Sudden cardiac death affects 220,000 US adults annually, most of whom have no previous symptoms of a heart problem. By identifying rare DNA variants that significantly increase the risk of sudden cardiac death, researchers led by researchers from the Massachusetts Hospital (MGH) and the MIT and Harvard Broad Institute have laid the foundations for efforts to identify people who could benefit from prevention strategies before experiencing symptoms.
Scientists also determine that such variants are present in approximately 1
The results were presented at scientific sessions of the American Heart Association and published in the Journal of the American College of Cardiology .
The authors sequenced genes in 600 cases of sudden cardiac death in adults and 600 controls that remained healthy – the largest such study to date and the first control group used. A clinical geneticist examined all identified DNA variants, classifying 15 as clinically important pathogenic variants.
"It is amazing that all 15 of these pathogenic variants were in cases of sudden cardiac death without any control," says lead author Amit V. Kera, MD, cardiologist and associate director of the Precision Medicine Unit at the MGH Center for Genomic Medicine and the Greater Institute for Cardiovascular Diseases. The prevalence of the pathogenic variant was found to be 2.5 percent in cases and 0 percent in controls.
The researchers then examined the genes of 4,525 middle-aged adults without any sign of heart disease, finding that 41 (0.9 percent) carried the pathogenic variant. These individuals have been followed for more than 14 years, and those who have inherited the pathogenic variant were more than 3 times more likely to die from cardiovascular causes.
“In my clinical practice, I often meet families devastated by sudden and unexpected death. This finding indicates that genetic testing – if widely available – can provide a way to identify high-risk individuals currently flying under the radar. If identified, we have different approaches proven to prevent the onset of the disease within routine clinical practice
In addition to Kerr, the research team was led by Sekar Katiresan, MD, CEO of Verve Therapeutics; Anthony Philippakis, MD, Cardiologist and Chief Data Officer at the Broad Institute; and Christine Albert, MD, MD, Department of Cardiology at the Smiths Heart Institute in Keders-Sinai
Based on these results, Kher and colleagues plan to perform genetic sequencing tests on thousands of adult patients at MGH and affiliated hospitals who have voluntarily joined a research program designed to understand how genetic and environmental influences the risk of major diseases. They aim to find 1% of people with rare genetic variants related to heart disease, and offer tailored prevention programs at the Cardiovascular Genetics Program or the new MGH Preventive Genealogy Clinic, which Khera is a leader in primary care.  "It is our hope to enable our patients to better understand, predict and prevent poor health outcomes – especially irreversible tragedies such as sudden cardiac death – using genetic information," Kera said.
Molecular autopsy may shed light on sudden death in young
Amit V. Khera et al, Rare genetic variants associated with sudden cardiac death in adults, Journal of the American College of Cardiology (2019). Doi: 10.1016 / j.jacc.2019.08.1060
Rare genetic variants predispose to sudden cardiac death (2019, November 16)
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