Silent disease progression in clinically stable heart failure
1Henry Ford Health System, Detroit, MI, USA.
Insights
Heart failure with reduced ejection fraction (HFrEF) silently progresses, increasing mortality risk. New therapies are crucial to address underlying cardiac dysfunction mechanisms beyond current treatments.
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.
Abstract:
Heart failure with reduced ejection fraction (HFrEF) is a progressive disorder whereby cardiac structure and function continue to deteriorate, often despite the absence of clinically apparent signs and symptoms of a worsening disease state. This silent yet progressive nature of HFrEF can contribute to the increased risk of death-even in patients who are 'clinically stable', or who are asymptomatic or only mildly symptomatic-because it often goes undetected and/or undertreated. Current therapies are aimed at improving clinical symptoms, and several agents more directly target the underlying causes of disease; however, new therapies are needed that can more fully address factors responsible for underlying progressive cardiac dysfunction. In this review, mechanisms that drive HFrEF, including ongoing cardiomyocyte loss, mitochondrial abnormalities, impaired calcium cycling, elevated LV wall stress, reactive interstitial fibrosis, and cardiomyocyte hypertrophy, are discussed. Additionally, limitations of current HF therapies are reviewed, with a focus on how these therapies are designed to counteract the deleterious effects of compensatory neurohumoral activation but do not fully prevent disease progression. Finally, new investigational therapies that may improve the underlying molecular, cellular, and structural abnormalities associated with HF progression are reviewed.
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