Myocardial hypertrophy and its role in heart failure with preserved ejection fraction

Area of Science:

• Cardiology
• Cardiovascular Research
• Heart Failure Pathophysiology

Background:

• Left ventricular hypertrophy (LVH) is the most frequent structural cardiac abnormality in heart failure with preserved ejection fraction (HFpEF).
• LVH is associated with comorbidities like hypertension, kidney disease, and diabetes, driven by neurohormonal activation and mechanical stress.
• LVH is linked to diastolic dysfunction, a key feature of HFpEF, though underlying mechanisms require further elucidation.

Purpose of the Study:

• To review experimental and clinical evidence connecting LVH to diastolic dysfunction in HFpEF.
• To explore the mechanisms contributing to diastolic dysfunction in the context of LVH.
• To evaluate the clinical relevance of LVH as a diagnostic marker and therapeutic target in HFpEF.

Main Methods:

• Review of existing experimental data on cardiomyocyte function and myocardial remodeling in LVH.
• Analysis of clinical trial evidence examining the impact of interventions on LVH, diastolic function, and HFpEF outcomes.
• Discussion of the role of comorbidities in HFpEF pathophysiology.

Main Results:

• LVH is strongly associated with diastolic dysfunction, a hallmark of HFpEF.
• Mechanisms of diastolic dysfunction in LVH may involve extracellular matrix changes, vascular dysfunction, and altered cardiomyocyte properties (e.g., impaired Ca(2+) handling and relaxation).
• Current therapeutic strategies aimed at reducing LVH have not demonstrated significant improvements in HFpEF symptoms or prognosis.

Conclusions:

• LVH serves as a diagnostic marker for HFpEF, linked to diastolic dysfunction through various structural and functional myocardial changes.
• Diastolic dysfunction in HFpEF can occur independently of LVH, particularly in patients with multiple comorbidities.
• Exercise training improves HFpEF exercise tolerance and diastolic function without reducing LVH, indicating that LVH regression is not a necessary surrogate for short-term clinical improvement.