Different heart failure phenotypes of valvular heart disease: the role of mitochondrial dysfunction

Abstract

Valvular heart disease (VHD)-related heart failure (HF) is a special subtype of HF with an increasingly concerned heterogeneity in pathophysiology, clinical phenotypes, and outcomes. The mechanism of VHD-related HF involves not only mechanical damage to the valve itself but also valve lesions caused by myocardial ischemia. The interactions between them will lead to the occurrence and development of VHD-related HF subtypes. Due to the spatial (combination of different valvular lesions) and temporal effects (sequence of valvular lesions) of valvular damages, it can make the patient's condition more complicated and also make the physicians deal with a dilemma when deciding on a treatment plan. This indicates that there is still lack of deep understanding on the pathogenic mechanism of VHD-related HF subtypes. On the other hand, mitochondrial dysfunction (MitD) is not only associated with the development of numerous cardiac diseases such as atherosclerosis, hypertension, diabetes, and HF but also occurs in VHD. However, the role of MitD in VHD-related HF is still not fully recognized. In this comprehensive review, we aim to discuss the current findings and challenges of different valvular damages derived from HF subtypes as well as the role of MitD in VHD-related HF subtypes.

Deep Learning Model of Diastolic Dysfunction Risk Stratifies the Progression of Early-Stage Aortic Stenosis

“…For example, inflammation and oxidative stress are major factors contributing to the evolution of AS (47)(48)(49). These may be mediated by mitochondrial dysfunction and dysregulation of autophagy that extend even beyond the valve and underlie the development of adverse LV remodeling and DD (12)(13)(14). Thus, the identification of DD may capture this underlying systemic milieu of cellular impairment that affects both the valve and the myocardium.…”

“…Additionally, the compromised myocardial energetics and mitochondrial dysfunction associated with AS also contribute to DD (12)(13)(14).…”

“…Notably, among different myocardial changes, the alterations in diastolic function – an active, adenosine triphosphate-dependent process – occur early and may explain the association of subclinical DD with AV sclerosis, independent of the aforementioned cardiovascular risk factors (11). Additionally, the compromised myocardial energetics and mitochondrial dysfunction associated with AS also contribute to DD (12–14).…”