Towards precision medicine for heart failure and myocardial disease: myocardial genomics, single cell transcriptomics, and plasma profiling

Myocardial diseases are leading causes of morbidity and mortality in the population, ultimately by resulting in heart failure (HF).

Improved strategies for etiological assessment, prevention and individualization of therapy are greatly needed.My translational research group combines methods in molecular biology and epidemiology to (a) identify genetic, myocardial and circulating markers of myocardial disease (b) characterize effects of identified molecules in human heart cells (c) characterize dynamics and clinical utility of identified molecules for precision medicine.Workplan: (1) genome-wide discovery of variants associated with myocardial disease and HF, by resequencing and microarrays in up to 100 000 cases and 2 million controls (2) determination of downstream consequences of genetic variants by population-scale transcriptomic profiling of 6 million individual cells (scRNAseq) from human hearts coupled to genome sequencing (3) proteomic and metabolomic plasma profiling in population and clinical cohorts and time-dependent association with invasive hemodynamics (4) evaluate clinical utility in a randomized trial of precision medicine in HF, a prospective repeated-sampling study of decompensated HF, and a prospective study of genetic testing and scRNAseq.This research program is expected to result in new insights on the pathophysiology of myocardial disease and HF, identification of therapeutic targets and clinical biomarkers, and evaluation of precision medicine for HF.