Abstract 1894: Cost Comparison Between Postmortem Genetic Testing and First Degree Relative Clinical Testing Following Autopsy Negative Sudden Unexplained Death
Background: Cardiac testing among living first degree relatives of an autopsy negative sudden unexplained death (SUD) victim or postmortem genetic testing identify catecholaminergic polymorphic ventricular tachycardia (CPVT) and long QT syndrome (LQTS) in about 25 – 35% of families. Costs associated with a decedent-focused molecular autopsy compared to the recommended cardiac evaluation of relatives have not been examined.
Methods: Mutational analysis of RYR2, KCNQ1, KCNH2, and SCN5A using PCR, DHPLC, and DNA sequencing was completed for 146 SUD cases (89 males, 18 ± 13 years). The estimated cost of postmortem genetic testing was based on commercially available tests and compared to recommended cardiac evaluation (tier 1 - ECG, Holter, treadmill stress test, echocardiography and consultation; tier 2 -epinephrine QT stress test, procainamide challenge, and cardiac MR) of 4 first degree relatives/decedent. Pathogenic mutations were assumed heritable and an estimated 50% of the mutation positive decedent’s first degree relatives would be genotype negative.
Results: 40 (26.7%) SUD victims hosted either a CPVT (18) or LQTS (22) mutation. The cost of primary postmortem genetic testing for the 146 decedents followed by family specific mutation testing among the 160 relatives of positive index cases, directed cardiologic testing, and clinical testing for the 424 relatives of the mutation negative SUDS cases would have been $6,780,558 (molecular autopsy, $1,165,554; family mutation testing, $144,000, directed cardiologic testing, $70,516; cardiac evaluation for mutation negative family members, $5,400,488). In contrast, the total cost associated with primary cardiac evaluation of all 584 SUD victim relatives followed by directed genetic testing would have exceeded $7.7 million ($2,743,048 for tier 1 testing, $4,695,360 for tier 2 tests, and $285,282 for genetic testing).
Conclusions: The cost of comprehensive clinical testing of first degree relatives of an autopsy negative SUD victim was $1 million higher than a primary, decedent focused cardiac channel molecular autopsy. Currently however, evaluations of the surviving family members are insurance covered medical expenses whereas postmortem genetic testing has generally been denied.
This research has received full or partial funding support from the American Heart Association, National Center.