Association of Pathogenic DNA Variants Predisposing to Cardiomyopathy With Cardiovascular Disease Outcomes and All-Cause Mortality

In keeping with our theme of promoting early diagnosis this month, we’re focusing on a  trial published in JAMA Cardiology which reviewed the association of pathogenic DNA variants linked to the development of cardiomyopathy and the consequent outcomes of cardiovascular disease.

According to our research, by 2031, eight million people are expected to live with cardiomyopathy.³ While most of those patients will be in the US, here at home with our high rates of obesity, diabetes and chronic alcohol abuse, indications are that our public healthcare burden from cardiovascular disease will be significant. That’s good news for Pharma companies such as Pfizer, Bristol Myers and Alnylam, who all scored FDA approval for their blockbuster cardiomyopathy drugs last year^1_, less good news for the rest of us.

The genetic variant for inherited cardiomyopathy is well documented, and if caught early, treatment for these patients is clinically actionable, significantly reducing the mortality and morbidity rate in these cases. However, as with most inherited conditions, these patients frequently only present once the condition is established, negating the early-diagnosis effect. On this basis, several clinicians have stated that genomic screening for the pathological variant should, where possible, become standard practice.

Study Method

The study we looked at had enrolled 59 409 individuals from 2 large prospective cohort studies.
The participants were between 40 and 60 years of age, 52% (31,374) were female, and, in both studies, were predominantly white, although other ethnicities were representative. 

Findings

The researchers found that 0.7% of the total cohort had an actionable or likely pathogenic variant that was associated with either cardiomyopathy (0.61% [59]) or hypertrophic cardiomyopathy (73% [364]).
The risk of death increased 1.5-1.7-fold in these patients.
Despite clinical care given, there was a 1.7-1.2-fold increased risk of heart failure and a 2.0-2.9-fold increase in atiral fibrillation in these patients.

Conclusions

The authors state that the success in identifying these patients through standard practice diagnostics, such as ECG, would be variable. Therefore adopting a 'genome-first approach' may significantly improve early diagnosis and adoption of appropriate risk management strategies, thereby reducing mortality and morbidity associated with these conditions.

Access the original research investigation here

Patel AP, Dron JS, Wang M, et al. Association of Pathogenic DNA Variants Predisposing to Cardiomyopathy With Cardiovascular Disease Outcomes and All-Cause Mortality. JAMA Cardiol. 2022;7(7):723–732. doi:10.1001/jamacardio.2022.0901 
 

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