Heart Failure (HF) is a complex clinical syndrome characterized by
compromised cardiac output that leads to inadequate blood supply failing to meet the
requirements of the metabolizing tissues of the body. HF is a silent epidemic that
affects ~2% of the general population in the western world and its prevalence is
steadily increasing. Although survival has improved, high morbidity and mortality
render HF the most devastating cardiovascular disorder with considerable financial
burden on public health care. The phenotypic variability of HF syndrome reflects the
complexity of the underlying genetic background of the disease, as well as the interindividual
susceptibility to external triggers. Although acquired clinical conditions
account for the majority of HF development, a proportion of HF cases are due to
inherited pathological states comprising myocardial disorders, mitochondrial diseases,
metabolic disorders and congenital heart defect syndromes. Among those, inherited
forms of cardiomyopathies constitute “naturally-occurring” disease models that provide
the opportunity for an in depth investigation of the genotype–phenotype relationships.
Advances in technology permitting high-throughput whole genome genotyping and
sequencing, have provided invaluable insights into the genetic architecture, disease
evolution and therapeutic response. However, despite the enormous wealth of genetic
information derived from those studies and their contribution towards the identification of disease-specific genetic variants in complex diseases such as HF, a considerable
amount of genetic information related to heritability is missing. In this chapter, we will
review knowledge regarding the underlying complex genetic architecture of both
acquired and inherited forms of HF, the role of epigenetics as a significant modifier
mechanism in disease susceptibility and phenotypic heterogeneity, as well as advances
in the field of pharmacogenetics of HF.
Keywords: Cardiomyopathies, Chromatin remodelling, Congenital heart defects,
DNA methylation, Epigenetics, Genetics, Genetic testing, Heart failure, Histone,
MicroRNAs, Pharmacogenetics, Single nucleotide polymorphisms.
