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Review
. 2023 Nov 20:1:e34.
doi: 10.1017/pcm.2023.24. eCollection 2023.

Precision therapy in dilated cardiomyopathy: Pipedream or paradigm shift?

Saad Javed  1   2 , Brian P Halliday  1   2
Affiliations
Review

Precision therapy in dilated cardiomyopathy: Pipedream or paradigm shift?

Saad Javed et al. Camb Prism Precis Med. .

Abstract

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.

Keywords: cardiovascular genetics; dilated cardiomyopathy; gene therapy; heart failure; precision medicine.

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Conflict of interest statement

B.P.H. has served on an advisory board for Astra Zeneca. S.J. declares no competing interest.

Figures

Figure 1.
Figure 1.
Dilated cardiomyopathy (DCM) – a family of diseases. Selected syndromic causes of dilated cardiomyopathy include Barth syndrome, haemochromatosis, Kearns–Sayre syndrome, and Carvajal syndrome (adapted with permission from Halliday, 2022).
Figure 2.
Figure 2.
Precision therapies for genotype-positive, phenotype-negative (G+ P−) individuals would likely involve genotype-specific therapies, and lifestyle interventions. Treatments that could be introduced at an early disease stage include anti-fibrotic agents, and therapies to target cardiac metabolism (such as SGLT2 inhibitors) whereas advanced disease therapies include antiarrhythmics for those at the highest risk, ICD therapy and guideline-directed heart failure therapy (GDMT) (HF, heart failure; LVSD, left ventricular systolic dysfunction).
Figure 3.
Figure 3.
Cellular locations of some of the proteins with their respective genes associated with dilated cardiomyopathy.
Figure 4.
Figure 4.
Precision medicine for dilated cardiomyopathy.
See this image and copyright information in PMC

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