Treatment of Heart Failure with Preserved Ejection Fraction

Abstract

Heart failure with preserved ejection fraction (HFpEF) is a growing epidemiologic problem affecting more than half of the patients with heart failure (HF). HFpEF has a significant morbidity and mortality and so far no treatment has been clearly demonstrated to improve the outcomes in HFpEF, in contrast to the efficacy of treatment in heart failure with reduced ejection fraction (HFrEF).The failure of proven beneficial drugs in HFrEF to influence the outcome of patients with HFpEF could be related to the heterogeneity of the disease, its various phenotypes and multifactorial pathophysiology, incompletely elucidated yet. The diagnosis of HFpEF could be demanding or even inaccurate. Moreover, the therapeutic strategies were influenced by different cut-offs used to define preserved ejection fraction (EF). From this perspective, the current guidelines have classified HFpEF by an EF ≥ 50%, together with a distinct entity, heart failure with mid-range ejection fraction (HFmrEF), defined by an EF ranging from 41-49%.New therapies have been developed to interfere with the mediator pathways of HFpEF at the cellular and molecular level, including mineralocorticoid receptor antagonists, soluble guanylate cyclase stimulators, or angiotensin receptor-neprilysin inhibitors. A number of antidiabetic drugs, such as sodium/glucose cotransporter 2 inhibitors and dipeptidyl peptidase-4 inhibitors are promising options, being under research in large clinical trials. Until the results of ongoing trials shed light on these therapies, guidelines recommend empirical treatment for established HFpEF, and emphasize the crucial role of addressing cardiovascular comorbidities leading to HFpEF, in particular arterial hypertension.

Macrophage Plasticity and Function in the Eye and Heart

“…Moreover, antibody-mediated CCR2 inhibition early in pressure overload resulted in reduced monocyte numbers and macrophage recruitment, reduced fibrosis and hypertrophy, as well as improvement in systolic function compared to untreated mice [69]. An additional study further supported the detrimental role of recruited CCR2 + macrophages in heart failure with preserved ejection fraction (HFpEF), a condition currently lacking effective therapies [70]. Similar to the TAC pressure overload model, mice with reduced diastolic function due to hypertension or advanced age exhibited increased numbers of circulating monocytes and recruitment of macrophages relative to healthy mice [71].…”

Heart Failure with Reduced Ejection Fraction (HFrEF) and Preserved Ejection Fraction (HFpEF): The Diagnostic Value of Circulating MicroRNAs

“…In the CHARM-preserved trial, candesartan (one of the ARBs) was shown to reduce HF admissions in HFpEF patients [39]. Diuretics and acute vasodilator therapy can reduce congestion and provide symptomatic relief of edema and dyspnea in HFpEF patients [20,40]. A recent systematic review and meta-analysis of data from 25 randomized clinical trials suggested that β-blockers provide modest reduction in all-cause (22%) and cardiovascular (25%) mortality in patients with HFpEF [41].…”

Associations of inflammatory markers with impaired left ventricular diastolic and systolic function in collagen-induced arthritis

“…Heart failure with a preserved ejection fraction (HFpEF) accounts for more than 50% of all heart failure cases and is associated with an increased morbidity and mortality [1]. There are currently no effective treatment strategies for HFpEF [2], which highlights the need for a better understanding of its pathophysiology. Impaired left ventricular (LV) diastolic function has been proposed as a pre-clinical measure that underlies the pathophysiology of, and frequently progresses to HFpEF [3].…”