ABC | Volume 111, Nº5, November 2018

Original Article Lima et al High-intensity interval training and heart failure Arq Bras Cardiol. 2018; 111(5):699-707 Methods Study design and patients This before-and-after (quasi-experimental) study was conducted between June 2014 and November 2015. Nineteen patients with HFpEF, according to the European Society of Cardiology criteria, 25 were sequentially recruited in an outpatient cardiology clinic of a tertiary hospital in southern Brazil. Eligibility criteria were presence of signs and symptoms of heart failure, preserved ejection fraction (> 50%), diastolic dysfunction (left ventricular end-diastolic volume index < 97 mL/m 2 ) with increased filling pressure (E/e’ > 8), and in the case of E/e’ < 15, at least one diagnostic criterion for HFpEF, according to the abovementioned document. Age between 40–75 years, New York Heart Association (NYHA) functional class I to III, and clinical stability under optimal drug therapy in previous 3 months, was also considered criteria for eligibility. Patients with severe lung disease, moderate‑to‑severe valvular disease and peripheral arterial disease were excluded. Similarly, autonomic neuropathy, unstable angina, a history of complex arrhythmias induced by stress, patients with implantable cardiac electronic devices and those with cognitive and/or limiting musculoskeletal conditions, were excluded. Firstly, patients underwent a Doppler echocardiography with color flow mapping to confirm the diagnosis criteria for HFpEF. Then, a maximal cardiopulmonary exercise testing was performed to assess ventilatory thresholds and peak oxygen consumption, as well as heart rate response to exercise. Up to 14 days after the cardiopulmonary exercise testing, brachial artery diameter, flow-mediated dilation (FMD) and endothelium-independent dilation were assessed immediately before and 30 minutes after a HIIT session. In the same experimental session, BP and heart rate were measured at two different moments before and after exercise as described below. Measurements and instruments Patients’ characteristics at baseline Demographic and clinical data were collected on the first day through a questionnaire and verified in the medical records of each patient. Anthropometric data were collected at the time the questionnaire was completed. Transthoracic echocardiogram All echocardiographic examinations were performed using equipment Envisor C HD or HD 11 (Philips, USA) with a standard multifrequency sectorial transducer by a trained cardiologist. Images were acquired following a standardized protocol, following recommendations present in the current guidelines. 25,26 Cine loops and static images of 3 consecutive beats were recorded on standard 2D, M-mode, Doppler and tissue Doppler echocardiographic views. Left ventricular ejection fraction was calculated using the Teichholz formula from the parasternal long-axis view. For patients with regional wall motion abnormalities, the Simpson rule was used to calculate the ejection fraction. Left atrium volume was measured at ventricular systole, just before mitral valve opening, and calculated from apical 4‑and 2-chamber views using the biplane method of disks. Left ventricular diastolic function was evaluated with transmitral pulsed Doppler (peak E velocity, peak A velocity, E/A ratio and deceleration time) and mitral annulus tissue Doppler velocity (early diastolic velocity – e’, late diastolic velocity – a’). Cardiopulmonary exercise test The test was performed on a treadmill (General Electric T-2100, GEHealthcare,Waukesha, USA), and breath‑by‑breath expired gas analysis was carried out using a Cortex Metalyzer 3B system (Cortex Medical, Leipzig, Germany). Heart rate was monitored with a 12-lead electrocardiograph (Nihon Kohden Corporation, Tokyo, Japan), with electrode placement as described by Mason and Likar. 27 BP was measured with a sphygmomanometer (PA 2001, P.A. MED, São Paulo, Brazil) every 3 minutes during the test and also at the physician’s discretion. All tests were performed in the morning, with room temperature between 18 and 22°C and relative humidity around 60%, and they were conducted always by the same researcher (ADS), a cardiologist with expertise in cardiopulmonary exercise testing, certified by the Department of Exercise Testing and Cardiovascular Rehabilitation of the Brazilian Society of Cardiology. An individualized ramp protocol was used as described elsewhere in this study. 28 Tests were considered maximal when the respiratory quotient (R) was equal to or higher than 1.10. Blood pressure BP was measured with a digital device (G-Tech MA100, Shenzen, China) at four different points in time: 1) pre- assessment of endothelial function (after 15 minutes seating at rest); 2) immediately before HIIT session; 3) 5 minutes after HIIT session; 4) 30 minutes after HIIT session. Endothelial function Patients were instructed not to do any type of exercise, not to smoke, and not to dear or drink any caffeine or alcohol for 24 hours before the evaluation. The evaluation started after 15 minutes of seated rest in a roomwith temperature between 18 and 22ºC. Patients stood in the supine position with their left arm positioned comfortably. Noninvasive measurements of endothelial function were performed using a two-dimensional Philips EnVisor Ultrasound system (Philips, USA) with an electrocardiogram module and a high-frequency (7-12 MHz) vascular transducer. An image of the brachial artery was obtained 2-5 cm from the antecubital fossa on a longitudinal plane. Artery diameter was manually measured from the anterior and posterior intimal layer. Visual inspection of single frames was performed and calipers were placed at discrete points along the long axis of the B-mode image, when means were calculated. 700

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