Mechanisms, diagnosis, and treatment of heart failure with preserved ejection fraction and diastolic dysfunction

Abstract

Heart failure with preserved ejection fraction (HFpEF) continues to be a major challenge for clinicians. Many crucial aspects of the syndrome remain unclear, including the exact pathophysiology, early diagnosis, and treatment. Patients with HFpEF are often asymptomatic late into the disease process, and treatment with medications commonly used in heart failure with reduced ejection fraction (HFrEF) has not been proven to be beneficial. In addition, the confusion of similar terms with HFpEF, such as diastolic heart failure, and diastolic dysfunction (DD), has led to a misunderstanding of the true scope of HFpEF. Areas covered: In this review, authors highlight the differences in terminology and critically review the current knowledge on the underlying mechanisms, diagnosis, and latest treatment strategies of HFpEF. Expert commentary: While significant advances have been made in the understanding of HFpEF, the definitive diagnosis of HFpEF continues to be difficult. The development of improved and standardized methods for detecting DD has shown promise in identifying early HFpEF. However, even with early detection, there are few treatment options shown to provide mortality benefit warranting further investigation.

Keywords: Biomarkers; Diastolic dysfunction; HFpEF; HFrEF; Inflammation.

Figure 1:

Following systemic inflammation due to obesity, hypertension, diabetes or COPD in a patient, ROS molecules build up and deplete NO, causing decreased active PKG proteins. Decreased levels of PKG cause concentric hypertrophy and decreased titin phosphorylation leading to HFpEF. COPD, chronic obstructive pulmonary disease; ROS, reactive oxygen species; NO, nitric oxide; PKG, protein kinase G; HFpEF, heart failure with preserved ejection fraction.

Figure 2:

The release of biomarkers of interest and their potential role in the development of diastolic dysfunction and heart failure with preserved ejection fraction. Tnt, high-sensitivity troponin T; BNP, brain natriuretic peptide; NT-proBNP, N-terminal pro-brain natriuretic peptide; ST2, suppression of tumorgenicity 2; CT-1, cardiotrophin-1; GDF-15, growth differentiation factor-15; IL-6, interleukin 6.