Forty percent of deaths attributed to stated cardiac arrest were not sudden or unexpected, and nearly half of presumed SCDs were not arrhythmic. These findings have implications for the accuracy of SCDs as defined by WHO criteria or emergency medical services records in aggregate mortality data, clinical trials, and cohort studies.

Interrogations and autopsies of sudden deaths with cardiac implantable electronic devices (CIEDs) are rarely performed. Therefore, causes of sudden deaths with these devices and the incidence of device failure are unknown.OBJECTIVE To determine causes of death in individuals with CIEDs in a prospective autopsy study of all sudden deaths over 35 months as part of the San Francisco, California, Postmortem Systematic Investigation of Sudden Cardiac Death (POST SCD) study. DESIGN, SETTING, AND PARTICIPANTS Full autopsy, toxicology, histology, and device interrogation were performed on incident sudden cardiac deaths with pacemakers or implantable cardioverter defibrillators (ICDs). The setting was the Office of the Chief Medical Examiner, City and County of San Francisco. Participants included all sudden deaths captured through active surveillance of all deaths reported to the medical examiner and San Francisco residents with an ICD (January 1, 2011, to November 30, 2013). MAIN OUTCOMES AND MEASURESIdentification of a device concern in sudden deaths with CIEDs, including hardware failures, device algorithm issues, device programming issues, and improper device selection. For the ICD population, outcomes were the cumulative incidence of death and sudden cardiac death and the proportion of deaths with an ICD concern.RESULTS Twenty-two of 517 sudden deaths (4.3%) had CIEDs, and autopsy revealed a noncardiac cause of death in 6. Six of 14 pacemaker sudden deaths and 7 of 8 ICD sudden deaths died of ventricular tachycardia or ventricular fibrillation. Device concerns were identified in half (4 pacemakers and 7 ICDs), including 3 hardware failures contributing directly to death (1 rapid battery depletion with a sudden drop in pacing output and 2 lead fractures), 5 ICDs with ventricular fibrillation undersensing, 1 ICD with ventricular tachycardia missed due to programming, 1 improper device selection, and a pacemaker-dependent patient with pneumonia and concern about lead fracture. Of 712 San Francisco residents with an ICD during the study period, 109 died (15.3% cumulative 35-month incidence of death), and the 7 ICD concerns represent 6.4% of all ICD deaths. CONCLUSIONS AND RELEVANCE Systematic interrogation and autopsy of sudden deaths in one city identified concerns about CIED function that might otherwise not have been observed. Current passive surveillance efforts may underestimate device malfunction. These methods can provide unbiased data regarding causes of sudden death in individuals with CIEDs and improve surveillance for CIED problems.

Background Sudden cardiac death (SCD) remains a major public health problem; however, its true burden remains unknown with widely variable estimates of its incidence. We aimed to examine the contemporary epidemiology and autopsy characteristics of SCD in an ethnically diverse community. Methods 3 physicians reviewed all deaths age ≥ 20 years reported to the San Francisco Medical Examiner (ME) in 2007 for presentations fitting WHO SCD criteria -- within 1 hour of symptom onset (witnessed) or within 24 hours of being observed alive and symptom-free (unwitnessed). After comprehensive review of ME investigation, WHO SCDs were classified as sudden arrhythmic death (SAD) or non-arrhythmic death. Coronary artery disease (CAD) and cardiac mass were evaluated in all SADs undergoing autopsy and compared to demographically similar accidental trauma control deaths. Results We identified 252 WHO SCDs; 145 were SADs. Men had a 2.2-fold higher SAD rate (p<0.0005). Blacks had a 3.15-fold higher SAD rate compared to Caucasians (p = 0.003). Significant CAD was present in 38.9% of SADs and associated with higher SAD risk compared to control deaths (OR 2.58, 95% CI 1.12–5.97, p=0.026). Mean cardiac mass was linearly associated with risk for SAD in cases without significant CAD (OR 2.06 per 100g, 95% CI 1.43–2.98, p<0.0005). Conclusions In a diverse, urban population, SAD incidence varied substantially by gender and race. Significant CAD accounted for far fewer SADs than previous studies, but remained associated with a 2.6-fold higher risk as compared to control deaths. These findings may reflect the evolving contemporary epidemiology of SCD.

IMPORTANCE QT-prolonging medications (QTPMs) are a reported risk factor for sudden cardiac death (SCD) when defined by consensus criteria that presume an arrhythmic cause. The effect of QTPM on autopsy-defined sudden arrhythmic death (SAD) is unknown.OBJECTIVE To evaluate the association between QTPM and autopsy-defined SAD vs nonarrhythmic cause of sudden death. DESIGN, SETTING, AND PARTICIPANTS This prospective countywide case-control study included World Health Organization-defined (presumed) SCD cases who underwent autopsy as part of the San Francisco Postmortem Systematic Investigation of Sudden Cardiac Death Study (POST SCD) to determine arrhythmic or nonarrhythmic cause, and control deaths due to trauma (hereinafter referred to as trauma controls) in San Francisco County, California, from February 1, 2011, to March 1, 2014. Multivariate regression was used to evaluate the association of QTPM with the risk of presumed SCD, autopsy-defined SAD, and non-SAD compared with trauma controls. Medication exposure, determined by prescription lists and postmortem toxicologic findings, was used to calculate a summative QTPM exposure score (range, 0-20). Data were analyzed from September 1, 2018, to June 15, 2019. EXPOSURE QT-prolonging medication exposure, as measured by QTPM score (1 indicated low; 2-4, moderate; and >4, high). MAIN OUTCOMES AND MEASURES Death due to trauma, presumed SCD, and autopsy-defined non-SAD and SAD with no postmortem findings of extracardiac cause. RESULTS A total of 629 patients (mean [SD] age, 61.4 [15.7] years; 439 men [69.8%]) were included, 525 with presumed SCDs and 104 traumatic death controls. Individuals with presumed SCDs had higher exposure and were more likely to be taking any QTPM (291 [55.4%] vs 28 [26.9%]; P < .001) than trauma controls. Use of QTPMs was associated with increased risk of presumed SCD in low (odds ratio [OR], 2.25 [95% CI, 1.03-4.96]; P = .04) and high (OR, 6.70 [95% CI,]; P = .01) exposure groups. After autopsy adjudication, use of QTPMs was associated with increased risk of non-SAD (low-risk OR, 2.88 [95% CI, 1.18-6.99; P = .02]; moderate-risk OR, 2.62 [95% CI, 1.20-5.73; P = .02]; and high-risk OR, 14.22 [95% CI, 2.91-69.30; P = .001]) but not SAD in all exposure groups. This association was attenuated by the exclusion of occult overdose non-SADs in the highest exposure group. CONCLUSIONS AND RELEVANCEThese findings confirm the association between QTPMs and presumed SCD; however, after autopsy, this risk was specific for nonarrhythmic causes of sudden death. Studies using consensus SCD criteria may overestimate the association of QTPMs with the risk of SAD.

Polymerase chain reaction (PCR) technique is widely used in the diagnosis of lymphoma, and PCR amplification products are typically detected by polyacrylamide gel electrophoresis (PAGE). However, the identification of small clonal populations, or the distinction of clonal PCR products in a polyclonal milieu remains difficult, requiring technically demanding alterations to gel analysis. This study describes an alternative approach using a capillary electrophoresis (CE) system to produce an accurately sized electropherogram. A variety of patient samples were examined, including solid tissue, peripheral blood, bone marrow aspirates, and paraffin-embedded tissue. A total of 28 samples were evaluated by PCR for B-cell clonality by detection of immunoglobulin heavy chain gene rearrangement and 29 samples for T-cell clonality by detection of T-cell gamma locus gene rearrangement. Standard 10% PAGE analysis of PCR products was compared with CE. There was a 100% concordance in the assessment of both B-cell and T-cell clonality. Dilution studies with the SUP-B15 cell line showed a detection limit of 0.03% for B-cell clonality and 0.05% for T-cell clonality using CE, versus 0.2% to 1%, respectively for PAGE. Automated, fluorescent analysis of PCR products by CE seems to be at least equally as effective as gel-based analysis for the detection of clonal B-cell and T-cell populations. Moreover. CE offers superior resolution and improved sensitivity, thus representing a significant improvement over traditional gel electrophoretic techniques in these regards.