The Impact Of Severe Obesity (Class II/III) In The Middle-age On Cardiac Remodeling And Exercise Capacity

PURPOSE: Individuals with class II/III obesity and heart failure (HF) are a distinct phenotype of HF that is difficult to treat. While much is known about the cardiovascular (CV) effects of class I obesity, less is known about the CV adaptations to severe obesity that occur prior to the development of HF. The purpose of this study was to determine the effects of severe obesity on CV structure, function and exercise capacity in high risk adults. METHODS: We studied 96 non-obese sedentary middle-aged (40-64 years) controls (CON; BMI: 25.8 [23.6-28.6] kg/m2) and 126 middle aged high risk (HR) adults with stage A & B HF (elevated cardiac biomarkers and/or obesity). HR adults were stratified by BMI: <30 kg/m2: non-obese (HRNO, n = 28); 30-35 kg/m2: HRClass I (n = 39); and ≥ 35 kg/m2: HRClass II/III(n = 59). We assessed cardiac structure (echo), cardiac output (Q̇c; acetylene rebreathe) and peak oxygen uptake (VO2) during graded exercise testing. RESULTS: Left ventricular end diastolic volume indexed to body surface area is elevated in HRClass II/III compared to CON and HRNO (p < 0.03, A). There was no difference in peak VO2 (L/min) between groups (p = 0.35, B). In CON, there was a strong positive relationship between absolute LVEDV and peak VO2 (slope = 0.02 L/min•mL, r2 = 0.51, C), but this relationship was attenuated in HRClass I (slope = 0.01 L/min•mL, r2 = 0.17, p < 0.001 vs CON) and HRClass II/III (slope = 0.004 L/min•mL, r2 = 0.05, p < 0.001 vs CON). All HR groups had a higher peak Q̇c (all p < 0.005 vs CON, D) and lower a-vO2 difference (all p < 0.001 vs CON, E). CONCLUSIONS: Class II/III obesity in HR adults is associated with cardiac enlargement without increased exercise capacity, in contrast to the positive relationship between cardiac size and exercise capacity in CON. During exercise, individuals with severe obesity have a greater Q̇c and blunted peripheral O2 extraction indicating that defects in muscle O2 utilization may be a key contributor to exercise intolerance in obese HR adults.This study was supported by the National Institutes of Health (grant AG017479) and by the American Heart Association Strategically Focused Research Network (14SFRN20600009-03).