The Cardiomyocyte in Heart Failure with Preserved Ejection Fraction-Victim of Its Environment?

Angela Rocca,Ruud B Van Heeswijk,Philippe Meyer,Jonas Richiardi,Roger Hullin

doi:10.3390/cells11050867

Abstract

Heart failure (HF) with preserved left ventricular ejection fraction (HFpEF) is becoming the predominant form of HF. However, medical therapy that improves cardiovascular outcome in HF patients with almost normal and normal systolic left ventricular function, but diastolic dysfunction is missing. The cause of this unmet need is incomplete understanding of HFpEF pathophysiology, the heterogeneity of the patient population, and poor matching of therapeutic mechanisms and primary pathophysiological processes. Recently, animal models improved understanding of the pathophysiological role of highly prevalent and often concomitantly presenting comorbidity in HFpEF patients. Evidence from these animal models provide first insight into cellular pathophysiology not considered so far in HFpEF disease, promising that improved understanding may provide new therapeutical targets. This review merges observation from animal models and human HFpEF disease with the intention to converge cardiomyocytes pathophysiological aspects and clinical knowledge.

Highlights

Heart failure (HF) afflicts an estimated 64 million people world-wide [1] and the high hospitalization rate of HF patients, among the elderly [2], accounts for up to 10% of the healthcare costs for cardiovascular disease [3]
Definitions of the societies of cardiology [4] divide the HF population into two large categories as a function of the left ventricular ejection fraction (LVEF): HF with LVEF < 50%, which is further subdivided into HF with mildly reduced LVEF from 40 to 49% (HFmrEF) and HF with reduced LVEF < 40% (HFrEF), while HF patients with a preserved LVEF ≥ 50% (HFpEF) make up the other large category
HFpEF already comprises more than half of the total HF population [5,6], and this proportion is supposed to rise in the near future, since the annual HFpEF incidence has increased by about 1% relative to the incidence of HF with LVEF < 50% in the last years [7,8]

Summary

Introduction

Heart failure (HF) afflicts an estimated 64 million people world-wide [1] and the high hospitalization rate of HF patients, among the elderly [2], accounts for up to 10% of the healthcare costs for cardiovascular disease [3]. The fact that molecules of different pharmacological classes are effective in HF patients with LVEF < 60% but not in HF patients with LVEF ≥ 60% challenges the current categorization of HF patients on the basis of the definition provided by the societies of cardiology [12], suggesting that based on the results the available clinical trial results, HF can be categorized into HF with reduced or normal LVEF This is in coherence with arguments suggesting that HF is a heterogeneous disease with a dynamic evolution of functional and structural changes, leading to unique disease trajectories and a spectrum of phenotypes with overlapping and distinct characteristics [13]. An individual collection of systemic abnormalities such as aging, hypertension, and metabolic stress is possibly at the origin of the disease [7,15] While this multifaceted cause may explain phenotype heterogeneity in HFpEF [16], it has complicated comprehension of the interplay between these systemic abnormalities and cardiomyocyte structure and function. The goal of this review is to join state-of-the-art understanding of cardiomyocyte pathology in HFpEF disease with current clinical knowledge for a synoptic view on this challenging category of HF disease

The Dilemma of HFpEF Definition

Structural and Functional Changes of the Cardiomyocyte in HFpEF

The Impact of Age, Hypertension, Obesity, and Diabetes in HFpEF

Impact of Systemic Inflammation on Cardiomyocyte Function, Cardiac Fibrosis, and Vascular Function

Findings

Conclusions