Exercise limitations in heart failure with reduced and preserved ejection fraction

Area of Science:

• Cardiology
• Exercise Physiology
• Pathophysiology

Background:

• Chronic heart failure (HF) is characterized by severe exercise intolerance.
• Impaired oxygen (O2) transport, affecting both perfusion and diffusion, significantly limits physical capacity and maximal O2 uptake in HF patients.
• HF presents as two main phenotypes: heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF).

Purpose of the Study:

• To review the disturbances in the O2 transport pathway contributing to exercise intolerance in both HFpEF and HFrEF.
• To identify potential clinical intervention targets by examining HF-induced impairments in O2 conductances.
• To discuss adaptations in skeletal muscle O2 delivery-utilization with therapies like exercise training and inorganic nitrate supplementation.

Main Methods:

• Analysis of human studies using varying exercise protocols (e.g., small vs. large muscle mass exercise).
• Review of animal research employing techniques such as intravital microscopy and phosphorescence quenching.
• Examination of evidence regarding skeletal muscle O2 delivery-utilization system adaptations.

Main Results:

• HF leads to impairments in both perfusive and diffusive O2 conductances, impacting exercise capacity.
• Research in both humans and animals has elucidated pathophysiological mechanisms underlying HF-related exercise intolerance.
• Skeletal muscle dysfunction and impaired O2 transport are critical factors in HF exercise intolerance.

Conclusions:

• Limited understanding of HFpEF pathophysiology hinders effective treatment development for this subpopulation.
• Elucidating the mechanisms of skeletal muscle dysfunction and exercise intolerance is crucial for refining HF treatments.
• Targeting O2 transport pathways offers potential for improved therapeutic strategies in HF management.