Targeted postmortem testing to identify genetic mutations associated with sudden unexplained death (SUD) is an effective and less expensive way to determine risk to relatives than comprehensive cardiac testing of first degree relatives, according to research presented at the American Heart Association's Scientific Sessions 2009.
Postmortem genetic testing can identify mutations that cause cellular dysfunctions leading to heart rhythm disturbances that can cause sudden cardiac death. Such inherited genetic defects occur in 25 to 30 percent of SUD victims, according to lead researcher Michael J. Ackerman, M.D., Ph.D., pediatric cardiologist and director of the Long QT Syndrome Clinic and the Windland Smith Rice Sudden Death Genomics Laboratory at the Mayo Clinic in Rochester, Minn.
Ackerman and senior research technologist David Tester, B.S., compared the yield and costs of postmortem genetic/molecular autopsy testing in 146 SUD cases. They found that 40 of the victims (26.7 percent) had either a catecholaminergic polymorphic ventricular tachycardia (CPVT) mutation (18) or a long QT syndrome mutation (22), both known contributors to sudden death.
Researchers estimated the costs of testing 160 relatives of victims who tested positive for mutations. The tests included genetic tests and either treadmill stress tests or electrocardiograms.
For the 424 relatives of the 106 victims who tested negative for mutations, researchers estimated the cost to do more extensive clinical cardiac testing.
Researchers estimated that the total cost of doing postmortem genetic testing, genetic confirmation testing of relatives of mutation-positive victims, followed by cardiac tests for both relatives of mutation-positive and mutation-negative SUD victims, was $6.78 million.
In contrast, the total cost associated with what is currently recommended - comprehensive cardiac testing for all 584 relatives of the SUD victims, regardless of mutation status, followed by directed genetic testing - would have exceeded $7.7 million.
The researchers' primary endpoint, which they reached, was to see if the postmortem testing model would be less expensive and, if so, how great the savings might be.
"With less than 150 SUD cases, use of a cardiac channel molecular autopsy would be estimated to save almost $1 million dollars indicating a much less expensive way of evaluating those left behind," Tester said. "If you identify a mutation in a sudden unexplained death victim, you can do a simple genetic test in first-degree relatives to assess their risk and perform a disorder-directed clinical evaluation rather than a full clinical evaluation. If a relative is negative for the causative mutation, they may not need to undergo further clinical evaluation at all, and that saves money."