Molecular and cellular biology and genetic factors in chronic heart failure

Heart failure (HF) may have either an acute, gradual, or insidious onset, as in the case of hemodynamic pressure or volume overloading. This may be hereditary, as in the case of genetic cardiomyopathies. Cardiomyopathy is a disease with dysfunction of the myocardium due to the cardiac muscle protein abnormality with progressive cardiomyocyte loss leading to HF by means of either necrotic, apoptotic, or autophagic cell death pathways. There are two major types of intrinsic cardiomyopathies and they include hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM), which are most often determined as genetic cardiomyopathies associated with HF. It seems that about 40%–60% of subjects with HCM and DCM have been recognized as genetic diseases with mutations in the sarcomere. A meta-analysis examined genome-wide association studies of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci were associated with HF, all of which demonstrated one or more associations with either coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, indicating shared genetic etiology. Functional analysis of non-CAD-associated loci implicates genes that are involved in cardiac development (MYOZ1, SYNPO2L), protein homeostasis (BAG3), and cellular senescence (CDKN1A). It is concluded that genetic analysis can provide improved diagnosis and management of HF with hereditary cardiomyopathy.