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[The significance of myocardial hypertrophy in heart failure]
1Institut für Pathophysiologie, Martin-Luther-Universität Halle-Wittenberg.
Insights
Myocardial hypertrophy, a response to wall stress, can compensate for heart failure but also causes detrimental changes. These include altered myocyte function and reduced coronary reserve, impacting heart health.
Area of Science:
- Cardiology
- Molecular Biology
- Pathophysiology
Context:
- Myocardial hypertrophy is a key adaptation to increased myocardial wall stress.
- In congestive heart failure, hypertrophy serves both compensatory and detrimental roles.
- Understanding these dual roles is crucial for managing heart failure.
Purpose:
- To elucidate the complex mechanisms of myocardial hypertrophy in response to elevated wall stress.
- To detail the cellular and tissue-level changes associated with maladaptive hypertrophy.
- To highlight the critical implications of impaired calcium homeostasis and reduced coronary reserve.
Summary:
- Myocardial hypertrophy, driven by myocyte hypertrophy, initially reduces wall stress during hemodynamic overload.
- However, "overload-hypertrophy" leads to myocyte phenotype changes, increased connective tissue, and reduced coronary reserve.
- Impaired calcium handling (Ca(++)-homeostasis) and diastolic dysfunction contribute to critical cardiac issues.
Impact:
- Provides insights into the pathophysiology of heart failure.
- Identifies potential targets for therapeutic interventions.
- Enhances understanding of the structural and functional alterations in the hypertrophied heart.
Abstract:
Myocardial hypertrophy in response to elevated myocardial wall stress largely results from myocyte hypertrophy. In congestive heart failure, this hypertrophy can have compensatory as well as critical relevance. On the one hand, it reduces myocardial wall stress in the case of hemodynamic overload by enhancing ventricular wall thickness. On the other hand, risks and problems may result from the tissue changes associated with myocardial "overload-hypertrophy", such as alterations in myocyte phenotype, augmentation of connective tissue in the myocardium, reductions in coronary reserve (even without altherosclerotic coronary stenoses), and alterations in the local formation of growth cofactors (i.e., enhanced myocardial expression of angiotensinogen and converting enzyme). Changes in myocyte phenotype occur in receptor signal transduction, in isoform shifts of contractile proteins and of key enzymes in energy metabolism towards a more fetal-like pattern, and in a "fragility" of Ca(++)-homeostasis (due to reduced expression of sarcoplasmic reticulum Ca(++)-ATPase and enhanced expression of membrane Na+/Ca(++)-exchange in presence of maintained density of Ca(++)-channels). Additionally, the fraction of contractile fibers and mitochondria per myocyte cross-section can be reduced with attenuated systolic function. The fragility of Ca(++)-homeostasis must be regarded as potentially critical because of retarded inactivation of contraction and because of susceptibility to diastolic Ca(++)-overload with delayed after-depolarizations. Additionally, diastolic dysfunction may result from interstitial fibrosis and ischemia due to reduced coronary reserve (altered vascular structure and endothelial dysfunction).(ABSTRACT TRUNCATED AT 250 WORDS)