Our understanding of the molecular processes which regulate cardiac function has 
grown immeasurably in recent years. Even with the advent of β-blockers, 
angiotensin inhibitors and calcium modulating agents, heart failure (HF) still 
remains a seriously debilitating and life-threatening condition. Here, we review 
the molecular changes which occur in the heart in response to increased load and 
the pathways which control cardiac hypertrophy, calcium homeostasis, and immune 
activation during HF. These can occur as a result of genetic mutation in the 
case of hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) or as 
a result of ischemic or hypertensive heart disease. In the majority of cases, 
calcineurin and CaMK respond to dysregulated calcium signaling and adrenergic 
drive is increased, each of which has a role to play in controlling blood 
pressure, heart rate, and left ventricular function. Many major pathways for 
pathological remodeling converge on a set of transcriptional regulators such as 
myocyte enhancer factor 2 (MEF2), nuclear factors of activated T cells (NFAT), 
and GATA4 and these are opposed by the action of the natriuretic peptides ANP 
and BNP. Epigenetic modification has emerged in recent years as a major 
influence cardiac physiology and histone acetyl transferases (HATs) and histone 
deacetylases (HDACs) are now known to both induce and antagonize hypertrophic 
growth. The newly emerging roles of microRNAs in regulating left ventricular 
dysfunction and fibrosis also has great potential for novel therapeutic 
intervention. Finally, we discuss the role of the immune system in mediating 
left ventricular dysfunction and fibrosis and ways this can be targeted in the 
setting of viral myocarditis.