weeks |
| |+ rifampicin 300–450 mg p.o. every 8 h 4–6 |
| |weeks |
| |+ gentamicin 1.0 mg/kg i.v. every 8 h 2 |
| |weeks |
Management of complications
Rapid and effective antimicrobial treatment may help to prevent embolism. If the patient is on long-term oral anticoagulation, coumarin therapy should be discontinued and replaced by heparin immediately after the diagnosis of IE has been established.
After embolic complication, the risk for recurrent episodes is high. After manifestation of cerebral embolism, cardiac surgery to prevent a recurrent episode is not contraindicated if performed early (best within 72 h) and cerebral haemorrhage has been excluded by cranial computed tomography immediately before the operation. If surgery is not performed early, it is advisable to be postponed for 3–4 weeks.
Surgery for active NVE
The following indications for urgent valve surgery are accepted:
– heart failure due to acute aortic regurgitation;
– heart failure due to acute mitral regurgitation;
– persistent fever and demonstration of bacteraemia for more than 8 days despite adequate antimicrobial therapy;
– demonstration of abscesses, pseudoaneurysms, abnormal communications like fistulas or rupture of one or more valves, conduction disturbances, myocarditis or other findings indicating local spread (locally uncontrolled infection);
– involvement of microorganisms which are frequently not cured by antimicrobial therapy (e.g., fungi; Brucella and Coxiella) or microorganisms which have a high potential for rapid destruction of cardiac structures (e.g., S. lugdunensis).
If vegetations are larger than 10 mm on the mitral valve or if they are increasing in size despite antibiotic therapy or if they represent mitral kissing vegetations, early surgery should also be considered. The prognosis of right-sided IE is favourable. Surgery is necessary if tricuspid vegetations are larger than 20 mm after recurrent pulmonary emboli.
Surgery for active PVE
The following indications are accepted:
– early PVE (less than 12 months after surgery);
– late PVE complicated by prosthesis dysfunction including significant perivalvular leaks or obstruction, persistent positive blood cultures, abscess formation, conduction abnormalities, and large vegetations, particularly if staphylococci are the infecting agents.
Cardiac conditions in which antimicrobial prophylaxis is indicated:
– prosthetic heart valves;
– complex congenital cyanotic heart diseases;
– previous infective endocarditis;
– surgically constructed systemic or pulmonary conduits;
– acquired valvular heart diseases;
– mitral valve prolapse with valvular regurgitation or severe valve thickening;
– non-cyanotic congenital heart diseases (except for secundum type ASD) including bicuspid aortic valves;
– hypertrophic cardiomyopathy.
Patient-related noncardiac conditions:
– older age;
– conditions: promoting nonbacterial thrombotic vegetation; compromising host defence; compromising local non-immune defence mechanisms; and increased risk/frequency/amount of bacteraemia are considered patient-related, noncardiac risk conditions.
Diagnostic and therapeutic interventions likely to produce bacteraemia: bronchoscopy (rigid instrument), cystoscopy during urinary tract infection, biopsy of urinary tract/prostate, dental procedures with the risk of gingival/mucosal trauma, tonsillectomy and adenoidectomy, instrumentation of obstructed biliary tracts, oesophageal dilation/sclerotherapy, transurethral resection of prostate, urethral instrumentation/dilation, lithotripsy, gynaecological procedures in the presence of infection.
Prophylaxis is not recommended for cardiac catheterization.
Prophylactic antibiotic regimens
Prophylaxis aims primarily at viridans streptococci and HACEK organisms before dental, oral, respiratory, and oesophageal procedures, and at enterococci and Streptococcus bovis before gastrointestinal and genitourinary procedures.
Prognosis
Untreated, infective endocarditis is always fatal. Even with treatment, death is more likely and the prognosis is generally poorer for older people and people who have infection with resistant organisms, an underlying disorder, or a long delay in treatment. The prognosis is also poorer for people with aortic or multiple valve involvement, large vegetations, polymicrobial bacteraemia, prosthetic valve infections, mycotic aneurysms, valve ring abscess, and major embolic events. The mortality rate for viridans streptococcal endocarditis without major complications is < 10% but is virtually 100% for Aspergillus endocarditis after prosthetic valve surgery.
The prognosis is better with right-sided than left-sided endocarditis because tricuspid valve dysfunction is tolerated better, systemic emboli are absent, and right-sided S. aureus endocarditis responds better to antimicrobial therapy.
Table 22 – Prophylactic antibiotic regimens
|Dental, oral, respiratory, and oesophageal procedures (Р) |
|Not allergic to penicillin |Amoxillin 2.0 g (children 50 mg/kg) p.o.1 h before P unable |
| |to take oral medication: amoxicillin or ampicillin 2.0 g |
| |(children 50 mg/kg) i.v. – 1 h before P |
|Allergic to penicillin |Clindamycin 600 mg (children 20 mg/kg) or |
| |azithromycin/clarithromycin 500 mg (children 15 mg/kg) 1 h |
| |before P |
|Genitourinary and gastrointestinal procedures (P) |
|Not allergic to penicillin, |Ampicillin or amoxicillin 2.0 g i.v. plus gentamicin 1.5 |
|high-risk group |mg/kg i.v. – 1 h before P; 6 h later, ampicillinor |
| |amoxicillin 1.0 g p.o. |
|Not allergic to penicillin, |Ampicillin or amoxicillin 2.0 g i.v. (children 50 mg/kg) –|
|moderate-risk group |1 h before P; or amoxicillin 2.0 g (children 50 mg/kg) p.o. |
| |1 h before P |
|Allergic to penicillin, |Vancomycin 1.0 g (children 20 mg/kg) over 1–2 h before P|
|high-risk group |plus gentamicin 1.5 mg/kg i.v. or i.m. |
|Allergic to penicillin, |Vancomycin (see above) without gentamicin |
|moderate-risk group | |
MYOCARDITIS
Myocarditis is an inflammation of myocardium, disease with infectious or noninfectious aetiology.
Сlassification of myocarditis
According to aetiology:
1. Infectious:
– viral (Coxsackie A, B; influenza A,B, measles, infectious mononucleosis, hepatitis B and C, chickenpox, cytomegalovirus; Epstein-Barr virus; acquired immunodeficiency syndrome);
– bacterial (Corynebacterium diphtheriae, Staphylococcus, Streptococcus β-haemolytic, Mycoplasma pneumoniae, Salmonella, Meningococcus, Gonococcus, etc.;
– rickettsial (Coxiella burnetii – Q fever; Rickettsia rickettsii – Rocky mountain spotted fever);
– spirochetal (Borrelia burgdorferi – Lyme disease; recurrent fever; syphilis; leptospirosis);
– protozoal (Trypanosoma cruzi – Chagas disease; Toxoplasma gondii);
– methazoal (Trichinellosis; Echinococcosis);
– fungous (Candidiasis; Cryptococcosis).
2. Noninfectious:
a) allergic (immunologic):
– medicament (serum sickness, antibiotics, sulfanilamides, methyldopa, etc.);
– at system diseases of connective tissue;
– asthma;
– transplantation illness;
– brush.
b) toxic (uremia; radiation; phenothiazines; industrial exposure to toxic chemicals; cobalt, alcohol, narcotic, etc.).
According to the course:
– acute;
– latent;
– chronic;
– recurring;
According to prevalence:
– focal;
– diffusive;
According to form of disease:
– mild (the size of heart is not changed);
– moderate (coming cardiomegaly; HI is not present);
– severe (cardiomegaly, HI, system and lung tromboembolism);
According to clinical displays:
– oligosymptomatic;
– pseudocoronary;
– decompensation;
– arrhythmic;
– pseudovalval;
– thromboembolic;
– mixed.
Clinical and laboratory data
Mild form of disease
Complaints: moderately expressed general weakness, constant stabbing and aching pain in heart, palpitation and fault in heart, small dyspnoea at physical activity.
Objective inspection: general state of the patient is satisfactory, oedema, cyanosis, dyspnoea is not present. Pulse is in norm or a little accelerated, sometimes it is not rhythmical. Arterial pressure is in norm. Cardiomegaly is absent, I sound is slightly weakened, low amplitude systolic murmur is on apex of heart
Laboratory data. Clinical blood examination is in norm or there is low erythrocyte sedimentation rate (ESR). Biochemical blood examination: small increase of alanine aminotranspherase, lactate dehydrogenase, creatine phosphokinase, α2- and γ-globulin, cialic acid, seromucoid, haptoglobin. Antibodies credits to activators are increased.
ECG: decrease of T wave or ST segments, increase of PQ interval.
Roentgenological and echocardiography examination shows no pathology.
Moderate form of disease
Complaints: expressed weakness, constant stabbing and anginal pain in heart, palpitation and fault in heart, dyspnoea at rest and physical activity, subfebrile temperature.
Objective inspection: general state of the patient is of moderate severity. Acrocyanosis, oedema, and dyspnoea are not present. Rapid pulse, not rhythmical. Arterial pressure is in norm. Heart border is extended to the left, I sound is weakened, systolic heart murmur, sometimes friction rub.
Laboratory data. Clinical blood examination: increase of erythrocyte sedimentation rate (ESR), displacement of leukogram to the left, at virus myocarditis – leukopenia. Biochemical blood examination: increase of alanine aminotranspherase, lactate dehydrogenase, creatine phosphokinase, α2- and γ-globulin, cialic acid, seromucoid, haptoglobin, C-reactive protein. Immunologic examination: ↑ antibody titre to myocardium, detection of antibodies to myosin, actin, myolemma
ECG: decrease of T wave or ST segments, downward T wave, upward ST segments, atrioventricular block, extrasystole, auricular fibrillation or flutter.
Roentgenological and echocardiography examination shows cardiac dilatation and increase of the heart chamber.
Severe form of disease
Complaints: dyspnoea at rest and physical activity, tachycardia, cardiac arrhythmia, and pain in heart, pain in the right hypochondrium, oedema on legs, cough.
Objective inspection: general state of the patient is severe. Acrocyanosis. Forced patient’s position, orthopnoea, oedema on legs, dyspnoea. Swift pulse, weak pulse, not rhythmic pulse. Arterial pressure is low. Cardiomegaly heart sound is quiet, “gallop” rhythm, systolic heart murmur, friction rub.
Auscultation of lungs: pulmonary congestion and crepitation as a symptom of acute LV insufficiency.
Increase of the liver, oedema, ascites. There is occurrence of tricuspid heart disease and tromboembolic complications at expressed cardiomegaly.
Laboratory data. Clinical blood examination: increase of erythrocyte sedimentation rate (ESR), displacement of leukogram to the left, at virus myocarditis – leukopenia. Biochemical blood examination: increase of alanine aminotranspherase, lactate dehydrogenase, creatine phosphokinase, α2- and γ-globulin, cialic acid, seromucoid, haptoglobin, C-reactive protein. Immunologic examination: ↑ antibody titre to myocardium, detection of antibodies to myosin, actin, myolemma.
ECG: decrease of T wave or ST segments, downward T wave, upward ST segments, atrioventricular and intraventricular blocks, extrasystole, auricular fibrillation or flutter.
Roentgenological and echocardiography examination shows cardiac dilatation and increase of the heart chamber.
Auscultation of heart
Weakening of the I and II heart sound, sometimes quiet and inaudible heart sounds. Protodiastolic “gallop” rhythm testifies decrease of systolic LV function. Cardiac arrhythmia.
Systolic murmur at myocarditis is caused by the defeat of papillary muscles or by expansion of fibrous ring of mitral valve with development of mitral valve incompetence. The dilatation of right ventricle promotes occurrence of pulmonary artery stenosis, then systolic murmur in II-III intercostal to the left of sternum arises.
Diastolic murmur auscultation at the patients expressed dilatation of LV, that promotes formation of left atrioventricular aperture.
[pic]
Figure 6 – Example of ECG: the amplitude of ECG waves is reduced, splitting of the I sound and occurrence of pathological III sound. The short systolic murmur, which has arisen in result of dysfunction of valvular apparatus.
Complications: cardiac arrhythmia (extrasystole, paroxysmal tachycardia, ventricular tachycardia, atrial fibrillation, etc.); heart block (intraventricular and intra-auricular blocks); intraventricular thrombosis and thromboembolis; sudden heart death.
Diagnosis
ECG: the changes of processes repolarization of ventricles are most constantly registered: upward or depression of ST segments, downward T wave.
Heart block: intraventricular and atrioventricular block (AV block) of II degree (tape of Mobitz II).
Cardiac arrhythmia: extrasystole, auricular fibrillation or flutter, paroxysmal ventricular and atrial tachycardia, ventricular fibrillation.
QRS complex changes: low amplitude of R waves, pathological Q waves.
Roentgenological investigation
Cardiomegaly signs:
– increase of the cross size of the cardiac shadow up to 15.5 cm and more in men and up to 14.5 cm and more in women;
– increase of cardiothorax index (relation of the cross size of the heart shadow to internal cross size of thorax) up to 50% and more;
– roentgenological signs of heart chambers dilatation on the background of effective treatment considerably decrease or disappear absolutely.
Endomyocardial biopsy (Dallas criterion (USA, 1986))
The detection in biopsy of two morphological signs is considered necessary and sufficient:
1) inflammatory cellular infiltrate;
2) necrosis or damage of cardiomyocytes.
At virus myocarditis lymphocytes prevail in infiltrate, at bacterial myocarditis – neutrophiles, at allergic – eosinophiles. Gigantocytes infiltrate is characteristic for myocarditis of the most severe course with lethal outcome.
In real clinical conditions the indication for lifetime endomyocardial biopsy can be served by the most severe course of disease, refractory to medicament therapy, when there is a problem of differential diagnosis between severe diffusive myocarditis and dilatation cardiomyopathy (DCM) and the problem of heart transplantation is solved.
Diagnostic criteria. The recommendations (New York Heart
Association – NYHA).
Major criteria
Combination of eatiological factors with occurrence of symptoms:
1. Cardiomegaly.
2. Cardiac insufficiency.
3. Cardiogenic shock.
4. Morgani-Adams-Stokes syndrome.
5. Pathological changes of ECG.
6. Increase of cardiospecific ferments activity: creatine phosphokinase, lactate dehydrogenase, increase of antibody titre to myocardium, detection of antibodies to myosin, actin, myolemma, troponins.
Minor criteria
1. Laboratory confirmation of the transmitted infection (e.g., high credits of antiviral antibodies).
2. Weakening of the heart sound.
3. Protodiastolic “gallop” rhythm.
Myocarditis is diagnosed on the basis of presence of chronological combination of signs of the transmitted infection (allergy, toxic, etc.):
– with two “large” criteria myocarditis;
– with one “large” + two “small” criteria.
Idiopathic Abramov-Fiedler myocarditis (AFM)
The most severe form is nonrheumatic myocarditis of unknown aetiology, which proceeds with expressed diffusion with defeats of heart muscle.
Clinical symptoms of AFM
– expressed HF;
– expressed cardiomegaly;
– arterial pressure is low;
– intraventricular thrombosis and thromboembolis;
– ECG: decrease of T wave or ST segments, downward T wave, upward ST segments, pathological Q waves, arrhythmia and blocks.
Мorphologic signs of AFM
– myocardial hypertrophy, especially papillary muscle, subendomyocardial layers of myocardium;
– presence of the large myolysis fields with replacement of muscle with fibrous tissue;
– presence of intracavitary thrombus;
– presence of vasculitis of coronary arteries fine vessels;
– inflammatory cellular infiltrate on a course of vessels.
Laboratory, roentgenological, and echocardiographic data of idiopathic AFM correspond to severe form of myocarditis.
Treatment of myocarditis
Medical programme:
– correction of haemodynamic infringements;
– therapy of the basic disease;
– correction of immune status and immunopathologic reactions;
– treatment and preventive maintenance of infringements of the cordial rhythm and conductivity;
– treatment and prevention of thromboembolic complications.
1. Treatment of HF:
– restriction of physical activity;
– restriction of salt consumption up to 2–3 gr per day;
– restriction of liquid consumption up to 1.0–1.2 l per day (but is not less 0.8 l per day);
– prescription of potassium and magnesium in a diet.
Pharmacologic therapy:
– diuretics;
– ACE inhibitors;
– beta blockers;
– digitalis;
– spironolactone, etc.
2. Anti-inflammatory therapy:
Aminochinolinae group (delagil, rezochin, chlorochin) 0.25–0.5 gr per day. The application of placvenil (0.4 gr per day) is possible. These preparations apply to treatment of myocarditis during 6–9 months, and at recurring course – up to 1 year.
Acetylsalicylic acid – in a doze up to 3 gr per day within 4–5 weeks.
Indometacin – in a doze 75–100 gr per day within 4–6 weeks.
Movalis, diclofenac (voltaren)
Pyrazolinae derivatives (butadionum, brufen, ibuprofenum) are poorly effective.
Antibacterial therapy is shown only in case of widespread of bacterial infection, on the background of which myocarditis develops. Efficiency of application of antiviral preparations at viral myocarditis is studied now.
3. Glucocorticoid. Indications for prescription at myocarditis:
– at acute course with the expressed allergic component or immunology by infringements;
– long and recurring course;
– at myocarditis, accompanying pericarditis;
– expressed painful syndrome at severe gigantocellular myocarditis, and also in the patients with acquired immunodeficiency syndrome.
In these cases prednisolonum is nominated usually in a doze of 0.4–0.75 mg/kg of body weight per day. The duration of reception is 1.5–2 months with gradual decrease of a doze and cancellation of a preparation.
4. Heparinum:
Nominate at the severe forms of myocarditis subcutaneously with the expressed clinical and laboratory activity. In a doze 5000–10 000 IM 4 times per day for 7 days. Then reduce dosage, continuing injections up to 10–14 days. In subsequent nominate indirect anticoagulant or antiaggregant.
5. Metabolic preparations.
Myocarditis prognosis
– recovery with absence of changes on ECG;
– recovery with presence of changes on ECG;
– progressing decrease of systole function of heart and transformation in dilated cardiomyopathy.
CARDIOMYOPATHY
Dilated Cardiomyopathy (DCM)
DCM is myocardial dysfunction producing heart failure in which ventricular dilation and systolic dysfunction predominate. Symptoms include dyspnoea, fatigue, and peripheral oedema. Diagnosis is clinical and by chest X-ray and echocardiography. Treatment is directed at the cause; heart transplantation may be needed.
Aetiology of DCM (acute or chronic)
– chronic diffuse myocardial ischaemia (coronary artery disease);
– infections (acute or chronic): bacteria, spirochetes, rickettsia, viruses (including HIV), fungi, protozoa, helminths;
– granulomatous diseases: sarcoidosis, granulomatous or giant cell myocarditis, Wegener's granulomatosis;
– metabolic disorders: nutritional disorders (beriberi, selenium deficiency, carnitine deficiency, kwashiorkor), familial storage disorders, uremia, hypokalemia, hypomagnesemia, hyperthyroidism, hypothyroidism, hypophosphatemia, diabetes mellitus, acromegaly, pheochromocytoma, morbid obesity;
– drugs and toxins: ethanol, cocaine, anthracyclines, cobalt, psychotherapeutic drugs (tricyclic and quadricyclic antidepressants, phenothiazine), catecholamines, cyclophosphamide, radiation;
– tumours;
– connective tissue disorders;
– isolated familial (mendelian dominant);
– hereditary neuromuscular and neurologic disorders (Friedreich's ataxia);
– pregnancy (peripartum period).
In some patients, DCM is believed to start with acute myocarditis (probably viral in most cases), followed by a variable latent phase, a phase with diffuse necrosis of myocardial myocytes (due to an autoimmune reaction to virus-altered myocytes), and chronic fibrosis. Regardless of the cause, the remaining myocardium dilates, thins, and hypertrophies in compensation, often leading to functional mitral or tricuspid regurgitation and atrial dilation. The disorder affects both ventricles in most patients, only the left ventricle (LV) in a few, and only the right ventricle (RV) rarely.
Pathophysiology:
– systolic dysfunction.
Clinical examination:
– LV and RV failure;
– cardiomegaly;
– functional AV valve regurgitation of the 3rd heart sound and 4th heart sound.
ECG: nonspecific ST- and T-wave abnormalities; Q waves ± BBB.
Echocardiography: dilated hypokinetic ventricles ± mural thrombus. Low EF.
X-ray: cardiomegaly. Pulmonary venous congestion.
Haemodynamics: normal or high EDP, low EF, diffusely dilated hypokinetic ventricles ± AV valve regurgitation. Low CO.
Prognosis: 70% patients with DCM 5-yr mortality.
[pic]
Figure 7 – Heart systolic and diastolic dysfunction
Treatment
Diuretics, ACE inhibitors, angiotensin II receptor blockers, β-blockers, spironolactone or eplerenone (inspra), internal cardioverter-defibrillator, biventricular pacing, inotropic drugs, anticoagulants.
Hypertrophic Cardiomyopathy (HCM)
HCM is a complex and relatively common genetic cardiac disorder (about 1:500 in the general adult population) that has been the subject of intense scrutiny and investigation for over 40 years. HCM affects men and women equally and occurs in many races and countries, although it appears to be under-diagnosed in women, minorities, and under-served populations. HCM is a particularly common cause of sudden cardiac death in young people (including trained athletes) and may cause death and disability in patients of all ages, although it is also frequently compatible with normal longevity.
Hypertrophic cardiomyopathy is a congenital or acquired disorder characterized by marked ventricular hypertrophy with diastolic dysfunction but without increased afterload (valvular aortic stenosis, coarctation of aorta, systemic hypertension). Symptoms include chest pain, dyspnoea, syncope, and sudden death. A systolic murmur, increased by Valsalva maneuver, is typically present in the hypertrophic obstructive type. Diagnosis is by echocardiography. Treatment is with β-blockers, verapamil, disopyramide, and sometimes chemical reduction or surgical removal of outflow tract obstruction.
Aetiology and pathophysiology of HCM
Autosomal dominant inheritance, pheochromocytoma, acromegaly, neurofibromatosis.
Pathophysiology: diastolic dysfunction ± outflow obstruction.
Clinical examination: angina, exertional dyspnoea, syncope, sudden death; ejection ± mitral regurgitation murmurs S4; Bifid carotid pulse with a brisk upstroke and rapid downstroke.
ECG: LV hypertrophy and ischaemia; deep septal Q waves.
Echocardiography: hypertrophied ventricle ± mitral systolic anterior motion ± asymmetric hypertrophy ± LV gradient.
X-ray: no cardiomegaly.
Haemodynamics: high EDP (end-diastolic pressure), high EF ± outflow subvalvular gradient ± mitral regurgitation. Normal or low CO.
Prognosis: 4% patients with HCM 1-yr mortality.
Treatment
Reduced contractility with β-blockers ± verapamil, ± disopyramide, ± septal myotomy, ± catheter alcohol ablation; AV pacing.
[pic]
Figure 8 – Clinical presentation and treatment strategies for patient subgroups within the broad clinical spectrum of hypertrophic cardiomyopathy (HCM)
Note: AF – atrial fibrillation; DDD – dual-chamber; ICD – implantable cardioverter-defibrillator; SD – sudden death.
Risk factors for sudden death in HCM
Major: cardiac arrest (ventricular fibrillation); spontaneous sustained ventricular tachycardia; family history of premature sudden death; unexplained syncope; LV thickness greater than or equal to 30 mm; abnormal exercise blood pressure; nonsustained ventricular tachycardia (Holter).
Possible in individual patients: atrial fibrillation; myocardial ischaemia; LV outflow obstruction; high-risk mutation; intense (competitive) physical exertion.
Restrictive Cardiomyopathy (RCM)
RCM is characterized by noncompliant ventricular walls that resist diastolic filling; one or both ventricles, most commonly the left, may be affected. Symptoms include fatigue and exertional dyspnoea. Diagnosis is by echocardiography. Treatment is often unsatisfactory and is best directed at the cause. Surgery is sometimes useful.
Aetiology and pathophysiology of RCM
Amyloidosis, diffuse systemic sclerosis, fibroelastosis, endocardial fibrosis, Fabry's disease, Gaucher's disease, haemochromatosis, Löffler's syndrome, sarcoidosis, hypereosinophilia syndrome, tumours.
Pathophysiology: diastolic dysfunction.
Clinical examination: exertional dyspnoea and fatigue LV ± RV failure; functional AV valve regurgitation.
ECG: LV hypertrophy or low voltage.
Echocardiography: increased wall thickness ± cavity obliteration LV diastolic dysfunction asymmetry.
X-ray: no or mild cardiomegaly.
Hemodynamics: high EDP, dip and plateau diastolic LV pressure curve; normal or low CO.
Prognosis: 70% patients with RCM 5-yr mortality.
Treatment
– phlebotomy for haemochromatosis;
– endocardial resection;
– hydroxyurea for hypereosinophilia.
Table 23 – Diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy (ARVC)
|Major criterion |Minor criterion |
|Severe dilation and reduction of right |Mild global right ventricular dilation and/or|
|ventricular ejection fraction with no (or |ejection fraction reduction with normal LV |
|only mild) left ventricular impairment | |
|Localized right ventricular aneurysms |Mild segmental dilation of the right |
|(akinetic or dyskinetic areas with |ventricle |
|diastolic bulging) | |
|Severe segmental dilation of the right |Regional right ventricular hypokinesia, |
|ventricle; fibrofatty replacement of |inverted T waves in right precordial leads |
|myocardium on endomyocardial biopsy |(V2 and V3) (people older than 12 years of |
| |age; in the absence of right bundle branch |
| |block) |
|Epsilon waves or localized prolongation (> |Late potentials (signal averaged |
|110 ms) of the QRS complex in right |electrocardiogram) |
|precordial leads (V1–V3) | |
|Familial disease confirmed at necropsy or |Left bundle branch block type ventricular |
|surgery |tachycardia (sustained and nonsustained) |
| |(electro-cardiogram, Holter monitor, exercise|
| |testing); frequent ventricular extrasystoles |
| |(> 1000/ 24 h) on Holter monitor; familial |
| |history of premature sudden death |
| |(< 35 years of age) due to suspected ARVC; |
| |familial history (clinical diagnosis based on|
| |present criteria) |
PERICARDITIS
Pericarditis (pericardial syndromes) is inflammation of the pericardium, often with fluid accumulation. Pericarditis may be caused by many disorders but is often idiopathic.
In progressive human immunodeficiency virus (HIV) the incidence of echocardiographically detected pericardial effusion is up to 40%. Purulent pericarditis in adults is rare, but always fatal if untreated. Mortality rate in treated patients is 40%, mostly due to cardiac tamponade, toxicity, and constriction. In the last decade TBC pericarditis in the developed countries has been primarily seen in immunocompromised patients (AIDS). The mortality rate in untreated acute effusive TBC pericarditis approaches 85%. Pericardial constriction occurs in 30–50%.
Blunt chest trauma is the major risk of car accidence. The deceleration force can lead to myocardial contusion with intrapericardial haemorrhage, cardiac rupture, pericardial rupture, or herniation. Transoesophageal echocardiography in the emergency room or immediate computed tomography should be performed. Pericardial laceration and partial extrusion of the heart into the mediastinum and pleural space may also occur after injury.
In dissection of the ascending aorta (pericardial effusion can be found in 17–45% of the patients and in 48% of the autopsy cases. In a clinical series of aortic dissection, pericardial tamponade was found by CT, MRI, or echocardiography in 17–33% of patients with type I dissection and 18–45% in type II dissection and 6% in type III dissection.
Pericardial constriction may happen in up to 20% of patients with radiation-induced pericarditis, requiring pericardiectomy. The operative mortality is high (21%) and the postoperative five years survival rate is very low (1%) mostly due to myocardial fibrosis.
Classifications
According to aetiology of the causative agent:
1. Infectious:
– viral (Coxsackie A9, B1-4, Echo 8, mumps, EBV, CMV, varicella, rubella, HIV, parvo B19...). Incidence is 30–50%1;
– bacterial (pneumo-, meningo-, gonococcosis, haemophilus, treponema pallidum, borreliosis, chlamydia, tuberculosis...). Incidence is 5–10%1;
– fungal (candida, histoplasma...) – rare1;
– parasitary ( entameba histolytica, echinococcus, toxoplasma...) – rare1.
2. Pericarditis in systemic autoimmune diseases
Systemic lupus erythematosus – incidence is 30%2; rheumatoid arthritis – 30%2; spondylitis ankylosans – 1%2; systemic sclerosis – > 50%2; dermatomyositis – rare2; periarteritis nodosa – rare2; Reiter’s syndrome – 2%; familial mediterranean fever – 0.7%2.
3. Type 2 (auto)immune process
Rheumatic fever – incidence is 20–50%2; postcardiotomy syndrome – 20%2 (10–14 days after surgery); postmyocardial infarction syndrome – 1–5%2; autoreactive (chronic) pericarditis – 23.1%2.
4. Pericarditis and pericardial effusion in diseases of surrounding organs
Acute MI (P. Epistenocardica) – incidence is 5–20%2 (1–5 days after transmural MI); myocarditis – 30%2; paraneoplastic pericarditis – frequent2; aortic aneurysm – rare2; lung infarction – rare2 pneumonia – rare2; oesophageal diseases – rare2; hydropericardium in CHF – rare2.
5. Pericarditis in metabolic disorders
Renal insufficiency (uraemia) – frequent2; myxedema – 30%2; Addison’s disease – rare2; diabetic ketoacidosis – rare2; cholesterol pericarditis – very rare2.
6. Pregnancy – rare
7. Traumatic pericarditis
Direct injury (penetrating thoracic injury, oesophageal perforation, foreign bodies) – rare2; indirect injury (nonpenetrating thoracic injury, mediastinal irradiation) – rare.
8. Neoplastic pericardial disease – 35%1
Primary tumours – rare2; secondary metastatic tumours – frequent2.
9. Idiopathic – 3.5 – 50%1
10. Congenital defects of the pericardium (congenital defects of the pericardium (1/10.000 autopsies)):
– comprise partial left (70%2);
– right (17%2);
– total bilateral (extremely rare2) pericardial absence.
Note:
1 - Marburg pericarditis registry 1988–2001;
2 - percentage related to the incidence of pericarditis in the specific population of patients.
Clinical-morphological classification
1. Acute pericarditis:
a) dry;
b) fibrinous;
c) effusive:
– with cardiac tamponade;
– without cardiac tamponade.
2. Chronic pericardial (inflammation (> 3 months)):
– effusive;
– adhesive;
– constrictive forms.
3. Recurrent pericarditis:
– intermittent type (widely varying symptom-free interval without therapy);
– incessant type (discontinuation of anti-inflammatory therapy always ensures a relapse).
Acute pericarditis
Acute pericarditis is either dry, fibrinous or effusive, independent from its aetiology. A prodrome of fever (usually < 39 ºC), malaise, and myalgia is common, but elderly patients may not be febrile. Major symptoms are retrosternal or left precordial chest pain (radiates to the trapezius ridge, can be pleuritic or simulate ischaemia, and varies with posture), nonproductive cough, and shortness of breath.
Auscultation: pericardial rub (mono-, bi-, or triphasic).
ECG:
Stage I: anterior and inferior concave ST segment elevation. PR segment deviations opposite to P polarity.
Early stage II: ST junctions return to the baseline, PR deviated.
Late stage II: T waves progressively flatten and invert.
Stage III: generalized T wave inversions.
Stage IV: ECG returns to prepericarditis state.
Typical lead involvement: I, II, aVL, aVF, and V3-V6. The ST segment is always depressed in VR, frequently in V1, and occasionally in V2.
Echocardiography: effusion types B-D (Horowitz); signs of tamponade.
Blood analysis:
– ↑ ESR, CRP, LDH, leukocytes (inflammation markers);
– troponin I, CK-MB (markers of myocardial lesion).
Chest X-ray: ranging from normal to “water bottle” heart shadow. Revealing additional pulmonary/mediastinal pathology.
Pericardiocentesis and drainage (mandatory in tamponade (indication class I), optional in large/recurrent effusions or if previous tests inconclusive (indication class IIa) in small effusions (indication class IIb)): PCR and histochemistry for aetiopathogenetic classification of infection or neoplasia.
|[pic] |Type A: no effusion. |
| |Type B: separation of epicardium and |
| |peri-cardium (3–16 ml). |
| |Type C 1: systolic and diastolic separation of |
| |epicardium and pericardium (small effusion > 16 |
| |ml). |
| |Type C 2: systolic and diastolic separation of |
| |epicardium and pericardium with attenuated |
| |pericardial motion. |
| |Type D: pronounced separation of epicardium and |
| |pericardium with large echo-free space. |
| |Type E: pericardial thickening (> 4 mm) |
Figure 9 – Horowitz classification of pericardial effusions (Copyrights American Heart Association)
Optional or if previous tests are inconclusive (IIa):
– CT – effusions, peri-, and epicardium;
– MRI – effusions, peri-, and epicardium;
– pericardioscopy, pericardial biopsy – establishing the specific aetiology.
Treatment
Hospitalization is warranted for most patients to determine the aetiology, observe for tamponade, and start anti-inflammatory and symptomatic treatment.
1. Specific therapy depending on the aetiology factor.
2. Nonsteroidal anti-inflammatory drugs (NSAID)(IB):
– ibuprofen is preferred for its rare side effects, favourable effect on the coronary flow and the large dose range.
– ibuprofen 300–800 mg every 6–8 h may be initially required and can be continued for days or weeks, best until the effusion has disappeared.
– gastrointestinal protection must be provided in all patients.
3. Colchicine (0.5 mg bid) (IIa, B).
4. Systemic corticosteroid therapy should be restricted to connective tissue diseases, autoreactive or uremic pericarditis (IIa, B).
Pericardiocentesis
Indication:
– pericardiocentesis is life saving in cardiac tamponade (IB);
– in effusions > 20 mm in echocardiography in diastole or for diagnostic purposes.
Contraindication:
– aortic dissection;
– relative contraindications include uncorrected coagulopathy, anticoagulant therapy, thrombocytopenia < 50,000/mm³, small, posterior, and loculated effusions;
– pericardiocentesis in acute traumatic haemopericardium and purulent pericarditis is probably less appropriate than surgical drainage.
Pericardiocentesis guided by fluoroscopy is performed in the cardiac catheterisation laboratory with ECG monitoring. Direct ECG monitoring from the puncturing needle is not an adequate safeguard. Right-heart catheterisation can be performed simultaneously, allowing exclusion of constriction. It is prudent to drain the fluid in < 1 steps to avoid the acute right-ventricular dilatation. The subxiphoid approach has been used most commonly, with a long needle with a mandrel (Tuohy or thin-walled 18-gauge) directed towards the left shoulder at a 30° angle to the skin. This route is extrapleural and avoids the coronary, pericardial, and internal mammary arteries.
Echocardiographic guidance of pericardiocentesis is technically less demanding and can be performed at the bedside. Echocardiography should identify the shortest route where the pericardium can be entered intercostally (usually in the sixth or seventh rib space in the anterior axillary line). Prolonged pericardial drainage is performed until the volume of effusion obtained by intermittent pericardial aspiration (every 4–6 h) fall to < 25 ml per day. The feasibility is high (93%) in patients with anterior effusion ≥ 10 mm while the rate of success is only 58% with small, posteriorly located effusions.
Complications of pericardiocentesis are:
– laceration and perforation of the myocardium and the coronary vessels;
– air embolism, pneumothorax, arrhythmias (usually vasovagal bradycardia), and puncture of the peritoneal cavity or abdominal viscera;
– internal mammary artery fistulas, acute pulmonary oedema, and purulent pericarditis were rarely reported.
Chronic pericarditis
Chronic (> 3 months) pericarditis includes effusive (inflammatory or hydropericardium in heart failure), adhesive, and constrictive forms.
Symptoms are usually mild (chest pain, palpitations, fatigue), related to the degree of cardiac compression and pericardial inflammation. The diagnostic algorithm is similar as in acute pericarditis. The detection of the curable causes (e.g., tuberculosis, toxoplasmosis, myxedema, autoimmune, and systemic diseases) allows successful specific therapy.
Symptomatic treatment and indications for pericardiocentesis are as in acute pericarditis. For frequent and symptomatic recurrences balloon pericardiotomy or pericardiectomy should be considered (IIb, nB).
Recurrent pericarditis
The term “recurrent pericarditis” encompasses:
– intermittent type (symptom – free intervals without therapy);
– incessant type (discontinuation of anti-inflammatory therapy ensures a relapse). Massive pericardial effusion, overt tamponade or constriction are rare.
Evidence for an immunopathological process include:
– latent period lasting for months;
– presence of antiheart antibodies;
– quick response to steroid treatment and the similarity and co-existence of recurrent pericarditis with other autoimmune conditions (lupus, serum sickness, polyserositis, postpericardiotomy/ postmyocardial infarction syndrome, celiac disease, dermatitis herpetiformis, frequent arthralgias, eosinophilia, allergic drug reaction, and history of allergy);
– genetic disorders were also reported: autosomal dominant inheritance with incomplete penetrance and sex-linked inheritance (recurrent pericarditis associated with ocular hypertension).
Symptomatic management relies on exercise restriction and the regimen used in acute pericarditis. The colchicine – recommended dose is 2 mg/day for one or two days, followed by 1 mg/day (I, B). Corticosteroids should be used only in patients with poor general condition or in frequent crises (IIa, C). The recommended regimen is: prednisone 1–1.5 mg/kg, for at least one month. If patients do not respond adequately, azathioprine (75–100 mg/day) or cyclophosphamide can be added. Corticoids should be tapered over a three-month period. If symptoms still recur, return to the last dose that suppressed the manifestations, maintain that dose for 2–3 weeks and then recommence tapering. Towards the end of the taper, introduce anti-inflammatory treatment with colchicine or NSAID. Renewed treatment should continue for at least three months. Pericardiectomy is indicated only in frequent and highly symptomatic recurrences resistant to medical treatment (Iia, B). Before pericardiectomy, the patient should be on a steroid-free regimen for several weeks.
Pericardial effusion and cardiac tamponade
Pericardial effusion may appear as transudate (hydropericardium), exudate, pyopericardium or haemopericardium.
Large effusions are common with neoplastic, tuberculous, cholesterol, uremic pericarditis, myxedema, and parasitoses. Effusions that develop slowly can be remarkably asymptomatic, while rapidly accumulating smaller effusions can present with tamponade.
Loculated effusions are more common when scarring has supervened (e.g., postsurgical, posttrauma, purulent pericarditis).
Massive chronic pericardial effusions are rare (2–3.5% of all large effusions).
Cardiac tamponade is the decompensated phase of cardiac compression caused by effusion accumulation and the increased intrapericardial pressure. In “surgical” tamponade intrapericardial pressure is rising rapidly, in the matter of minutes to hours (i.e., haemorrhage), whereas a low-intensity inflammatory process is developing days to weeks before cardiac compression occurs (“medical” tamponade).
Clinical presentation: orthopnoea, cough and dysphagia, occasionally with episodes of unconsciousness can be observed. Elevated systemic venous pressure, hypotension, pulsus paradoxus, tachycardia, dyspnoea or tachypnoea with clear lungs. Insidiously developing tamponade may present with the signs of its complications (renal failure, abdominal plethora, shock liver and mesenteric ischaemia). Heart sounds are distant.
Determination of pulsus paradoxus
Pulsus paradoxus is defined as a drop in systolic blood pressure > 10 mmHg during inspiration whereas diastolic blood pressure remains unchanged. It is easily detected by feeling the pulse. During inspiration, the pulse may disappear or its volume diminishes significantly. Clinically significant pulsus paradoxus is apparent when the patient is breathing normally. When present only in deep inspiration it should be interpreted with caution. The magnitude of pulsus paradoxus is evaluated by sphygmomanometry. If the pulsus paradoxus is present, the first Korotkoff sound is heard only during expiration. The blood pressure cuff is therefore inflated above the patient's systolic pressure. During deflation, the first Korotkoff sound is intermittent. Correlation with the patient's respiratory cycle identifies a point at which the sound is audible during expiration, but disappears in inspiration. As the cuff pressure drops, another point is reached when the first blood pressure sound is audible throughout the respiratory cycle. The difference is the measure of pulsus paradoxus.
Electrocardiography may demonstrate diminished QRS and T-wave voltages, PR-segment depression, ST-T changes, bundle branch block, and electrical alternans (rarely seen in the absence of tamponade).
In chest radiography: enlarged cardiac silhouette with clear lungs. The separation of pericardial layers can be detected in echocardiography, when the pericardial fluid exceeds 15–35 ml. The size of effusions can be graded as:
1. small (echo-free space in diastole < 10 mm);
2. moderate (10–20 mm);
3. large (≥ 20 mm);
4. very large (≥ 20 mm and compression of the heart).
At the M mode/2D echocardiogram: diastolic collapse of the anterior RV free wall, RA collapse, LA and very rarely LV collapse, increased LV diastolic wall thickness “pseudohypertrophy”, VCI dilatation (no collapse in inspirium), “swinging heart”.
Doppler:
1. Tricuspid flow increases and mitral flow decreases during inspiration (reverse in expiration).
2. Systolic and diastolic flows are reduced in systemic veins in expirium and reverse flow with atrial contraction is increased.
Cardiac catheterisation:
1. Confirmation of the diagnosis and quantification of the haemodynamic compromise; RA pressure is elevated (preserved systolic x descent and absent or diminished diastolic y descent); intrapericardial pressure is also elevated and virtually identical to RA pressure (both pressures fall in inspiration); RV mid-diastolic pressure elevated and equal to the RA and pericardial pressures (no dip-and-plateau configuration); pulmonary artery diastolic pressure is slightly elevated and may correspond to the RV pressure; pulmonary capillary wedge pressure is also elevated and nearly equal to intrapericardial and right atrial pressure; LV systolic and aortic pressures may be normal or reduced.
2. Documenting that pericardial aspiration is followed by haemodynamic improvement.
3. Detection of the coexisting haemodynamic abnormalities (LV failure, constriction, pulmonary hypertension).
4. Detection of associated cardiovascular diseases (cardiomyopathy, coronary artery disease).
RV/LV angiography: atrial collapse and small hyperactive ventricular chambers.
Coronary angiography: coronary compression in diastole.
Computer tomography: no visualisation of subepicardial fat along both ventricles, which show tube-like configuration and anteriorly drawn atrias.
Treatment
Pericardiocentesis is not necessary when the diagnosis can be made otherwise or the effusions are small or resolving under anti-inflammatory treatment. Haemodynamic compromise and cardiac tamponade is an absolute indication for drainage. Treatment should be aimed at the underlying aetiology. Even in idiopathic effusions extended pericardial catheter drainage (3±2 days, range 1–13 days) was associated with a lower recurrence rates (6% vs. 23%) than in those without catheter drainage during the follow-up of 3.8±4.3 years.
Resistant neoplastic processes require intrapericardial treatment, percutaneous balloon pericardiotomy or rarely pericardiectomy. Surgical approach is recommended only in patients with very large chronic effusion in whom repeated pericardiocentesis and/or intrapericardial therapy were not successful.
Constrictive pericarditis
Constrictive pericarditis is a rare but severely disabling consequence of the chronic inflammation of the pericardium, leading to an impaired filling of the ventricles and reduced ventricular function. Until recently, increased pericardial thickness has been considered an essential diagnostic feature of constrictive pericarditis. However, in the large surgical series from the Mayo clinic constriction was present in 18% of the patients with normal pericardial thickness. Tuberculosis, mediastinal irradiation, and previous cardiac surgical procedures are frequent causes of the disease, which can present in several pathoanatomical forms.
Clinical presentation: severe chronic systemic venous congestion associated with low cardiac output, including jugular venous distension, hypotension with a low pulse pressure, abdominal distension, oedema and muscle wasting.
ECG: can be normal, or reveal low QRS voltage, generalized T-wave inversion/flattening, LA abnormalities, atrial fibrillation, atrioventricular block, intraventricular conduction defects, or rarely pseudoinfarction pattern.
M mode/2D echocardiogram: pericardial thickening and calcificationsa as well as the indirect signs of constriction: RA and LA enlargement with normal appearance of the ventricles, and normal systolic function, early pathological outward and inward movement of the interventricular septum (“dip-plateau phenomenon”), flattering waves at the LV posterior wall, LV diameter is not increasing after the early rapid filling phase, VCI and the hepatic veins are dilated with restricted respiratory fluctuations.
Chest X-ray: pericardial calcifications, pleural effusions.
Doppler: restricted filling of both ventricles with respiratory variation > 25% over the AV-valves).
[pic]
Figure 10 – Pathoanatomical forms of constrictive pericarditis vs. restrictive cardiomyopathy
(a) Annular form of pericardial constriction with bilateral thickening of the pericardium along the atrial ventricular grooves with normal configuration of both ventricles and enlargement of both atria.
(b) Left-sided form of pericardial constriction with thickened pericardium along the left ventricle and right sided bending of the interventricular septum with tube-like configuration of mainly left ventricle and enlargement of both atria (lateral sternotomy and partial pericardiectomy is indicated).
(c) Right-sided form of pericardial constriction with thickened pericardium along the right ventricle and left sided bending of the interventricular septum with tube-like configuration of mainly right ventricle and enlargement of both atria (median sternotomy and partial pericardiectomy is indicated).
(d) Myocardial atrophy and global form of pericardial constriction with bilateral thickening of the pericardium along both ventricles separated from the right myocardial wall by a thin layer of subepicardial fat. Tube-like configuration of both ventricles and enlargement of both atria, however, thinning of the interventricular septum and posterolateral wall of the left ventricle below 1 cm is suggesting myocardial atrophy (pericardiectomy is contraindicated).
(e) Perimyocardial fibrosis and global form of pericardial constriction with bilateral thickening of the pericardium along both ventricles, however, the right-sided thickened pericardium cannot be separated from the wave-like thin form of right-sided ventricular wall suggesting perimyocardial fibrosis (pericardiectomy is contraindicated).
(f) Global form of pericardial constriction with bilateral thickening of the pericardium along both ventricles separated from the right myocardial wall by a thin layer of subepicardial fat. Tube-like configuration of both ventricles and enlargement of both atria (median sternotomy and pericardiectomy is indicated).
(g) Restrictive cardiomyopathy with normal thin pericardium along both ventricles that show normal configuration and with enlargement of both atria.
Transoesophageal echocardiography: measurement of the pericardial thickness.
CT/MRI: thickened and/or calcified pericardium, tube-like configuration of one or both ventricles, narrowing of one or both atrioventricular grooves, congestion of the caval veins enlargement of one or both atria.
Cardiac catheterisation: “dip and plateau” or “square route” sign in the pressure curve of the right and/or left ventricle; equalisation of LV/RV end-diastolic pressures in the range of 5 mmHg or less.
RV/LV angiography: the reduction of RV&LV size and increase of RA&LA size, during diastole a rapid early filling with stop of further enlargement (“dip-plateau”).
Coronary angiography: in all patients over 35 years and in patients with a history of mediastinal irradiation, regardless of the age.
Treatment
Pericardiectomy is the only treatment for permanent constriction. The indications are based upon clinical symptoms, echocardiography findings, CT/MRI, and heart catheterisation.
Specific forms of pericarditis
Viral pericarditis
Viral pericarditis is the most common infection of the pericardium. Inflammatory abnormalities are due to direct viral attack, the immune response (antiviral or anticardiac), or both. Various viruses cause pericarditis (entero-, echo-, adeno-, cytomegalovirus, Ebstein Barr, herpes simplex, influenza, parvo B19, hepatitis C, HIV, etc.). Attacks of enteroviral pericarditis follow the seasonal epidemics of Coxsackie virus A+B and Echovirus infections. Cytomegalovirus pericarditis has an increased incidence in immunocompromised and HIV infected hosts. Infectious mononucleosis may also present with pericarditis. The diagnosis of viral pericarditis is not possible without the evaluation of pericardial effusion and/or pericardial/epicardial tissue, preferably by PCR or in-situ hybridisation (Ia, B). A four-fold rise in serum antibody levels is suggestive but not diagnostic for viral pericarditis (Ib, B).
Treatment of viral pericarditis is directed to resolve symptoms (see acute pericarditis), prevent complications, and eradicate the virus. In patients with chronic or recurrent symptomatic pericardial effusion and confirmed viral infection the following specific treatment is under investigation:
– сytomegalovirus pericarditis: hyperimmunoglobulin – 1 time per day 4 ml/kg on day 0, 4, and 8; 2 ml/kg on day 12 and 16;
– Coxsackie B pericarditis: interferon alpha or beta 2.5 Mio. IU/m2 surface area s.c. 3 x per week;
– adenovirus and parvovirus B19 perimyocarditis: immuno-globulin treatment: 10 g intravenously at day 1 and 3 for 6–8 hours.
Pericardial manifestation of human immunodeficiency virus (HIV) infection can be due to infective, non-infective and neoplastic diseases (Kaposi’s sarcoma and/or lymphoma). Infective (myo)pericarditis results from the local HIV infection and/or from the other viral (cytomegalovirus, herpes simplex), bacterial (S. aureus, K. pneumoniae, M. avium, and M. tuberculosis) and fungal coinfections (Cryptococcus neoformans). During the treatment with retroviral compounds, lipodystrophy can develop with intense paracardial fat deposition leading to heart failure. Treatment is symptomatic, while in large effusions and cardiac tamponade pericardiocentesis is necessary. The use of corticoid therapy is contraindicated except in patients with secondary tuberculous pericarditis (I, A).
Table 24 – Differential diagnosis of the specific forms of pericarditis
| |Viral |Bacterial |Tuberculous |Autoreactive |
|Cardio-tropic |Entero-, echo-, |Staphylo-, |Myco-bacterium |Autoimmune |
|microbial |adeno-, |pneumo-, |tuberculosis |process in the |
|agents |cytomegalo-virus, |strepto-cocci, | |absence of viral |
| |Epstein Barr, herpes|Neisseria, | |and |
| |simplex, influenza, |proteus, | |bacterial |
| |parvo B19, |gram nega- | |agents |
| |hepatitis A, B, C |tive rods, | | |
| |virus, HIV |legionella | | |
|Aetiologi-cal |PCR or in-situ |Gram stain, |Ziehl-Neelsen, |Ig-binding to |
|evidence |hybridisation (IIa, |bacterial |auramin 0 stain, |peri- and |
| |B) |culture, |culture, PCR (IB) |epicardium, |
| | |PCR for Borrelia| |negative |
| | |and chlamydia | |PCR for |
| | |pneumo- | |cardiotropic |
| | |niae (IB) | |agents, |
| | | | |epicarditis |
| | | | |(IIa, B) |
|Incidence (%) |30 |5–10.5 |< 4 (more in |20–30 |
|in | |per |Africa and | |
|Western | |100,000 patients|South America) | |
|countries | | | | |
|Male: female |3:1 |1:1 |1:1 |1:1 |
|ratio | | | | |
|Predis-positio|Unknown |Chronic alcohol |Alcohol abuse, |Association |
|n | |abuse, |HIV infection |to autoimmune |
| | |immuno-suppressi| |disorders |
| | |on | | |
|Clinical |Identical to acute |Spiking |Subfebrile, |Subfebrile, |
|features |pericarditis, often |fever, |chronic |chronic |
| |subfebrile |fulminant, | | |
| | |tachycardia, | | |
| | |pericardial rubs| | |
Table 24 continuation
| |Viral |Bacterial |Tuberculous |Autoreactive |
|Effusion |Variable, mostly |Variable |Variable, |Variable |
|size |small | |mostly large | |
|Tamponade |Infrequent |80% |Frequent |Infrequent |
|Sponta-nious |Frequent |None |None |Rare |
|remission | | | | |
|Recurrence |30–50% |Rare |Frequent |Frequent; |
|rate | | | |> 25% |
|Aspect of |Serous/sero-sangui|Purulent |Sero-sanguinous |Serous |
|PE |nous | | | |
|Protein |> 3 g/dL |High |High/inter-mediate|Intermediate |
|content | | | | |
|Leukocyte |> 5000/ml |>10000/ml |Intermediate |Intermediate |
|count (PE) | | |> 8000 |< 5000 |
|Pericardial |Activated |Granulo-cytes |Granulocytes |Activated |
|fluid analysis |lymphocytes and |and macro-phages|and macro-phages |lymphocytes |
| |macro-phages. |(massive) |(intermediate) |and macro-phages |
| |Adenosindea-minase|ADA-negative |ADA positive |(sparse) |
| |(ADA)-negative | |(> 40 U/ml) |ADA-negative |
|Peri- and |Lymphocytic peri-/|Leukocytic |Caseous |Lymphocytic |
|epicardial |epicarditis, PCR |epicarditis |granuloma, |peri-/ |
|biopsy |positive for | |PCR |epicarditis, |
| |cardio-tropic | | |PCR negative |
| |virus | | | |
|Mortality if |Depending on agent|100% |85% |In untreated |
|untreated |and tamponade | | |tamponade |
|Intraperi-cardia|Drainage, if |Drainage and |Drainage, |Drainage, i.p. |
|l |needed, no |rinsing (saline)|if needed |triamcinolon |
|treatment |intraper-cardial |gentamycin 80 mg| |(IIa, B) |
| |corticoids |i.p. | | |
Table 24 continuation
| |Viral |Bacterial |Tuberculous |Autoreactive |
|Peri-cardiotomy/|Rarely |Promptly needed |Rarely |Rarely |
|pericardi-ectomy|needed |(evidence level |needed |needed |
| | |B, indication I)| | |
|Systemic |I.V.immuno-globuli|I.V. antibiotics|Tuberculo-static |NSAIDs, |
|treatment |ns, IFN (in | |+prednisone |colchicine, |
| |enteroviral | | |prednisolone/azath|
| |pericarditis) | | |ioprin |
|Constriction |Rare |Frequent |Frequent (30–50%) |Rare |
Bacterial pericarditis
It is usually a complication of an infection originating elsewhere in the body, arising by contiguous spread or haematogenous dissemination. Predisposing conditions are pericardial effusion, immunosuppression, chronic diseases (alcohol abuse, rheumatoid arthritis, etc.), cardiac surgery and chest trauma. The disease appears as an acute, fulminant infectious illness with short duration. Percutaneous pericardiocentesis must be promptly performed. Obtained pericardial fluid should undergo urgent Gram, acid-fast and fungal staining (I, B).
Pericarditis in renal failure
Renal failure is a common cause of pericardial disease, producing large pericardial effusions in up to 20% of patients. Two forms have been described:
1. Uremic pericarditis – in 6–10% of patients with advanced renal failure (acute or chronic) before dialysis has been instituted or shortly thereafter. It results from inflammation of the visceral and parietal pericardium and correlates with the degree of azotemia (BUN > 60 mg/dl).
2. Dialysis-associated pericarditis – in up to 13% of patients on maintenance haemodialysis, and occasionally with chronic peritoneal dialysis due to inadequate dialysis and/or fluid overload.
The clinical features may include fever and pleuritic chest pain but many patients are asymptomatic. Pericardial rubs may persist even in large effusions or may be transient. Due to autonomic impairment in uremic patients, heart rate may remain slow (60–80 beats/min) during tamponade, despite fever and hypotension. Anaemia, due to induced resistance to erythropoietin may worsen the clinical picture. The ECG does not show the typical diffuse ST/T wave elevations observed with other causes of acute pericarditis due to the lack of the myocardial inflammation. If the ECG is typical of acute pericarditis, intercurrent infection must be suspected. Most patients with uremic pericarditis respond rapidly to haemo- or peritoneal dialysis with resolution of chest pain and pericardial effusion.
Autoreactive pericarditis and pericardial involvement in systemic autoimmune diseases
Pericarditis occurs in systemic autoimmune diseases. The diagnosis of autoreactive pericarditis is established using the following criteria:
– increased number of lymphocytes and mononuclear cells > 5000/mm3 (autoreactive lymphocytic), or the presence of antibodies against heart muscle tissue (antisarcolemmal) in the pericardial fluid (autoreactive antibody-mediated);
– inflammation in epicardial/endomyocardial biopsies by ≥ 14 cells/mm2;
– exclusion of active viral infection both in pericardial effusion and endomyocardial/epimyocardial biopsies (no virus isolation, no IgM-titre against cardiotropic viruses in pericardial effusion, and negative PCR for major cardiotropic viruses);
– tuberculosis, Borrelia burgdorferi, Chlamydia pneumoniae, and other bacterial infection excluded by PCR and/or cultures;
– neoplastic infiltration absent in pericardial effusion and biopsy samples;
– exclusion of systemic, metabolic disorders, and uraemia.
Postcardiac injury syndrome: postpericardiotomy syndrome
Postcardiac injury syndrome develops within days to months after cardiac, pericardial injury or both. It resembles the postmyocardial infarction syndrome, both appearing to be variants of a common immunopathic process. Unlike postmyocardial infarction syndrome, postcardiac injury syndrome acutely provokes a greater antiheart antibody response (antisarcolemmal and antifibrillary).
Symptomatic treatment is as in acute pericarditis (NSAIDs or colchicine for several weeks or months, even after disappearance of effusion). Long term (3–6 months) oral corticoids or preferably pericardiocentesis and intrapericardial instillation of triamcinolone (300 mg/m²) are therapeutic options in refractory forms.
Postinfarction pericarditis
Two forms of postinfarction pericarditis can be distinguished:
1. “Early” form (pericarditis epistenocardica).
2. “Delayed” form (Dressler's syndrome).
Epistenocardiac pericarditis, caused by direct exudation, occurs in 5–20% of transmural myocardial infarctions but is clinically discovered rarely. Dressler's syndrome occurs from one week to several months after clinical onset of myocardial infarction with symptoms and manifestations similar to the postcardiac injury syndrome. Its incidence is 0.5–5% and is still lower in patients treated with thrombolytics (< 0.5%), but was more frequent in cases of pericardial bleeding after antithrombotic treatment. Of note, ECG changes are often overshadowed by myocardial infarction changes.
Stage I ECG changes are uncommon and suggest “early” postmyocardial infarction syndrome whereas failure to evolve or “resurrection” of previously inverted T waves strongly suggest myocardial infarction pericarditis. Postinfarction pericardial effusion > 10 mm is most frequently associated with haemopericardium, and two thirds of these patients may develop tamponade/free wall rupture. Urgent surgical treatment is life saving.
Treatment
Ibuprofen, which increases coronary flow, is the agent of choice. Aspirin, up to 650 mg every 4 hours for 2 to 5 days has also been successfully applied. Other nonsteroidal agents risk thinning the infarction zone. Corticosteroid therapy can be used for refractory symptoms only but could delay myocardial infarction healing (Ia, B).
Neoplastic pericarditis
Primary tumours of the pericardium are 40 times less common than the metastatic ones. Mesothelioma, the most common of the primary tumours, is almost always incurable. The most common secondary malignant tumours are lung cancer, breast cancer, malignant melanoma, lymphomas, and leukemias. Effusions may be small or large with an imminent tamponade (frequent recurrences) or constriction. It even may be the initial sign of malignant disease. With small malignant effusions most patients are asymptomatic. The onset of dyspnoea, cough, chest pain, tachycardia, jugular venous distension is observed when the volume of fluid exceeds 500 ml. The analyses of pericardial fluid, pericardial or epicardial biopsy are essential for the confirmation of malignant pericardial disease (I, B).
Rare forms of pericardial disease
Fungal pericarditis
Fungal pericarditis occurs mainly in immunocompromised patients or in the course of endemic-acquired fungal infections.The clinical picture comprises the full spectrum of pericardial diseases including fungal myocarditis. Fungal pericarditis is mainly due to endemic fungi (Histoplasma, Coccidioides), or nonendemic – opportunistic fungi (Candida, Aspergillus, Blastomyces) and semifungi (Nocardia, Actinomyces). Diagnosis is obtained by staining and culturing pericardial fluid or tissue. Antifungal antibodies in serum are helpful in establishing the diagnosis of fungal infection.
Antifungal treatment with fluconazole, ketoconasole, itraconasole, amphotericin B is indicated (I, B). Corticosteroids and NSAIDs can support the treatment with antifungal drugs (Iia, C). Patients with pericarditis in the course of histoplasmosis do not need antifungal therapy, but respond to nonsteroidal anti-inflammatory drugs given during 2–12 weeks. Sulfonamides are the drugs of choice for a nocardiosis infection. Combination of three antibiotics including penicillin should be given for actinomycosis (I, C). Pericardiocentesis or surgical treatment is indicated for haemodynamic impairment. Pericardiectomy is indicated in fungal constrictive pericarditis (I, C).
Chylopericardium
Chylopericardium refers to a communication between the pericardial sac and the thoracic duct, as a result of trauma, congenital anomalies, or as a complication of open-heart surgery, mediastinal lymphangiomas, lymphangiomatous hamartomas, lymphangiectasis, and obstruction or anomalies of the thoracic duct. The chylous nature of the fluid is confirmed by its alkaline reaction, specific gravity between 1010 and 1021, Sudan III stain for fat, high concentrations of triglycerides (5–50 g/l) and protein (22–60 g/l). Treatment depends on the aetiology and the amount of chylous accumulation. Chylopericardium after thoracic or cardiac operation is preferably treated by pericardiocentesis and diet (medium chain triglycerides) and surgical treatment (I, B).
Radiation pericarditis
The probability to develop radiation-induced pericarditis is influenced by the applied source, dose, its fractionation, duration, radiation exposed volume, form of mantel field therapy, and the age of the patients. Radiation induced pericarditis may occur already during the therapy or months and years later – with latency of up to 15–20 years. The effusion may be serous or haemorrhagic, later on with fibrinous adhesions or constriction, typically without tissue calcification. The symptoms may be masked by the underlying disease or the applied chemotherapy.
Drug- and toxin-related pericarditis
Pericardial reactions to drugs are rare. However, several medications and toxic substances can induce pericarditis, tamponade, adhesions, fibrosis, or constriction. Mechanisms include drug induced: drug-induced lupus erythematosus (procainamide, hydralazine, methyldopa, mesalazine, isoniazid, hydantoins); hypersensitivity reaction (penicillins, tryptophan, cromolyn sodium); idiosyncratic reaction or hypersensitivity (amiodarone, streptokinase, thiazides, streptomycin, thiouracils, cyclophosphamide, cyclosporine, mesalazine), 5-fluorouracil, vaccines (smallpox, yellow fever, cytarabine); serum sickness (foreign antisera (e.g., antitetanus), blood products); venom (scorpion fish sting); foreign-substance reactions (direct pericardial application) (silicones, tetracycline/other sclerosants, iron in ß-thalasssemia, asbestos); Secondary pericardial bleeding/haemopericardium (anticoagulants, thrombolytic agents); polymer fumes fever – inhalation of the burning fumes of polytetrafluoroethylene (teflon).
Pericardial effusion in thyroid disorders
Pericardial effusion occurs in 5–30% of patients with hypothyroidism. Fluid accumulates slowly and tamponade occurs rarely. In some cases cholesterol pericarditis may be observed. The diagnosis of hypothyroidism is based on serum levels of thyroxin and thyroid stimulating hormone. Therapy with thyroid hormone decreases pericardial effusion (I, B).
Pericardial effusion in pregnancy
There is no evidence that pregnancy affects susceptibility to pericardial disease. However, many pregnant women develop a minimal to moderate clinically silent hydropericardium by the third trimester. Cardiac compression is rare. ECG changes of acute pericarditis in pregnancy should be distinguished from the slight ST-segment depressions and T-wave changes seen in normal pregnancy. Occult constriction becomes manifest in pregnancy due to the increased blood volume. Most pericardial disorders are managed as in nonpregnant.
SYNDROME OF CHRONIC CARDIAC FAILURE
Much is now known about the epidemiology of heart failure (HF). The ESC represents countries with a population of > 900 million, and there are at least 15 million patients with HF in those 51 countries. The prevalence of asymptomatic ventricular dysfunction is similar, so that HF or asymptomatic ventricular dysfunction is evident in ~4% of the population. The overall prevalence of HF is increasing because of the ageing of the population. The prevalence of HF is between 2 and 3% and rises sharply at ~75 years of age, so the prevalence in 70- to 80-year-old people is between 10 and 20%. In younger age groups HF is more common in men because the most common cause, coronary heart disease, occurs in earlier decades. In the elderly, the prevalence is equal between the sexes.
In some countries the age-adjusted mortality from HF is falling at least in part due to modern treatment. The mean age of patients with HF in the community in developed countries is 75 years. HFPEF is more common in the elderly, women, and those with hypertension or diabetes. HF is the cause of 5% of acute hospital admissions, is present in 10% of patients in hospital beds, and accounts for ~2% of national expenditure on health, mostly due to the cost of hospital admissions.
The outlook is, in general, gloomy, although some patients can live for many years. Overall 50% of patients are dead at 4 years. Forty per cent of patients admitted to hospital with HF are dead or readmitted within 1 year.
HF should never be the only diagnosis.
Definition
1) symptoms of heart failure (SHF) (at rest or during exercise);
2) objective evidence (preferably by echocardiography) of cardiac dysfunction (systolic and/or diastolic) (at rest) and (in cases where the diagnosis is in doubt);
3) response to treatment directed towards heart failure.
Criteria I and II should be fulfilled in all cases.
HF is characterized by overflow and congestion of blood in venous system because of infringement of process:
– contraction and expel of the oxygenation of blood in vascular channel in systole;
– relaxations and fillings of veins with blood in diastole.
Classification of HF
According to aetiology:
1. Coronarogenic: IHD.
2. Noncoronarogenic: arterial hypertension, valvular disease, myocarditis, endocarditis, pericarditis, infringement of heart rate, neoplasm, cor pulmonale.
According to the course:
1. Acute: pulmonary oedema and cardiogenic shock.
2. Chronic (CHF).
According to the degree:
– asymptomatic;
– symptomatic;
– refractory.
According to the tolerance to physical activity: I-IV FC (NYHA, 1964).
New York heart association (NYHA,1964) classification of HF
I FC – patients have no palpitation, dyspnoea, fatigue or attacks of angina at usual physical loadings.
II FC – patients with cardiovascular pathology have palpitation, dyspnoea, fatigue or attacks of angina at usual physical loadings. At rest clinical signs are absent.
III FC – patients with cardiovascular pathology at which the physical activity is considerably limited. They have palpitation, dyspnoea, fatigue or attacks of angina at minimal physical loadings. At rest clinical signs are expressed а little or absent.
IV FC – patients with cardiovascular pathology, which can not carry out any physical loading. They have clinical symptoms of heart insufficiency at rest. Any physical loading results in deterioration of health state.
Types of CHF
1. Leftcardiac CHF – characterized by transient or constant hypervolemia of pulmonary circulation, caused by pump insufficiency of the left part of heart.
2. Rightcardiac CHF – characterized by transient or constant hypervolemia of systemic circulation, caused by pump insufficiency of the right part of heart.
3. Combined (total) – combination of the above stated criteria.
Table 25 – Classification of HF by structural abnormality (ACC/AHA), or by symptoms relating to functional capacity (NYHA)
|ACC/AHA stages of heart failure (Stage of HF |NYHA functional classification |
|based on structure and damage to heart |(Severity based on symptoms and physical |
|muscle) |activity) |
|Stage A. At high risk for developing HF. No |Class I. No limitation of physical |
|identified structural or functional |activity. Ordinary physical activity does |
|abnorma-lity; no signs or symptoms |not cause undue fatigue, palpitation, or |
| |dyspnoea |
|Stage B. Developed structural heart disease |Class II. Slight limitation of physical |
|that is strongly associated with the |activity. Comfortable at rest, but ordinary|
|development of HF, but without signs or |physical activity results in fatigue, |
|symptoms |palpitation, or dyspnoea |
|Stage C. Symptomatic heart failure associated|Class III. Marked limitation of physical |
|with underlying structural heart disease |activity. Comfortable at rest, but less |
| |than ordinary activity results in fatigue, |
| |palpitation, or dyspnoea |
|Stage D. Advanced structural heart disease |Class IV. Unable to carry on any physical |
|and marked symptoms of heart failure at rest |activity without discomfort. Symptoms at |
|despite maximal medical therapy |rest. If any physical activity is |
| |undertaken, discomfort is increased |
Variants of CHF
1. Systolic – infringement of haemodynamics is caused by insufficient ventricular systolic function (is characteristic for inflammations of myocardium defeats, dilated cardiomyopathy, postinfarction cardiosclerosis with LV dilatation, decompensation of valves regurgitations).
The basic criterion is fraction of reduced LV emission (< 45–50%).
2. Diastolic – infringement of haemodynamics is caused by insufficient ventricular diastolic function (is characteristic for hypertrophy and restrictive cardiomyopathy, constrictive pericarditis, cardiac hypertension, compensated aortic stenosis).
The basic criterion:
– pulmonary oedema, cardiac asthma or X-rays signs of pulmonary congestion at the LV emission fraction is more than 50 %;
– reduction of the size (volume) of ventricular cavity.
3. Combined – combination of the above stated criteria. Is characteristic for ischaemic heart disease, myocardiosclerosis, decompensation of heart hypertension, combined valvular disease.
The pathophysiology cause of SHF development
1. Damage of myocardium:
1) primary damage:
– physical (trauma of myocardium, electric trauma, radioactive radiation);
– chemical (toxic effect of neurohormones, medicinal and not medicinal substances);
– biological (toxin, viruses, parasites and microorganisms);
– not specified and/or genetic determination (cardiomyopathy);
2) secondary damage (ischaemic heart disease, diseases of endocrine system, connective tissue, heredity myopathy, deficiency of vitamins and enzyme, etc.).
2. The increased haemodynamic loading on myocardium results in:
– overloads by pressure (arterial hypertension, primary vascular pulmonary hypertension, stenosis of aorta or pulmonary artery);
– overloads by volume (incompetence of mitral, aortic, and tricuspid valves, some inherent defects of heart);
– combined overload.
3. Infringement of heart rate (tachycardia, bradycardia).
4. Age changes (aging).
5. Extracardiac reasons (compression of heart with exudates or tumour, changes in pericardium, cardiac tamponade, infringement of endocrine organs function, e.g., in case of hypothyrosis, diabetes mellitus, etc.).
Neurohumoral activation in case of SHF:
1. Activation of sympathoadrenal system (SAS).
2. Increased secretion of natriuretic peptide.
3. Activation of renin-angiotensin-aldosterone system (RAAS).
4. Secretion of prostaglandin E2 and prostacyklin I2.
5. Secretion of antidiuretic hormone.
6. Secretion of NO and endoteline-1.
Table 26 – Negative effects of long SAS activation
|Negative effect |Consequence |
|Vasoconstriction. |Increase of before and post |
|Retention of Na+ and liquors. |loading |
|Activation of other neurohumoral systems (RAAS) | |
|Increase of heart wall pressure. |Increase of needs in O2 and |
|Increase of myocardial ischaemia |energy |
|Straight cardiotoxic effect of catecholamines | |
|Infringement receptor of the device: |Infringement of normal function |
|desensetization (or tachyphylaxis) postsynaptic |separate cardiomyocytes and |
|adrenoreceptors (mainly β1); |myocardium as a whole |
|change of activity and expression of protein-G. | |
|Infringement outputs, return capture and concentration | |
|noradrenaline. | |
|Remodeling of myocardium. | |
|Stimulations of pathological myocardial hypertrophy | |
|Decrease of threshold of ventricular fibrillation |Development of ventricles rhythm |
Table 27 – Atrials natriuretic peptide (ANUP)
|Favourable effect |Consequence |
|Increase of baroreceptor sensitivity |Decrease of SAS activation |
|Decreased noradrenaline release from nervous |Decrease of vasoconstriction effect of |
|synapses |SAS |
|Suppression of renin and angiotensin II |Decrease of vasoconstriction |
|development | |
|Decrease of aldosterone and vasopressin |Decrease of vasoconstriction, diuretic |
|development |effect |
Cardial mechanisms of compensations:
1. Frank-Starling mechanism – tonogenesis dilatation of heart ventricle (factor of immediate adaptation).
2. Remodeling of the left ventricle – set changes of its form, size of cavity and weight of myocardium, that is clinically shown in its hypertrophy, dilatation, and geometrical deformation.
[pic]
Figure 11– Scheme of activation of renin-angiotensin-aldosterone system
Table 28 – Effects of angiotensin II
|Organs |Effects |
| |Acute |Chronic |
|Heart | Inotropic effect |myocardial hypertrophy; |
| | |increased collagen synthesis |
|Artery |Vasoconstriction |Remodeling of vessels |
|Kidney |vasoconstriction of efferent | |
| |arteriole; | |
| |increased synthesis of | |
| |prostaglandin; | |
| |increased reabsortion of Na and | |
| |water | |
|Adrenal |aldosterone secretion; |Hypertrophy of adrenal gland |
|gland |catecholamines secretion | |
|Encepha-lon |stimulation of thirst; | |
| |increase of vasopressin | |
| |secretion; | |
| |stimulation of SAS | |
Diagnosis
Breathlessness, tiredness, and fatigue are the characteristic symptoms, but elicitation and assessment of these symptoms requires experience and skill particularly in the elderly. The clinical signs of HF (table 29) should be assessed in a careful clinical examination, including observation, palpation, and auscultation. The signs of early HF can be difficult to interpret both in the elderly and in the obese.
Clinical picture of CHF:
– orthopnoea;
– dyspnoea at rest or at physical loading;
– general weakness or increased fatigue;
– night cough (cough in the laying position);
– delay of liquid in organism (peripheral oedema, swelling veins of neck, ascites);
– cardiomegaly;
– additional III and protodiastolic heart sound;
– murmur in heart at development of dilatation of heart cavities;
– pulmonary congestion;
– hepatomegalya;
– nycturia.
Table 29 – Symptoms and signs of HF
|Dominant |Symptom |Sign |
|clinical feature | | |
|Peripheral |Breathlessness, |Peripheral oedema, raised jugular venous |
|oedema/ |tiredness, fatigue, |pressure, hepatomegaly, pulmonary oedema, |
|congestion |anorexia |ascites, fluid overload (congestion), |
| | |cachexia |
|Pulmonary |Severe |Crackles or rales over lungs, effusion, |
|oedema |breath-lessness at |tachycardia, tachypnoea |
| |rest | |
|Cardiogenic |Confusion, |Poor peripheral perfusion. |
|shock (low output |weakness, |SBP < 90 mmHg. |
|syndromes) |cold periphery |Anuria or oliguria |
|High BP |Breathlessness |Usually raised BP, LV hypertrophy, and |
|(hypertensive HF) | |preserved EF |
|Right HF |Breathlessness, |Evidence of RV dysfunction. |
| |fatigue |Raised JVP, peripheral oedema, |
| | |hepatomegaly, gut congestion |
There is a poor relationship between symptoms and the severity of cardiac dysfunction. Symptoms relate more closely to prognosis if persistent after therapy and can then be used to classify the severity of HF and to monitor the effects of therapy.
The severity of heart failure is most often classified using the NYHA functional classification. A more recent classification is based on both the structure of the heart and symptoms. In the context of MI, two other classifications of HF severity, Killip’s and Forrester’s classifications, are used.
ECG:
– normal electrocardiogram (ECG) suggests that the diagnosis of CHF should be carefully reviewed;
– sinus tachycardia (causes decompensated HF, anaemia, fever, hyperthyroidism);
– sinus bradycardia (causes β-Blockade, digoxin, antiarrhythmics, hypothyroidism, sick sinus syndrome);
– atrial tachycardia/flutter/fibrillation (causes hyperthyroidism, infection, mitral valve diseases, decompensated HF, infarction);
– ventricular arrhythmias (cause ischaemia, infarction, cardiomyopathy, myocarditis hypokalaemia, hypomagnesaemia, digitalis overdose);
– ischaemia/infarction (causes coronary artery disease);
– the presence of pathological Q-waves may suggest myocardial infarction as the cause of cardiac dysfunction;
– LV hypertrophy (causes hypertension, aortic valve disease, hypertrophic cardiomyopathy);
– AV block (causes infarction, drug toxicity, myocarditis, sarcoidosis, Lyme disease);
– microvoltage (causes obesity, emphysema, pericardial effusion, amyloidosis);
– QRS width > 120 ms suggests that cardiac desynchronization may be present.
Chest X-ray is an essential component of the diagnostic work-up in heart failure. It permits assessment of pulmonary congestion and may demonstrate important pulmonary or thoracic causes of dyspnoea. Chest X-ray (in two planes) is useful to detect:
– cardiomegaly (causes dilated LV, RV, atrial
pericardial effusion);
– ventricular hypertrophy (causes hypertension, aortic stenosis, hypertrophic cardiomyopathy);
– normal pulmonary findings (cause pulmonary congestion unlikely);
– pulmonary venous congestion and interstitial oedema (cause elevated LV filling pressure);
– pleural effusions (cause elevated filling pressures, HF likely if bilateral, pulmonary infection, surgery, or malignant effusion);
– Kerley B lines (cause increased lymphatic pressures);
– hyperlucent lung fields (cause emphysema or pulmonary embolism);
– pulmonary infection (causes pneumonia may be secondary to pulmonary congestion);
– pulmonary infiltration (causes systemic disease).
Table 30 – Common echocardiographic abnormalities in heart failure
|Measurement |Abnormality |Clinical implication |
|LV ejection fraction |Reduced |Systolic dysfunction |
| |(< 45–50%) | |
|LV function, |Akinesis, hypo-kinesis, |MI/ischaemia, myocarditis, |
|global and focal |dyskinesis |cardiomyopathy |
|End-diastolic diameter|Increased |Volume overload, HF likely |
| |(> 55–60 mm) | |
|End-systolic diameter |Increased |Volume overload, HF likely |
| |(> 45 mm) | |
|Fractional shortening|Reduced (< 25%) |Systolic dysfunction |
|Left atrial size |Increased |Increased filling pressures, |
| |(> 40 mm) |MV-dysfunction, AF |
|Left ventricular |Hypertrophy (>|Hypertension, hypertrophic |
|thickness |11–12 mm) |cardiomyopathy, aortic |
| | |stenosis |
|Valvular |Valvular stenosis or |May be primary cause of HF or |
|structure and |regurgitation (especially |complicating factor, assess |
|function |aortic stenosis and mitral|haemodynamic consequences, assess |
| |insufficiency) |gradients and regurgitant fraction, |
| | |consider surgery |
Table 30 continuation
|Measurement |Abnormality |Clinical implication |
|Mitral diastolic |Abnormalities of the early|Indicates diastolic dysfunction and |
|flow profile |and late diastolic filling|suggests mechanism |
| |patterns | |
|Tricuspid |Increased (> 3 m/s) |Increased right ventricular systolic |
|regurgitation | |pressure, suspect pulmonary |
|peak velocity | |hypertension |
|Pericardium |Effusion, |Consider tamponade, uraemia, |
| |haemopericardium, |malignancy, systemic disease, acute or |
| |thickening |chronic pericarditis, |
| | |constrictive pericarditis |
|Aortic outflow |Reduced (< 15 cm) |Reduced low stroke volume |
|velocity time integral| | |
|Inferior vena cava |Dilated retrograde flow |Increased right atrial pressures, |
| | |hepatic congestion, right ventricular |
| | |dysfunction |
Table 31 – Common laboratory test abnormalities in heart failure
|Abnormality |Cause |Clinical implication |
|Increased serum |Renal disease |Calculate GFR, consider reducing |
|creatinine |ACEI/ARB, aldosterone |ACEI/ARB, or aldosterone blocker |
|(> 150 µmol/L) |blockade |dose, check potassium and BUN |
|Anaemia |CHF, haemodilution, iron loss|Diagnostic work-up, |
|(< 13 g/dL in men, |or poor tilization, renal |consider treatment |
|< 12 in women) |failure, chronic disease | |
|Hyponatraemia |Chronic HF, AVP release, |Consider water restriction, |
|(< 135 mmol/L) |diuretics, haemodilution |reducing diuretic dosage, |
| | |ultrafiltration, vasopressin |
| | |antagonist |
|Hypernatraemia |Hyperglycaemia. |Assess water intake, |
|(> 150 mmol/L) |Dehydratation |diagnostic work-up |
Table 31 continuation
|Abnormality |Cause |Clinical implication |
|Hypokalaemia |Diuretics, secondary |Risk of arrhythmia, ACEIs/ARB, |
|(< 3.5 mmol/L) |hyperaldosteronism |consider potassium supplements, |
| | |aldosterone blockers |
|Hyperkalaemia |Renal failure, |Stop potassium-sparing treatment, |
|(>5.5 mmol/L) |potassium supplement, |(ACEIs/ARB, aldosterone blockers),|
| |renin-angiotensin-aldosterone| |
| |system blockers |assess renal function and pH, risk|
| | |of bradycardia |
|Hyperglycaemia |Diabetes, |Evaluate hydration, treat glucose |
|(> 6.5 mmol/L) |insulin resistance |intolerance |
|Hyperuricaemia (> 500 |Diuretic treatment, gout, |Allopurinol. |
|µmol/L) |malignancy |Reduce diuretic dose |
|BNP > 400 pg/mL, |Increased ventricular wall |HF likely, indication for echo, |
|NT-proBNP- > 2000 |stress |consider treatment |
|pg/mL | | |
|BNP < 100 pg/mL, |Normal wall stress |Re-evaluate diagnosis of |
|NT-proBNP- | |HF unlikely if untreated |
|< 400 pg/mL | | |
|Albumin high |Dehydratation, myeloma |Rehydrate |
|(> 45 g/L) | | |
|Albumin low |Poor nutrition, renal loss |Diagnostic work-up |
|(< 30 g/L) | | |
|Transaminase increase |Liver dysfunction. |Diagnostic work-up. |
| |Right heart failure. |Liver congestion. |
| |Drug toxicit |Reconsider therapy |
|Troponin I or T |Acute coronary |An elevated troponin is a strong |
| |syndrome, episodes of HF |prognostic marker in HF, |
| |decompensation, acute |especially in the presence of |
| |myocarditis |elevated natriuretic peptides |
|Elevated troponins |Myocyte necrosis, |Evaluate pattern of increase (mild|
| |prolonged ischaemia, |increases common in severe HF), |
| |pulmonary embolism, |coronary angiography, evaluation |
| |myocarditis, sepsis, renal |for |
| |failure, severe HF |revascularization |
Table 31 continuation
|Abnormality |Cause |Clinical implication |
|Abnormal thyroid |Amiodarone. |Treat thyroid abnormality |
|tests |Hyper-/hypothyroidism | |
|Urinalysis |Proteinuria, glycosuria, |Diagnostic work-up. |
| |bacteria |Rule out infection |
|INR > 2.5 |Anticogulant overdose, |Evaluate anticoagulant dosage, |
| |liver congestion |assess liver function, assess |
| | |anticoagulant dose |
|CRP > 10 mg/L, |Infection, inflammation |Diagnostic work-up |
|neutrophilic | | |
|leukocytosis | | |
|Hyperkalaemia |Renal failure, potas-sium |Stop potassium-sparing treatment |
|(> 5.5 mmol/L) |supplement, |(ACEIs/ARB, aldosterone blockers), |
| |renin-angiotensin- | |
| |aldosterone system blockers |assess renal function and pH, risk |
| | |of bradycardia |
Laboratory tests
A routine diagnostic evaluation of patients with suspected HF includes a complete blood count (haemoglobin, leukocytes, and platelets), serum electrolytes, serum creatinine, estimated glomerular
filtration rate (GFR), glucose, liver function tests, and urinalysis. Additional tests should be considered according to the clinical picture (table 31). Marked haematological or electrolyte abnormalities are uncommon in untreated mild to moderate HF, although mild anaemia, hyponatraemia, hyperkalaemia, and reduced renal function are common, especially in patients treated with diuretics and ACEI/ARB/aldosterone antagonist therapy. Appropriate laboratory monitoring is essential during the initiation, titration, and follow-up phases in patients receiving drug therapy for HF.
Treatment
Nonpharmacological management:
1. Weight monitoring (I, C)
Increases in body weight are often associated with deterioration of HF and fluid retention. In the case of a sudden unexpected weight gain of > 2 kg in 3 days, patients may increase their diuretic dose.
Weight reduction in obese (body mass index (BMI) > 30 kg/m²) persons with HF should be considered in order to prevent the progression of HF, decrease symptoms, and improve well-being.
2. Diet and nutrition (IIa, C)
Sodium restriction is recommended in symptomatic HF to prevent fluid retention.
3. Fluid restriction (IIb, C) of 1.5–2 L/day may be considered in patients with severe symptoms of HF especially with hyponatraemia.
4. Alcohol (IIa, C) intake should be limited to 10–20 g/day (1–2 glasses of wine/day).
5. Smoking (I, C)
It is recommended that patients receive support and advice and be motivated to stop smoking.
6. Traveling.
7. Rest and exercise.
Objectives of treatment in chronic heart failure
1. Prognosis:
– reduce mortality.
2. Morbidity:
– relieve symptoms and signs;
– improve quality of life;
– eliminate oedema and fluid retention;
– increase exercise capacity;
– reduce fatigue and breathlessness;
– reduce need for hospitalization;
– provide for end of life care.
3. Prevention:
– occurrence of myocardial damage;
– progression of myocardial damage;
– remodelling of the myocardium;
– reoccurrence of symptoms and fluid accumulation;
– hospitalization.
Pharmacological management:
– angiotensin-converting enzyme inhibitors (ACEIs) (I, A);
– β-Blockers (I, A);
– aldosterone antagonists (I, B);
– angiotensin receptor blockers (ARBs) (I, A);
– hydralazine and isosorbide dinitrate (H-ISDN) (IIa, B);
– digitalis (I, C);
– diuretics (I, B);
– anticoagulants (vitamin K antagonists) (I, A);
– antiplatelet agents (IIb, B);
– HMG CoA reductase inhibitors (‘statins’) (IIb, B).
Angiotensin-converting enzyme inhibitors (ACEIs)
Indications, based upon the patients enrolled in the RCTs: LVEF ≤ 40%, irrespective of symptoms. Treatment with an ACEI improves ventricular function and patient well-being, reduces hospital admission for worsening HF, and increases survival. In hospitalized patients, treatment with ACEI should be initiated before discharge.
Contraindications: history of angioedema, bilateral renal artery stenosis, serum potassium concentration > 5.0 mmol/L, serum creatinine > 220 µmol/L (~2.5 mg/dL), severe aortic stenosis.
Initiation of ACEI: check renal function and serum electrolytes, recheck renal function and serum electrolytes within 1–2 weeks of starting treatment.
Dose up-titration: consider dose up-titration after 2–4 weeks. Do not increase dose if significant worsening of renal function or hyperkalaemia. Recheck renal function and serum electrolytes 1 and 4 weeks after dose increasing. Recheck renal function and serum electrolytes 1, 3, and 6 months after achieving maintenance dose and 6 monthly thereafter.
Table 32 – Recommended ACE-inhibitor maintenance dose
|Drug |Initiating dose |Maintenance dose |
| Captopril |6.25 mg t.i.d. |50–100 mg t.i.d. |
| Enalapril |2.5 mg b.i.d. |10–20 mg b.i.d. |
| Lisinopril |2.5–5 mg o.d. |20–35 mg o.d. |
| Ramipril |2.5 mg o.d. |5 mg b.i.d. |
| Trandolapril |0.5 mg o.d. |4 mg o.d. |
Potential adverse effects: worsening of renal function, hyperkalaemia, symptomatic hypotension, cough.
β-Blockers
Indications: LVEF ≤ 40%; mild to severe symptoms (NYHA functional class II–IV); patients with asymptomatic LV systolic dysfunction after MI also have an indication for a β-blocker.
Contraindications: asthma (chronic obstructive pulmonary disease (COPD) is not a contraindication); second- or third-degree heart block, sick sinus syndrome (in the absence of a permanent pacemaker), sinus bradycardia (< 50 b.p.m.).
Dose up-titration: visits every 2–4 weeks to up-titrate the dose of β-blocker (slower dose up-titration may be needed in some patients). Do not increase dose if there are signs of HF worsening, symptomatic hypotension (e.g., dizziness), or excessive bradycardia (pulse rate < 50/min) at each visit.
Table 33 – Recommended β-blockers maintenance dose
|Drug |Initiating dose |Maintenance dose |
|Bisoprolol |1.25 mg o.d. |10 mg o.d. |
|Carvedilol |3.125 mg b.i.d. |25–50 mg b.i.d. |
|Metoprolol succinate |12.5/25 mg o.d. |200 mg o.d. |
|Nebivolol |1.25 mg o.d. |100 mg o.d. |
Potential adverse effects: symptomatic hypotension, HF worsening, excessive bradycardia.
Aldosterone antagonists
Indications: LVEF ≤ 35%; moderate to severe symptoms (NYHA functional class III-IV); optimal dose of β-blocker and ACEI or ARB (but not ACEI and ARB).
Contraindications: serum potassium concentration > 5.0 mmol/L; serum creatinine > 220 µmol/L (~2.5 mg/dL); concomitant potassium sparing diuretic or potassium supplements; combination of ACEI and ARB.
Initiation of spironolactone (or eplerenone): check renal function and serum electrolytes; starting dose: spironolactone 25 mg o.d. (or eplerenone 25 mg o.d.). Recheck renal function and serum electrolytes 1 and 4 weeks after starting treatment.
Table 34 – Recommended aldosterone antagonist maintenance dose
|Drug |Initiating dose |Maintenance dose |
|Eplerenone |25 o.d. |50 o.d. |
|Spironolactone |25 o.d. |25–50 o.d. |
Dose up-titration: сonsider dose up-titration after 4–8 weeks. Do not increase dose in case of renal function worsening or hyperkalaemia.
Recheck renal function and serum electrolytes 1 and 4 weeks after increasing dose.
In absence of the above-mentioned problems, aim for evidence-based target dose – spironolactone 50 mg o.d. or eplerenone 50 mg o.d. – or maximum tolerated dose.
Recheck renal function and serum electrolytes 1, 2, 3, and 6 months after achieving maintenance dose, and 6 monthly thereafter.
Potential adverse effects: hyperkalaemia, worsening renal function – if creatinine rises to > 220 µmol/L (~2.5 mg/dL) halve dose of spironolactone, breast tenderness and/or enlargement.
Angiotensin receptor blockers (ARBs)
Treatment with ARB improves ventricular function and patient well-being, and reduces hospital admission for HF worsening. Treatment reduces the risk of death from cardiovascular causes.
Indications: LVEF ≤ 40% and either; as an alternative in patients with mild to severe symptoms (NYHA functional class II–IV) who are intolerant of ACEI, or in patients with persistent symptoms (NYHA functional class II–IV) despite treatment with ACEI and β-blocker; ARBs may cause worsening of renal function, hyperkalaemia, and symptomatic hypotension with an incidence similar to ACEI. They do not cause cough.
Contraindications: as with ACEIs, with exception of angioedema; patients treated with ACEI and aldosterone antagonist; ARB should only be used in patients with adequate renal function and normal serum potassium concentration; serial monitoring of serum electrolytes and renal function is mandatory, especially if ARB is used in conjunction with ACEI.
Initiation of an ARB: check renal function and serum electrolytes; starting dose: either candesartan 4–8 mg o.d. or valsartan 40 mg b.i.d.; recheck renal function and serum electrolytes within 1 week of starting treatment.
Dose up-titration: consider dose up-titration after 2–4 weeks. Do not increase dose in case of renal function worsening or hyperkalaemia. Recheck renal function and serum electrolytes 1 and 4 weeks after dose increasing.
In absence of the above-mentioned problems, aim for evidence-based target dose – candesartan 32 mg o.d. or valsartan 160 mg b.i.d. – or maximum tolerated dose.
Recheck renal function and serum electrolytes 1, 3, and 6 months after achieving maintenance dose, and 6 monthly thereafter.
Table 35 – Recommended ARBs maintenance dose
|Drug |Initiating dose |Maintenance dose |
|Candesartan |4 or 8 o.d. |32 o.d. |
|Valsartan |40 b.i.d. |160 b.i.d. |
Potential adverse effects: as with ACEIs except for cough.
Hydralazine and isosorbide dinitrate (H-ISDN)
In symptomatic patients with LVEF ≤ 40%, the combination of H-ISDN may be used as an alternative if there is intolerance to both ACEI and ARB. Adding the combination of H-ISDN should be considered in patients with persistent symptoms despite treatment with ACEI, β-blocker, and ARB or aldosterone antagonist.
Indications: an alternative to ACEI/ARB when both of the latter are not tolerated; as add-on therapy to ACEI if ARB or aldosterone antagonist is not tolerated; evidence is the strongest in patients of African-American descent.
Contraindications: symptomatic hypotension; lupus syndrome; severe renal failure (dose reduction may be needed).
Initiation: starting dose: hydralazine 37.5 mg and ISDN 20 mg tid.
Dose up-titration: consider dose up-titration after 2–4 weeks. Do not increase dose with symptomatic hypotension.
If tolerated, aim for evidence-based target dose – hydralazine 75 mg and ISDN 40 mg t.i.d. – or maximum tolerated dose.
Potential adverse effects: symptomatic hypotension (e.g., dizziness) – often improves with time; consider reducing dose of other hypotensive agents (except ACEI/ARB/β-blocker/aldosterone antagonist). Asymptomatic hypotension does not require intervention.
Arthralgia/muscle aches, joint pain or swelling, pericarditis/pleuritis, rash or fever – consider drug-induced lupus-like syndrome; check ANA, discontinue H-ISDN.
Digoxin
Indications:
– atrial fibrillation: with ventricular rate at rest > 80 b.p.m., at exercise > 110–120 b.p.m.
– sinus rhythm: LV systolic dysfunction (LVEF ≤ 40%); mild to severe symptoms (NYHA functional class II–IV); optimal dose of ACEI or/and ARB, β-blocker and aldosterone antagonist, if indicated.
Contraindications: second- or third-degree heart block (without a permanent pacemaker); caution if suspected sick sinus syndrome; pre-excitation syndromes; previous evidence of digoxin intolerance.
Initiation of digoxin: starting dose: loading doses of digoxin are generally not required in stable patients with sinus rhythm. A single daily maintenance dose of 0.25 mg is commonly employed in adults with normal renal function. In the elderly and in those with renal impairment, reduced dose of 0.125 or 0.0625 mg o.d. should be used.
Digoxin concentration should be checked early during chronic therapy in those with normal renal function. Steady state may take longer to be achieved in those with renal impairment. There is no evidence that regular digoxin concentration measurements confer better outcomes. The therapeutic serum concentration should be between 0.6 and 1.2 ng/mL, lower than previously recommended.
Certain drugs may increase plasma digoxin levels (amiodarone, diltiazem, verapamil, certain antibiotics, quinidine).
Potential adverse effects: sinoatrial and AV block; atrial and ventricular arrhythmias, especially in the presence of hypokalaemia (digoxin-specific Fab antibody fragments should be considered for ventricular arrhythmias caused by toxicity); signs of toxicity include: confusion, nausea, anorexia, and disturbance of colour vision.
Diuretics
Diuretics are recommended in patients with HF and clinical signs or symptoms of congestion.
Table 36 – Practical considerations in treatment of heart failure with loop diuretics (management of diuretic resistance)
|Problem |Suggested action |
|Hypokalaemia/ |increase ACEI/ARB dosage; |
|hypomagnesaemia |add aldosterone antagonist; |
| |potassium supplements; |
| |magnesium supplements |
|Hyponatraemia |Fluid restriction: |
| |stop thiazide diuretic or switch to loop diuretic, if possible; |
| |reduce dose/stop loop diuretics, if possible; |
| |consider AVP antagonist, e.g., tolvaptan, if available; |
| |i.v. inotropic support; |
| |consider ultrafiltration |
|Hyperuricaemia/ |Consider allopurinol: |
|gout |for symptomatic gout use colchicine for pain relief ; |
| |avoid NSAIDs |
|Hypovolaemia/ |Assess volume status: |
|dehydration |consider diuretic dosage reduction |
|Insufficient |Check compliance and fluid intake: |
|response or |increase dose of diuretic; |
|diuretic resistance |consider switching from furosemide to bumetanide or torasemide; |
| |add aldosterone antagonist; |
| |combine loop diuretic and thiazide/ metolazone; |
| |administer loop diuretic twice daily or on empty stomach; |
| |consider short-term i.v. infusion of loop diuretic |
|Renal failure |Check for hypovolaemia/dehydration: |
|(excessive rise |exclude the use of other nephrotoxic agents, e.g., NSAIDs, |
|in urea/BUN |trimethoprim; |
|and/or creatinine) |withhold aldosterone antagonist; |
| |if using concomitant loop and thiazide diuretic, stop thiazide |
| |diuretic; |
| |consider reducing dose of ACEI/ARB; |
| |consider ultrafiltration |
Initiation of diuretic therapy
Check renal function and serum electrolytes. Most patients are prescribed loop diuretics rather than thiazides due to the higher efficiency of induced diuresis and natriuresis.
Diuretic dosages (table 37)
Start with a low dosage and increase until clinical improvement of the symptoms and signs of congestion.
Dose must be adjusted, particularly after restoration of dry body weight, to avoid the risk of renal dysfunction and dehydration. Aim to maintain “dry weight” with the lowest achievable dose.
Self-adjustment of diuretic dose based on daily weight measurements and other clinical signs of fluid retention should be encouraged in HF outpatient care. Patient’s education is required.
Table 37 – Diuretic dosages in patients with heart failure
|Diuretic |Initial dose (mg) |Usual daily dose (mg) |
|Loop diuretics* |
|Furosemide |20–40 |40–240 |
|Bumetanide |0.5–1.0 |1–5 |
|Torasemide |5–10 |10–20 |
|Thiazides** |
|Bendroflumethiazide |2.5 |2.5–10 |
|Hydrochlorothiazide |25 |12.5–100 |
|Metolazone |2.5 |2.5–10 |
|Indapamide1 |2.5 |2.5–5 |
|Potassium-sparing diuretics*** |
| |+ ACEI/ |– ACEI/ |+ACEI/ |–ACEI/ |
| |ARB |ARB |ARB |ARB |
|Spironolactone/ |12.5–25 |50 |50 |100–200 |
|Eplerenone | | | | |
|Amiloride |2.5 |5 |20 |40 |
|Triamterene |25 |50 |100 |200 |
|*Dose might need to be adjusted according to volume status/weight; excessive doses may |
|cause renal impairment and ototoxicity. |
|**Do not use thiazides if eGFR < 30 mL/min, except when prescribed synergistically with |
|loop diuretics. |
|***Aldosterone antagonists should always be preferred to other potassium-sparing |
|diuretics. |
|1Indapamide is not-thiazides sulphonamide. |
Anticoagulants (vitamin K antagonists)
Warfarin (or an alternative oral anticoagulant) is recommended in patients with HF and permanent, persistent, or paroxysmal AF without contraindications to anticoagulation. Adjusted dose anticoagulation reduces the risk of thromboembolic complications including stroke.
Antiplatelet agents
Antiplatelet agents are not as effective as warfarin in reducing the risk of thromboembolism in patients with AF. In a pooled analysis of two small trials comparing warfarin and aspirin in patients with HF, the risk of HF hospitalization was significantly greater in aspirin-treated, compared with warfarin-treated, patients. There is no evidence that antiplatelet agents reduce atherosclerotic risk in patients with HF.
HMG CoA reductase inhibitors (“statins”)
In elderly patients with symptomatic chronic HF and systolic dysfunction caused by CAD, statin treatment may be considered to reduce cardiovascular hospitalization.
COR PULMONALE
Cor pulmonale is right ventricular enlargement secondary to a lung disorder that produces pulmonary artery hypertension. It results from a disorder of the lung or its vasculature or deformation of chest.
Cor pulmonale is estimated to account for 6–7% of all types of adult heart disease in the United States, with chronic obstructive pulmonary disease (COPD) due to chronic bronchitis or emphysema causative factor in more than 50% of cases. At present, cor pulmonale accounts for 10–30% of decompensated heart failure related admissions in the United States. Acute massive pulmonary thromboembolism is the most common cause of acute life-threatening cor pulmonale in adults. In the United States, 50,000 deaths are estimated to occur per year from pulmonary emboli and about half occur within the first hour due to acute right heart failure.
Development of cor pulmonale as a result of a primary pulmonary disease usually heralds a poorer prognosis. For example, patients with COPD who develop cor pulmonale have a 30% chance of surviving for 5 years. In haemodynamically stable patients with pulmonary embolism, the following factors may be independent predictors of inhospital mortality: age over 65 years, bed rest for longer than 72 hours, chronic cor pulmonale, sinus tachycardia, tachypnoea.
Pathophysiology
Lung disorders cause pulmonary hypertension by several mechanisms:
1. Loss of capillary beds (due to bullous changes in COPD or thrombosis in pulmonary embolism);
2. Vasoconstriction caused by hypoxia, hypercapnia, or both;
3. Increased alveolar pressure (COPD, during mechanical ventilation);
4. Medial hypertrophy in arterioles (often a response to pulmonary hypertension due to other mechanisms).
These pathogenetic mechanisms include (1) pulmonary vasoconstriction due to alveolar hypoxia or blood acidemia, (2) anatomic compromise of the pulmonary vascular bed secondary to lung disorders (e.g., emphysema, pulmonary thromboembolism, interstitial lung disease), (3) increased blood viscosity secondary to blood disorders (e.g., polycythemia vera, sickle cell disease, macroglobulinemia), and (4) idiopathic primary pulmonary hypertension. The result is increased pulmonary arterial pressure.
Causes of cor pulmonale
Acuity: massive pulmonary embolization; injury due to mechanical ventilation (most commonly for acute respiratory distress syndrome).
Chronic: COPD, extensive loss of lung tissue due to surgery or trauma, chronic, unresolved pulmonary emboli, pulmonary veno-occlusive disorders, scleroderma, pulmonary interstitial fibrosis, kyphoscoliosis, obesity with alveolar hypoventilation, neuromuscular disorders involving respiratory muscles; idiopathic alveolar hypotension.
Symptoms
Physical findings may reflect the underlying lung disease or pulmonary hypertension, RVH, and RV failure.
On inspection, an increase in chest diameter, labored respiratory efforts with retractions of the chest wall, distended neck veins with prominent A or V waves, and cyanosis may be seen. Initially, cor pulmonale is asymptomatic, although patients usually have significant symptoms due to the underlying lung disorder (dyspnoea, exertional fatigue). Later, as RV pressures increase, physical signs commonly include a left parasternal systolic lift, a loud pulmonic component of the 2nd heart sound, and murmurs of functional tricuspid and pulmonic insufficiency. Later, RV gallop rhythm (3rd and 4th heart sounds) augmented during inspiration, distended jugular veins (with a dominant A wave unless tricuspid regurgitation is present), hepatomegaly, and lower-extremity oedema may occur.
Clinical manifestations of cor pulmonale generally are nonspecific:
1. The patient may complain of fatigue, tachypnoea, exertional dyspnoea, and cough.
2. Anginal chest pain also can occur and may be due to right ventricular ischaemia (it usually does not respond to nitrates) or pulmonary artery stretching.
3. Haemoptysis may occur because of rupture of the dilated or atherosclerotic pulmonary artery.
4. Rarely, the patient may complain of hoarseness due to compression of the left recurrent laryngeal nerve by a dilated pulmonary artery.
5. A variety of neurologic symptoms (syncope) may be seen due to decreased cardiac output and hypoxemia.
6. In advanced stages, passive hepatic congestion secondary to severe right ventricular failure may lead to anorexia, right upper quadrant abdominal discomfort, and jaundice.
7. Peripheral oedema.
Diagnosis test
Laboratory investigations are directed toward defining the potential underlying aetiologies as well as evaluating complications of cor pulmonale. In specific instances, appropriate laboratory studies may include the following: hematocrit for polycythemia, which can be a consequence of underlying lung disease but which can also increase pulmonary arterial pressure by increasing viscosity; serum alpha1-antitrypsin, if deficiency is suspected; antinuclear antibody level for collagen vascular disease, such as scleroderma; coagulations studies to evaluate hypercoagulability states (e.g., serum levels of proteins S and C, antithrombin III, factor V Leyden, anticardiolipin antibodies, homocysteine).
ECG: right axis deviation, right ventricular hypertrophy, p pulmonale pattern low-voltage QRS, incomplete or complete right bundle branch bock.
Chest X-ray: right-sided cardiac enlargement, enlargement of pulmonary arteries, oligemic peripheral lung fields, right-sided pleural effusion.
Echocardiography: evidence of abnormal right ventricular structure and/or function. Evidence of increased pulmonary pressure. Septal flattening during systole.
CT scan of the chest and cardiac catheterization
Treatment
1. Elimination of the cause is the most important intervention. Smoking must be stopped, exposure to dust, flames, household smoke, and cold weather is avoided. If there is evidence of respiratory infection, it should be treated with appropriate antibiotics after culture and sensitivity.
2. Diuretics for RVF.
3. In pulmonary embolism, thrombolysis (enzymatic dissolution of the blood clot) is advocated by some authorities if there is dysfunction of the right ventricle, and is otherwise treated with anticoagulants. In COPD, long-term oxygen therapy may improve cor pulmonale. Cor pulmonale may lead to congestive heart failure (CHF), with worsening of respiration due to pulmonary oedema, swelling of the legs due to peripheral oedema and painful congestive hepatomegaly (enlargement of the liver due to tissue damage as explained in the Complications section. This situation requires diuretics (to decrease strain on the heart), sometimes nitrates (to improve blood flow), phosphodiesterase inhibitors such as sildenafil or tadalafil and occasionally inotropes (to improve heart contractility). CHF is a negative prognostic indicator in cor pulmonale. Oxygen is often required to resolve shortness of breath. Plus, oxygen to the lungs also helps relax the blood vessels and eases right heart failure. Oxygen is given at the rate of 2 litres per minute. Excess oxygen can be harmful to patients because hypoxia is the main stimulus to respiration. If such hypoxia is suddenly corrected by overflow of oxygen, such stimulus to the respiratory centre is suddenly withdrawn and respiratory arrest occurs.
4. When wheezing is present, majority of the patients require bronchodilators. A variety of drugs have been developed to relax the blood vessels in the lung. Calcium channel blockers are used but work only in a few cases. Other novel medications that need to be inhaled or given intravenously include prostacyclin derivatives.
5. Cases of COPD with chronic cor pulmonale present with secondary polycythemia, if severe, it may increase the blood viscosity and contribute to pulmonary hypertension. If hematocrit (PCV) is above 60%, it is better to reduce the red blood cell count by phlebotomies.
6. Mucolytic agents like bromhexine and carbocisteine help bring out excessive bronchial secretions more easily by coughing.
7. All patients with pulmonary heart disease are maintained on blood thinning medications to prevent formation of blood clots.
8. When medical therapy fails, one may require a transplant. However, since the lungs are damaged, both the heart and lungs need to be transplanted. With a shortage of donors this therapy is only done 10–15 times a year in North America.
PULMONARY EMBOLISM
Acute pulmonary embolism (PE) is a major cause of complications and death associated with surgery, injury, and medical illnesses, and it may occur after long-distance air travel. Venous thromboembolism is responsible for up to 15% of all in-hospital deaths, and it also accounts for 20 to 30% of deaths associated with pregnancy and delivery in the United States and Europe. Overall, the annual incidence of pulmonary embolism has been reported to range between 23 and 69 cases per 100,000 population. Case fatality rates vary widely depending on the severity of the disease; at an average case fatality rate within 2 weeks of diagnosis of approximately 11%, the Surgeon General estimates that venous thromboembolism accounts for at least 100,000 deaths each year.
Classification of PE:
– massive (shock and/or hypotension (defined as a systolic blood pressure < 90 mmHg or a pressure drop of ≥ 40 mmHg for > 15 min if not caused by new-onset arrhythmia, hypovolaemia or sepsis));
– submassive (markers of RV hypokinesia);
– not massive (RV function is not changed).
Epidemiology
1. The patient may have annual incidence of deep vein thrombosis. DVT and PE is estimated at 1.0 and 0.5 per 1000 in the Western world, respectively.
2. DVT and PE are both part of one entity: venous thromboembolism (VTE).
3. Both acquired and inherited risk factors have been identified.
Risk factors for venous thromboembolism
Primary: antithrombin deficiency, protein C deficiency, congenital dysfibrinogenemia, factor V Leiden (APC-R), thrombomodulin, plasminogen deficiency, hyperhomocysteinemia, dysplasminogenemia, anticardiolipin antibodies, protein S deficiency, excessive plasminogen activator inhibitor, factor XII deficiency, prothrombin 20210A mutation.
Secondary: trauma/fractures, surgery, stroke, immobilisation, advanced age, malignancy±chemotherapy, central venous catheters, obesity, chronic venous insufficiency, heart failure, smoking, long distance travel, pregnancy/puerperium, oral contraceptives, Crohn’s disease, lupus anticoagulant, nephrotic syndrome, prosthetic surface, hyperviscosity (polycythemia, Waldenstrom’s macroglobulinemia), platelet abnormalities.
Strong predisposing factors: fracture (hip or leg), hip or knee replacement, major general surgery, major trauma, spinal cord injury.
Moderate predisposing factors:
– arthroscopic knee surgery, central venous lines, chemotherapy, chronic heart;
– respiratory failure, hormone replacement therapy, malignancy, oral contraceptive therapy, paralytic stroke, pregnancy/postpartum, previous VTE, thrombophilia.
Weak predisposing factors: bed rest > 3 days, immobility due to sitting (e.g., prolonged car or air travel), increasing age, laparoscopic surgery (e.g., cholecystectomy), obesity, pregnancy/antepartum, varicose veins.
Pathophysiology
The consequences of acute PE are primarily haemodynamic and become apparent when > 30–50% of the pulmonary arterial bed is occluded by thromboemboli. The contribution of reflex or humoral pulmonary vasoconstriction is less important in humans.
Table 38 – The consequences of pulmonary embolism
|Change |Haemodynamic consequence of PE |
|(A) Changes of pulmonary haemodynamics |
|Precapillary hypertension |Reduced vascular bed |
| |Bronchoconstriction |
| |Arteriolar vasoconstriction |
|Development of collateral vessels |Bronchopulmonary arterial |
| |Anastomoses |
| |Pulmonary arteriovenous shunts |
|Blood flow changes |Flow redistribution |
| |Flow resumption (lysis, etc.) |
|(B) Changes of systemic circulation and cardiac function |
|Arterial hypotension | |
|Tachycardia | |
|RV overload and dilation | |
Table 38 continuation
|Change |Haemodynamic consequence of PE |
|Increased central venous pressure | |
|LV geometrical changes | |
|(C) Changes of coronary circulation |
|Reduced transcoronary |Aortic hypotension |
|pressure gradient | |
| |Right atrial hypertension |
|Reduced flow per myocardial unit | |
|Relative hypoperfusion of RV subendocardium| |
|Change |Respiratory consequence of PE |
|(A) Changes of respiratory dynamics |
|Hyperventilation |Pulmonary arterial hypertension |
| |Reduced compliance |
| |Atelectasis |
|Increased airway resistance |Local hypocapnia |
| |Chemical mediators |
|(B) Changes of alveolar ventilation |
|Alveolar hyperventilation (hypocapnia, alkalemia) or relative alveolar hypoventilation |
|(C) Changes of respiratory mechanics |
|Reduced dynamic compliance |Decreased surfactant |
| |Atelectasis |
| |Bronchoconstriction |
|(D) Changes of diffusing capacity |
|Reduced capillary blood volume | |
|Reduced membrane permeability | |
|(E) Changes of ventilation/perfusion ratio |
Haemodynamic consequences of PE are directly related to the size and number of emboli and the pre-existing cardiac and respiratory status.
Pulmonary infarction is a relatively rare complication.
Diagnosis
Clinical presentation. Clinical signs, symptoms and routine laboratory tests do not allow the exclusion or confirmation of acute PE but increase the index of its suspicion.
Table 39 – Signs, symptoms, and findings in suspected PE
| |PE confirmed (n = |PE excluded (n = |
| |219) |546) |
|Symptoms |
|Dyspnoea |80% |59% |
|Chest pain (pleuritic) |52% |43% |
|Chest pain (substernal) |12% |8% |
|Cough |20% |25% |
|Haemoptysis |11% |7% |
|Syncope |19% |11% |
|Signs |
|Tachypnoea (≥ 20/min) |70% |68% |
|Tachycardia (> 100/min) |26% |23% |
|Signs of DVT |15% |10% |
|Fever (>38.58C) |7% |17% |
|Cyanosis |11% |9% |
|Chest X-ray |
|Atelectasis or infiltrate |49% |45% |
|Pleural effusion |46% |33% |
|Pleural-based opacity |23% |10% |
|(infarction) | | |
|Elevated diaphragm |36% |25% |
|Decreased pulmonary vascularity |36% |6% |
|Amputation of hilar artery |36% |1% |
|Blood gases |
|Hypoxaemia |75% |81% |
|Electrocardiogram |
|Right ventricular overload |50% |12% |
Clinical evaluation makes it possible to classify patients into probability categories corresponding to an increasing prevalence of PE, whether assessed by implicit clinical judgement or by a validated prediction rule.
Table 40 – The most frequently used clinical prediction rule is the Canadian rule, by Wells et al. (2000) and revised Geneva score (2006)
|Revised Geneva score |Wells score |
|Variable |Point |Variable |Point |
|Predisposing factor |+1 |Predisposing factor | |
|Age > 65 years |+3 | | |
|Previous DVT or PE |+2 |Previous DVT or PE |+1.5 |
|Surgery or fracture within 1 |+2 |Recent surgery or immobilization |+1.5 |
|month | | | |
|Active malignancy | | | |
|Symptom | |Symptom | |
|Unilateral lower limb pain |+3 | | |
|Haemoptysis |+2 |Haemoptysis |+1 |
|Clinical sign | |Clinical sign | |
|Heart rate | |Heart rate | |
|75–94 beats/min |+3 |>100 beats/min |+1.5 |
|≥ 95 beats/min |+5 | | |
|Pain on lower limb deep vein at |+4 |Clinical signs of DVT |+3 |
|palpation and unilateral oedema | | | |
| | |Clinical judgement | |
| | |Alternative diagnosis less likely |+3 |
| | |than PE | |
|Clinical probability |Total |Clinical probability |Total |
| | |(3 levels) | |
|Low |0–3 |Low |0–1 |
|Intermediate |4–10 |Intermediate |2–6 |
|High |≥ 11 |High |≥ 7 |
| | |Clinical probability | |
| | |(2 levels) | |
| | |PE unlikely |0–4 |
| | |PE likely |> 4 |
D-dimer
Plasma D-dimer, a degradation product of crosslinked fibrin. D-dimer levels are elevated in plasma in the presence of an acute clot because of simultaneous activation of coagulation and fibrinolysis. The specificity of fibrin for VTE is poor because fibrin is produced in a wide variety of conditions, such as cancer, inflammation, infection, necrosis, dissection of the aorta, and the positive predictive value (PPV) of D-dimer is low. Therefore, D-dimer is not useful for confirming PE. A negative D-dimer result in a highly sensitive assay safely excludes PE in patients with a low or moderate clinical probability. D-dimer is most useful in emergency ward patients. In elderly or inpatients, D-dimer retains a high negative predictive value, but it is normal (D-dimer < 500 mg/l) in less than 10% of patients.
Lung scintigraphy
Approximately 25% of patients with suspected PE will have the diagnosis refuted by a normal perfusion lung scan and anticoagulants may be safely withheld.
Around 25% of patients with suspected PE will have a high probability lung scan and anticoagulant therapy may be instituted.
The remaining patients will require further diagnostic tests as a part of a wider diagnostic strategy.
Pulmonary angiography
The safety of pulmonary angiography has improved over the past decade.
Pulmonary angiography is the reference method, but should be reserved for patients in whom non-invasive diagnostic tests remain indeterminate.
It is safe to withhold anticoagulant therapy in patients with suspected PE and normal angiogram.
Indirect signs of PE on angiography have not been validated.
Spiral computed tomography
Spiral CT is more accurate in the demonstration of central or lobar PE than segmental PE.
A normal sCT does not rule out isolated subsegmental PE.
The safety of withholding anticoagulant therapy in patients with a normal sCT angiogram needs further confirmation.
Echocardiography
Echocardiography is useful in patients with suspected massive PE.
Whether echocardiography may identify patients who could benefit from thrombolytic therapy in the absence of systemic hypotension or shock remains to be confirmed in prospective studies.
Echocardiographic criteria: RV hypokinesis and dilatation, RVD, RV > 30 mm or tricuspid insufficiency > 2.8 m/s. At least one of the following: RV > 30 mm or RV/LV > 1; paradox septal systolic motion, acceleration time of right ventricular ejection (AcT) < 90 ms or tricuspid insufficiency peak gradient (TIPG) > 30 mmHg.
Detection of deep vein thrombosis
Ultrasonography shows a proximal DVT in 50% of patients with proven PE.
A normal ultrasonography exam of the leg veins does not rule out PE.
Serial leg testing may replace angiography in patients with non-diagnostic lung scan findings. However, its practical use seems limited.
Diagnostic strategies
Principal markers useful for risk stratification in acute pulmonary embolism
1. Clinical markers: shock; hypotension (defined as a systolic blood pressure < 90 mmHg or a pressure drop of ≥ 40 mmHg for > 15 min if not caused by new-onset arrhythmia, hypovolaemia or sepsis).
2. Markers of RV dysfunction: RV dilatation, hypokinesis or pressure overload on echocardiography; RV dilatation on spiral computed tomography; brain natriuretic peptide (BNP) or N-terminal-proBNP elevation; elevated right heart pressure at right heart catheterization (RHC).
3. Markers of myocardial injury: cardiac troponin T or I positive.
Suspected high-risk PE
In high-risk PE, as indicated by the presence of shock or hypotension, mergency CT or bedside echocardiography (depending on availability and clinical circumstances) is recommended for diagnostic purposes.
Suspected non-high-risk PE
Low clinical probability:
– normal D-dimer level using either a highly or moderately sensitive assay excludes PE (I, A);
– normal perfusion lung scintigraphy excludes PE (I, A);
– non-diagnostic (low or intermediate probability) ventilation-perfusion scintigraphy (V/Q scan) may exclude PE (IIa, B); particularly when combined with negative proximal CUS (IA);
– negative multidetector coputer tomography (MDCT) safely excludes PE (I, A);
– negative single-detector CT excludes PE when combined with negative proximal compression venous ultrasonography (CUS) (I, A);
– high-probability V/Q scan may confirm PE (IIa, B);
– further testing may be considered in selected patients to confirm PE (IIb, B);
– CUS showing a proximal DVT confirms PE (I, B);
– if CUS shows only a distal DVT, further testing should be considered to confirm PE (IIa, B);
– SDCT or MDCT showing a segmental or more proximal thrombus confirms PE (I, A);
– further testing should be considered to confirm PE if SDCT or MDCT shows only subsegmental clots (IIa, B).
Intermediate clinical probability:
– normal D-dimer level using a highly sensitive assay excludes PE (I, A);
– further testing should be considered if D-dimer level is normal when using a less sensitive assay (IIa, B);
– normal perfusion lung scintigraphy excludes PE (I, A);
– in case of a non-diagnostic V/Q scan, further testing is recommended to exclude or confirm PE (I, B);
– negative MDCT excludes PE (I, A);
– negative SDCT only excludes PE when combined with negative proximal CUS (I, A);
– high-probability ventilation-perfusion lung scintigraphy confirms PE (I, A);
– CUS showing a proximal DVT confirms PE (I, B);
– if CUS shows only a distal DVT, further testing should be considered (IIa, B);
– SDCT or MDCT showing a segmental or more proximal thrombus confirms PE (I, A);
– further testing may be considered in case of subsegmental clots to confirm PE (IIb, B).
High clinical probability:
– D-dimer measurement is not recommended in high clinical probability patients as a normal result does not safely exclude PE even when using a highly sensitive assay (III, C);
– in patients with a negative CT, further tests should be considered in selected patients to exclude PE (IIa, B);
– high-probability ventilation-perfusion lung scintigraphy confirms PE (I, A);
– CUS showing a proximal DVT confirms PE (I, B);
– if CUS shows only a distal DVT, further testing should be considered (IIb, B);
– SDCT or MDCT showing a segmental or more proximal thrombus confirms PE (I, A);
– further testing may be considered where there are subsegmental clots, to confirm PE (IIb, B).
Treatment
Haemodynamic and respiratory support:
1. Haemodynamic and respiratory support is necessary in patients with suspected or confirmed PE presenting with shock or hypotension.
2. Dobutamine and dopamine may be used in patients with PE, low cardiac index and normal blood pressure.
3. Vasopressive drugs may be used in hypotensive patients with PE.
4. Monitored oxygen therapy is beneficial in patients with PE and hypoxaemia.
5. The usefulness of fluid challenge is controversial and should not exceed 500 ml.
Thrombolytic treatment:
1. Thrombolytic therapy is indicated in patients with massive PE. Thrombolytic therapy is the first-line treatment in patients with high-risk PE presenting with cardiogenic shock and/or persistent arterial hypotension, with very few absolute contraindications.
2. Routine use of thrombolysis in non-high-risk patients is not recommended, but may be considered in selected patients with intermediate-risk PE and after thorough consideration of conditions increasing the risk of bleeding.
3. Thrombolytic therapy should be not used in patients with low-risk PE.
Table 41 – Approved thrombolytic regimens for pulmonary embolism
|Streptokinase |250 000 IU as a loading dose over 30 min, followed by |
| |100 000 IU/h over 12–24 h. |
| |Accelerated regimen: 1.5 million IU over 2 h |
|Urokinase |4400 IU/kg as a loading dose over 10 min, followed by |
| |4400 IU/kg/h over 12–24 h. |
| |Accelerated regimen: 3 million IU over 2 h |
|rtPA |100 mg over 2 h |
| |or 0.6 mg/kg over 15 min (maximum dose 50 mg) |
|rtPA = recombinant tissue plasminogen activator |
Table 42 – Contraindications to fibrinolytic therapy
|Absolute contraindication |Relative contraindication |
|Haemorrhagic stroke or stroke of unknown |Transient ischaemic attack in preceding 6 |
|origin at any time |months |
|Ischaemic stroke in preceding 6 months|Oral anticoagulant therapy |
|Central nervous system damage or neoplasms|Pregnancy or within 1 week post partum |
|Recent major trauma/surgery/ head injury |Noncompressible punctures |
|(within preceding 3weeks) | |
|Gastrointestinal bleeding within the last |Refractory hypertension (systolic blood |
|month |pressure > 180 mmHg) |
|Known bleeding |Traumatic resuscitation |
| |Advanced liver disease |
| |Infective endocarditis |
| |Active peptic ulcer |
Surgical embolectomy
With current surgical techniques pulmonary embolectomy is a valuable therapeutic option in patients with high-risk PE in whom thrombolysis is absolutely contraindicated or has failed.
Percutaneous catheter embolectomy and fragmentation
Catheter embolectomy or fragmentation of proximal pulmonary arterial clots may be considered as an alternative to surgical treatment in high-risk PE patients when thrombolysis is absolutely contraindicated or has failed.
Anticoagulant therapy
Anticoagulation with unfractionated heparin, low-molecular-weight heparin (LMWH) or fondaparinux should be initiated without delay in patients with confirmed PE and those with a high or intermediate clinical probability of PE while the diagnostic workup is still ongoing. Except for patients at high risk of bleeding and those with severe renal dysfunction, subcutaneous LMWH or fondaparinux rather then intravenous unfractionated heparin should be considered for initial treatment.
Table 43 – Adjustment of intravenous unfractionated heparin dosage based on the activated partial thromboplastin time
|Activated partial thromboplastin time |Change of dosage |
|< 35 s (< 1.2 times control) |80 U/kg bolus; increase infusion rate by 4 |
| |U/kg/h |
|35–45 s (1.2–1.5 times control) |40 U/kg bolus; increase infusion rate by 2 |
| |U/kg/h |
|46–70 s (1.5–2.3 times control) |No change |
|71–90 s (2.3–3.0 times control) |Reduce infusion rate by 2 U/kg/h |
|> 90 s (> 3.0 times control) |Stop infusion for 1 h, then reduce infusion |
| |rate by 3 U/kg/h |
Table 44 – Subcutaneous regimens of low molecularweight heparins and fondaparinux approved for the treatment of pulmonary embolism
| |Dose |Interval |
|Enoxaparin |mg/kg |Every 12 h, |
| |or 1.5 mg/kg |once daily |
|Tinzaparin |175 U/kg |Once daily |
|Fondaparinux |5 mg (body weight < 50 kg); |Once daily |
| |7.5 mg (body weight 50–100 kg); 10 mg (body| |
| |weight >100 kg) | |
Therapeutic strategies
High-risk pulmonary embolism
1. Anticoagulation with unfractionated heparin should be initiated without delay in patients with high-risk PE (I, A).
2. Systemic hypotension should be corrected to prevent progression of RV failure and death due to PE (I, C).
3. Vasopressive drugs are recommended for hypotensive patients with PE (I, C).
4. Dobutamine and dopamine may be used in patients with PE, low cardiac output and normal blood pressure (IIa, B).
5. Aggressive fluid challenge is not recommended (III, B).
6. Oxygen should be administered in patients with hypoxaemia (I, C).
7. Thrombolytic therapy should be used in patients with high-risk PE presenting with cardiogenic shock and/or persistent arterial hypotension (I, A).
8. Surgical pulmonary embolectomy is a recommended therapeutic alternative in patients with high-risk PE in whom thrombolysis is absolutely contraindicated or has failed (I, C).
9. Catheter embolectomy or fragmentation of proximal pulmonary arterial clots may be considered as an alternative to surgical treatment in high-risk patients when thrombolysis is absolutely contraindicated or has failed (IIb, C).
Non-high-risk pulmonary embolism
1. Anticoagulation should be initiated without delay in patients with high or intermediate clinical probability of PE while diagnostic workup is still ongoing (I, C).
2. Use of LMWH or fondaparinux is the recommended form of initial treatment for most patients with non-high-risk PE (I, A).
3. In patients at high risk of bleeding and in those with severe renal dysfunction, unfractionated heparin with an aPTT target range of 1.5–2.5 times normal is a recommended form of initial treatment (I, C).
4. Initial treatment with unfractionated heparin, LMWH or fondaparinux should be continued for at least 5 days and (I, A) may be replaced by vitamin K antagonists (VKA) only after achieving target INR levels for at least 2 consecutive days (I, C).
5. Routine use of thrombolysis in non-high-risk PE patients is not recommended, but it may be considered in selected patients with intermediate-risk PE (IIb, B).
6. Thrombolytic therapy should be not used in patients with low-risk PE (III, B).
Long-term anticoagulation and secondary prophylaxis
1. For patients with PE secondary to a transient (reversible) risk factor, treatment with a VKA is recommended for 3 months (I, A).
2. For patients with unprovoked PE, treatment with a VKA is recommended for at least 3 months (I, A).
3. Patients with a first episode of unprovoked PE and low risk of bleeding, and in whom stable anticoagulation can be achieved, may be considered for long-term oral anticoagulation (IIb, B).
4. For patients with a second episode of unprovoked PE, long-term treatment is recommended (I, A).
5. In patients who receive long-term anticoagulant treatment, the risk/benefit ratio of continuing such treatment should be reassessed at regular intervals (I, C).
6. For patients with PE and cancer, LMWH should be considered for the first 3–6 months (IIa, B) after this period, anticoagulant therapy with VKA or LMWH should be continued indefinitely or until the cancer is considered cured (I, C).
7. In patients with PE, the dose of VKA should be adjusted to maintain a target INR of 2.5 (range 2.0–3.0) regardless of treatment duration (I, A).
Venous filters
Recommendations:
– IVC filters may be used when there are absolute contraindications to anticoagulation and a high risk of VTE recurrence (IIb, B);
– the routine use of IVC filters in patients with PE is not recommended (III, B).
NEUROCIRCULATORY DYSTONIA
As it is known, neurocirculatory dystonia (NCD) is defined as a condition characterized by disturbance of the normal activity of the autonomous nervous system due to the change in the tone of its sympathetic and parasympathetic parts, and prevalence of the ton of one of those.
Causes
The NCD, vasoneurosis has the functional nature. Disorders of neuroendocrinal regulation of cardiovascular system activity are characteristic for it. At teenagers and young men NCD is caused by a mismatch of physical development and degree of maturity of the excitatory-endocrine apparatus more often. At other age dystonia development can be promoted by psychological attrition in an outcome of acute and chronic infectious diseases and intoxications, by sleep loss, overfatigue, and irregular diets, to sexual life, physical activity (lowered or too intensive).
The causes of dystonia are not yet known or understood; however, they are categorized as follows on the theoretical basis:
Primary dystonia is suspected to be caused by a pathology of the central nervous system, likely originating in those parts of the brain concerned with motor function, such as the basal ganglia, and the GABA (gamma-aminobutyric acid) producing Purkinje neurons. The precise cause of primary dystonia is unknown. In many cases it may involve some genetic predisposition towards the disorder combined with environmental conditions.
Secondary dystonia refers to dystonia brought on by some identified cause, usually involving brain damage, or by some unidentified cause such as chemical imbalance. Some cases of (particularly focal) dystonia are brought on after trauma, are induced by certain drugs (tardive dystonia), or may be the result of diseases of the nervous system such as Wilson's disease.
Environmental and task-related factors are suspected to trigger the development of focal dystonias because they appear disproportionately in individuals who perform high precision hand movements such as musicians, engineers, architects, and artists. At adults disturbance of regulatory functions of the vegetative nervous system sometimes proceeds in the form of attacks – vegetative crises.
Classification
Types of dystonia:
– generalized;
– focal;
– segmental;
– intermediate;
– acute dystonic reaction.
Generalized dystonias:
– normal birth history and milestones;
– autosomal dominant;
– childhood onset;
– starts in lower limbs and spreads upwards;
– also known as “idiopathic torsion dystonia” (old terminology “dystonia musculorum deformans”).
Focal dystonias
Symptoms vary according to the kind of dystonia involved. In most cases, dystonia tends to lead to abnormal posturing, particularly on movement. Many sufferers have continuous pain, cramping and relentless muscle spasms due to involuntary muscle movements. Early symptoms may include loss of precision muscle coordination (sometimes first manifested in declining penmanship, frequent small injuries to the hands, dropped items and a noticeable increase in dropped or chipped dishes), cramping pain with sustained use and trembling. Significant muscle pain and cramping may result from very minor exertions like holding a book and turning pages. It may become difficult to find a comfortable position for arms and legs with even the minor exertions associated with holding arms crossed causing significant pain similar to restless leg syndrome.
Affected persons may notice trembling in the diaphragm while breathing, or the need to place hands in pockets, under legs while sitting or under pillows while sleeping to keep them still and to reduce pain. Trembling in the jaw may be felt and heard while lying down, and the constant movement to avoid pain may result in the grinding and wearing down of teeth. The voice may crack frequently or become harsh, triggering frequent throat clearing. Swallowing can become difficult and accompanied by painful cramping.
Electrical sensors (EMG) inserted into affected muscle groups, while painful, can provide a definitive diagnosis by showing pulsating nerve signals being transmitted to the muscles even when they are at rest. The brain appears to signal portions of fibers within the affected muscle groups at a firing speed of about 10 Hz causing them to pulsate, tremble and contort. When called upon to perform an intentional activity, the muscles fatigue very quickly and some portions of the muscle groups do not respond (causing weakness) while other portions over-respond or become rigid (causing micro-tears under load). The symptoms worsen significantly with use, especially in the case of focal dystonia, and a “mirror effect” is often observed in other body parts: use of the right hand may cause pain and cramping in that hand as well as in the other hand and legs that were not being used. Stress, anxiety, lack of sleep, sustained use and cold temperatures can worsen symptoms.
Direct symptoms may be accompanied by secondary effects of the continuous muscle and brain activity, including disturbed sleep patterns, exhaustion, mood swings, mental stress, difficulty concentrating, blurred vision, digestive problems and short temper. People with dystonia may also become depressed and find great difficulty adapting their activities and livelihood to a progressing disability. Side effects from treatment and medications can also present challenges in normal activities.
In some cases, symptoms may progress and then plateau for years, or stop progressing entirely. The progression may be delayed by treatment or adaptive lifestyle changes, while forced continued use may make symptoms progress more rapidly. In others, the symptoms may progress to total disability, making some of the more risky forms of treatment worth considering.
An accurate diagnosis may be difficult because of the way the disorder manifests itself. Sufferers may be diagnosed as having similar and perhaps related disorders including Parkinson's disease, essential tremor, carpal tunnel syndrome, TMD, Tourette's syndrome, or other neuromuscular movement disorders.
These are the most common dystonias and they tend to be classified as follows:
1. Cervical dystonia (spasmodic torticollis) affects the muscles of the neck, causing the head to rotate to one side, to pull down towards the chest, or back, or a combination of these postures.
2. Blepharospasm affects the muscles around the eyes. The sufferer experiences rapid blinking of the eyes or even their forced closure causing effective blindness.
3. Oculogyric crisis is an extreme and sustained (usually) upward deviation of the eyes often with convergence causing diplopia. It is frequently associated with backwards and lateral flexion of the neck and either widely opened mouth or jaw clenching. Frequently it is a result of antiemetics such as neuroleptics or metoclopramide.
4. Oromandibular dystonia affects the muscles of the jaw and tongue, causing distortions of the mouth and tongue.
5. Spasmodic dysphonia/laryngeal dystonia affects muscles of the larynx, causing the voice to sound broken or reducing it to a whisper.
6. Focal hand dystonia (also known as musician's or writer's cramp) affects a single muscle or small group of muscles in the hand. It interferes with activities such as writing or playing a musical instrument by causing involuntary muscular contractions. The condition is sometimes “task-specific”, meaning that it is generally only apparent during certain activities. Focal hand dystonia is neurological in origin, and is not due to normal fatigue. The loss of precise muscle control and continuous unintentional movement results in painful cramping and abnormal positioning that makes continued use of the affected body parts impossible.
The combination of blepharospasmodic contractions and oromandibular dystonia is called cranial dystonia or Meige's syndrome. There is a group called myoclonus dystonia or myoclonic dystonia, where some cases are hereditary and have been associated with a missense mutation in the dopamin-D2 receptor. Some of these cases have responded remarkably to alcohol.
Segmental dystonias affect two adjoining parts of the body:
1. Hemidystonia affects arm and leg on one side of the body.
2. Multifocal dystonia affects many different parts of the body.
3. Generalized dystonia affects most of the body, frequently involving legs and back.
Treatment
Treatment has been limited to minimizing the symptoms of the disorder as there is no successful treatment for its cause. Reducing the types of movements that trigger or worsen dystonic symptoms provides some relief, as does reducing stress, getting plenty of rest, moderate exercise, and relaxation techniques. Various treatments focus on sedating brain functions or blocking nerve communications with the muscles via drugs, neurosuppression or denervation. All current treatments have negative side effects and risks.
The prevention of a vascular dystonia should begin with tempering at children's and youthful age, the organization of a rational regimen of work and rest. It is necessary to avoid the excitatory overstrains, at disease carefully to observe a regimen and other appointments of the doctor.
Mainly not medicament methods: normalization of the mode of life, tempering procedures, employment by physical culture and some kinds of sports (swimming, track, and field athletics). The physiotherapy, a balneotherapy, sanatorium treatment is used. At irritability, sleep disorders – preparations of valeriana, leonurus, valocordin, sometimes tranquilizers. At a hypotensive type – physiotherapy exercises, belloidum, caffeine, phethanolum. At a hypertensive type – beta adrenoblockers, rauwolfia preparations. The balanced regimen of day, sleep – the best rest (8–10 hours).
Adequate physical activity. Only teenagers from a BP 140–90 and above are engaged in preparatory sports bunch, the others – basically. Good effect is given by employment pool render, run, skis, aerobics, dances, skis. It is possible to use a bicycle.
A diet containing all necessary ingredients, vitamin-rich, the products keeping salts of a potassium – a potato, eggplants, cabbage, prunes, apricots, raisin, a fig, a green peas, parsley, tomatoes, a rhubarb, a beet, fennel, a string bean, a dock are shown. A part of animal adepses to change vegetative (corn, olive). With the raised BP – the products keeping salts of magnesium buckwheat, oat, wheaten groats, nuts, a soya, a string bean, carrots, a dogrose are necessary. Patients need to exclude from pickle nutrition, marinades, to confine salt to 4–5g. Strong tea, coffee, and chocolate are contraindicative.
Psychotherapy: relaxation methods, a combination of autogenic training and direct suggestion, the permission of a psychologic problem. The purpose of psychotherapy is to normalise the attitude of the person to associates, putting off of psychologic intensity. Massage of a head, collar region С1–С4, backs. Duration of sessions of 8–10–15 minutes, a course 18–20 of procedures. With the lowered BP massage of a trunk, extremities brushes.
Phytotherapy: valeriana, viburnum red, a peony, leonurus, a basis a sedation, possess the same action and the soft diuretic a quince, a birch mushroom, a poppy, almonds, carrots, mint, a parsnip, a liquorice. In the absence of BP normalisation add agents about reserpinum similar and beta adrenoblocking action: a running myrtle, a butter-bur, a vervain, a dragonhead, a magnolia, rauwolfia, a black mountain ash, an arnica, a Labrador tea, the shepherd's ascus.
In the absence of effect from the described actions it is necessary to pass to medicamental therapy.
Treatment of a NCD – complex with application of medicines and physiotherapeutic procedures, is spent on doctor's orders. With a view of improvement of patients physiotherapy exercises, country walks, tourism, sanatorium treatment, the normalisation of a mode of life tempering procedures are widely applied. At irritability, sleep disorders – preparations of valeriana, leonurus, valocordin, sometimes tranquilizers. At hypotensive type – physiotherapy exercises, belloidum, caffeine, phethanolum. At hypertensive type – beta adrenoblockers, rauwolfia preparations.
Physicians may prescribe a series of different medications on a trial basis in an effort to find a combination that is effective for a specific patient. Not all patients will respond well to the same medications. Drugs that have had positive results in some patients include antiparkinsonian agents trihexyphenidyl, trihexyphenidyl-hydrochloride (pakisonal), muscle relaxers (valium), keppra, and beta-blockers including “off-label” uses for some blood pressure medications.
Drugs such as anticholinergics, which act as inhibitors of the neurotransmitter acetylcholine, may provide some relief. Clonazepam, an antiseizure medicine, is also sometimes prescribed. However, for most sufferers their effects are limited and side effects like mental confusion, sedation, mood swings, and short-term memory loss occur.
Botulinum toxin injections into affected muscles have proved quite successful in providing some relief for around 3–6 months, depending on the kind of dystonia. Botox injections have the advantage of ready availability (the same form is used for cosmetic surgery) and the effects are not permanent. There is a risk of temporary paralysis of the muscles being injected or the leaking of the toxin into adjacent muscle groups causing weakness or paralysis in them. The injections have to be repeated as the effects wear off and around 15% of recipients will develop immunity to the toxin. There is a Type A and Type B toxin approved for treatment of dystonia; often those that develop resistance to Type A may be able to use Type B. Surgery, such as the denervation of selected muscles, may also provide some relief; however, the destruction of nerves in the limbs or brain is not reversible and should only be considered in the most extreme cases. Recently, the procedure of deep brain stimulation has proven successful in a number of cases of severe generalised dystonia. DBS as treatment for medication-refractory dystonia, on the other hand, may increase the risk of suicide in patients. Reference data of patients without DBS therapy are lacking.
One type of dystonia, dopamine-responsive dystonia, can be completely treated with regular doses of L-DOPA in a form such as Sinemet (carbidopa/levodopa). Although this doesn't remove the condition, it does alleviate the symptoms most of the time.
In the case of Oculogyric crisis, benadryl may be administered with excellent results. Symptoms subside in a matter of minutes.
A baclofen pump has been used to treat patients of all ages exhibiting muscle spasticity along with dystonia. The pump delivers baclofen via a catheter to the thecal space surrounding the spinal cord. The pump itself is placed in the abdomen. It can be refilled periodically by access through the skin.
Physical therapy can sometimes help with focal dystonia. A structured set of exercises is tailored to help the affected area.
Some focal dystonias have been proven treatable through movement retraining in the Taubman approach, particularly in the case of musicians. However other focal dystonias may not respond and may even be made worse by this treatment.
In the case of acute dystonic reaction, diphenhydramine (benadryl) 25–50 mg IV push is often used in the prehospital and emergency department setting to relieve to muscle contractions associated with dystonic reactions. Although antihistamine, diphenhydramine also possesses some anticholinergic properties. Although diphenhydramine (benadryl) is used to treat this reaction, it is not an allergic reaction to the medication. The patient should be informed of this distinction.
QUESTIONS
Тopic 1. Arterial hypertension
1. A 50-year-old male with a history of diabetes mellitus presents for a routine clinic visit. He has been feeling well and has no complaints. He has been exercising regularly and dieting as instructed for his diabetes. His medications include metformin and glypizide. His blood pressure is 180/90, heart rate – 70, and respirations – 20. His physical examination is normal. Which of the following is the most appropriate management at this time?
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A. Continue diet and lifestyle modifications only.
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B. Start lisinopril and hydrochlorothiazide.
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C. Start amlodipine.
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D. Start hydrochlorothiazide.
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E. Start spironolactone.
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2. A 29-year-old female with a history of hypertension presents for a routine clinic visit without any physical complaints. Her blood pressure is 180/100 which she admits it has been at home as well. Physical examination reveals normal lung sounds, regular rhythm with hyperdynamic apical impulse and S4 heart sound, abdominal bruit is heard, there is no lower extremity oedema. Her pulses are 2+ in upper and lower extremities. Her blood pressure medications include lisinopril, amlodipine, atenolol, hydrochlorothiazide, hydralazine, and clonidine which she states she takes regularly. Screening for secondary causes of hypertension thus far has been negative which has included electrolytes, a complete blood count, creatinine, urinary and serum catecholamines, AM cortisol levels, renin/aldosterone levels, thyroid stimulating hormone levels, and dexamethasone suppression test. Which of the following tests should be ordered next?
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A. CT aortogram of the thoracic aorta.
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B. Serum erythropoietin levels.
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C. CT scan of the adrenal glands.
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D. Magnetic resonance angiography of the renal arteries.
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Topic 2. Atherosclerosis
3. A 55-year-old male with a history of hypertension has the following fasting lipid profile: total cholesterol 240 mg/dL, LDL cholesterol 98 mg/dL, HDL cholesterol 35 mg/dL, triglycerides 140 mg/dL. Which of the following is the most appropriate treatment?
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A. Diet and lifestyle modifications.
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B. Start niacin.
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C. Start gemfibrozil.
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D. Start HMG-CoA reductase inhibitor.
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E. No therapy is needed.
Topic 3. Ischaemic heart disease
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4. A 72-year-old female with a history of diabetes mellitus and no history of heart disease presents to the emergency department with chest pains at rest intermittently for the past 4 hours. She has associated shortness of breath and diaphoresis. Her heart rate is 59, blood pressure – 134/72, respiratory rate – 20, and oxygen saturation is 95% on room air. Physical examination reveals normal lung sounds and S4 gallop. Her ECG reveals ST segment depression in leads V1 to V3. She is given aspirin immediately. Her troponin levels remain negative. She is currently chest pain free. Which of the following is the correct diagnosis?
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A. Stable angina.
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B. Unstable angina.
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C. Non-ST segment elevation myocardial infarction.
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D. ST segment elevation myocardial infarction.
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5. A 48-year-old male with a history of hypertension presents to the emergency room with chest pain. He is diaphoretic and also complaining of shotness of breath. His temperature is 37.1 ºC, blood pressure – 120/82, heart rate – 82, and respirations – 20. His physical examination is significant for S4 heart sound. ECG reveals an inferior wall ST elevation myocardial infarction and appropriate treatment is undertaken. He is discharged home and was doing well. Two months later he develops acute chest pain worse with laying flat radiating to his left neck. He returns to his cardiologist and his temperature is 38.5 C, blood pressure – 118/82, heart rate – 80, and respirations – 18. Physical examination is normal. ECG reveals ST segment elevation in leads I, II, III, aVF, aVL, and V1-V4 as well as PR depression in lead II. What is the most likely diagnosis at this time?
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A. Left ventricular rupture.
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B. Anterior myocardial infarction.
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C. Dressler's syndrome.
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D. Early repolarization.
6. A 58-year-old male with a history of hypertension and diabetes presents to the emergency room with chest pain at rest. He states the pain is substernal, pressure-like, and associated with diaphoresis and shortness of breath. He is afebrile, blood pressure is 110/70, heart rate – 70, and respirations – 18. Physical examination reveals normal lung sounds, normal jugular venous pressure, and S4 heart sound. Laboratory studuies are initially normal. His ECG is below. What is the appropriate diagnosis?
[pic]
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Figure 12 – Patient’s ECG
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A. Unstable angina with anterior ischaemia.
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B. Posterior wall myocardial infarction.
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C. Inferior wall myocardial infarction.
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Начало формы
D. Noncardiac chest pain.
Тopic 4. Congenital heart disease
7. A 18-year-old male with no significant past medical history presents to his primary care physcician for a routine physical examination. He has no physical complaints. His blood pressure is 115/85, heart rate – 80, respirations – 12, and he is afebrile. His physical examination reveals normal lung sounds, V/VI holosystolic murmur with a thrill at the left lower sternal border and no change in intensity with inspiration, no gallops or extra heart sounds, and normal jugular venous pressures. His ECG and laboratory studies are normal. What is his most likely diagnosis?
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A. Mitral regurgitation.
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B. Patent ductus arteriosis.
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C. Tricuspid regurgitation.
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D. Ventricular septal defect.
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8. A 36-year-old female with no past medical history presents to her primary care office a complaint of chest pains for the past few months. She states that intermittently she has a feeling that she is going to die and develops severe chest pains and palpitations. The pain is substernal, pressure-like, and radiating to her left arm. It can last for minutes or hours at a time. Her blood pressure is 120/80, heart rate – 80, and respirations – 20. Physical examination reveals normal lung sounds, no murmurs, and a mid-systolic click that moves to early systole with standing from a squatting position. Her ECG is normal. Which of the following is the most likely diagnosis?
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A. Mitral valve regurgitation.
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B. Myocardial ischaemia.
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C. Mitral valve prolapse.
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D. Mitral valve stenosis.
Тopic 5. Heart valvular disease
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9. A 27-year-old female with no significant past medical history is 40 weeks pregnant and labor has just begun. She begins to complain of shortness of breath, which worsens throughout delivery to the point of requiring intubation. She had never previously complained of any dyspnoea or chest pains. Her temperature is 37.0 ºC, blood pressure – 90/50, heart rate – 130, respirations – 26, and oxygen saturation – 100% on 60% FiO2 on the ventilator. Physical examination reveals diffuse pulmonary rales, II/IV early diastolic murmur, and no lower extremity oedema. Laboratory studies are normal. ECG shows sinus tachycardia and left atrial enlargement. Her chest X-ray has significant pulmonary oedema. Which of the following is the most likely diagnosis?
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A. Aortic dissection.
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B. Coronary artery dissection.
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C. Aortic valve stenosis.
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D. Mitral valve stenosis.
10. A 27-year-old female with no significant past medical history is 40 weeks pregnant and labor has just begun. She begins to complain of shortness of breath, which worsens throughout delivery to the point of requiring intubation. She had never previously complained of any dyspnoea or chest pains. Her temperature is 37.0 ºC, blood pressure – 90/50, heart rate – 130, respirations – 26, and oxygen saturation – 100% on 60% FiO2 on the ventilator. Physical examination reveals diffuse pulmonary rales, II/IV early diastolic murmur, and no lower extremity oedema. Laboratory studies are normal. ECG shows sinus tachycardia and left atrial enlargement. Her chest X-ray has significant pulmonary oedema. Which of the following is the most likely diagnosis?
Начало формы
A. Aortic dissection.
Конец формы
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B. Coronary artery dissection.
Конец формы
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C. Mitral valve stenosis.
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D. Aortic valve stenosis.
Тopic 6. Infective endocarditis
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11. A 62-year-old male with a history of mitral valve prolapse, rhematoid arthritis, and colon cancer presents to the emergency room with increased dyspnoea on exertion, lower extremity swelling, and fevers slowly worsning over the past month. His temperature is 38.0 ºC, blood pressure – 95/65, heart rate – 80, respirations – 20, and oxygen saturation – 92% on room air. Physical examination reveals normal breath sounds, II/VI holosystolic murmur at the apex, and 1+ bilateral lower extremity pitting oedema. Laboratory studies show a WBC count of 20 thousand and an ESR of 100. Echocardiogram reveals 8 mm mobile vegitation on the anterior leaflet of the mitral valve. Which of the following is the most likely pathogen?
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A. Staphylococcus aureus.
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B. Pseudomonas auriginosa.
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C. Candida albicans.
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D. Streptococcus bovis.
Тopic 7. Мyocarditis and cardiomyopathy
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12. A 17-year-old male with no significant past medical history pasess out while running. He states that he was feeling a little dizzy prior to the event, but no chest pains or palpitations. His blood pressure is 115/85, heart rate – 80, respirations – 12, and he is afebrile. His physical examination reveals normal lung sounds, II/VI mid-sytolic creshendo-decreshndo murmur is heard at the right upper sternal border which increases in intensity with Valsalva, S4 heart sound is also present. Laboratory studies are normal. What is his most likely diagnosis?
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A. Congenital pulmonic valve stenosis.
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B. Hypertrophic obstructive cardiomyopathy.
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C. Congential aortic valve stenosis.
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D. Commotio cordis.
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E. Atrial setpal defect.
Тopic 8. Pericarditis
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13. A 71-year-old female with a history of tobacco use, diabetes mellitus, rheumatoid arthritis, breast cancer is seen by her primary care physician for a routine follow-up visit. She has been feeling gerenally weak. She can only walk about 1/2 block before getting short of breath and dizzy. She denies chest pain. Her blood pressure is 90/60, heart rate – 90, respirations – 20, and she is afebrile. Her physical examination reveals normal breath sounds and no cardiac murmurs but heart sounds are distant. Her chest X-ray is below. What is her most likely diagnosis?
Начало формы
Конец формы
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A. Pericardial effusion.
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B. Congestive heart failure.
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C. Pulmonary hypertension.
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D. Mitral valve stenosis.
Конец формы
[pic]
Figure 13 – Patient’s X-ray
14. A 68-year-old female with a history of hypertension, diabetes, coronary artery disease treated with coronary artery bypass grafting 20 years ago, presents to the emergency room with increasing shortness of breath and lower extremity oedema. She denies any chest pains and does not drink alcohol. Her temperature is 37.0 ºC, blood pressure – 110/70, heart rate – 110, and respirations – 20. Physical examination reveals a cachectic appearance, marked jugular venous distension worse with inspiration, decreased breath sounds at the left base, pulmonary rales throughout the lung fields, a regular rhythm with extrasystolic heart sound, hepatomegaly with ascites, and 3+ pitting lower extremity oedema above the knees. ECG is normal. Laboratory studies reveal elevated AST, ALT, and total bilirubin. Hepatitis profile is normal. Which of the following is the most likely diagnosis?
Начало формы
A. Restrictive cardiomyopathy.
Конец формы
Начало формы
B. Systolic congestive heart failure.
Конец формы
Начало формы
C. Tricuspid regurgitation.
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D. Cardiac tamponade.
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E. Constrictive pericarditis.
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15. A 32-year-old male with no significant past medical history presents to the emergency room with 3 hours of chest pain at rest. He recently has had an upper respiratory tract infection for which he has been taking over the counter medications for symptoms relief. His blood pressure is 120/80, heart rate – 80, and respirations – 20. Physical examination is normal. Laboratory and chest X-ray is normal. His ECG is below. Which of the following is the most likely diagnosis?
Начало формы
Начало формы
A. Dilated cardiomyopathy.
Конец формы
Начало формы
B. Pericarditis.
Конец формы
Начало формы
C. Constrictive pericarditis.
Конец формы
Начало формы
D. Myocardial ischaemia.
Конец формы
[pic]
Figure 14 – Patient’s ECG
Тopic 9. Arrhythmias and conduction disorders
16. A 22-year-old college student with no prior past medical history presents to the emergency room with complaints of palpiations and dizziness. He states he was at a party recently and had been drinking heavily when he noted the symptoms. No chest pains or shortness of breath. His blood pressure is 90/60, heart rate – 160, respirations – 20, and oxygen saturation – 95% on room air. A portion of his ECG is below. What is his most likely diagnosis?
A. Multifocal atrial tachycardia.
17. Конец формы
18. Начало формы
B. Ventricular tachycardia.
19. Конец формы
20. Начало формы
C. Atrial fibrillation.
21. Конец формы
22. Начало формы
D. Atrial flutter.
[pic]
Figure 15 – Patient’s ECG
Начало формы
Конец формы
17. A 82-year-old male with a history of recent aortic valve replacement, hypertension, and diabetes presents to the emergency department with fevers for 5 days. No chest pains or shortness of breath. His medications include lisinopril, hydrochlorothiazide, aspirin, and coumadin. His temperature is 38.4 ºC, blood pressure is 160/60, heart rate – 100, respirations – 20, and oxygen saturation – 99% on room air. Physical examination reveals normal lung sounds, II/IV early diastolic decrescendo murmur, and a very soft 1st heart sound. Laboratory studies reveal a white blood cell count of 15 thousand and an ESR of 110. A portion of his ECG is below. Which of the following is causing his abnormal finding on his ECG?
[pic]
Figure 16 – Patient’s ECG
Начало формы
A. Aortic valve endocarditis.
Конец формы
Начало формы
B. Aortic valve regurgitation.
Конец формы
Начало формы
C. Aortic valve annular abscess.
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D. Aortic valve stenosis.
Конец формы
18. A 67-year-old male with a history of severe chronic obstructive pulmonary disease (COPD), hypertension, and congestive heart failure presents to the emergency room with increasing shortness of breath over the past week. He denies any chest pains or fevers. His temperature is 37.0 ºC, blood pressure – 130/70, heart rate – 120, respirations – 24, and oxygen saturation – 87% on room air. Physical examination reveals diffuse expiratory wheezing without rales, heart sounds are normal without murmurs and in irregularly irregular rhythm is noted. There is trace lower extremity pitting oedema. Laboratory studies reveal a mildly elevated b-type naturatic peptide and an elevated white blood cell count. His chest X-ray shows hyperexpanded lungs and no evidence of pulmonary oedema. His ECG is below. What is the appropriate treatment for his heart rhythm disorder?
A. Propranolol.
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B. Verapamil.
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C. Amiodarone.
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D. No specific medication treatment.
[pic]
Figure 17 – Patient’s ECG
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19. A 82-year-old male with a history of benign prostatic hypertrophy and osteoarthritis presents to the emergency room with an episode of syncope while watching TV. He has felt generally weak for the past 5 days. He denies any chest pains, shortness of breath, or fevers. His medications include tamsulosin and celecoxib. His blood pressure is 115/65, heart rate – 40, respirations – 12, and he is afebrile. His physical examination reveals normal lung sounds, a regular, bradycardic rhythm with varying intensities of the S1 heart sound, and intermittent large cannon A waves in the jugular venous pulsation. His laboratory studies are normal. His ECG is below. What is the appropriate treatment?
[pic]
Figure 18 – Patient’s ECG
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A. No treatment needed.
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B. Discontinue tamsulosin.
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C. Permanent pacemaker implantation.
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D. Defibrillator implantation.
Конец формы
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20. A 55-year-old male has complains of weakness, dyspnoea during exertion and sometimes at rest, cough, has periodical palpitation and arrythmia. Anamnesis: myocardial infarction 2 years ago. During examination: pale skin, central cyanosis. Auscultation: inspiratory basilar crackles in lungs, loud S2. Pansystolic murmur at the apex, accentuated pulmonic component (P2) of the 2nd heart sound (S2). Irregular heart rate – 92/min, BP – 120/80. Palpation of the abdomen is painless, enlargerment of liver – absent. Peripheral oedema is absent. Which condition has this patient?
A. Left-sided failure.
B. Right-sided failure.
C. Biventricular failure.
D. Cor pulmonale.
[pic]
Figure 19 – Patient’s ECG
Answers
№ of question |1 |2 |3 |4 |5 |6 |7 |8 |9 |10 | |Correct answer |D |B |A |B |C |B |D |C |D |C | |№ of question |11 |12 |13 |14 |15 |16 |17 |18 |19 |20 | |Correct answer |D |B |A |E |B |C |C |D |C |A | |ECG Quiz
ECG 1
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ECG 2
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ECG 3
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ECG 4
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ECG 5
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ECG 6
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ECG 7
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ECG 8
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ECG 9
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ECG 10
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ECG 11
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ECG 12
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ECG findings include:
ECG 1:
1. Atrial fibrillation with rapid ventricular rate.
2. Old inferior MI.
3. Poor R-wave progression.
4. ST-segment abnormality, consider myocardial ischaemia (lateral in leads V6, I, and VL).
ECG 2:
1. Atrial fibrillation.
2. Ventricular pacing.
ECG 3:
1. Sinus bradycardia.
2. Old inferior MI.
3. Left ventricular hypertrophy.
4. Poor R-wave progression.
ECG 4:
1. Atrial fibrillation with rapid ventricular response.
2. RBBB.
ECG 5: Ventricular tachycardia (VT).
ECG 6:
1. Normal sinus rhythm.
2. Right ventricular hypertrophy with strain pattern.
3. Left atrial enlargement.
4. Right atrial enlargement.
ECG 7:
1. Normal sinus rhythm.
2. Old inferior myocardial infarction.
3. Old anterior myocardial infarction.
4. Non-specific ST-T-wave changes.
ECG 8:
1. Normal sinus rhythm.
2. Left atrial enlargement.
3. Premature ventricular contractions in a pattern of ventricular bigeminy.
ECG 9: inferior localization of myocardial infarction (acute coronary syndrome with ST segment elevation).
ECG 10: anterior localization of Q-wave infarction.
ECG 11:
1. Sinus rhythm.
2. Left axis deviation (deep S waves in leads II and III).
3. Wide QRS complex (duration 160 ms).
4. RSR pattern in lead V.
5. Second degree (2:1) block with left anterior hemiblock and RBBB.
ECG 12:
1. Sinus rhythm.
2. LBBB.
LIST OF REDUCTIONS
ACEIs – angiotensin-converting enzyme inhibitors
ACS – acute coronary syndrome
AF – atrial flutter
Af – atrial fibrillation
AFM – Abramov-Fiedler myocarditis
AH – arterial hypertension
ANA – antinuclear antibody
AP – arterial pressure
APB – arterial premature beat
AR – aortic regurgitation
ARB – angiotensin receptor antagonists
AS – aortic stenosis
AT – atrial tachycardia
AV – aortic valve
AVNRT – atrioventricular nodal reciprocating tachycardia
AVRT – atrioventricular reciprocating tachycardia
BB – β-blockers
BBB – bundle branch block
BC – blood cultures
BMI – body mass index
BP – blood pressure
BSA – body surface area
CA – calcium antagonists
CABG – coronary artery bypass grafting
CHD – coronary heart disease
CHF – chronic heart failure
CIC – circulating immune complexes
CK – creatine kinase
CNE – culture negative endocarditis
CO – cardiac output (minute volume)
CrCl – creatinine clearance
CRP – c-reactive protein
CT – computer tomography
cTnT (cTnI) – troponins T or I
CVD – cardiovascular disease
CUS – compression venous ultrasonography
DCM – dilatation cardiomyopathy
DVT – deep vein thrombosis
ECG – electrocardiogram
EF – ejection fraction
ESD – end-systolic dimension
ESRD – end-stage renal disease
GI – gastrointestinal
GU – genitourinary
HCM –hypertrophic cardiomyopathy
HDL-C – high-density lipoprotein cholesterol
HF – heart failure
IE – infective endocarditis
IHD – ischaemic heart disease
IMT – intima-media thickness
ISH – isolated systolic hypertension
IV – intravenous
IVDA – intravenous drug abuse
IVS – interventricular septum
LA – left atrium
LBBB – left bundle branch block
LDH – lactate dehydrogenase
LDL-C – low-density lipoprotein cholesterol
LMWH – low-molecular-weight heparin
LV – left ventricle
LVH – left ventricular hypertrophy
LVMI – left ventricular mass index
M – men
MB – myoglobin
MI – myocardial infarction
MV – mitral valve
NCD – neurocirculatory dystonia
NSTEMI – non ST-segment elevation MI
NVE – native valve endocarditis
P – procedures
PCI – percutaneous coronary intervention
PCR – polymerase chain reaction
PE – pulmonary embolism
PMC – percutaneous mitral commissurotomy
PO – per os
PVE – prosthetic valve endocarditis
QTc – QT interval corrected for heart rate
RA – right atrium
RAAS – renin-angiotensin-aldosterone system
RCM – restrictive cardiomyopathy
RF – risk factors
RV – right ventricle
SAS – sympathoadrenal system
SBP – systolic blood pressure
SES – speed of erythrocyte sedimentation
SHF – symptoms of heart failure
STEMI – ST-segment elevation MI
SVT – supraventricular tachycardia
TEE – transesophageal echocardiography
TG – triglycerides
TIA – transient ischaemic attack
TPR – total peripheral vascular resistance
TR – tricuspid regurgitation
TS – tricuspid stenosis
TTE – transthoracic echocardiography
TV – tricuspid valve
VF – ventricular fibrillation
VPB – ventricular premature beat
VT – ventricular tachycardia
VTE – venous thromboembolism
W – women
Levels of evidence
Level of evidence A – data derived from multiple randomized clinical trials or meta-analyses.
Level of evidence B – data derived from a single randomized clinical trials or multiple trials with etherogeneous results.
Level of evidence C – consensus of opinion of the experts and/or small studies, retrospective studies, registries.
Grading using classes of recommendation
Class I – evidence and/or general agreement that a given diagnostic procedure/treatment is beneficial, useful and effective.
Class II – conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of the treatment.
Class IIa – weight of evidence/opinion is in favour of usefulness/efficacy.
Class IIb – usefulness/efficacy is less well established by evidence/opinion.
Class III – evidence or general agreement that the treatment is not useful/effective and in some cases may be harmful. Use of Class III is discouraged by the European Society of Cardiology.
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CONTENTS P.
Introduction………………………………………………………...3
Arterial hypertension……………………………………………....4
Secondary hypertension…………………………………………..22
Atherosclerosis …………………………………………………....30
Ischaemic heart disease…………………………………………...36
Acute coronary syndrome…………………………….……36
Myocardial infarction………………………………………52
Stable angina ………………………………………...…….66
Differential diagnosis of chest pain ……………………….76
Cardiac arrhythmias …………………………………….…80
Congenital heart valvular disease………..……………………….95
Atrial septal defect………………………………………....95
Ventricular septal defect…………………………………...97
Patent ductus arteriosus……………………………………99
Coarctation of aorta ……………………………….……...101
Heart valvular disease…………………………………………...104
Aortic regurgitation……………………………………….104
Aortic stenosis ………………………………..……….….107
Mitral regurgitation………………………………...……..110
Mitral stenosis…………………………………………….113
Tricuspid regurgitation…………………………………...116
Tricuspid stenosis..……………………………………….117
Infective endocarditis……………………………………...…….119
Myocarditis…………………………………………………….....136
Cardiomyopathy ……………………………… ………………..144
Pericarditis………………………………………...……………..150
Syndrome of chronic cardiac failure…………………………...171
Cor pulmonale …………………………………………………...192
Pulmonary embolism…………………………………………….196
Neurocirculatory dystonia ……………………………………..209
Questions……….………………………………………………...216
List of reductions………………………………………………...234
References………………………………………………………..238
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