Heart failure & cardiomyopathies
Clinical Phenogroup Diversity and Multiplicity: Impact on Mechanisms of Exercise Intolerance in Heart Failure with Preserved Ejection Fraction
Authors' conclusion
Though cardiac output response to exercise is limited in patients with HFpEF compared to those with non-cardiac dyspnoea, the relative contributions of cardiac and peripheral limitations vary with differing numbers and types of clinical phenotypic traits present. Patients fulfilling criteria for greater multiplicity and diversity of HFpEF phenogroup traits have poorer exercise capacity, worsening haemodynamic perturbations, and greater risk for adverse outcome.
Study context
- Population
- Patients with heart failure with preserved ejection fraction (HFpEF) or non-cardiac dyspnoea undergoing invasive cardiopulmonary exercise testing
- Participants
- 643 vs 219
- Exposure
- HFpEF vs non-cardiac dyspnoea controls; HFpEF phenogroup trait multiplicity
- HFpEFn = 643
- Controlsn = 219reference
- Outcome
- Contribution of cardiac and peripheral impairments to O2 delivery and utilisation to exercise intolerance and risk of adverse events
Methodological detailsinvasive cardiopulmonary exercise testing, a priori phenogroups
- Invasive cardiopulmonary exercise testing
- A priori phenogroups
Main finding
As reported in the abstract
| Group | Cardiac output reserve with exercise | Peripheral O2 extraction augmentation |
|---|---|---|
| HFpEF | 2.3 L/min | 4.5 ml/dl |
| Controls | 2.8 L/min | 3.8 ml/dl |
Cardiac output reserve with exercise
Peripheral O2 extraction augmentation
- HFpEF vs Controls: P = 0.025 — cardiac output reserve
- HFpEF vs Controls: P < 0.001 — peripheral O2 extraction augmentation
Observational data: associations, not effects.
Further findings
| Outcome | HR (95% CI) | |
|---|---|---|
| HF hospitalisation or death, by phenogroup trait multiplicity≥2 phenogroup traitsvs 0-1 phenogroup traitsAs printed: 0-1vs ≥2 phenogroup traits present | 1.74 (1.08–2.79) | |
| 0.20.5125Hazard ratio (log scale) |
Phenogroup membership (HFpEF)
- Met criteria for ≥1 clinical phenogroup
- 94%
- Fulfilled criteria for multiple overlapping phenogroups
- 67%
Limitations by phenogroup
- Greater peripheral limitations in cardiometabolic phenogroup; greater cardiac output limitations and higher pulmonary vascular resistance during exertion in other phenogroups
HF hospitalisation or death, by phenogroup trait multiplicity
- Increasing trait multiplicity associated with worse exercise haemodynamics, poorer exercise capacity, lower cardiac output reserve
Original publication
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