Physical Functioning in Heart Failure With Preserved Ejection Fraction

Heart failure with preserved ejection fraction (HFpEF) is increasingly prevalent, yet interventions and therapies to improve outcomes remain limited. There has been increasing attention towards the impact of comorbidities and physical functioning (PF) on poor clinical outcomes within this population. In this review, we summarize and discuss the literature on PF in HFpEF, its association with clinical and patient-centered outcomes, and future advances in the care of HFpEF with respect to PF. Multiple PF metrics have been demonstrated to provide prognostic value within HFpEF, yet the data are less robust compared with other patient populations, highlighting the need for further investigation. The evaluation and detection of poor PF provides a potential strategy to improve care in HFpEF, and future studies are needed to understand if modulating PF improves clinical and/or patient-reported outcomes.Lay Summary• Patients with heart failure with preserved ejection fraction (HFpEF) commonly have impaired physical functioning (PF) demonstrated by limitations across a wide range of common PF metrics.• Impaired PF metrics demonstrate prognostic value for both clinical and patient-reported outcomes in HFpEF, making them plausible therapeutic targets to improve outcomes.• Clinical trials are ongoing to investigate novel methods of detecting, monitoring, and improving impaired PF to enhance HFpEF care.Heart failure with preserved ejection fraction (HFpEF) is increasingly prevalent, yet interventions and therapies to improve outcomes remain limited. As such, there has been increasing focus on the impact of physical performance (PF) on clinical and patient-centered outcomes. In this review, we discuss the state of PF in patients with HFpEF by examining the multitude of PF metrics available, their respective strengths and limitations, and their associations with outcomes in HFpEF. We highlight future advances in the care of HFpEF with respect to PF, particularly regarding the evaluation and detection of poor PF.     

Sudden Cardiac Death in Heart Failure Patients With Preserved Ejection Fraction

BackgroundWhereas sudden cardiac death (SCD) risk has been recognized in heart failure (HF) patients with reduced ejection fraction (HFrEF), less is known about SCD risk in HF patients with preserved EF (HFpEF). We examined the incidence and predictors of SCD in HFpEF in a large population sample.Methods and ResultsMedical records of patients discharged with a primary diagnosis of HF from hospitals in Minneapolis–St Paul in 1995 and 2000 were abstracted. HFpEF was defined as EF ≥45%. SCD was defined as cardiac arrest or out-of-hospital death due to coronary heart disease (CHD) on death certificates. A total of 2,203 patients (age 70 ± 11 years, 53% male) were included. The 787 patients (36%) with HFpEF were older, more often female and more likely to have hypertension than the 1,416 (64%) with HFrEF. All-cause mortality (52% vs 58%; P = .01) and SCD (6% vs 14%; P < .0001) rates were lower in HFpEF than in HFrEF 5 years after hospital discharge. Age, sex, CHD, and length of index hospitalization were the only independent predictors of SCD in HFpEF.ConclusionsIncidence of SCD in HFpEF is lower than in HFrEF. Present markers of SCD in HFpEF are sparse and insufficient to identify the patient at risk.     

Comparison of Beta-Blocker Effectiveness in Heart Failure Patients With Preserved Ejection Fraction Versus Those With Reduced Ejection Fraction

BackgroundThe aim of this study was to compare the benefit of beta-blockers (BB) in heart failure (HF) with preserved versus reduced ejection fraction (EF).Methods and ResultsThis was a retrospective study of insured patients who were hospitalized for HF from January 2000 to June 2008. Pharmacy claims were used to estimate BB exposure over 6-month rolling windows. The association between BB exposure and all-cause hospitalization or death was tested with the use of time-updated proportional hazards regression, with adjustment for baseline covariates and other HF medication exposure. The groups were compared by stratification (EF <50% vs ≥50%) and with the use of an EF-group × BB exposure interaction term. A total of 1,835 patients met the inclusion criteria, 741 (40%) with a preserved EF. Median follow-up was 2.1 years. In a fully adjusted multivariable model, BB exposure was associated with a decreased risk of death or hospitalization in both groups (EF <50%: hazard ratio [HR] 0.53 [P < .0001]; EF ≥50%: HR 0.68 [P = .009]). There was no significant difference in this protective association between groups (interaction: P = .32).ConclusionsBB exposure was associated with a similar protective effect regarding time to death or hospitalization in HF patients regardless of whether EF was preserved or reduced. An adequately powered randomized trial of BB in HF with preserved EF is warranted.     

Heart Failure With Preserved Ejection Fraction in Diabetes: Mechanisms and Management

Diabetes mellitus (DM) is a major cause of heart failure in the Western world, either secondary to coronary artery disease or from a distinct entity known as “diabetic cardiomyopathy.” Furthermore, heart failure with preserved ejection fraction (HFpEF) is emerging as a significant clinical problem for patients with DM. Current clinical data suggest that between 30% and 40% of patients with HFpEF suffer from DM. The typical structural phenotype of the HFpEF heart consists of endothelial dysfunction, increased interstitial and perivascular fibrosis, cardiomyocyte stiffness, and hypertrophy along with advanced glycation end products deposition. There is a myriad of mechanisms that result in the phenotypical HFpEF heart including impaired cardiac metabolism and substrate utilization, altered insulin signalling leading to protein kinase C activation, advanced glycated end products deposition, prosclerotic cytokine activation (eg, transforming growth factor-β activation), along with impaired nitric oxide production from the endothelium. Moreover, recent investigations have focused on the role of endothelial-myocyte interactions. Despite intense research, current therapeutic strategies have had little effect on improving morbidity and mortality in patients with DM and HFpEF. Possible explanations for this include a limited understanding of the role that direct cell-cell communication or indirect cell-cell paracrine signalling plays in the pathogenesis of DM and HFpEF. Additionally, integrins remain another important mediator of signals from the extracellular matrix to cells within the failing heart and might play a significant role in cell-cell cross-talk. In this review we discuss the characteristics and mechanisms of DM and HFpEF to stimulate potential future research for patients with this common, and morbid condition.     

Impact of Right Atrial Remodeling in Heart Failure With Preserved Ejection Fraction

BackgroundFew studies have investigated right atrial (RA) remodeling in heart failure (HF) with preserved ejection fraction (HFpEF). This study sought to characterize the RA remodeling in HFpEF and to determine its prognostic significance.Methods and ResultsPatients with HFpEF were classified based on the presence of RA enlargement (RA volume index >39 mL/m² in men and >33 mL/m² in women). Compared with patients with normal RA size (n = 234), patients with RA dilation (n = 67) showed a higher prevalence of atrial fibrillation (AF), worse right ventricular systolic function, more severe pulmonary hypertension, and a greater prevalence of mild tricuspid regurgitation, as well as impaired RA reservoir function, with increased hepatobiliary enzyme levels. AF was strongly associated with the presence of RA dilation (odds ratio [OR] 10.2, 95% confidence interval [CI] 4.00–26.1 in current AF vs no AF and odds ratio 3.38, 95% CI 1.26–9.07, earlier AF vs no AF). Patients with RA dilation had more than a two-fold increased risk of composite outcomes of all-cause mortality or HF hospitalization (adjusted hazard ratio 2.01, 95% CI 1.09–3.70, P = .02). The presence of RA dilation also displayed an additive prognostic value over left atrial dilation alone.ConclusionsThese data demonstrate that HFpEF with RA remodeling is associated with distinct echocardiographic features characterizing advanced right heart dysfunction with an increased risk of adverse outcomes.     

Hypertension as an Underlying Factor in Heart Failure With Preserved Ejection Fraction

J Clin Hypertens (Greenwich). The unique pathophysiology of heart failure with a preserved ejection fraction (HF-PEF) and the involvement of hypertension in its development are only poorly understood. The upregulation of the renin-angiotensin-aldosterone system (RAAS) has been identified as a key pathologic pathway contributing to fibrosis, cardiomyocyte abnormalities, inflammation, and endothelial dysfunction, all of which have been implicated in the progression of hypertension to HF-PEF. In addition, pharmacologic inhibition of the RAAS has been shown in animal models of diastolic dysfunction and in clinical trials to reduce these deleterious processes and to improve diastolic function. Despite these data, clinical trials performed with RAAS inhibitors in patients with HF-PEF have failed to demonstrate morbidity and mortality benefits. To date, there is no proven effective therapy specifically for HF-PEF. The deleterious effects of hypertension on mechanisms underlying the development of HF-PEF underscore the importance of effective and early control of hypertension for the prevention of HF-PEF.