Table 2.
Study Populations and Selected Findings
| General Community | Myocardial Injury | Intermediate HF Phenotypes | Symptomatic HF | Outcomes in HF | |
|---|---|---|---|---|---|
| Context | Population-based, risk factors | Acute myocardial infarction or myocarditis | Myocardial remodeling | Symptom onset and diagnosis | Decompensation, arrhythmia, death, LVAD, or transplantation |
| Genetic variants | >300 independent SNPs for blood pressure, 113 for diabetes | 73 SNPs for CAD | >150 SNPs for systolic function, diastolic function, left ventricular mass, left ventricular diameter, QRS duration, QT duration and heart rate, 25 for AF, 7 for valvular disease | Sarcomere gene mutations (including MYBPC3 founder mutations, TTNtv), 8 SNPs for HF and cardiomyopathy | Mutations in LMNA, LAMP2, and MYH7; SNP at 5q22 (death), SNPs at 4q25 and 16q22 for AF, an SNP near hypocretin receptor-2 for myocardial recovery |
| Myocardial profile | — | — | — | Sarcomere changes (α- to β-myosin switch, titin isoform switch), reduced calcium channel expression, increased NP expression, metabolic changes (reduced mitochondrial fatty acid and glucose oxidation, reduced phosphocreatine, increased ketone oxidation) | Same as for HF (death) Increased glycolytic metabolites, lactate and amino acids (LVAD unloading) |
| Plasma profile | BCAAs for diabetes | TMAO for CAD | — | Increased catecholamines, angiotensin II, NPs, ST2, galectin-3, endothelin, CRP, TNFα, ketone bodies, lactate, reduced iron | Same as for HF, TMAO (death) |
| Microbiome composition | Strains that generate BCAAs for diabetes | Strains that generate TMAO for CAD | — | — | Strains that generate TMAO |
Overview of populations under study in the molecular epidemiology of heart failure, with a selection of key findings from different molecular sets. Some forms of HF are not preceded by myocardial injury or overload, such as monogenic cardiomyopathies, but likely influence intermediate phenotypes.
AF = atrial fibrillation; BCAAs = branched-chain amino acids; CAD = coronary artery disease; HF = heart failure; LVAD = left ventricular assist device; NPs = natriuretic peptides; SNP = single nucleotide polymorphism; TMAO = trimethylamine-N-oxide; TTNtv = titin-truncating variants.