A Need to Preserve Ejection Fraction during Heart Failure

Figures

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  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.

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  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.

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  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.