Exercise Intolerance in Heart Failure With Preserved Ejection Fraction: Diagnosing and Ranking Its Causes Using...

Area of Science:

• Cardiology
• Exercise Physiology
• Pulmonary Medicine

Background:

• Heart failure with preserved ejection fraction (HFpEF) is a prevalent condition with limited therapeutic options.
• Exercise intolerance is a primary symptom of HFpEF, but its underlying mechanisms are not fully understood.

Purpose of the Study:

• To investigate the mechanisms of exercise intolerance in patients with HFpEF.
• To identify specific defects in the oxygen (O2) transport and utilization pathway contributing to reduced exercise capacity.

Main Methods:

• Cardiopulmonary exercise testing with invasive monitoring was performed on 79 HFpEF patients and 55 controls.
• Quantified six steps of the O2 pathway to identify defects impacting peak oxygen consumption (Vo2).
• Calculated the potential improvement in exercise capacity from correcting individual O2 pathway defects.

Main Results:

• HFpEF patients exhibited a 34% reduction in peak Vo2 compared to controls.
• Nearly all HFpEF patients (97%) had multiple O2 pathway defects, with cardiac output and skeletal muscle O2 diffusion being significantly impaired.
• Correcting single defects yielded minor improvements; cardiac output correction predicted a 7% improvement, while muscle diffusion correction predicted a 27% improvement.

Conclusions:

• Exercise capacity in HFpEF is compromised by multiple O2 pathway defects, including reduced cardiac output and skeletal muscle diffusion.
• Patient heterogeneity in defect profiles contributes to disease variability.
• Personalized analysis can guide treatment, but a systems approach, like exercise training, is favored for addressing multiple defects simultaneously.