DISSECTING FUNCTIONAL IMPAIRMENT IN HYPERTROPHIC ...



DISSECTING FUNCTIONAL IMPAIRMENT IN HYPERTROPHIC CARDIOMYOPATHY BY

DYNAMIC ASSESSMENT OF DIASTOLIC RESERVE AND OUTFLOW OBSTRUCTION:

A COMBINED CARDIOPULMONARY-ECHOCARDIOGRAPHIC STUDY

Federica Rea ,Elisabetta Zacharaa, Andrea Avellaa, Pasquale Barattaa, Michele di Maurob,

Massimo Uguccionia, Iacopo Olivottoc

aCardiology Division, Cardiac Arrhythmia Center and Cardiomyopathies Unit, St.Camillo-Forlanini Hospital, Rome, Italy. bCardiology, University of L’Aquila, Italy. cReferral Center for Cardiomyopathies,Careggi University Hospital Florence, Italy

Running title: Diastolic reserve and VO2 max in HCM

Corresponding Author: Federica Re, MD, Cardiology Division, Cardiac Arrhythmia Center and Cardiomyopathies Unit, St.Camillo-Forlanini Hospital, Via Portuense 332, 00149 Rome, Italy.

Tel/fax: +39-06-58704539

E-mail address: re.federica77@

Word count: 4525

ABSTRACT

Background: Exercise limitation in patients with hypertrophic cardiomyopathy (HCM) is often attributed to left ventricular outflow tract (LVOT) obstruction and diastolic impairment. However, these features assessed at rest fail to predict performance. In order to evaluate their variations and interplay during effort in HCM, we performed real-time echocardiographic assessment of diastolic function and outflow obstruction during cardiopulmonary test (CPX).

Methods: We included 197 consecutive HCM patients (mean age 45±15 years, 129 males), undergoing CPX. Mitral inflow, annular velocities and diastolic dysfunction (DD) grade were measured at baseline and at peak exercise. Oxygen consumption (VO2 max) values < 75% of maximum predicted were considered abnormal.

Results: One hundred-seven patients (54%) had DD grade II-III at rest (Rest DD), whereas 40 (20%) showed preserved diastolic function (grade 0/I) both at rest and on effort (No DD). The remaining 50 patients (25%) had a grade 0/I pattern at rest but exhibited impaired diastolic reserve on exercise (Latent DD). Latent DD was associated with higher prevalence of patients with VO2 13 or septal E/e’ ratio ≥ 15 and lateral E/e’ ratio > 12.18 Subjects were required to meet two Doppler criteria for moderate or severe DD to be so classified. Mitral regurgitation was evaluated with semiquantitative method and graded as following: none or trivial (0), mild (1), moderate (2), and severe (3).19

Exercise echocardiography and cardiopulmonary test

After the baseline echocardiogram was obtained, symptom-limited CPX was performed on a bicycle ergometer in the upright position. To facilitate simultaneous echocardiographic assessment, we limited the ramp steep to a maximum of 10 watts per minute. All patients were encouraged to perform to exhaustion. Oxygen saturation monitoring was performed by pulse oximetry. Twelve-lead ECG, blood pressure and heart rate were recorded at rest and at each exercise step. An abnormal blood pressure response was defined by either a failure of systolic blood pressure to rise > 20 mm Hg or any fall in systolic blood pressure during exercise.20

Cardiopulmonary variables, oxygen uptake (VO2 ml/min) and carbon dioxide production (CO2 ml/min), were continuously measured with breath-by-breath analysis. Anaerobic threshold (AT) was determined by the analysis of ventilatory equivalents. Exercise was considered adequate if the respiratory gas exchange ratio (RER) exceeded the value of 1.0. Peak oxygen uptake (peak VO2) was defined as the highest VO2 level achieved during the final 30 seconds of the exercise test. The peak VO2 was expressed both as an absolute value relative to body weight (ml/kg/min) and as a percentage of the maximum predicted value (peak VO2%). Values ................
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