Table 3.

Design Considerations in Prospective Molecular Epidemiology Studies of HF

Study Design Feature	HF Implications	Cohort Examples
Sample size	Very large cohorts or combined cohorts needed due to disease heterogeneity	PMI (n = 1 million), UK Biobank (n = 500,000), consortia for genomics (CHARGE-HF, GENIUS-CHD, HERMES, MGC, TOPMed) and plasma profiles (HOMAGE, inHForm)
Phenotypic characterization	Heterogeneous phenotype: need for standardized definitions and cardiac imaging	ESC diagnostic algorithm in several cohorts, Framingham criteria
Tissue sampling	Multiple tissues involved, heart most important but difficult to obtain	Multi-tissue: GTEx, heart tissue: MAGNet
Follow-up	Repeat sampling warranted	Biannual examinations in Framingham Heart Study, annual sampling in inHForm project

CHARGE-HF = Heart Failure working group of the Cohorts for Heart and Aging Research consortium; GENIUS-CHD = GENetIcs of sUbSequent Coronary Heart Disease; GTEx = Genotype-Tissue Expression project; HERMES = Heart Failure Molecular Epidemiology for Therapeutic Targets; HOMAGE = Heart Omics in AGEing consortium; inHForm = INtegrative omics of Heart Failure to infORM discovery of novel drug targets and clinical biomarkers; MAGNet = Myocardial Applied Genomics Network; MGC = Myocardial Genetics Consortium; PMI = Precision Medicine Initiative; TOPMed = National Heart Lung Blood Institute Trans-Omics for Precision Medicine Program; other abbreviations as in Table 2.