Patients with isolated DHF have similar though not as severe pathophysiologic characteristics compared with patients with typical SHF, including severely reduced exercise capacity, neuroendocrine activation, and impaired quality of life.

Importance More than 80% of patients with heart failure with preserved ejection fraction (HFPEF), the most common form of HF among older persons, are overweight/obese. Exercise intolerance is the primary symptom of chronic HFPEF and a major determinant of reduced quality-of-life (QOL). Objective To determine whether caloric restriction (Diet), or aerobic exercise training (Exercise), improves exercise capacity and QOL in obese older HFPEF patients. Design Randomized, attention-controlled, 2x2 factorial trial conducted from February 2009 November 2014. Setting Urban academic medical center. Participants 100 older (67±5 years) obese (BMI=39.3±5.6kg/m2) women (n=81) and men (n=19) with chronic, stable HFPEF enrolled from 577 patients initially screened (366 excluded by inclusion / exclusion criteria, 31 for other reasons, 80 declined participation). Twenty-six participants were randomized to Exercise alone, 24 to Diet alone, 25 to Diet+Exercise, and 25 to Control; 92 completed the trial. Interventions 20 weeks of Diet and/or Exercise; Attention Control consisted of telephone calls every 2 weeks. Main Outcomes and Measures Exercise capacity measured as peak oxygen consumption (VO2, ml/kg/min; primary outcome) and QOL measured by the Minnesota Living with HF Questionnaire (MLHF) total score (co-primary outcome; score range: 0–105, higher scores indicate worse HF-related QOL). Results By main effects analysis, peak VO2 was increased significantly by both interventions: Exercise main effect 1.2 ml/kg/min (95%CI: 0.7,1.7; p<0.001); Diet main effect 1.3 ml/kg/min (95%CI: 0.8,1.8; p<0.001). The combination of Exercise+Diet was additive (complementary) for peak VO2 (joint effect 2.5 ml/kg/min). The change in MLHF total score was non-significant with Exercise (main effect −1 unit; 95%CI: −8,5; p=0.70) and with Diet (main effect −6 units; 95%CI: −12,1; p=0.078). The change in peak VO2 was positively correlated with the change in percent lean body mass (r=0.32; p=0.003) and the change in thigh muscle/intermuscular fat ratio (r=0.27; p=0.02). There were no study-related serious adverse events. Exercise attendance was 84±14%; Diet compliance was 99±1%. Body weight decreased by 7±1 kg (7%) in Diet, 4±1 kg (3%) in Exercise, 11±1 kg (10%) in Exercise+Diet, and 1±1 kg (1%) in Control. Conclusion and Relevance Among obese older patients with clinically stable heart failure and preserved ejection fraction, caloric restriction diet or aerobic exercise training increased peak oxygen consumption, and the effects may be additive. Neither intervention had a significant effect on quality of life as measured by the Minnesota Living with Heart Failure Questionnaire, Clinical Trial Registration Clinicaltrials.gov, NCT00959660; https://clinicaltrials.gov/ct2/show/NCT00959660

Objectives To determine the mechanisms responsible for reduced aerobic capacity (peak VO2) in heart failure patients with preserved ejection fraction (HFPEF). Background HFPEF is the predominant form of HF in older persons. Exercise intolerance is the primary symptom among patients with HFPEF and a major determinant of reduced quality of life. In contrast to patients with HF and reduced EF, the mechanism of exercise intolerance in HFPEF is less well understood. Methods Left ventricular volumes (2D echocardiography), cardiac output (CO), VO2 and calculated arterial-venous oxygen content difference (A-VO2 Diff) were measured at rest and during incremental, exhaustive upright cycle exercise in 48 HFPEF patients (age 69±6 years) and 25 healthy age-matched controls (HC). Results In HFPEF compared to HC, VO2 was reduced at peak exercise (mean±SE: 14.3±0.5 vs. 20.4±0.6 mL·kg min−1; p<0.0001) and was associated with a reduced peak CO (6.3±0.2 vs. 7.6±0.2 L·min−1, p<0.0001) and A-VO2 Diff (17±0.4 vs. 19±0.4 ml·dl−1, p<0.0007). The strongest independent predictor of peak VO2 was the change in A-VO2 Diff from rest to peak exercise (A-VO2 Diff reserve) for both HFPEF (partial correlant 0.58, standardized β coefficient 0.66; p=0.0002) and HC (partial correlant 0.61, standardized β coefficient 0.41; p=0.005) Conclusions Both reduced CO and A-VO2 Diff contribute significantly to the severe exercise intolerance in elderly HFPEF patients. The finding that A-VO2 Diff reserve is an independent predictor of peak exercise VO2 suggests that peripheral, ‘non-cardiac’ factors are important contributors to exercise intolerance in these patients.

Background-Heart failure (HF) with preserved left ventricular ejection fraction (HFPEF) is the most common form of HF in the older population. Exercise intolerance is the primary chronic symptom in patients with HFPEF and is a strong determinant of their reduced quality of life (QOL). Exercise training (ET) improves exercise intolerance and QOL in patients with HF with reduced ejection fraction (EF). However, the effect of ET in HFPEF has not been examined in a randomized controlled trial. Methods and Results-This 16-week investigation was a randomized, attention-controlled, single-blind study of medically supervised ET (3 days per week) on exercise intolerance and QOL in 53 elderly patients (mean age, 70Ϯ6 years; range, 60 to 82 years; women, 46) with isolated HFPEF (EF Ն50% and no significant coronary, valvular, or pulmonary disease). Attention controls received biweekly follow-up telephone calls. Forty-six patients completed the study (24 ET, 22 controls). Attendance at exercise sessions in the ET group was excellent (88%; range, 64% to 100%). There were no trial-related adverse events. The primary outcome of peak exercise oxygen uptake increased significantly in the ET group compared to the control group (13.8Ϯ2.5 to 16.1Ϯ2.6 mL/kg per minute [change, 2.3Ϯ2.2 mL/kg per minute] versus 12.8Ϯ2.6 to 12.5Ϯ3.4 mL/kg per minute [change, Ϫ0.3Ϯ2.1 mL/kg per minute]; Pϭ0.0002). There were significant improvements in peak power output, exercise time, 6-minute walk distance, and ventilatory anaerobic threshold (all PϽ0.002). There was improvement in the physical QOL score (Pϭ0.03) but not in the total score (Pϭ0.11). Conclusions-ET

Objectives To evaluate the effects of endurance exercise training (ET) on endothelial dependent flow-mediated arterial dilation (FMD) and carotid artery stiffness and their potential contributions to the training-related increase in peak exercise oxygen consumption (VO2) in older patients with heart failure with preserved ejection fraction (HFPEF). Background Elderly HFFEF patients have severely reduced peak VO2 which improves with ET, however the mechanisms of this improvement are unclear. FMD and arterial distensibility are critical components of the exercise response and are reduced with aging. However, it's unknown whether these improve with ET in elderly HFPEF or contribute to the training-related improvement in peak VO2. Methods 63 HFPEF patients (70±7 years) were randomized to 16 weeks of ET (walking, arm and leg ergometry, n=32) or attention control (CT; n=31). Peak VO2, brachial artery FMD in response to cuff ischemia, carotid artery distensibility by high-resolution ultrasound, LV function, and QOL were measured at baseline and follow-up. Results ET increased peak VO2 (ET: 15.8±3.3 vs. CT: 13.8±3.1 ml/kg/min, p=0.0001) and QOL. However, brachial artery FMD (ET: 3.8±3.0% vs. CT: 4.3±3.5%, p=0.88), and carotid arterial distensibility (ET: 0.97±0.56 vs. CT: 1.07±0.34 × 10-3mm × mmHg-1 p=0.65) were unchanged. Resting LV systolic and diastolic function were unchanged by ET. Conclusions In elderly HFPEF patients, 16 weeks of ET improved peak VO2 without altering endothelial function or arterial stiffness. This suggests that other mechanisms, such as enhanced skeletal muscle perfusion and / or oxygen utilization, may be responsible for the ET-mediated increase in peak VO2 in older HFPEF patients.

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