Obesity may be considered a distinct phenotype in heart failure with preserved EF

Evidence Supporting the Existence of a Distinct Obese Phenotype of Heart Failure With Preserved Ejection Fraction

Literature - Obokata M, Reddy YNV, Pislaru SV, et al. - Circulation. 2017;136:6-19


To date, there is no evidence of treatment that improves the prognosis of heart failure with preserved ejection fraction (HFpEF), although it seems that the phenotyping of patients and consequent classification into pathophysiological homogenous groups, leads to a better targeting of treatments [1,2]. Obesity is common among HFpEF patients, and its negative impact on the cardiovascular system implies that obesity-related HFpEF may represent a clinical relevant phenotype within the broader spectrum of HFpEF [3-5].

In this study, a detailed characterization of cardiovascular structure, function and reserve capacity in subjects with HFpEF and class II or greater obesity was performed and compared with this of non-obese HFpEF and non-HF controls. For this purpose, participants were categorized according to BMI into non-obese HFpEF patients, defined as BMI<30kg/m2 or obese HFpEF patients, defined as class II obesity or greater (BMI ≥ 35 kg/m2). Patients with class I obesity (BMI 30-34.9 kg/m2) were excluded to maximize phenotypic differences associated with greater body mass. Obese and non-obese HFpEF subjects were also compared to non-obese controls (BMI <30kg/m2), without heart failure.

Main results

  • Compared with non-obese HFpEF patients and controls, obese HFpEF subjects had larger left ventricular (LV) dimensions, volumes and mass, with increased LV mass-to-volume ratios, indicating greater concentric remodeling.
  • LV ejection fraction (LVEF) was similar in the three groups, but the LV systolic function was impaired in both the obese and the non-obese HFpEF groups as compared to controls. Doppler estimates of diastolic function and filling pressures were similarly abnormal in the HFpEF groups as compared to controls.
  • Right ventricular (RV) size was significantly larger in obese HFpEF compared to both controls and non-obese HFpEF patients. The RV systolic function was depressed in obese HFpEF as compared to controls. The RV size was directly correlated with body mass but not with height.
  • Compared to non-obese HFpEF and controls, obese subjects with HFpEF had higher right atrium pressures and pulmonary capillary wedge pressure (PCWP) at rest.
  • The PCWP was directly correlated with NT-proBNP in all HFpEF subjects, but PCWP was higher for any given NT-proBNP value in obese HFpEF subjects.
  • In obese HFpEF patients, elevations in PCWP were directly correlated with greater body mass and estimated plasma volume, but PCWP had no relationship with body size or plasma volume in non-obese HFpEF patients.
  • The peak exercise workload achieved was lower in obese subjects with HFpEF and in non-obese subjects with HFpEF as compared to controls (36±17 and 39±19 vs 69±29 W; P<0.0001). The peak VO2 achieved during exercise testing was inversely correlated with body weight.
  • During exercise, left and right heart filling pressures as well as the exercise-induced pulmonary hypertension were higher in obese HFpEF patients as compared to both non-obese HFpEF patients and controls.
  • The epicardial fat thickness was 20 and 50% higher in obese HFpEF patients as compared to non-obese HFpEF individuals and controls, respectively.
  • LV eccentricity was greater in obese HFpEF patients for any given value of pulmonary artery pressure, but the increase in LV eccentricity was more amplified in obese HFpEF subjects, as RV afterload increased, compared with non-obese subjects (interaction P<0.05 for both).
  • The RA pressure was directly correlated with the LV eccentricity index (r=0.36; P<0.0001) and the total heart volume (r=0.34; P<0.0001).


Obese patients with HFpEF had greater biventricular remodeling, volume overload, more RV dysfunction, greater ventricular interaction and pericardial restraint, worse exercise capacity, more profound hemodynamic derangements and impaired pulmonary vasodilation. These findings suggest that obesity may be considered as a specific HFpEF phenotype.

Editorial comment

In their editorial article [6], Kitzman and Lam comment on the lack of data regarding obese patients with HFpEF, and welcome the study of Obokata et al, since they ‘….add dramatically to evidence supporting obese HFpEF as a valid HFpEF phenotype, and effectively usher obese HFpEF from pariah to its rightful place as a central player in the HFpEF syndrome.’

The authors adopt the opinion that dyspnea in obese patients with HFpEF is not due to the mechanical burden of their excess weight, but the excess adipose tissue has a negative impact on several mechanisms that lead to real heart failure. And they conclude: ‘As we work to differentiate and better understand specific mechanisms of the various HFpEF phenotypes, including obese HFpEF, even greater rewards may result from efforts to identify the fundamental factors that underlie the HFpEF syndrome and unite its phenotypes.’


1. Reddy YN, Borlaug BA. Heart failure with preserved ejection fraction. Curr Probl Cardiol. 2016;41:145-188.

2. Shah SJ, Kitzman DW, Borlaug BA, et al. Phenotype-specific treatment of heart failure with preserved ejection fraction: A multiorgan roadmap. Circulation. 2016;134:73-90.

3. Lauer MS, Anderson KM, Kannel WB, et al. The impact of obesity on left ventricular mass and geometry. The framingham heart study. JAMA. 1991;266:231-236.

4. Abel ED, Litwin SE, Sweeney G. Cardiac remodeling in obesity. Physiol Rev. 2008;88:389-419.

5. Lavie CJ, Alpert MA, Arena R, et al. Impact of obesity and the obesity paradox on prevalence and prognosis in heart failure. JACC Heart Fail. 2013;1:93-102.

6. Kitzman DW and Lam CSP. Obese Heart Failure With Preserved Ejection Fraction Phenotype: From Pariah to Central Player Circulation. 2017;136:20-23.

Find this article online at Circulation

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