Heart Failure With Preserved Ejection Fraction: A Review of Cardiac and Noncardiac Pathophysiology

Abstract

Heart failure with preserved ejection fraction (HFpEF) is one of the largest unmet clinical needs in 21st-century cardiology. It is a complex disorder resulting from the influence of several comorbidities on the endothelium. A derangement in nitric oxide bioavailability leads to an intricate web of physiological abnormalities in the heart, blood vessels, and other organs. In this review, we examine the contribution of cardiac and noncardiac factors to the development of HFpEF. We zoom in on recent insights on the role of comorbidities and microRNAs in HFpEF. Finally, we address the potential of exercise training, which is currently the only available therapy to improve aerobic capacity and quality of life in HFpEF patients. Unraveling the underlying mechanisms responsible for this improvement could lead to new biomarkers and therapeutic targets for HFpEF.

Expression of the Novel Cardiac Biomarkers sST2, GDF-15, suPAR, and H-FABP in HFpEF Patients Compared to ICM, DCM, and Controls

“…This is partially related to its complex pathophysiology [9]. Given the increasing prevalence of HFpEF and the high rates of misdiagnosis, the need for new diagnostic tools is evident [5]. Accordingly, we aimed…”

“…This is partially related to its complex pathophysiology [9]. Given the increasing prevalence of HFpEF and the high rates of misdiagnosis, the need for new diagnostic tools is evident [5]. Accordingly, we aimed for a head-to-head analysis of four novel cardiovascular biomarkers and their diagnostic benefit in patients with HFpEF compared to controls to address this evident gap.…”

“…The cellular processes involved in the development of HFpEF are heterogeneous. One of the most generally accepted hypotheses is that cellular hypertrophy combined with a reduction in cellular relaxation and an increase in tissue fibrosis could contribute strongly to the development of ventricular stiffening [4,5]. Furthermore, obesity, which is a very frequent co-morbidity of HF, leads to adipose tissue dysfunction along with elevated leptin levels and can trigger an upregulation of aldosterone, leading to sodium retention [6].…”

Designing Novel Therapies to Mend Broken Hearts: ATF6 and Cardiac Proteostasis

“…More recently, a less well-defined form of pathological cardiac hypertrophy, heart failure with preserved ejection fraction (HFpEF), has emerged as an important pathology due to its clinical prevalence and association with ever increasing metabolic diseases [63]. HFpEF is characterized by concentric cardiac hypertrophy without overt systolic impairment, and is associated with a patient population diagnosed with the comorbidities of obesity, type II diabetes mellitus and chronic hypertension [63][64][65].…”

“…More recently, a less well-defined form of pathological cardiac hypertrophy, heart failure with preserved ejection fraction (HFpEF), has emerged as an important pathology due to its clinical prevalence and association with ever increasing metabolic diseases [63]. HFpEF is characterized by concentric cardiac hypertrophy without overt systolic impairment, and is associated with a patient population diagnosed with the comorbidities of obesity, type II diabetes mellitus and chronic hypertension [63][64][65]. While initially thought of as a form of diastolic heart failure, HFpEF is further characterized by impaired active myocardial relaxation and increased passive stiffness, as well as increased pulmonary capillary wedge pressures that can rise to levels above that of even hypertensive patients, or those with aortic stenosis [66,67].…”