Omote, Kazunori

Approximately half of all patients with heart failure (HF) have a preserved ejection fraction, and the prevalence is growing rapidly given the aging population in many countries and the rising prevalence of obesity, diabetes, and hypertension. Functional capacity and quality of life are severely impaired in heart failure with preserved ejection fraction (HFpEF), and morbidity and mortality are high. In striking contrast to HF with reduced ejection fraction, there are few effective treatments currently identified for HFpEF, and these are limited to decongestion by diuretics, promotion of a healthy active lifestyle, and management of comorbidities. Improved phenotyping of subgroups within the overall HFpEF population might enhance individualization of treatment. This review focuses on the current understanding of the pathophysiologic mechanisms underlying HFpEF and treatment strategies for this complex syndrome.

Abstract Aims Circulating blood volume is functionally divided between the unstressed volume, which fills the vascular space, and stressed blood volume (SBV), which generates vascular wall tension and intravascular pressure. With decreases in venous capacitance, blood functionally shifts to the SBV, increasing central venous pressure and pulmonary venous pressures. Obesity is associated with both elevated venous pressure and heart failure with preserved ejection fraction (HFpEF). To explore the mechanisms underlying this association, we evaluated relationships between blood volume distribution, venous compliance, and body mass in patients with and without HFpEF. Methods and results Subjects with HFpEF ( n = 62) and non‐cardiac dyspnoea (NCD) ( n = 79) underwent invasive haemodynamic exercise testing with echocardiography. SBV was estimated (eSBV) from measured haemodynamic variables fit to a comprehensive cardiovascular model. Compared to NCD, patients with HFpEF displayed a leftward‐shifted central venous pressure–dimension relationship, indicating reduced venous compliance. eSBV was 81% higher at rest and 69% higher during exercise in HFpEF than NCD (both P < 0.0001), indicating reduced venous capacitance. Despite greater augmented eSBV with exercise, the increase in cardiac output was reduced in HFpEF, suggesting operation on the plateau of the Starling curve. Exercise eSBV was directly correlated with higher body mass index (r = 0.77, P < 0.0001) and inversely correlated with right ventricular–pulmonary arterial coupling (r = −0.57, all P < 0.0001). Conclusions Patients with HFpEF display reductions in systemic venous compliance and increased eSBV related to reduced venous capacitance, abnormalities in right ventricular–pulmonary artery interaction, and increased body fat. These data provide new evidence supporting an important role of venous dysfunction in obesity‐related HFpEF and suggest that therapies that improve venous function may hold promise to improve clinical status in this cohort.

Aims To investigate the prognostic value of diagnostic scores for heart failure (HF) with preserved ejection fraction (HFpEF). Methods and results Consecutive patients with HFpEF admitted for unequivocal decompensated HF treated with intravenous loop diuretics were evaluated ( n = 443; mean age 78 ± 12 years; 60% women). The HFA‐PEFF and H 2 FPEF scores were calculated for all patients with echocardiography data available within 1 year and the population was stratified according to HFA‐PEFF scores 2–4 ( n = 79), 5 ( n = 93), or 6 ( n = 271) and H 2 FPEF score probabilities <90% ( n = 80), 90–95% ( n = 61), and 96–100% ( n = 293). HF readmission rates (95% confidence intervals) increased from 28.9 (22.7–35.0) per 100 patient‐years in HFA‐PEFF 2–4 to 46.0 (38.5–53.5) in HFA‐PEFF 5 and 45.0 (40.1–49.8) in HFA‐PEFF 6. Similarly, HF readmission rates increased with increasing H 2 FPEF probability: <0.90 [31.8 (25.3–38.2) per 100 patient‐years], 0.90–0.95 [41.5 (32.9–50.1)], and 0.96–1.00 [45.9 (41.2–50.6]. Median survival was 65 months (36–89 months) in HFA‐PEFF score 2–4, 45 months (26–59 months) in HFA‐PEFF score 5, and 28 months (22–42 months) in HFA‐PEFF score 6 ( P < 0.001), while the hazard ratio (95% confidence interval) for all‐cause mortality was 1.16 (1.02–1.32) per 0.10 increase in H 2 FPEF probability. Conclusions Among patients hospitalized with HFpEF, higher HFpEF probability according to diagnostic scores is associated with increased risk of subsequent HF readmissions and all‐cause mortality.