University of Dundee
The year 2019 in cardiology: aorta and peripheral circulationChristian Heiss,1 Alex Pitcher,2 Jill JF Belch,3 Marco De Carlo,4 Holger Reinecke,5 Iris Baumgartner,6 Lucia Mazzolai,7 Victor Aboyans,8 on behalf of the ESC Working Group on Aorta and Peripheral Vascular Diseases. 1Department of Clinical and Experimental Medicine, University of Surrey, Guildford GU2 7XH and Surrey and Sussex Healthcare NHS Trust, Redhill RH1 5RH, UK2Division of Cardiovascular Medicine, Radcliffe Dept. of Medicine, University of Oxford, Oxford, UK; 3The Institute of Cardiovascular Research, University of Dundee, Ninewells Hospital and Medical School, Dundee, Scotland, UK4Cardiac Catheterization Laboratory, Cardiothoracic and Vascular Department, Azienda Ospealiero-Universitaria Pisana, via Paradisa2, 56100 Pisa, Italy5Department of Cardiology I - Coronary and Peripheral Vascular Disease, Heart Failure.University Hospital Muenster, Albert Schweitzer Campus 1, A1, 48149 Muenster, Germany6Klinik und Poliklinik fu?r Angiologie, Departement Herz und Gefa?sse, Universita?t Bern, Bern, Switzerland7Division of Angiology, Department of Heart and Vessel, Lausanne University Hospital, Ch du Mont-Paisible 18, Lausanne, 1011, Switzerland8Department of Cardiology, Dupuytren University Hospital, 2, Martin Luther King Ave., and Inserm 1094, Limoges School of Medicine, Ave Dr. Marcland, 87025 Limoges, FranceAddress for correspondence:Prof. Dr. Christian HeissDepartment of Clinical and Experimental MedicineUniversity of SurreyStag HillGuildford GU2 7XH, United KingdomPhone: +44 (0) 1737 231749Email: c.heiss@surrey.ac.ukPreambleSimilar to previous years,PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5EZSBDYXJsbzwvQXV0aG9yPjxZZWFyPjIwMTc8L1llYXI+
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ADDIN EN.CITE.DATA 1-3 the current article reviews ground breaking science published 2019 in the area of aortic and peripheral arterial diseases (PAD) as well as venous thromboembolic disease (VTE) that will affect our daily clinical practise. With the growing recognition of PAD, it will be necessary to consolidate imprecisions in terminology. Formerly many of us are used to the acronym PAD for atherosclerotic disease of the lower extremity arteries. Others have used the same acronym to qualify atherosclerotic disease of the lower extremities arteries and carotid arteries. In the current article and in line with the ESC guidelines,PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BYm95YW5zPC9BdXRob3I+PFllYXI+MjAxODwvWWVhcj48
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ADDIN EN.CITE.DATA 4 we have stringently used the specific terms lower extremity arterial disease (LEAD) and reserved PAD as the umbrella term encompassing all arterial diseases other than aorta and coronaries. Vascular biology/translational research The extent to which genetic factors contribute to PAD development and if they are shared or distinct between LEAD, cerebral, and coronary arteries is largely unknown. In a genome-wide association study in the Million Veteran Program, ~32 million DNA sequence variants were tested for PAD (31,307 cases, 211,753 controls) and combined with electronic health records.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5LbGFyaW48L0F1dGhvcj48WWVhcj4yMDE5PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 5 The results were replicated in an independent sample of 5,117 PAD cases and 389,291 controls from the UK Biobank. They identified 19 LEAD loci, 18 of which have not been previously reported. Eleven of the 19 loci were associated with disease in three vascular beds (coronary, cerebral, lower extremity), including LDLR, LPL, and Lp(a). Four of the variants appeared to be specific for LEAD, including F5 p.R506Q (Factor V Leiden variant), highlighting the pathogenic role of thrombosis in the lower extremity vascular bed and providing genetic support for Factor Xa inhibition as a therapeutic strategy for LEAD. Despite the fact that numerous long non-coding RNAs (lncRNA) have been identified, only a few of them have been studied with respect to endothelial cell homeostasis or vascular disease development. One of them, the pro-angiogenic lncRNA MANTIS (named after the carnivorous insect based on its secondary structure), may be clinically relevant in carotid disease.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MZWlzZWdhbmc8L0F1dGhvcj48WWVhcj4yMDE5PC9ZZWFy
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ADDIN EN.CITE.DATA 7 Myeloid cell-specific deletion of NCOR1 in LDL receptor knockout mice aggravated atherosclerosis development. Macrophage NCOR1-deficiency led to increased foam cell formation, enhanced expression of pro-inflammatory cytokines, and atherosclerotic lesions characterized by larger necrotic cores and thinner fibrous caps. The immunometabolic effects of NCOR1 were mediated via suppression of peroxisome proliferator-activated receptor gamma (PPARγ) target genes in mouse and human macrophages, which lead to an enhanced expression of the CD36 scavenger receptor and subsequent increase in oxidized LDL uptake in the absence of NCOR1. Interestingly, in human atherosclerotic plaques, the expression of NCOR1 was reduced whereas the PPARγ signature was increased, and this signature was more pronounced in ruptured compared with non-ruptured carotid plaques. The data suggest that stabilizing the NCOR1-PPARγ binding could be a promising strategy to block the pro-atherogenic functions of plaque macrophages and lesion progression in atherosclerotic patients.Radiotherapy-induced CVD is an emerging problem in a growing population of cancer survivors where traditional vascular treatments have limited benefits. Using a translational approach (Figure 1), it was now shown that human irradiated blood vessels exhibit elevated levels of inflammation signals associated with inflammasome activation long after radiotherapy, and similar changes occurred in a mouse model of localized irradiation to the heart and carotids.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DaHJpc3RlcnNkb3R0aXI8L0F1dGhvcj48WWVhcj4yMDE5
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ADDIN EN.CITE.DATA 8 In the model, the localized inflammatory response was ameliorated by treatment with an IL-1 receptor antagonist. Clinical studies in humans now need to evaluate IL-1 blockade as a potential treatment of radiotherapy-induced CVD. Deciding time of intervention so as not to ameliorate the radiotherapy benefits will be crucial.Subjects with Lp(a) elevation have increased arterial wall inflammation and cardiovascular risk. Stiekema et alPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TdGlla2VtYTwvQXV0aG9yPjxZZWFyPjIwMTk8L1llYXI+
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ADDIN EN.CITE.DATA 10Another large study characterized serum metabolic signatures associated with atherosclerosis in the carotid and coronary arteries and subsequently their association with incident cardiovascular disease among 3,867 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), with replication among 3569 participants from the Rotterdam and LOLIPOP studies.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Uem91bGFraTwvQXV0aG9yPjxZZWFyPjIwMTk8L1llYXI+
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Pn==
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Pn==
ADDIN EN.CITE.DATA 12 using hybrid 18F-FDG PET and MRI, arterial inflammation was detected in 48% of participants of 40-54 years of age, increasing steadily by the number of risk factors. Aortic, carotid and/or ilio-femoral plaques were present in 90% of cases, but most inflammation was depicted in the plaque-free zones. Inflammation was present only in 11% of plaques, suggesting arterial inflammation in early stage of atherosclerosis process. Atherosclerosis is even identifiable in adolescence, especially in case of unhealthy lifestyle: in an observational studyPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DaGFyYWtpZGE8L0F1dGhvcj48WWVhcj4yMDE5PC9ZZWFy
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ADDIN EN.CITE.DATA 13 including 1,266 young participants aged 13 to 17 years, aortic stiffness, estimated by carotid-femoral pulse-wave velocity (cfPWV) was proportionally increased by the tobacco smoking and alcohol drinking intensities, with a strong potentiation when both were combined (Figure 2). At these ages, smoking and drinking cessation lead to normalization of cfPWV. In the other lifespan tip, vascular markers could be useful to downgrade the estimated risk in elderly people who would have an indication for statins based on risk scores, highly affected by age. In a cohort of 5,805 healthy elderly participants (mean age 69 years), normal (<10) coronary calcium score and no carotid plaque on ultrasound were the most powerful vascular markers to downgrade the predicted CV risk, with respective net reclassification index of 0.29 and 0.14, avoiding unnecessary statin prescription in 34% and 21% of cases. ADDIN EN.CITE <EndNote><Cite><Author>Mortensen</Author><Year>2019</Year><RecNum>4071</RecNum><DisplayText><style face="superscript">14</style></DisplayText><record><rec-number>4071</rec-number><foreign-keys><key app="EN" db-id="2eap02ffjxpzases2r750adgffdvf5xefvpp" timestamp="1569061380">4071</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mortensen, M. B.</author><author>Fuster, V.</author><author>Muntendam, P.</author><author>Mehran, R.</author><author>Baber, U.</author><author>Sartori, S.</author><author>Falk, E.</author></authors></contributors><auth-address>Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark. Electronic address: martin.bodtker.mortensen@clin.au.dk.
Cardiovascular Institute, Mount Sinai Medical Center, Icahn School of Medicine at Mount Sinai, New York, New York.
scPharmaceuticals, Lexington, Massachusetts.
Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.</auth-address><titles><title>Negative Risk Markers for Cardiovascular Events in the Elderly</title><secondary-title>J Am Coll Cardiol</secondary-title></titles><pages>1-11</pages><volume>74</volume><number>1</number><keywords><keyword>elderly</keyword><keyword>galectin-3</keyword><keyword>prevention</keyword><keyword>risk prediction</keyword><keyword>statins</keyword><keyword>subclinical atherosclerosis</keyword></keywords><dates><year>2019</year><pub-dates><date>Jul 9</date></pub-dates></dates><isbn>1558-3597 (Electronic)
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ADDIN EN.CITE.DATA 15 randomized 3,532 individuals >40 years attending a screening programme; the control group received regular risk factors screening and guidelines-based management but the results of carotid ultrasound were not disclosed, while the intervention group received, along with their general practitioners, a pictorial presentation of the carotid ultrasound results, including colour-scaled presentations of vascular age based on intima-media thickness, and plaque identification. A nurse called 2-4 weeks later to reassure participants and provide any information needed. The same pictorial information was repeated after 6 months. The baseline Framingham risk score (FRS) and SCORE were respectively at 12.9 and 1.28. At one year, both scores were significantly lower in the intervention group (-1.07, p=0.0017 for FRS and – 0.16, p=0.001 for SCORE), with more striking results in the high-risk group (-2.16 and -2.85, respectively). The persistence of these results and their consequences on CVD events need further evaluation.Lower extremity artery disease (LEAD) LEAD is an increasing public health problem according to the latest global epidemiology report.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Tb25nPC9BdXRob3I+PFllYXI+MjAxOTwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA 16 In 2010, LEAD, defined as ABI ≤0.9, affected 202 million subjects worldwide; this number increased by 22% to 237 million in 2015. Overall prevalence in subjects aged ≥25 years was 5.6% (95%CI: 3.8-8.6), higher in high-income countries than in low- and middle-income countries (LMIC) (7.4% vs. 5.1%), although the vast majority of patients (73%) lived in LMIC. This prevalence was similar between sexes, with higher rates of young (<50 years) patients in LMIC. The association of LEAD with major adverse cardiovascular events (MACE) is well documented, whereas its association with limb events is less clear. In the Veterans Aging Cohort Study, including 125,674 subjects without history of prior amputation, the rate of incident amputation over a median of 9.3 years of follow-up was 1.2 per 1000 person-years.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CZWNrbWFuPC9BdXRob3I+PFllYXI+MjAxOTwvWWVhcj48
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ADDIN EN.CITE.DATA 17 The presence of LEAD conferred a 13.9-fold increase in amputation risk, but microvascular disease (MVD), defined as retino-, neuro- and/or nephropathy, was also associated with a 3.7-fold risk increase, and the combination of LEAD and MVD lead to a 22.7-fold increased risk. Importantly, MVD alone was associated with 15% of all below-the-knee amputations.Among the 13,885 patients with an ABI ≤0.8 or prior lower extremity revascularization (LER) randomized to ticagrelor vs. clopidogrel in the Examining Use of Ticagrelor in Peripheral Artery Disease (EUCLID) trial, the rate of acute limb ischaemia (ALI) requiring hospitalization was 0.8 per 100 patient-years, with no difference between treatment arms.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IZXNzPC9BdXRob3I+PFllYXI+MjAxOTwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA 18 ALI was strongly associated with subsequent MACE (adjusted hazard ratio [aHR] 1.4, 95%CI 1.0–2.1), all-cause mortality (aHR 3.3, 95%CI 2.4–4.6), and major amputation (aHR 34.2, 95%CI 9.7–20.8). Previous LER, baseline atrial fibrillation, and baseline ABI ≤0.60 were independent predictors of ALI. In this trial, a second analysis showed that 12.5% of patients experienced LER during the trial.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CYXVtZ2FydG5lcjwvQXV0aG9yPjxZZWFyPjIwMTg8L1ll
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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CYXVtZ2FydG5lcjwvQXV0aG9yPjxZZWFyPjIwMTg8L1ll
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ADDIN EN.CITE.DATA 19 Independent predictors of post-randomization LER were prior history and type of prior LER (p<0.0001), living in North America or Europe (p<0.0001), presence of limb symptoms at baseline (HR 1.3; 95%CI 1.2–1.5), diabetes (HR 1.3; 95%CI 1.1–1.4), and smoking (HR 1.2; 95%CI 1.1–1.4). Cardiac and limb events were numerically higher in patients undergoing surgical procedures, but surgical patients experienced fewer LERs after the index LER.A growing proportion of ALI hospitalizations occurs in cancer patients who experience arterial thromboembolism. In the population-based Surveillance Epidemiology and End Results-Medicare linked dataset, 374,331 patients ≥67 years with primary diagnosis of breast, lung, prostate, colorectal, bladder, uterine, pancreatic, gastric cancer, or non-Hodgkin lymphoma were identified. ADDIN EN.CITE <EndNote><Cite><Author>Navi</Author><Year>2019</Year><RecNum>4084</RecNum><DisplayText><style face="superscript">20</style></DisplayText><record><rec-number>4084</rec-number><foreign-keys><key app="EN" db-id="2eap02ffjxpzases2r750adgffdvf5xefvpp" timestamp="1569593653">4084</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Navi, B. B.</author><author>Reiner, A. S.</author><author>Kamel, H.</author><author>Iadecola, C.</author><author>Okin, P. M.</author><author>Tagawa, S. T.</author><author>Panageas, K. S.</author><author>DeAngelis, L. M.</author></authors></contributors><auth-address>Department of Neurology and.
Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY.
Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY.
Department of Medicine, Division of Cardiology, and.
Department of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY; and.
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY.</auth-address><titles><title>Arterial thromboembolic events preceding the diagnosis of cancer in older persons</title><secondary-title>Blood</secondary-title></titles><pages>781-789</pages><volume>133</volume><number>8</number><dates><year>2019</year><pub-dates><date>Feb 21</date></pub-dates></dates><isbn>1528-0020 (Electronic)
0006-4971 (Linking)</isbn><accession-num>30578253</accession-num><urls><related-urls><url> Risk of arterial thromboembolic events began to increase 150 days before date of cancer diagnosis in older patients and peaked in the 30 days before cancer diagnosis, when 0.62% of patients suffered an arterial thromboembolic event vs 0.11% in control subjects (odds ratio: 5.63; 95%CI 5.07-6.25).Lipid lowering is a key element of LEAD treatment PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BYm95YW5zPC9BdXRob3I+PFllYXI+MjAxODwvWWVhcj48
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ZT4A
ADDIN EN.CITE.DATA 21 After a median follow-up of 2.8 years, the 1,554 patients with atherosclerotic disease in 2 or 3 vascular beds (coronary, lower limb and/or cerebrovascular) showed a significantly larger absolute risk reduction with alirocumab, as compared to patients with isolated coronary artery disease (CAD). The absolute risk reduction regarding MACE was 1.9% (95%CI -2.4–6.2%) and 13.0% (95%CI -2.0–28.0%) for two and three vascular beds, respectively, while regarding all-cause mortality was 1.3% (95%CI -1.8–4.3%) and 16.2% (95%CI 5.5–26.8%), respectively. Another pillar of the medical treatment of LEAD is optimal control of arterial hypertension.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5XaWxsaWFtczwvQXV0aG9yPjxZZWFyPjIwMTg8L1llYXI+
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ADDIN EN.CITE.DATA 4, 22 A recent analysis from the Atherosclerosis Risk in Communities (ARIC) study evaluated the impact of different stages of hypertension on the development of LEAD. ADDIN EN.CITE <EndNote><Cite><Author>Lu</Author><Year>2019</Year><RecNum>4116</RecNum><DisplayText><style face="superscript">23</style></DisplayText><record><rec-number>4116</rec-number><foreign-keys><key app="EN" db-id="2eap02ffjxpzases2r750adgffdvf5xefvpp" timestamp="1570194405">4116</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lu, Y.</author><author>Ballew, S. H.</author><author>Tanaka, H.</author><author>Szklo, M.</author><author>Heiss, G.</author><author>Coresh, J.</author><author>Matsushita, K.</author></authors></contributors><auth-address>1 Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA. 2 Department of Kinesiology and Health Education, University of Texas at Austin, USA. 3 Department of Epidemiology, University of North Carolina at Chapel Hill Gillings School of Global Public Health, USA.</auth-address><titles><title>2017 ACC/AHA blood pressure classification and incident peripheral artery disease: The Atherosclerosis Risk in Communities (ARIC) Study</title><secondary-title>Eur J Prev Cardiol</secondary-title><short-title>2017 ACC/AHA blood pressure classification and incident peripheral artery disease: The Atherosclerosis Risk in Communities (ARIC) Study</short-title></titles><pages>2047487319865378</pages><edition>2019/08/01</edition><keywords><keyword>Blood pressure</keyword><keyword>critical limb ischemia</keyword><keyword>peripheral artery disease</keyword></keywords><dates><year>2019</year><pub-dates><date>Jul 30</date></pub-dates></dates><isbn>2047-4873</isbn><accession-num>31362534</accession-num><urls></urls><electronic-resource-num>10.1177/2047487319865378</electronic-resource-num><remote-database-provider>Nlm</remote-database-provider><language>eng</language></record></Cite></EndNote>23 During a median follow-up of 25.4 years, a systolic blood pressure (BP) ≥140 mmHg or diastolic BP ≥90 mmHg was associated with higher rate of incident LEAD diagnosis (HR 2.40; 95%CI 1.72–3.34), independent of the use of anti-hypertensive medications. Higher BP categories showed significant associations with incident LEAD starting from 120-129 mmHg for systolic BP and ≥90mmHg for diastolic BP. These data emphasise the need for BP control to prevent the development of LEAD.While supervised exercise training is a mainstay of the management of claudication,PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BYm95YW5zPC9BdXRob3I+PFllYXI+MjAxODwvWWVhcj48
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ADDIN EN.CITE.DATA 24 After 6 months, the 6‐minute walk distance improved only in the treadmill exercise group (36.1 m, 95%CI 13.9-58.3), but at 12 months neither treadmill nor resistance significantly differed from baseline or control (walking distance: +7.5 m and +6.1 m). These results highlight the need for long-term supervised exercise programs to maintain benefits. Additionally, a systematic review of 84 studies reported that alternative training modalities (circuit exercise, low-pain and pain-free walking, resistance training, upper/lower limb ergometry and pole striding) had significantly higher adherence and completion rates versus traditional exercise training (85.5% vs. 77.6%, and 86.6% vs. 80.8%, respectively). ADDIN EN.CITE <EndNote><Cite><Author>Lin</Author><Year>2019</Year><RecNum>4118</RecNum><DisplayText><style face="superscript">25</style></DisplayText><record><rec-number>4118</rec-number><foreign-keys><key app="EN" db-id="2eap02ffjxpzases2r750adgffdvf5xefvpp" timestamp="1570194405">4118</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lin, E.</author><author>Nguyen, C. H.</author><author>Thomas, S. G.</author></authors></contributors><auth-address>1 Training and Performance Laboratory, University of Toronto, Canada. 2 KITE, Toronto Rehab-University Health Network, Cardiovascular Prevention and Rehabilitation Program, Toronto, Canada.</auth-address><titles><title>Completion and adherence rates to exercise interventions in intermittent claudication: Traditional exercise versus alternative exercise - a systematic review</title><secondary-title>Eur J Prev Cardiol</secondary-title><short-title>Completion and adherence rates to exercise interventions in intermittent claudication: Traditional exercise versus alternative exercise - a systematic review</short-title></titles><pages>2047487319846997</pages><edition>2019/06/21</edition><keywords><keyword>Intermittent claudication</keyword><keyword>adherence</keyword><keyword>alternative</keyword><keyword>completion</keyword><keyword>exercise</keyword><keyword>peripheral arterial disease</keyword><keyword>systematic review</keyword><keyword>traditional</keyword></keywords><dates><year>2019</year><pub-dates><date>Jun 19</date></pub-dates></dates><isbn>2047-4873</isbn><accession-num>31216860</accession-num><urls></urls><electronic-resource-num>10.1177/2047487319846997</electronic-resource-num><remote-database-provider>Nlm</remote-database-provider><language>eng</language></record></Cite></EndNote>25 In lack of randomized controlled trials, a large gap in evidence regards the best revascularization strategy in chronic limb threatening ischaemia (CLTI). In a retrospective analysis, 16,800 patients with CLTI who had first surgical LER (36%) were compared to those with first endovascular LER (64%). ADDIN EN.CITE <EndNote><Cite><Author>Lin</Author><Year>2019</Year><RecNum>4119</RecNum><DisplayText><style face="superscript">26</style></DisplayText><record><rec-number>4119</rec-number><foreign-keys><key app="EN" db-id="2eap02ffjxpzases2r750adgffdvf5xefvpp" timestamp="1570194405">4119</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lin, J. H.</author><author>Brunson, A.</author><author>Romano, P. S.</author><author>Mell, M. W.</author><author>Humphries, M. D.</author></authors></contributors><auth-address>Division of Vascular Surgery (J.H.L., M.W.M., M.D.H.), University of California Davis Medical Center, Sacramento. Division of Hematology-Oncology (A.B.), University of California Davis Medical Center, Sacramento. Department of Internal Medicine (P.S.R.), University of California Davis Medical Center, Sacramento.</auth-address><titles><title>Endovascular-First Treatment Is Associated With Improved Amputation-Free Survival in Patients With Critical Limb Ischemia</title><secondary-title>Circ Cardiovasc Qual Outcomes</secondary-title><short-title>Endovascular-First Treatment Is Associated With Improved Amputation-Free Survival in Patients With Critical Limb Ischemia</short-title></titles><pages>e005273</pages><volume>12</volume><number>8</number><edition>2019/07/31</edition><keywords><keyword>aging</keyword><keyword>amputation</keyword><keyword>diabetes mellitus</keyword><keyword>heart failure</keyword><keyword>peripheral arterial disease</keyword><keyword>vascular surgical procedures</keyword></keywords><dates><year>2019</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>1941-7713</isbn><accession-num>31357888</accession-num><urls></urls><custom2>PMC6668925</custom2><custom6>NIHMS1531719</custom6><electronic-resource-num>10.1161/circoutcomes.118.005273</electronic-resource-num><remote-database-provider>Nlm</remote-database-provider><language>eng</language></record></Cite></EndNote>26 The endovascular group was younger, but suffered from more co-morbidities, including renal failure (36% vs. 24%), CAD (34% vs. 32%), heart failure (19% vs. 15%), and diabetes (65% vs. 58%; all p<0.05). 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ADDIN EN.CITE.DATA 27 The clinical use of paclitaxel-eluting devices was dramatically interrupted in November 2018 by the unexpected results of a meta-analysis including 28 RCTs with a total of 4,432 patients. ADDIN EN.CITE <EndNote><Cite><Author>Katsanos</Author><Year>2018</Year><RecNum>4121</RecNum><DisplayText><style face="superscript">28</style></DisplayText><record><rec-number>4121</rec-number><foreign-keys><key app="EN" db-id="2eap02ffjxpzases2r750adgffdvf5xefvpp" timestamp="1570194406">4121</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Katsanos, K.</author><author>Spiliopoulos, S.</author><author>Kitrou, P.</author><author>Krokidis, M.</author><author>Karnabatidis, D.</author></authors></contributors><auth-address>1 Patras University Hospital Rion Greece. 2 Attikon University Hospital Athens Greece. 3 Cambridge University Hospitals NHS Foundation Trust Cambridge UK.</auth-address><titles><title>Risk of Death Following Application of Paclitaxel-Coated Balloons and Stents in the Femoropopliteal Artery of the Leg: A Systematic Review and Meta-Analysis of Randomized Controlled Trials</title><secondary-title>J Am Heart Assoc</secondary-title><short-title>Risk of Death Following Application of Paclitaxel-Coated Balloons and Stents in the Femoropopliteal Artery of the Leg: A Systematic Review and Meta-Analysis of Randomized Controlled Trials</short-title></titles><pages>e011245</pages><volume>7</volume><number>24</number><edition>2018/12/19</edition><keywords><keyword>*balloon angioplasty</keyword><keyword>*paclitaxel</keyword><keyword>*paclitaxel-coated balloon</keyword><keyword>*paclitaxel-eluting stent</keyword></keywords><dates><year>2018</year><pub-dates><date>Dec 18</date></pub-dates></dates><isbn>2047-9980</isbn><accession-num>30561254</accession-num><urls><related-urls><url> The study described a 2-fold increase in all-cause mortality between 2 and 5 years of follow-up with paclitaxel-eluting DES/DCBs (HR 1.93, 95%CI 1.27-2.93), and a causal link between paclitaxel dose and mortality was hypothesized. These findings raised great concern, halted enrolment in RCTs on paclitaxel-eluting devices, and prompted a worldwide call for high-quality data collection and analysis. Most recently, a confutation of the above-mentioned study came from a large analysis of German health claims data, investigating long-term mortality with paclitaxel-eluting devices from 2007 until present in 64,771 patients undergoing 107,112 endovascular procedures. ADDIN EN.CITE <EndNote><Cite><Author>Freisinger</Author><Year>2019</Year><RecNum>4122</RecNum><DisplayText><style face="superscript">29</style></DisplayText><record><rec-number>4122</rec-number><foreign-keys><key app="EN" db-id="2eap02ffjxpzases2r750adgffdvf5xefvpp" timestamp="1570194406">4122</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Freisinger, E.</author><author>Koeppe, J.</author><author>Gerss, J.</author><author>Goerlich, D.</author><author>Malyar, NM.</author><author>Marschall, U.</author><author>Faldum, A.</author><author>Reinecke, H.</author></authors></contributors><titles><title>Mortality after use of paclitaxel-based devices in peripheral arteries: a real-world safety analysis</title><secondary-title>Eur Heart J</secondary-title></titles><volume>Epub ahead of print</volume><dates><year>2019</year></dates><urls></urls></record></Cite></EndNote>29 The use of paclitaxel-eluting devices was not associated with any signal of increased mortality up to 10 years of follow-up (Figure 3).Aortic diseaseA common challenge in the emergency room is to distinguish patients with symptoms suggestive of acute aortic syndrome (AAS) requiring a CT scan, from others. In a study of 839 patients attending the emergency room with suspected AAS, focused cardiac ultrasound, integrated into a strategy including clinical assessment and (for low-risk patients) D-Dimer testing, enabled the correct identification of all patients with aortic dissection (AD), although the sample size meant that the upper border of the 95% confidence interval was 1.2%.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5OYXplcmlhbjwvQXV0aG9yPjxZZWFyPjIwMTk8L1llYXI+
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ADDIN EN.CITE.DATA 31The term AAS has become commonplace, but constitutes a range of disease entities, which may not have the same pathophysiological mechanisms, responses to treatment or outlook. Among 1,012 patients, those with intra-mural haematoma (IMH) (n=340) had a much better short- and long-term mortality than those patients with AD (n=672).PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5BaG48L0F1dGhvcj48WWVhcj4yMDE5PC9ZZWFyPjxSZWNO
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ADDIN EN.CITE.DATA 32 The overall crude in-hospital mortality of type A AD was 15.0% with an adjusted hazard ratio (aHR) of 30.4; compared to type A IMH mortality of 8.0% with aHR of 4.85. Mortality of type B AD was 5.0%, with aHR?of 3.51, compared to type B IMH 1.5% with aHR of 1.00 (the reference group).Identifying patients with Marfan syndrome who are at particular risk of AD is currently based on the absolute diameter of the aorta, the growth rate, and the presence/absence of a family history of AD. A novel additional approach may be evaluation of the longitudinal strain of the proximal aorta by magnetic resonance imaging (MRI, Figure 4A).PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5HdWFsYTwvQXV0aG9yPjxZZWFyPjIwMTk8L1llYXI+PFJl
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ADDIN EN.CITE.DATA 33 Higher strain rates were associated with more rapid aortic expansion and appeared to predict clinical outcomes. If proximal aortic strain can be shown to be reproducible and if these findings are replicated in larger cohorts, this may help to inform the need for, and timing of, surgery in patients with Marfan syndrome.Pregnancy is associated with a spectacularly increased risk of aortic dissection (AD) in patients with Marfan syndrome compared to the normal population, particularly in the post-partum state. Oxytocin levels have been implicated in the pathogenesis of peri-partum AD in patients with Marfan syndrome. Antagonism of oxytocin signalling in a mouse model of Marfan syndrome protected pregnant mice from AD. ADDIN EN.CITE <EndNote><Cite><Author>Habashi</Author><Year>2019</Year><RecNum>4109</RecNum><DisplayText><style face="superscript">34</style></DisplayText><record><rec-number>4109</rec-number><foreign-keys><key app="EN" db-id="2eap02ffjxpzases2r750adgffdvf5xefvpp" timestamp="1569937789">4109</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Habashi, J. P.</author><author>MacFarlane, E. G.</author><author>Bagirzadeh, R.</author><author>Bowen, C.</author><author>Huso, N.</author><author>Chen, Y.</author><author>Bedja, D.</author><author>Creamer, T. J.</author><author>Rykiel, G.</author><author>Manning, M.</author><author>Huso, D.</author><author>Dietz, H. C.</author></authors></contributors><auth-address>Division of Pediatric Cardiology, Johns Hopkins University, Baltimore, MD 21287, USA.
Center for Medical Genetics, Johns Hopkins University, Baltimore, MD 21287, USA.
Division of Comparative Medicine, Johns Hopkins University, Baltimore, MD 21287, USA.
Department of Surgery, Johns Hopkins University, Baltimore, MD 21287, USA.
Department of Cancer Biology, University of Toledo College of Medicine, Toledo, OH 43614, USA.
Center for Medical Genetics, Johns Hopkins University, Baltimore, MD 21287, USA. hdietz@jhmi.edu.
Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.</auth-address><titles><title>Oxytocin antagonism prevents pregnancy-associated aortic dissection in a mouse model of Marfan syndrome</title><secondary-title>Sci Transl Med</secondary-title></titles><volume>11</volume><number>490</number><dates><year>2019</year><pub-dates><date>May 1</date></pub-dates></dates><isbn>1946-6242 (Electronic)
1946-6234 (Linking)</isbn><accession-num>31043570</accession-num><urls><related-urls><url> The implications of this finding require clinical studies.Aortic dissection is accompanied by complex flow patterns in the true and often the false lumen. Better understanding of the dynamics of this process may help to explain the widely differing behaviour of ADs seen over the long term. Recent insights into this process have become available from detailed study of flow patterns using echo Doppler. This approach allows the systematic identification of categorisation of abnormal flow patterns, and the potential for prognostic implications is discussed (Figure 4B). ADDIN EN.CITE <EndNote><Cite><Author>Desai</Author><Year>2019</Year><RecNum>4092</RecNum><DisplayText><style face="superscript">35</style></DisplayText><record><rec-number>4092</rec-number><foreign-keys><key app="EN" db-id="2eap02ffjxpzases2r750adgffdvf5xefvpp" timestamp="1569929744">4092</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Desai, D.</author><author>Miranda, W.</author><author>Connolly, H.</author><author>Tajik, A. J.</author></authors></contributors><auth-address>Aurora Cardiovascular Services, Aurora Sinai/Aurora St. Luke's Medical Centers, University of Wisconsin School of Medicine and Public Health, 2801 W. Kinnickinnic River Parkway, Ste 840, Milwaukee, WI, USA.
Department of Cardiovascular Medicine, Mayo Clinic, 200 First St. SW, Rochester, MN, USA.</auth-address><titles><title>Flow dynamics in the false lumen in distal aorta following surgery for type A aortic dissection</title><secondary-title>Eur Heart J</secondary-title></titles><pages>561</pages><volume>40</volume><number>6</number><dates><year>2019</year><pub-dates><date>Feb 7</date></pub-dates></dates><isbn>1522-9645 (Electronic)
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ADDIN EN.CITE.DATA 36 The odds of perioperative mortality were greater for open surgical repair and depended on the centre volume: high-volume centre, odds ratio (OR): 1.97 (95%CI 1.5 – 2.6); low-volume centre, OR: 3.62 (95%CI 2.9 – 4.5). The restricted mean survival time difference favoured TEVAR at 9 years,?-209?days (95%CI?-299 –?-120 days) for open surgical repair. Risk of re-intervention was lower for open surgical repair, hazard ratio: 0.40 (95%CI 0.34 – 0.60).In the last ESC guidelines on the management of aortic diseases,PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5FcmJlbDwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+PFJl
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ADDIN EN.CITE.DATA 31 both open surgery and endovascular aneurysm repair (EVAR) therapy received class I recommendation, based on several head-to-head trials enrolling patients with suitable anatomy for both options. While, in the short term, EVAR was associated with less mortality, this difference was gradually annihilated over time, while in turn, EVAR requested repeated (irradiating) imaging and re-interventions for endoleaks. The results of very long-term follow-up (14 years) of the Open Versus Endovascular Repair (OVER) trialPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MZWRlcmxlPC9BdXRob3I+PFllYXI+MjAxOTwvWWVhcj48
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ADDIN EN.CITE.DATA 37 are interesting in that they show no mortality or secondary procedure difference beyond the first years. These results support the recommendations made, although they contrast somehow with long-term results in other trials more in favour of open surgery. It is however noteworthy that most deaths in these patients were not aneurysm-related (only 2.7%, mostly post-operative), and that the first cause of death is cardiovascular, emphasizing the crucial necessity for maximal preventive measures in these patients. Last not least, significant evidence is still lacking in women as they constituted only for <10% of all participants.Cerebrovascular diseaseExcessive arterial pulsatility may contribute to cognitive decline and risk of dementia via damage to the fragile cerebral microcirculation. As part of the Whitehall II studyPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DaGllc2E8L0F1dGhvcj48WWVhcj4yMDE5PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA 38, peak forward-travelling compression wave intensity (FCWI) was assessed using Duplex ultrasound within the common carotid arteries in 3,191 individuals [mean age = 61 years; 75% male] and serial measures of cognitive function were taken at baseline and almost 10 years later. Higher FCWI at baseline was associated with accelerated cognitive decline during follow-up and this association was largely driven by cognitive changes in individuals with the highest FCWI. Compared to other participants, this group was approximately 50% more likely to exhibit cognitive decline, even after adjustments for multiple potential confounding factors. Patients with high stroke risk and atrial fibrillation who are unsuitable to oral anticoagulants (OACs) require other stroke prevention strategies. The multicenter, non-randomized, first-in-human clinical Carotid Artery Implant for Trapping Upstream Emboli for Preventing Stroke in Atrial Fibrillation Patients (CAPTURE) trial sought to determine the feasibility and safety of a novel permanent coil filter directly placed into both common carotid arteries designed to capture emboli >1.4 mm in diameter.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5SZWRkeTwvQXV0aG9yPjxZZWFyPjIwMTk8L1llYXI+PFJl
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ADDIN EN.CITE.DATA 39 Patients received aspirin/clopidogrel for 3 months, and aspirin thereafter. In 3 centres, 25 patients with atrial fibrillation, with CHA2DS2-VASc ≥2, who were unsuitable for OACs and had no carotid stenosis >30% were enrolled. The procedure success was 92%; 1 patient had unilateral deployment. There were no device/procedure-related major adverse events. After 6-month mean follow-up, asymptomatic thrombi were detected in 4 patients (1 bilateral, 4 unilateral) and the thrombi dissolved with subcutaneous heparin. Permanent carotid filter placement for stroke prophylaxis seems technically feasible and safe. Larger studies and a comparison with the use of left atrial appendage occluders are necessary.Venous thromboembolism (VTE)In 2019, the ESC issued updated guidelines for management of patients with acute pulmonary embolism (PE).PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Lb25zdGFudGluaWRlczwvQXV0aG9yPjxZZWFyPjIwMTk8
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ADDIN EN.CITE.DATA 40 Key points include use of age-adjusted D-dimer cut-off in preclinical risk assessment. Furthermore, categorization of PE events in “provoked” and “unprovoked” is no longer suggested. Rather, occurrence of index event in presence of “reversible risk factor,” or in absence of any “identifiable risk factor” is suggested for patient stratification and guidance of treatment duration. For the first time, direct oral anti-coagulants (DOACs) are recommended over vitamin K antagonists for PE treatment in eligible patients as for patients with atrial fibrillation. A reduced dose of apixaban or rivaroxaban for extended anticoagulation should be considered after the first 6 months of treatment. Edoxaban or rivaroxaban should be considered as an alternative to low molecular weight heparin in patients with non-gastrointestinal cancer who experience VTE. A new recommendation (class IIa, level A) proposes that carefully selected, low-risk PE patients should be considered for early discharge and home treatment, as long as proper outpatient care and anticoagulant therapy are possible (Figure 5). A recent prospective multicentre single-arm trial further corroborates this recommendation. Low-risk PE patients (no HESTIA criteria present, and absence of right ventricle enlargement/dysfunction) were early discharged (maximum of 2 nights in hospital) for home treatment with rivaroxaban. The study was prematurely terminated because of low symptomatic VTE recurrence and PE-related death rates (0.6%; one-sided upper 99.6% CI 2.1%), and low bleeding episodes (1.2%) at 3-months from diagnosis.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CYXJjbzwvQXV0aG9yPjxZZWFyPjIwMTk8L1llYXI+PFJl
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ADDIN EN.CITE.DATA 41 Careful selection of low-risk PE patients is key in successful home-treatment; in this regard, clinical severity scores alone may not be sufficient to identify such low-risk group especially with regard to subclinical RV dysfunction exclusion. Therefore, combining right ventricle assessment to clinical criteria further allow proper risk stratification as recently suggested by Barco et al..PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CYXJjbzwvQXV0aG9yPjxZZWFyPjIwMTk8L1llYXI+PFJl
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ADDIN EN.CITE.DATA 42The diagnosis of PE during pregnancy is challenging with wide pregnancy-related and PE suspicion symptoms overlap. Overall PE prevalence is however low thus exposing patients to unnecessary imaging tests. The 2019 ESC PE guidelines propose a dedicated diagnostic algorithm for suspected PE in pregnancy using stratification tools based on clinical presentation, D-Dimer testing, and compression ultrasonography of lower extremities. The pregnancy adapted YEARS algorithm, which takes into account these three parameters, was recently shown to safely rule out PE across all trimesters of pregnancy avoiding a significant number of imaging tests.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj52YW4gZGVyIFBvbDwvQXV0aG9yPjxZZWFyPjIwMTk8L1ll
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ADDIN EN.CITE.DATA 46, 47PerspectivesAll these new and exciting scientific data published in 2019 shed more light on the subtle, yet important, differences between atherosclerosis affecting the different peripheral vascular territories that have already started to change our clinical practice. The year 2020 is highly awaited for vascular specialists, with the completion of the Vascular Outcomes study of ASA along with rivaroxaban in endovascular or surgical limb revascularization for peripheral artery disease (VOYAGER PAD) study, that currently evaluates the efficacy and safety of bi-daily rivaroxaban at 2.5 mg in reducing the risk of major thrombotic vascular events in subjects with symptomatic peripheral artery disease undergoing peripheral revascularization procedures of the lower extremities (NCT02504216). Also a number trial data will become available addressing the safety of paclitaxel coated stents and balloons that will hopefully let us rest a peace again when using these devices. In the field of VTE, data from the CARAVAGGIO study (NCT03045406), comparing apixaban to dalteparin, for the treatment of acute VTE in cancer patients are awaited.Conflict of interestDr. Heiss reports research grants from Deutsche Forschungsgemeinschaft, Mitsubishi Cleansui, Wild Blueberry Association of North America, National Processed Raspberry Council, University of Surrey, Philips, Cranberry Institute, Rheacell; personal fees from Bayer, Novo Nordisk, Profil Institute outside the submitted work. Dr. Belch reports grants and personal fees from Bayer and Rexgenero, personal fees from Amgen, outside the submitted work. Dr. De Carlo reports personal fees from Bayer and Sanofi, outside the submitted work. Dr. Reinecke reports grants from Bard, Biotronik, Bayer, personal fees from Diaplan, MedUpdate, Daichi Sankyo, and NeoVasc, personal fees and other support from NovoNordisk ; other support from Bristol Myers Squibb and Pfizer; grants, personal fees, and other support from Pluristem outside the submitted work and is the senior author of a manuscript which is presented/reviewed in this article. Dr. Pitcher reports personal fees from Actelion Pharmaceuticals Ltd and from Bristol-Myers Squibb Pharmaceuticals Limited, outside the submitted work. Dr. Aboyans declares personal fees from Amgen, Bayer, Novartis, NovoNordisk, BMS/Pfizer alliance and Sanofi, as speaker or advisor. Dr. Mazzolai and Dr. Baumgartner have nothing to disclose. References ADDIN EN.REFLIST 1.De Carlo M, Mazzolai L, Bossone E, Brodmann M, Micari A, Muiesan ML, Ricco JB, Stabile E, Agnelli G, Aboyans V, Aorta ESCWGo, Peripheral Vascular D. The year in cardiology 2016: peripheral circulation. 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A translational model for therapeutic target discovery in radiation injury. Clinical event: Increased risk for cardiovascular disease at the site of previous radiotherapy. Human biobank: Gene expression array of paired (irradiated and non-irradiated) human arteries retrieved at the same time during microvascular autologous free tissue transfers for reconstructive cancer surgery. Radiotherapy induces a sustained inflammatory response in human arteries. Animal model: Establishment of an animal model of local irradiation with similar inflammatory patterns as observed in the human biobank. Treatment: Treatment with anakinra (IL-1R antagonist) reduced radiation-induced vascular inflammation in our Apoe-/- mouse model of local irradiation. Ctl, non-irradiated; Ccl2/Mcp-1, chemokine (C-C motif) ligand2/monocyte chemoattractant protein-1; DAMP, dam- age associated molecular pattern; IL-1R, interleukin-1 receptor; ROS, reactive oxygen species; VCAM1, vascular cell adhesion molecule-1; XRT, irradiated.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DaHJpc3RlcnNkb3R0aXI8L0F1dGhvcj48WWVhcj4yMDE5
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ADDIN EN.CITE.DATA 8Figure 2. (A) The combined effect of smoking over lifetime and intensity of drinking on arterial stiffness. The combination of high-intensity drinking with lifetime smoking exposure is shown. Pulse wave velocity measurements are expressed as mean values and 95% confidences intervals around the mean on the x-axis. The participants who had ?high‘ drinking intensity and ?high‘ smoking exposure had the highest pulse wave velocity compared with the ?low lifetime smoking exposure‘ and ?low drinking intensity‘. * p<0.05. (B) Unhealthy behaviours in adolescents (drinking and cigarette smoking) are associated with increased carotid to femoral pulse wave velocity (stiffer arteries) and accelerated atherosclerosis. Stopping smoking in adolescents and reducing binge drinking has potential for reversibility of arterial stiffening.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DaGFyYWtpZGE8L0F1dGhvcj48WWVhcj4yMDE5PC9ZZWFy
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ADDIN EN.CITE.DATA 13Figure 3. Long-term mortality after use of paclitaxel-based devices in LEAD. A multivariable Cox regression analysis was developed including numerous comorbidities and all devices that were applied in each treated patient. For each distinct device, the analysis accounted for its type (DES, DCB, BMS, and POBA) and application date. The model took also concern of any non-constant time-dependent effects: thus, a potentially detrimental effect of DED in the later course of time would become verifiable despite a potentially beneficial effect in the early years, or also any potential aggregation of subsequently applied devices. Combined HRs for any scenario including multiple devices that were applied various years ago can be determined as the product of elementary HRs. In summary, there was no signal that paclitaxel DCBs or DES were associated with increased mortality up to 11 years of Follow-up. ADDIN EN.CITE <EndNote><Cite><Author>Freisinger</Author><Year>2019</Year><RecNum>4122</RecNum><DisplayText><style face="superscript">29</style></DisplayText><record><rec-number>4122</rec-number><foreign-keys><key app="EN" db-id="2eap02ffjxpzases2r750adgffdvf5xefvpp" timestamp="1570194406">4122</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Freisinger, E.</author><author>Koeppe, J.</author><author>Gerss, J.</author><author>Goerlich, D.</author><author>Malyar, NM.</author><author>Marschall, U.</author><author>Faldum, A.</author><author>Reinecke, H.</author></authors></contributors><titles><title>Mortality after use of paclitaxel-based devices in peripheral arteries: a real-world safety analysis</title><secondary-title>Eur Heart J</secondary-title></titles><volume>Epub ahead of print</volume><dates><year>2019</year></dates><urls></urls></record></Cite></EndNote>29 Figure 4. New imaging techniques for risk stratification in patients with aortic diseases (A) Methods for proximal longitudinal strain measurement by MRI,PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5HdWFsYTwvQXV0aG9yPjxZZWFyPjIwMTk8L1llYXI+PFJl
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ADDIN EN.CITE.DATA 33 (B) Doppler approach to flow in aortic dissection ADDIN EN.CITE <EndNote><Cite><Author>Desai</Author><Year>2019</Year><RecNum>4092</RecNum><DisplayText><style face="superscript">35</style></DisplayText><record><rec-number>4092</rec-number><foreign-keys><key app="EN" db-id="2eap02ffjxpzases2r750adgffdvf5xefvpp" timestamp="1569929744">4092</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Desai, D.</author><author>Miranda, W.</author><author>Connolly, H.</author><author>Tajik, A. J.</author></authors></contributors><auth-address>Aurora Cardiovascular Services, Aurora Sinai/Aurora St. Luke's Medical Centers, University of Wisconsin School of Medicine and Public Health, 2801 W. Kinnickinnic River Parkway, Ste 840, Milwaukee, WI, USA.
Department of Cardiovascular Medicine, Mayo Clinic, 200 First St. SW, Rochester, MN, USA.</auth-address><titles><title>Flow dynamics in the false lumen in distal aorta following surgery for type A aortic dissection</title><secondary-title>Eur Heart J</secondary-title></titles><pages>561</pages><volume>40</volume><number>6</number><dates><year>2019</year><pub-dates><date>Feb 7</date></pub-dates></dates><isbn>1522-9645 (Electronic)
0195-668X (Linking)</isbn><accession-num>30085046</accession-num><urls><related-urls><url> 5. Pulmonary embolism management algorithm. ADDIN EN.CITE <EndNote><Cite><Author>Torbicki</Author><Year>2019</Year><RecNum>4097</RecNum><DisplayText><style face="superscript">48</style></DisplayText><record><rec-number>4097</rec-number><foreign-keys><key app="EN" db-id="2eap02ffjxpzases2r750adgffdvf5xefvpp" timestamp="1569936726">4097</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Torbicki, A.</author></authors></contributors><auth-address>Department of Pulmonary Circulation, Thromboembolic Diseases and Cardiology, Center for Postgraduate Medical Education, ECZ-Otwock, Otwock, Poland.</auth-address><titles><title>Assessing the severity of acute pulmonary embolism: back to the future?</title><secondary-title>Eur Heart J</secondary-title></titles><pages>911-913</pages><volume>40</volume><number>11</number><dates><year>2019</year><pub-dates><date>Mar 14</date></pub-dates></dates><isbn>1522-9645 (Electronic)
0195-668X (Linking)</isbn><accession-num>30726904</accession-num><urls><related-urls><url> Figure 1Figure 2Figure 3Figure 4 Figure 5 ................
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