Author + information
- Salvatore Carbone, MS∗ (, )
- Justin M. Canada, MS,
- Leo F. Buckley, PharmD,
- Cory R. Trankle, MD,
- Dave L. Dixon, PharmD,
- Raffaella Buzzetti, MD,
- Ross Arena, PhD,
- Benjamin W. Van Tassell, PharmD and
- Antonio Abbate, MD, PhD
- ↵∗VCU Pauley Heart Center, Virginia Commonwealth University, P.O. Box 980204, Richmond, Virginia 23298
Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome of exertional breathlessness and/or fatigue caused by impaired cardiac function, preserved left ventricular ejection fraction, and impaired diastolic function (1). The incidence and prevalence of HFpEF in the United States are increasing, paralleling the growing obesity epidemic. Recently, obesity was linked to worse clinical functional class in HFpEF (2). In this study, we measured aerobic exercise capacity in patients with HFpEF in relation to indices of obesity and adiposity.
Twenty-seven subjects with symptomatic HFpEF and impaired functional capacity assessed by cardiopulmonary exercise testing were enrolled. Diagnosis was made on the basis of clinical, Doppler echocardiography, laboratory, and/or hemodynamic data (3).
We used a metabolic cart and treadmill with a conservative ramping protocol (4) to measure exercise time, peak oxygen consumption (Vo2), minute ventilation (VE), carbon dioxide production (VCO2), VE/VCO2 slope, O2 uptake efficiency slope (OUES), and peak O2 pulse. We measured echocardiographic Doppler parameters of systolic and diastolic function (left ventricular ejection fraction, transmitral velocities E, A, E/A, E-wave deceleration time, average mitral annulus velocity at tissue Doppler lateral and septal E′, and E/E′ ratio, both at rest and at peak exercise.
We calculated body mass index (BMI) and used single-frequency bioimpedance analysis (Quantum IV, RJL System, Clinton Township, Michigan) to estimate body composition. Data are reported as median and interquartile range. We assessed for correlations between variables using the Spearman rank test SPSS 22.0 (IBM Corp., Armonk, New York).
Seventeen (63%) subjects were women, the median age was 53 years (49–56 years), 81% had systemic hypertension, and 70% had diabetes mellitus. Exercise time and peak Vo2 were significantly reduced (8.2 [7.0 to 9.7] min and 15.8 [13.5 to 17.9] ml/kg/min, respectively). Median BMI was 43.3 kg/m2 (39.9 to 47.2 kg/m2), and it was inversely correlated with exercise time (R = −0.54; p = 0.004) and peak Vo2 expressed as ml/kg/min (R = −0.62; p = 0.001). Fat mass index (FMI) (fat mass / body surface area) was 18.8 kg/m2 (16.7 to 21.5 kg/m2), and it was inversely correlated with peak Vo2 (R = −0.62; p = 0.001) (Figures 1A and 1B). Fat-free mass (FFM) index did not correlate with peak Vo2 (R = −0.18; p = 0.39). Moreover, both BMI (R= −0.58; p = 0.003) and FMI (R = −0.39; p = 0.059) were inversely associated with peak Vo2 corrected by the amount of FFM (ml/kg[FFM]/min). Plasma leptin levels, a surrogate for FM, also correlated with FMI (R = +0.77; p < 0.001), exercise time (R = −0.47; p = 0.036), and peak Vo2 (R = −0.54; p = 0.013). Conversely, BMI, FMI, and leptin levels did not correlate with other functional prognostic markers, including peak O2 pulse or Vo2 in absolute value, VE/VCO2 slope, and OUES, or with echocardiographic Doppler parameters of systolic function or diastolic function at rest or peak exercise (all p > 0.15).
We also performed dual-energy x-ray absorptiometry (DEXA) (QDR 4500a, Hologic, Marlborough, Massachusetts) in a subgroup of 9 subjects and validated bioimpedance analysis–derived FMI with DEXA-derived FMI, thereby showing a highly significant correlation (R = +0.93; p < 0.001).
In a cohort of patients with HFpEF, measures of obesity (BMI) and more specifically of adiposity (FMI and leptin levels) predicted worse exercise capacity (exercise time and Vo2), whereas they did not correlate with cardiac-specific functional and prognostic parameters, such as the VE/VCO2 slope, OUES, peak O2 pulse, E′, and E/E′, or with peak Vo2 expressed in absolute terms. This finding is in agreement with the finding that caloric restriction led to weight loss and increased weight-based peak Vo2, but not with any significant changes in absolute peak Vo2 or parameters of cardiac function (5). Altogether, within the limitations of this observational study, these data suggest that the reduction in exercise capacity in patients with obesity or adiposity may not be attributable to any specific derangement in cardiac function, but rather that obesity is a comorbid condition that further limits exercise capacity in HFpEF.
Please note: This study was funded by National Institutes of Health grants R34HL118348 and UL1TR000058. Dr. Dixon has reported being on the Speakers Bureau of Novartis; and has received a speaker honorarium from Sanofi. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
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