Incidence of cardiac fibrosis in SUDEP and control cases.

Abstract

Since cardic fibrosis was previously found more frequently in patients with sudden unexpected death in epilepsy (SUDEP) than control cases, we compared blinded and quantitative reviews of cardiac pathology in SUDEP to multiple control groups. We adjudicated causes of death in epilepsy patients as part of consecutive out-of-hospital sudden cardiac deaths (SCDs) from the Postmortem Systematic Investigation of Sudden Cardiac Death (POSTSCD) study. Blinded cardiac gross and microscopic examinations were performed by forensic and cardiac pathologists. Of 541 SCDs over 37 months (mean age 62.8 years, 69% male), 525 (97%) were autopsied; 25/525 (4.8%) had epilepsy (mean age 56.4 years ± 15.4, range 27-92; 67% male). The 25 epilepsy patients died of definite SUDEP/definite SUDEP-plus (n = 8), possible SUDEP (n = 10), or other causes (n = 7). Comparison groups included autopsy-defined sudden arrhythmic death (SAD; n = 285) and trauma (n = 104) and we adjusted for age, sex, HIV, coronary artery disease, congestive heart failure, and cardiomyopathy in the analyses. Compared to SAD cases, SUDEP cases had less gross and histologic evidence of cardiac pathology; significant for cardiac mass (p < 0.0011), coronary artery disease (p < 0.0024), total cardiac fibrosis (CF) (p = 0.022), and interstitial CF (p = 0.013). Compared to trauma cases, SUDEP cases had similar cardiac pathology including CF. Among SUDEP cases, cardiac pathology was less severe than in SAD cases but similar to trauma and epilepsy controls. Our data do not support prior studies finding elevated rates of CF among SUDEP cases compared to controls. Larger studies including molecular analyses would further our understanding of cardiac changes associated with SUDEP.