Dr. Robert Myerburg Explores Genetic Links to Sudden Cardiac Death

Renowned cardiologist publishes two papers in current issue of Circulation

Cardiologist Robert J. Myerburg, M.D., at the University of Miami Miller School of Medicine, and colleagues at the University of Oulu in Finland have uncovered genetic links that offer new explanations for some sudden cardiac deaths in young people.

Robert J. Myerburg, M.D.

Myocardial fibrosis — a pattern of scarring of the cardiac muscle — is a common postmortem finding in such cases. There is no known single cause, and in some individuals, there is no identifiable cause at all. This led the investigators to collaborate in an original research study to explore the hypothesis that some cases of myocardial fibrosis in relatively young victims of sudden death are associated with genetic variants.

Despite the geographic distance between Miami and Finland, the collaboration is no surprise. The leaders of the Finnish team, M. Juhani Junttila, M.D., and Heikki V. Huikuri, M.D., are both former research fellows at the Miller School. They and Myerburg formed a strong research relationship and have co-authored more than 50 papers together.

“They have a tremendous amount of pathology data available to them,” said Myerburg, who is professor of medicine and physiology and the American Heart Association Chair in Cardiovascular Research. “I suggested a study taking a genetic approach, and it was well worth the effort.”

The researchers began with tissue samples obtained during the autopsies of 4,031 people in northern Finland who had experienced sudden cardiac death. In 145 subjects, primary myocardial fibrosis was the only structural finding, and targeted next-generation sequencing was performed on the samples. Of those subjects, 96 had DNA samples that passed quality controls. After study, 26 subjects were found to have at least one of 24 genetic variants.

“Our research suggests that primary myocardial fibrosis can be an alternative phenotypic expression of structural disease-associated genetic variants or that risk-associated fibrosis was expressing before the primary disease,” said Myerburg. “These findings have clinical implications for postmortem screening and genetic testing of family members of the sudden death victims.”

The findings were reported in an article, “Primary Myocardial Fibrosis as an Alternative Phenotype Pathway of Inherited Cardiac Structural Disorders,” published in the journal Circulation on June 18. An accompanying editorial, “Bringing Autopsies into the Molecular Genetic Era,” written by two cardiovascular geneticists at the Medical University of South Carolina and Johns Hopkins University, strongly supported the research findings and the recommendations for postmortem genetic testing.

The same issue carried another article, “Prospective Countywide Surveillance and Autopsy Characterization of Sudden Cardiac Death,” which examined more than 20,000 deaths that occurred over a three-year period in San Francisco County and were attributed to out-of-hospital cardiac arrest.

“Forty percent of deaths attributed to stated cardiac arrest were not sudden or unexpected, and nearly half of presumed sudden cardiac deaths were not arrhythmic,” wrote the authors. “These findings have implications for the accuracy of sudden cardiac deaths as defined by World Health Organization criteria or emergency medical services records in aggregate mortality data, clinical trials, and cohort studies.”

Myerburg was asked to provide commentary on that study, and his editorial, “Cardiac and Noncardiac Causes of Apparent Sudden Arrhythmic Deaths: Shadows in a Spectrum,” also appeared in that issue of Circulation.

Myerburg called the study’s contributions important, but he cautioned against the assumptions that are often made in the absence of timely medical examiner-performed autopsies.

“The data provided in this report support the previous generalization that at least 50 percent of sudden cardiac deaths or sudden cardiac arrests are the first clinical manifestation of previously unrecognized heart disease,” he wrote. “However, the conclusion that 40 percent of events appearing to be sudden cardiac deaths were not sudden or unexpected is sobering and requires our attention as we classify sudden cardiac deaths, and also in the design and execution of future studies on this important topic.”

Tags: genetic variants, myocardial fibrosis, Robert Myerburg, sudden cardiac death