Sudden Cardiac Death With Autopsy Findings of Uncertain Significance

• DOI: 10.1161/circep.113.000111
• Publication Date: 2013-05-14T04:58:29Z
• Authors: Michael Papadakis; Hariharan Raju; Elijah R. Behr; Sofia V. De Noronha; Nicholas Spath; Alexandros Koulou...; Mary N. Sheppard; Sanjay Sharma
• Keywords: Adult; Male; Adolescent; Biopsy, Needle; DNA Mutational Analysis; Middle Aged; Immunohistochemistry; 3. Good health; Cohort Studies; Long QT Syndrome; 03 medical and health sciences; Death, Sudden, Cardiac; 0302 clinical medicine; Cause of Death; Child, Preschool; Humans; Female; Genetic Predisposition to Disease; Autopsy; Genetic Testing; Cardiomyopathies; Child; Retrospective Studies

Background— The sudden death of young individuals is commonly attributed to inherited cardiac disorders, and familial evaluation is advocated. The identification of pathognomonic histopathologic findings, or the absence of cardiac pathology (sudden arrhythmic death syndrome [SADS]) at postmortem, directs familial evaluation targeting structural disorders or primary arrhythmogenic syndromes, respectively. In a proportion of autopsies, structural abnormalities of uncertain significance are reported. We explored the hypothesis that such sudden cardiac deaths represent SADS.

Methods and Results—

Families (n=340) of index cases of sudden cardiac deaths who underwent postmortem evaluation were evaluated in specialist cardiogenetics clinics. Families in whom the deceased exhibited structural abnormalities of uncertain significance (n=41), such as ventricular hypertrophy, myocardial fibrosis, and minor coronary artery disease, were included in the study. Results were compared with 163 families with normal postmortem (SADS). Relatives underwent comprehensive cardiac evaluation. Twenty-one families (51%) with autopsy findings of uncertain significance received a diagnosis based on the identification of an inherited cardiac condition phenotype in ≥1 relatives: 14 Brugada syndrome; 4 long-QT syndrome; 1 catecholaminergic polymorphic ventricular tachycardia; and 2 cardiomyopathy. A similar proportion of families (47.2%) received a diagnosis in the SADS cohort ( P =0.727). An arrhythmogenic syndrome was the predominant diagnosis in both cohorts (46% versus 45%; P =0.863).

Conclusions— Familial evaluation after sudden cardiac deaths with autopsy findings of uncertain significance identified a similar proportion of primary arrhythmogenic syndromes to a contemporary series of SADS. Our study highlights the need for accurate interpretation of autopsy findings to avoid erroneous diagnoses, with potentially devastating implications.