AHA: Postmortem genetic testing may be inexpensive way to ID familial risk

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Orlando, Fla.—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 a study presented Sunday at the 2009 American Heart Association scientific sessions. The researchers also called for more health insurance coverage for these tests.

Postmortem genetic testing can identify mutations that cause cellular dysfunctions leading to heart rhythm disturbances that can cause sudden cardiac death, according to lead researcher Michael J. Ackerman, MD, PhD, director of the Long QT Syndrome Clinic and the Windland Smith Rice Sudden Death Genomics Laboratory at the Mayo Clinic in Rochester, Minn. Ackerman presented the research at the conference.

He said that “such inherited genetic defects occur in 25 to 30 percent of SUD victims.”

The researchers 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 mutation (18 percent) or a long QT syndrome mutation (22 percent), both known contributors to sudden death.

In the study, they 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.

Ackerman and colleagues 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 primary endpoint, which was achieved, was to see if the postmortem testing model would be less expensive, and to assess those actual savings.

"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," Ackerman 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."

Ackerman noted that insurance companies pay for comprehensive cardiac testing for family members despite the fact that commercial molecular/genetic testing of the deceased can provide just as accurate a risk profile and in many cases minimize the need for clinical testing.

"We are reporting that there is data available to make such cardiac risk evaluations on both sides of the grave," he said. "The real question is whether it is more prudent and effective to have sudden unexplained death surveillance in autopsy-negative cases. Some insurers cover postmortem gene testing, but it is the exception, not the rule."

The prevalence of the mutations in the SUD autopsies and first-degree relatives was comparable to rates reported by European researchers.

"Clinical screening can be much more selective if there is postmortem gene testing for the defects that result in sodium and potassium channelopathies," added Ackerman. "Currently, however, evaluations of the surviving family members are insurance-covered medical expenses whereas postmortem genetic testing has generally been denied."

Ackerman acknowledged that the study had limitations and needs to be corroborated by further research.

The study was funded in part by an American Heart Association research grant.