Affiliation:
1. Department of Cardiovascular Medicine Mayo Clinic Rochester MN USA
2. Department of Cardiology Odense University Hospital Odense Denmark
3. Steno Diabetes Center, Odense University Hospital Odense Denmark
4. Department of Cardiovascular Medicine Gunma University Graduate School of Medicine Maebashi Japan
5. Deutsches Herzzentrum der Charité, Department of Cardiology Angiology and Intensive Care Medicine, Campus Virchow‐Klinikum Berlin Germany
6. DZHK (German Centre for Cardiovascular Research), partner site Berlin Berlin Germany
Abstract
AbstractAimsWe aimed to clarify the extent to which cardiac and peripheral impairments to oxygen delivery and utilization contribute to exercise intolerance and risk for adverse events, and how this relates to diversity and multiplicity in pathophysiologic traits.Methods and resultsIndividuals with heart failure with preserved ejection fraction (HFpEF) and non‐cardiac dyspnoea (controls) underwent invasive cardiopulmonary exercise testing and clinical follow‐up. Haemodynamics and oxygen transport responses were compared. HFpEF patients were then categorized a priori into previously‐proposed, non‐exclusive descriptive clinical trait phenogroups, including cardiometabolic, pulmonary vascular disease, left atrial myopathy, and vascular stiffening phenogroups based on clinical and haemodynamic profiles to contrast pathophysiology and clinical risk. Overall, patients with HFpEF (n = 643) had impaired cardiac output reserve with exercise (2.3 vs. 2.8 L/min, p = 0.025) and greater reliance on peripheral oxygen extraction augmentation (4.5 vs. 3.8 ml/dl, p < 0.001) compared to dyspnoeic controls (n = 219). Most (94%) patients with HFpEF met criteria for at least one clinical phenogroup, and 67% fulfilled criteria for multiple overlapping phenogroups. There was greater impairment in peripheral limitations in the cardiometabolic group and greater cardiac output limitations and higher pulmonary vascular resistance during exertion in the other phenogroups. Increasing trait multiplicity within a given patient was associated with worse exercise haemodynamics, poorer exercise capacity, lower cardiac output reserve, and greater risk for heart failure hospitalization or death (hazard ratio 1.74, 95% confidence interval 1.08–2.79 for 0–1 vs. ≥2 phenogroup traits present).ConclusionsThough 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.
Funder
National Institutes of Health
Defense Human Resources Activity
National Center for Advancing Translational Sciences
Subject
Cardiology and Cardiovascular Medicine