High-Intensity Interval Training in Patients With Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Small studies have suggested that high-intensity interval training (HIIT) is superior to moderate continuous training (MCT) in reversing cardiac remodeling and increasing aerobic capacity in patients with heart failure with reduced ejection fraction. The present multicenter trial compared 12 weeks of supervised interventions of HIIT, MCT, or a recommendation of regular exercise (RRE). METHODS: Two hundred sixty-one patients with left ventricular ejection fraction ≤35% and New York Heart Association class II to III were randomly assigned to HIIT at 90% to 95% of maximal heart rate, MCT at 60% to 70% of maximal heart rate, or RRE. Thereafter, patients were encouraged to continue exercising on their own. Clinical assessments were performed at baseline, after the intervention, and at follow-up after 52 weeks. Primary end point was a between-group comparison of change in left ventricular end-diastolic diameter from baseline to 12 weeks. RESULTS: Groups did not differ in age (median, 60 years), sex (19% women), ischemic pathogenesis (59%), or medication. Change in left ventricular end-diastolic diameter from baseline to 12 weeks was not different between HIIT and MCT (P=0.45); left ventricular end-diastolic diameter changes compared with RRE were -2.8 mm (-5.2 to -0.4 mm; P=0.02) in HIIT and -1.2 mm (-3.6 to 1.2 mm; P=0.34) in MCT. There was also no difference between HIIT and MCT in peak oxygen uptake (P=0.70), but both were superior to RRE. However, none of these changes was maintained at follow-up after 52 weeks. Serious adverse events were not statistically different during supervised intervention or at follow-up at 52 weeks (HIIT, 39%; MCT, 25%; RRE, 34%; P=0.16). Training records showed that 51% of patients exercised below prescribed target during supervised HIIT and 80% above target in MCT. CONCLUSIONS: HIIT was not superior to MCT in changing left ventricular remodeling or aerobic capacity, and its feasibility remains unresolved in patients with heart failure. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00917046.

Age-related decline in mitral peak diastolic velocities is unaffected in well-trained runners.

OBJECTIVES: We examined whether diastolic left ventricular function in young and senior lifelong endurance runners was significantly different from that in sedentary age-matched controls, and whether lifelong endurance running appears to modify the age-related decline in diastolic left ventricular function. DESIGN: The study comprised 17 senior athletes (age: 59-75 years, running distance: 30-70 km/week), 10 young athletes (age: 20-36 years, matched for running distance), and 11 senior and 12 young weight-matched sedentary controls. Peak early (E) and late (A) mitral inflow and early (e') and late (a') diastolic and systolic (s') annular longitudinal tissue Doppler velocities were measured by echocardiography during four stages (rest, supine bike exercise at 30% and 60% of maximal workload, and recovery). RESULTS: The athletes had marked cardiac remodeling, while overall differences in mitral inflow and annular tissue Doppler velocities during rest and exercise were more associated with age than with training status. The senior participants had lower E/A at rest, overall lower E, e' and s', and greater E/e' compared to the young participants (all values of P < 0.05). The athletes had greater E/A (P = 0.004), but tissue Doppler velocities were not different from those of the controls. CONCLUSIONS: Lifelong endurance running was not found to be associated with major attenuation of the age-related decline in diastolic function at rest or during exercise.

Interval training does not modulate diastolic function in heart transplant recipients.

OBJECTIVES: This study investigates the effect of aerobic interval training on diastolic function at rest and during exercise in stable heart transplant (HTx) recipients. DESIGN: Twenty-three stable HTx recipients (74% males, mean age 50 ± 14.9 years) were recruited to a training programme. Intervention was 8 weeks intensive training or control in a randomized controlled design. RESULTS: At baseline, participants had normal or mild diastolic dysfunction at rest. During exercise, mean E/e' increased from 9.0 (± 2.8) to 12.8 (± 7.7) (p = 0.09), E/A increased from 2.1 (± 0.6) to 2.6 (± 0.7) (p = 0.02), and deceleration time decreased by over 50 ms, all markers of increased filling pressure. There were no correlations between diastolic function and VO 2 peak at baseline. After intervention VO 2 peak increased from 23.9 (± 4.5) to 28.3(± 6) ml/kg/min in the training group (difference between groups p = 0.0018). No consistent pattern of improvement in diastolic function at rest or during exercise was seen. CONCLUSION: The study does not support a role of diastolic dysfunction in the limited exercise capacity of HTx recipients and suggests that in these patients peripheral factors are of greater importance.

Coronary flow reserve predicts cardiopulmonary fitness in patients with coronary artery disease independently of systolic and diastolic function.

AIMS: Despite revascularization and optimal medical treatment, patients with coronary artery disease (CAD) have reduced exercise capacity. In the absence of coronary artery stenosis, coronary flow reserve (CFR) is a measure of coronary microvascular function, and a marker of future poor outcome in CAD patients. The aim of this study was to examine the relationship among CFR, systolic and diastolic function, peripheral vascular function, and cardiopulmonary fitness in CAD patients. METHODS AND RESULTS: Forty patients with median left ventricular ejection fraction (LVEF) 49 (interquartile 46-55) with documented CAD without significant left anterior descending artery (LAD) stenosis underwent cardiorespiratory exercise test with measurement of VO2 peak, digital measurement of endothelial function and arterial stiffness, and an echocardiography with measurement of LVEF using the biplane Simpson model, mitral early (E) and late (A) inflow velocities, and tissue Doppler diastolic (e') and systolic (s') velocities. Peak coronary flow velocity (CFV) was measured in the LAD using pulse-wave Doppler. CFR was calculated as the ratio between peak CFV at rest and during vasodilator stress. Median CFR was 2.22 (1.90-2.62) and VO2 peak was 21.8 (17.6-25.5). VO2 peak correlated significantly with CFR (r = 0.57, P < 0.001), E/e' (r = -0.35, P = 0.04), and s' (r = 0.41, P = 0.01) and with LVEF (r = 0.35, P = 0.03). CFR remained independently associated with VO2 peak after adjustment for systolic and diastolic function. CONCLUSIONS: Coronary flow reserve measured noninvasively predicts cardiopulmonary fitness independently of resting systolic and diastolic function in CAD patients, indicating that cardiac output during maximal exercise is dependent on the ability of the coronary circulation to adapt to the higher metabolic demands of the myocardium.

Insulin resistance and exercise tolerance in heart failure patients: linkage to coronary flow reserve and peripheral vascular function.

BACKGROUND: Insulin resistance has been linked to exercise intolerance in heart failure patients. The aim of this study was to assess the potential role of coronary flow reserve (CFR), endothelial function and arterial stiffness in explaining this linkage. METHODS: 39 patients with LVEF < 35% (median LV ejection fraction (LVEF) 31 (interquartile range (IQ) 26-34), 23/39 of ischemic origin) underwent echocardiography with measurement of CFR. Peak coronary flow velocity (CFV) was measured in the LAD and coronary flow reserve was calculated as the ratio between CFV at rest and during a 2 minutes adenosine infusion. All patients performed a maximal symptom limited exercise test with measurement of peak oxygen uptake (VO(2)peak), digital measurement of endothelial function and arterial stiffness (augmentation index), dual X-ray absorptiometry scan (DEXA) for body composition and insulin sensitivity by a 2 hr hyperinsulinemic (40 mU/min/m(2)) isoglycemic clamp. RESULTS: Fat free mass adjusted insulin sensitivity was significantly correlated to VO(2)peak (r = 0.43, p = 0.007). Median CFR was 1.77 (IQ 1.26-2.42) and was correlated to insulin sensitivity (r 0.43, p = 0.008). CFR (r = 0.48, p = 0.002), and arterial stiffness (r = -0.35, p = 0.04) were correlated to VO(2)peak whereas endothelial function and LVEF were not (all p > 0.15). In multivariable linear regression adjusting for age, CFR remained independently associated with VO2peak (standardized coefficient (SC) 1.98, p = 0.05) whereas insulin sensitivity (SC 1.75, p = 0.09) and arterial stiffness (SC -1.17, p = 0.29) were no longer associated with VO2peak. CONCLUSIONS: The study confirms that insulin resistance is associated with exercise intolerance in heart failure patients and suggests that this is partly through reduced CFR. This is the first study to our knowledge that shows an association between CFR and exercise capacity in heart failure patients and links the relationship between insulin resistance and exercise capacity to CFR.

Coronary flow reserve as a link between diastolic and systolic function and exercise capacity in heart failure.

AIMS: In heart failure, a reduced exercise capacity is the prevailing symptom and an important prognostic marker of future outcome. The purpose of the study was to assess the relation of coronary flow reserve (CFR) to diastolic and systolic function in heart failure and to determine which are the limiting factors for exercise capacity. METHODS AND RESULTS: Forty-seven patients with left ventricular ejection fraction (LVEF) <35 [median LVEF 31 (inter-quartile range 26-34)] underwent cardiorespiratory exercise test with measurement of VO2 peak, a dual X-ray absorptiometry scan for body composition, and a full echocardiography with measurement of LVEF using the biplane Simpson model, mitral inflow velocities, and pulsed wave tissue Doppler. Peak coronary flow velocity (CFV) was measured in the LAD, using pulsed-wave Doppler. CFR was calculated as the ratio between peak CFV at rest and during 2 min of adenosine stress. Fat-free-mass-adjusted VO2 peak correlated significantly with CFR (r = 0.48, P = 0.002), E/e' (r = -0.35, P = 0.02), and s' (r = 0.45, P = 0.001) but not with LVEF (r = 0.23, P = 0.11). CFR correlated significantly with E/e' (r = -0.46, P = 0.003) and s' (r = 0.36, P = 0.02), but not with LVEF (r = 0.18, P = 0.26). When adjusting for CFR in a multivariable linear model, s' but not E/e' remained independently associated with VO2 peak. CONCLUSION: In this group of heart failure patients, VO2 peak was correlated with CFR, E/e', and s' but not with traditional measures of systolic function. CFR remained associated with VO2 peak independently of diastolic and systolic function and is likely to be a limiting factor in functional capacity of heart failure patients.