Study Protocol for HeartMagic: A Prospective Observational Cohort Characterizing Subtypes of Heart Failure With Preserved Ejection Fraction.
Authors
Affiliations (8)
Affiliations (8)
- Cardiology Division University Hospital of Geneva Geneva Switzerland.
- Cardiology Division Lausanne University Hospital (CHUV) Lausanne Switzerland.
- Department of Radiology Lausanne University Hospital (CHUV) and University of Lausanne (UNIL) Lausanne Switzerland.
- Radiology Division, Diagnostic Department Geneva University Hospitals and University of Geneva Geneva Switzerland.
- Faculty Unit of Toxicology, CURML, Faculty of Biology and Medicine University of Lausanne Lausanne Switzerland.
- Unit of Forensic Toxicology and Chemistry, CURML Lausanne and Geneva University Hospitals Lausanne, Geneva Switzerland.
- Lausanne Genomic Technologies Facility, University of Lausanne Lausanne Switzerland.
- CIBM Center for Biomedical Imaging Lausanne and Geneva Switzerland.
Abstract
Heart failure (HF) is a life-threatening syndrome with significant morbidity and mortality. Although evidence-based drug treatments have effectively reduced morbidity and mortality in HF with reduced ejection fraction (EF), few therapies have been demonstrated to improve outcomes in HF with preserved EF. This may be caused by the existence of several HF with preserved EF subtypes that each need different treatments. There is therefore an unmet need for a comprehensive approach to subtype patients with HF with preserved EF. This protocol details the approach employed in the HeartMagic (Heart Failure Studied With a Machine Learning, Genomics, and Imaging Combination) study to address this gap. This prospective multicenter observational cohort study will include 500 consecutive patients with HF with preserved EF at 2 Swiss university hospitals, along with 50 age-matched patients with HF with reduced EF and 50 healthy controls. In addition to routine clinical workup, participants undergo genomic, transcriptomic, and metabolomic analyses, and the anatomy, composition, and function of the heart are quantified by comprehensive echocardiography and magnetic resonance imaging. Quantitative magnetic resonance imaging is also applied to characterize the kidney. The primary outcome is a composite of 1-year cardiovascular mortality or rehospitalization. Machine learning-based multimodal clustering will be employed to identify distinct HF with preserved EF subtypes. Statistical analysis will include group comparisons, survival analysis, and integrative multimodal clustering combining clinical, imaging, ECG, genomic, transcriptomic, and metabolomic data to identify and validate HF with preserved EF subtypes. The integration of comprehensive magnetic resonance imaging with extensive genomic and metabolomic profiling in this study will result in an unprecedented panoramic view of HF with preserved EF and help distinguish functional subgroups, which may provide a basis for personalized therapies.