A Need to Preserve Ejection Fraction during Heart Failure

Abstract

Heart failure (HF) is a significant global healthcare burden with increasing prevalence and high morbidity and mortality rates. The diagnosis and management of HF are closely tied to ejection fraction (EF), a crucial parameter for evaluating disease severity and determining treatment plans. This paper emphasizes the urgent need to maintain EF during heart failure, highlighting the distinct phenotypes of HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF). It discusses the complexities of HFrEF pathophysiology and its negative impact on patient outcomes, stressing the importance of ongoing research and the development of effective therapeutic interventions to slow down the progression from preserved to reduced ejection fraction. Additionally, it explores the potential role of renal denervation in preserving ejection fraction and its implications for HFrEF management. This comprehensive review aims to offer valuable insights into the critical role of EF preservation in enhancing outcomes for patients with heart failure.

Keywords: endothelial dysfunction; heart failure; mitochondrial dynamics; oxidative stress; reduced ejection fraction.

Figure 1

The impact of various cardiac stressors such as volume overload, hypertension, ischemia, etc. on oxyradical generation. For instance, chronic volume overload is a stressor that leads to oxyradical production, resulting in oxidative stress and inflammation. This stress impairs the endothelium’s ability to dilate in response to stimuli due to reduced nitric oxide availability. Endothelial dysfunction, characterized by impaired endothelium-dependent vasodilation, plays a significant role in the development of cardiovascular disorders, including heart failure. Notably, the endothelium’s capacity to dilate blood vessels is a critical predictor of cardiac mortality and hospitalization in individuals with HFrEF.

Figure 2

Chronic volume overload, an example of a cardiac stressor and pathologic activator of matrix metalloproteinases (MMPs), leads to the pathological remodeling of the extracellular matrix. In a failing myocardium, latent resident myocardial MMPs are activated, decreasing the elastin-to-interstitial collagen ratio. This, in turn, leads to the formation of an oxidized extracellular matrix. In HFrEF, the loss of fibrillar collagen reduces cardiomyocyte contraction, compromising systolic function.

Figure 3

Chronic volume overload is an example of a cardiac stressor and disruptor of mitochondrial function. It affects mitochondrial metabolic activity, including dynamics and bioenergetics. This disruption is closely associated with mitochondrial fragmentation, often observed during high stress and cellular death. In heart failure with reduced ejection fraction (HFrEF), the damage to mitochondrial structure and function is particularly significant, indicating a continuous autophagy process.