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Updated: Jul 12, 2026
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Lumped-Parameter and Finite Element Modeling of Heart Failure with Preserved Ejection Fraction
Published on: February 13, 2021
Distinct Exercise Response Patterns in Patients With Heart Failure With Preserved Ejection Fraction.
Stephanie De Schutter1,2, Nicola R Pugliese3, Laura M G Meems4
1Research group Cardiovascular Diseases, GENCOR Department University of Antwerp Antwerp Belgium.
Journal of the American Heart Association
|July 10, 2026
Summary
Five distinct heart failure with preserved ejection fraction (HFpEF) phenotypes were identified using exercise testing. These HFpEF subgroups show varied exercise responses and clinical outcomes, aiding personalized treatment and risk assessment.
Area of Science:
- Cardiology
- Exercise Physiology
- Medical Diagnostics
Background:
- Heart failure with preserved ejection fraction (HFpEF) is a complex condition with significant exercise intolerance.
- Current HFpEF subtyping relies on resting data, limiting personalized therapeutic approaches.
- Exercise limitations are a key feature of HFpEF, necessitating exercise-based phenotyping.
Purpose of the Study:
- To define distinct HFpEF phenotypes based on exercise limitations.
- To utilize combined cardiopulmonary exercise testing and stress echocardiography for HFpEF subtyping.
- To investigate the pathophysiological characteristics, exercise capacity, and clinical outcomes of identified HFpEF phenotypes.
Main Methods:
- 913 HFpEF patients were analyzed across derivation and validation cohorts.
- Unsupervised graph-based clustering was applied to 61 variables from cardiopulmonary exercise testing and stress echocardiography.
- Phenotypes were characterized by exercise responses, and clinical outcomes were compared.
Main Results:
- Five distinct HFpEF exercise phenotypes were identified: mild diastolic dysfunction, impaired peripheral oxygen extraction, RV-PA uncoupling, reduced LV systolic reserve, and chronotropic incompetence.
- Phenotypes 2 (impaired peripheral oxygen extraction), 4 (reduced LV systolic reserve), and 5 (chronotropic incompetence) exhibited significantly higher rates of death or hospitalization compared to phenotype 1.
- The identified HFpEF phenotypes and their outcome differences were validated in a separate patient cohort.
Conclusions:
- Deep phenotyping of exercise response in HFpEF reveals 5 distinct groups with differing pathophysiology and outcomes.
- This subclassification offers potential for personalized therapeutic strategies in HFpEF.
- The identified phenogroups can improve risk stratification for patients with HFpEF.
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