Response by Obokata and Borlaug to Letters Regarding Article, “Evidence Supporting the Existence of a Distinct Obese Phenotype of Heart Failure With Preserved Ejection Fraction”
Authors: Masaru Obokata, Barry A. Borlaug
Journal: Circulation (2018)

In Response:We thank Drs Koutsampasopoulos, Jin-shan, Carbone, and colleagues for their interest in our recent publication characterizing cardiovascular structure, function, and reserve capacity in patients with the obese phenotype of heart failure with preserved ejection fraction (HFpEF). 1 Koutsampasopoulos et al point out that diabetes mellitus was more prevalent in obese HFpEF and that this might confound interpretation.To address their concern, we have performed additional subanalyses.We observed no differences between obese HFpEF with (n=33) and without (n=66) diabetes mellitus in biventricular structure or function, ventricular interaction, rest and exercise hemodynamics, or exercise capacity (all P>0.2).This finding indicates that the observed differences in the obese HFpEF group are not simply ascribable to diabetes mellitus alone.Jin-shan and Xue-bin point out the high prevalence of hypertension and diabetes mellitus in patients with obese HFpEF in our study. 1The authors propose a study in patients with obese HFpEF with no hypertension or diabetes mellitus compared to nonobese HFpEF.Although this approach would be ideal, it would be difficult because these comorbidities are highly prevalent in patients with obesity as well as HFpEF.The authors question whether obesity causes a transition from HFpEF to heart failure with reduced ejection fraction.The cross-sectional nature of our study does not allow us to address this question, but previous studies have reported that this transition is uncommon unless coronary disease is present. 2Prospective longitudinal studies are needed to delineate this question further.Carbone and colleagues state their belief that obesity is not a specific phenotype of HFpEF but rather a coexisting condition.Our data do not support this belief. 1The authors imply that our study cohort was biased, but it was drawn from consecutive patients referred to our laboratory, reflecting what is seen in the community.The authors suggest that adiposity is not correlated with cardiac parameters, but previous studies have shown that adiposity and weight gain are directly associated with increases in ventricular stiffening, which is known to underlie progression to HFpEF. 3,4Our data show that directly measured pulmonary capillary wedge pressure was significantly correlated with body mass in the patients with obese HFpEF, a relationship not seen in the nonobese HFpEF group (see Figure 2 in our article). 1We observed even stronger correlations between exercise pulmonary capillary wedge pressure and weight (r=0.44,P<0.0001) as well as body mass index (r=0.50,P<0.0001).These data provide compelling evidence that adiposity does affect cardiac function in obese HFpEF.Carbone et al point out that we did not include a control group with obesity but no HFpEF.In response, we have analyzed data from patients with obesity free of heart failure who underwent the same evaluation (body mass index ≥35 kg/m 2 , n=13).We found that these control patients with obesity displayed normal pulmonary artery pressures (mean, 19±3 mm Hg standard deviation) and normal pul-Response by Obokata and Borlaug to Letters Regarding Article, "Evidence Supporting the Existence of a Distinct Obese Phenotype of Heart Failure With Preserved Ejection Fraction"