Obese heart failure with preserved ejection fraction phenotype is associated with progressive left ventricular remodeling

Introduction: Heart failure with preserved ejection fraction (HFpEF) represents a heterogeneous syndrome. Phenotyping patients into distinct groups based on the underlying causes could enable better and more precise treatments. Given its prevalence and cardiovascular implications, obesity is considered a key risk factor for cardiovascular diseases. However, HFpEF remains often underdiagnosed among patients with excess body fat. Our study aimed to examine how obesity relates to changes in cardiac function in HFpEF patients

Methods: We prospectively included  HFpEF patients who underwent clinical and laboratory routine assessment, body composition (with Bod Pod), and transthoracic echocardiography for the evaluation of cardiac structure and function. To understand the characteristics of obesity in HFpEF, we divided the patients according to their body mass index (BMI): obese HFpEF (BMI≥30 kg/m²), overweight HFpEF (BMI 25-29.99 kg/m²), and normal-weight HFpEF (18.5-24.99 kg/m²).

Results: Of the 40 HFpEF patients (76.4±6.6 years, 57.5% women, median NT-proBNP of 388 pg/ml) obese HFpEF was present in 25% of patients, the overweight HFpEF in 40%, and the normal-weight HFpEF in 35%. Clinical data included heart rate (65±9 bpm), systolic blood pressure (BP) (142±23 mmHg), diastolic BP (84±11 mmHg), and oxygen saturation (98±2%). The fat mass distribution was 48.4±14.9 kg in obese HFpEF, 32.2±5.3 kg in overweight HFpEF, and 21.0±4.9 kg in normal-weight HFpEF (P_global<0.001). Moreover, significant differences were observed between genders, with female HFpEF patients having an increased percentage of fat than males (41.5±8% vs. 36.1±7%, P=0.049). Left ventricular (LV) cavity dimensions, as assessed by LV end-diastolic diameter (LVEDD) and LV posterior wall thickness (PW), were higher in obese and overweight HFpEF patients as in HFpEF compared to those with normal-weight (LVEDD: 46.9±6.1 mm vs. 49.3±6.1 mm vs 44.4±5.1 mm, P_global=0.083, PW: 12.9±2.0 mm vs. overweight: 11.7±1.4 mm vs. normal-weight: 11.1±2.4 mm, P_global=0.089), respectively. Furthermore, significant differences were noted in the atria, with both right (asses by the surface area) and left atrial (assessed by the diameter) cavities being larger in obese patients (right atrial area: obese: 18.2±4.5 cm² vs. overweight: 20.5±4.2 cm² vs. normal-weight: 16.6±3.4 cm², P_global=0.036, overweight vs. normal-weight P_Bonferroni=0.033,  and LA diameter: obese: 47.5±6.6 mm, overweight: 45.9±4.1 mm, normal weight: 41.5±6.3 mm, P_global=0.029, obese vs. normal weight P_Bonferroni=0.041). In all patients, BMI correlated with LVEDD (r=0.429, P=0.006), LV end-systolic volumes (LVESV) (r=0.360, P=0.023), PW_ED (r=0.410, P=0.009) and LV mass (r=0.393, P=0.012). In all patients the fat-free mass was correlated with LV mass (r=0.532, P<0.001), LV end-diastolic volumes (LVEDV) (r=0.651, P< 0.001), LA volume (LAVi) (r=0.437, P=0.005), diameter (r=0.393, P=0.012) and LV mass (r=0.532, P<0.001). However, only in the obese HFpEF phenotype, the fat mass correlated to LVEDD (r=0.876, P<0.001) and in addition with LAESV (r=0.864, P=0.001). The LV mass was increased almost congruently with body weight (Figure 1A) and fat mass (Figure 1B). 

Conclusion: Patients with obese HFpEF phenotype have excess total body mass, a condition resulting from an overaccumulation of both fat and fat-free mass. Moreover, the obese HFpEF phenotype appears to be distinguished by more pronounced LV and particularly LA remodeling. 

1A

1B