Myocardial reverse remodeling: how far can we rewind?

Abstract

Heart failure (HF) is a systemic disease that can be divided into HF with reduced ejection fraction (HFrEF) and with preserved ejection fraction (HFpEF). HFpEF accounts for over 50% of all HF patients and is typically associated with high prevalence of several comorbidities, including hypertension, diabetes mellitus, pulmonary hypertension, obesity, and atrial fibrillation. Myocardial remodeling occurs both in HFrEF and HFpEF and it involves changes in cardiac structure, myocardial composition, and myocyte deformation and multiple biochemical and molecular alterations that impact heart function and its reserve capacity. Understanding the features of myocardial remodeling has become a major objective for limiting or reversing its progression, the latter known as reverse remodeling (RR). Research on HFrEF RR process is broader and has delivered effective therapeutic strategies, which have been employed for some decades. However, the RR process in HFpEF is less clear partly due to the lack of information on HFpEF pathophysiology and to the long list of failed standard HF therapeutics strategies in these patient's outcomes. Nevertheless, new proteins, protein-protein interactions, and signaling pathways are being explored as potential new targets for HFpEF remodeling and RR. Here, we review recent translational and clinical research in HFpEF myocardial remodeling to provide an overview on the most important features of RR, comparing HFpEF with HFrEF conditions.

Effect of ivabradine in patients with heart failure with preserved ejection fraction: the EDIFY randomized placebo‐controlled trial

“…This may be explained by the fact that HFpEF and HFrEF have different patterns of myocardial remodelling arising from their different pathophysiological mechanisms . Some evidence points towards the stronger involvement of systemic inflammation associated with HFpEF, which may also impact the remodelling process …”

Impact of diabetes on the predictive value of heart failure biomarkers

“…Experimental and human studies have suggested relationships between ST2 and myocardial stretch, fibrosis, adverse cardiac remodelling, inflammation, impaired haemodynamics, and vascular disease [23]. Indeed, in experimental studies ST2 appears to play a pivotal role in LV remodeling; this process comprises changes in cardiac structure, myocardial composition, myocyte deformation, and multiple biochemical and molecular alterations that impact heart function and reserve capacity [24]. The currently available data are insufficient to allow us to determine conclusively whether the value of ST2 as a marker of cardiac remodelling is different in patients with and without diabetes.…”

Hydrogen sulfide pretreatment improves mitochondrial function in myocardial hypertrophy via a SIRT3‐dependent manner

“…Myocardial hypertrophy may develop into heart failure, which is an independent risk factor of cardiovascular diseases (Lazzeroni et al , ). It is important to find more effective targets in the attempt to attenuate myocardial hypertrophy (Rodrigues et al , ).…”