Precision medicine for cardiomyopathies holds great promise to improve patient outcomes costs by shifting the focus to patient-specific treatment decisions, maximising the use of therapies most likely to lead to benefit and minimising unnecessary intervention. Dilated cardiomyopathy (DCM), characterised by left ventricular dilatation and impairment, is a major cause of heart failure globally. Advances in genomic medicine have increased our understanding of the genetic architecture of DCM. Understanding the functional implications of genetic variation to reveal genotype-specific disease mechanisms is the subject of intense investigation, with advanced cardiac imaging and mutliomics approaches playing important roles. This may lead to increasing use of novel, targeted therapy. Individualised treatment and risk stratification is however made more complex by the modifying effects of common genetic variation and acquired environmental factors that help explain the variable expressivity of rare genetic variants and gene elusive disease. The next frontier must be expanding work into early disease to understand the mechanisms that drive disease expression, so that the focus can be placed on disease prevention rather than management of later symptomatic disease. Overcoming these challenges holds the key to enabling a paradigm shift in care from the management of symptomatic heart failure to prevention of disease.

A female baby suffered from a rare association between histiocytoid cardiomyopathy, left ventricular non-compaction, and Wolff–Parkinson–White syndrome causing severe and recurrent arrhythmic storms. Antiarrhythmic drugs, radiofrequency ablation of Purkinje tissue, and sympathetic denervation were ineffective. The implant of a cardiac defibrillator allowed her to survive till heart transplant. Compound mutation of CACNA2D1 and RANGRF genes were found. To the best of our knowledge, this is the first comprehensive description of the concurrence of these two mutations and histiocytoid cardiomyopathy.