Silent disease progression in clinically stable heart failure.

Area of Science:

• Cardiology
• Molecular Biology
• Pathophysiology

Background:

• Heart failure with reduced ejection fraction (HFrEF) is a progressive condition characterized by deteriorating cardiac structure and function.
• The silent progression of HFrEF, even in clinically stable patients, contributes to increased mortality risk due to underdetection and undertreatment.

Purpose of the Study:

• To review the underlying mechanisms driving HFrEF progression.
• To evaluate the limitations of current HFrEF therapies.
• To explore novel investigational therapies targeting molecular, cellular, and structural abnormalities.

Main Methods:

• Review of scientific literature on HFrEF pathophysiology and therapeutic strategies.
• Analysis of mechanisms including cardiomyocyte loss, mitochondrial dysfunction, impaired calcium cycling, and fibrosis.
• Assessment of current treatment limitations and emerging therapeutic approaches.

Main Results:

• Identified key drivers of HFrEF progression: cardiomyocyte loss, mitochondrial abnormalities, impaired calcium handling, elevated LV wall stress, fibrosis, and hypertrophy.
• Current therapies primarily counteract neurohumoral activation but do not fully prevent disease progression.
• Emerging therapies show potential to address underlying molecular and cellular defects.

Conclusions:

• HFrEF progression involves multiple interconnected pathological pathways.
• Existing therapies offer symptomatic relief but fall short of halting disease advancement.
• Investigational therapies targeting fundamental mechanisms represent a promising future direction for HFrEF management.