Homelessness and Incidence and Causes of Sudden Death: Data From the POST SCD Study.

Importance: Over 580 000 people in the US experience homelessness, with one of the largest concentrations residing in San Francisco, California. Unhoused individuals have a life expectancy of approximately 50 years, yet how sudden death contributes to this early mortality is unknown. Objective: To compare incidence and causes of sudden death by autopsy among housed and unhoused individuals in San Francisco County. Design, Setting, and Participants: This cohort study used data from the Postmortem Systematic Investigation of Sudden Cardiac Death (POST SCD) study, a prospective cohort of consecutive out-of-hospital cardiac arrest deaths countywide among individuals aged 18 to 90 years. Cases meeting World Health Organization criteria for presumed SCD underwent autopsy, toxicologic analysis, and medical record review. For rate calculations, all 525 incident SCDs in the initial cohort were used (February 1, 2011, to March 1, 2014). For analysis of causes, 343 SCDs (incident cases approximately every third day) were added from the extended cohort (March 1, 2014, to December 16, 2018). Data analysis was performed from July 1, 2022, to July 1, 2023. Main Outcomes and Measures: The main outcomes were incidence and causes of presumed SCD by housing status. Causes of sudden death were adjudicated as arrhythmic (potentially rescuable with implantable cardioverter-defibrillator), cardiac nonarrhythmic (eg, tamponade), or noncardiac (eg, overdose). Results: A total of 868 presumed SCDs over 8 years were identified: 151 unhoused individuals (17.4%) and 717 housed individuals (82.6%). Unhoused individuals compared with housed individuals were younger (mean [SD] age, 56.7 [0.8] vs 61.0 [0.5] years, respectively) and more often male (132 [87.4%] vs 499 [69.6%]), with statistically significant racial differences. Paramedic response times were similar (mean [SD] time to arrival, unhoused individuals: 5.6 [0.4] minutes; housed individuals: 5.6 [0.2] minutes; P = .99), while proportion of witnessed sudden deaths was lower among unhoused individuals compared with housed individuals (27 [18.0%] vs 184 [25.7%], respectively, P = .04). Unhoused individuals had higher rates of sudden death (incidence rate ratio [IRR], 16.2; 95% CI, 5.1-51.2; P < .001) and arrhythmic death (IRR, 7.2; 95% CI, 1.3-40.1; P = .02). These associations remained statistically significant after adjustment for differences in age and sex. Noncardiac causes (96 [63.6%] vs 270 [37.7%], P < .001), including occult overdose (48 [31.8%] vs 90 [12.6%], P < .001), gastrointestinal causes (8 [5.3%] vs 15 [2.1%], P = .03), and infection (11 [7.3%] vs 20 [2.8%], P = .01), were more common among sudden deaths in unhoused individuals. A lower proportion of sudden deaths in unhoused individuals were due to arrhythmic causes (48 of 151 [31.8%] vs 420 of 717 [58.6%], P < .001), including acute and chronic coronary disease. Conclusions and Relevance: In this cohort study among individuals who experienced sudden death in San Francisco County, homelessness was associated with greater risk of sudden death from both noncardiac causes and arrhythmic causes potentially preventable with a defibrillator.

Mechanical Dispersion Discriminates between Arrhythmic and Non-Arrhythmic Sudden Death: From the POST SCD Study.

Background: Global longitudinal strain (GLS) and mechanical dispersion (MD) by speckle-tracking echocardiography can predict sudden cardiac death (SCD) beyond left ventricular ejection fraction (LVEF) alone. However, prior studies have presumed cardiac cause from EMS records or death certificates rather than gold-standard autopsies. Objectives: We sought to investigate whether abnormal GLS and MD, reflective of underlying myocardial fibrosis, are associated with autopsy-defined sudden arrhythmic death (SAD) in a comprehensive postmortem study. Methods: We identified and autopsied all World Health Organization-defined (presumed) SCDs ages 18-90 via active surveillance of out of hospital deaths in the ongoing San Francisco POstmortem Systematic InvesTigation of Sudden Cardiac Death (POST SCD) Study to refine presumed SCDs to true cardiac causes. We retrieved all available pre-mortem echocardiograms and assessed LVEF, LV-GLS, and MD. The extent of LV myocardial fibrosis was assessed and quantified histologically. Results: Of 652 autopsied subjects, 65 (10%) had echocardiograms available for primary review, obtained at a mean 1.5 years before SCD. Of these, 37 (56%) were SADs and 29 (44%) were non-SADs; fibrosis was quantified in 38 (58%). SADs were predominantly male, but had similar age, race, baseline comorbidities, and LVEF compared to non-SADs (all p>0.05). SADs had significantly reduced LV-GLS (median: -11.4% versus -18.5%, p=0.008) and increased MD (median: 14.8 ms versus 9.4 ms, p=0.006) compared to non-SADs. MD was associated with total LV fibrosis by linear regression in SADs (r=0.58, p=0.002). Conclusion: In this countywide postmortem study of all sudden deaths, autopsy-confirmed arrhythmic deaths had significantly lower LV-GLS and increased MD than non-arrhythmic sudden deaths. Increased MD correlated with higher histologic levels of LV fibrosis in SADs. These findings suggest that increased MD, which is a surrogate for the extent of myocardial fibrosis, may improve risk stratification and specification for SAD beyond LVEF. PERSPECTIVES: Competency in medical knowledge: Mechanical dispersion derived from speckle tracking echocardiography provides better discrimination between autopsy-defined arrhythmic vs non-arrhythmic sudden death than LVEF or LV-GLS. Histological ventricular fibrosis correlates with increased mechanical dispersion in SAD.Translational outlook: Speckle tracking echocardiography parameters, in particular mechanical dispersion, may be considered as a non-invasive surrogate marker for myocardial fibrosis and risk stratification in SCD.

Heart Failure Burden by Autopsy, Guideline-Directed Medical Therapy, and ICD Utilization Among Sudden Deaths.

BACKGROUND: Studies of heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF) report high sudden cardiac death (SCD) rates but presume cardiac cause. Underlying causes, guideline-directed medical therapy (GDMT), and implantable cardioverter-defibrillator (ICD) use in community sudden deaths with heart failure (HF) are unknown. OBJECTIVES: This study aims to assess the burden of HF, GDMT, and ICD use among autopsied sudden deaths in the POST SCD (Postmortem Systematic Investigation of Sudden Cardiac Death) study, a countywide postmortem study of all presumed SCDs. METHODS: Incident WHO-defined (presumed) SCDs for individuals of ages 18 to 90 years were autopsied via prospective surveillance of consecutive out-of-hospital deaths in San Francisco County from February 1, 2011, to March 1, 2014. Sudden arrhythmic deaths (SADs) had no identifiable nonarrhythmic cause (eg, pulmonary embolism), and are thus considered potentially rescuable with ICD. RESULTS: Of 525 presumed SCDs, 100 (19%) had HF. There were 85 patients with known HF (31 HFpEF, 54 HFrEF) and 15 with subclinical HF (postmortem evidence of cardiomyopathy and pulmonary edema without HF diagnosis). SADs comprised 56% (293 of 525) of all presumed SCDs, and 69% (69 of 100) of HF SCDs. The rates were similar in HFrEF (40 of 54 [74%]) and HFpEF (19 of 31 [61%], P = 0.45). Four SAD patients (4%) had ICDs, 3 of which experienced device failure. Twenty-eight SCDs had ejection fraction ≤35%: 22 (79%) with arrhythmic and 6 (21%) with noncardiac causes. Of the 22 SAD patients, 8 (36%) had no identifiable barrier to ICD referral. Complete use of GDMT in HFrEF was 6%. CONCLUSIONS: One in 5 community sudden deaths had HF; two-thirds had autopsy-confirmed arrhythmic causes. ICD prevention criteria captured only 8% (22 of 293) of all SAD cases countywide; GDMT and ICD use remain important targets for HF sudden death prevention.

Sudden Cardiac Death and Myocardial Fibrosis, Determined by Autopsy, in Persons with HIV.

BACKGROUND: The incidence of sudden cardiac death and sudden death caused by arrhythmia, as determined by autopsy, in persons with human immunodeficiency virus (HIV) infection has not been clearly established. METHODS: Between February 1, 2011, and September 16, 2016, we prospectively identified all new deaths due to out-of-hospital cardiac arrest among persons 18 to 90 years of age, with or without known HIV infection, for comprehensive autopsy and toxicologic and histologic testing. We compared the rates of sudden cardiac death and sudden death caused by arrhythmia between groups. RESULTS: Of 109 deaths from out-of-hospital cardiac arrest among 610 unexpected deaths in HIV-positive persons, 48 met World Health Organization criteria for presumed sudden cardiac death; of those, fewer than half (22) had an arrhythmic cause. A total of 505 presumed sudden cardiac deaths occurred between February 1, 2011, and March 1, 2014, in persons without known HIV infection. Observed incidence rates of presumed sudden cardiac death were 53.3 deaths per 100,000 person-years among persons with known HIV infection and 23.7 deaths per 100,000 person-years among persons without known HIV infection (incidence rate ratio, 2.25; 95% confidence interval [CI], 1.37 to 3.70). Observed incidence rates of sudden death caused by arrhythmia were 25.0 and 13.3 deaths per 100,000 person-years, respectively (incidence rate ratio, 1.87; 95% CI, 0.93 to 3.78). Among all presumed sudden cardiac deaths, death due to occult drug overdose was more common in persons with known HIV infection than in persons without known HIV infection (34% vs. 13%). Persons who were HIV-positive had higher histologic levels of interstitial myocardial fibrosis than persons without known HIV infection. CONCLUSIONS: In this postmortem study, the rates of presumed sudden cardiac death and myocardial fibrosis were higher among HIV-positive persons than among those without known HIV infection. One third of apparent sudden cardiac deaths in HIV-positive persons were due to occult drug overdose. (Supported by the National Heart, Lung, and Blood Institute.).

Factors Predisposing to Survival After Resuscitation for Sudden Cardiac Arrest.

BACKGROUND: In the POST SCD study, the authors autopsied all World Health Organization (WHO)-defined sudden cardiac deaths (SCDs) and found that only 56% had an arrhythmic cause; resuscitated sudden cardiac arrests (SCAs) were excluded because they did not die suddenly. They hypothesized that causes underlying resuscitated SCAs would be similarly heterogeneous. OBJECTIVES: The aim of this study was to determine the causes and outcomes of resuscitated SCAs. METHODS: The authors identified all out-of-hospital cardiac arrests (OHCAs) from February 1, 2011, to January 1, 2015, of patients aged 18 to 90 years in San Francisco County. Resuscitated SCAs were OHCAs surviving to hospitalization and meeting WHO criteria for suddenness. Underlying cause was determined by comprehensive record review. RESULTS: The authors identified 734 OHCAs over 48 months; 239 met SCA criteria, 133 (55.6%) were resuscitated to hospitalization, and 47 (19.7%) survived to discharge. Arrhythmic causes accounted for significantly more resuscitated SCAs overall (92 of 133, 69.1%), particularly among survivors (43 of 47, 91.5%), than WHO-defined SCDs in POST SCD (293 of 525, 55.8%; p < 0.004 for both). Among resuscitated SCAs, arrhythmic cause, ventricular tachycardia/fibrillation initial rhythm, and white race were independent predictors of survival. None of the resuscitated SCAs due to neurologic causes survived. CONCLUSIONS: In this 4-year countywide study of OHCAs, only one-third were sudden, of which one-half were resuscitated to hospitalization and 1 in 5 survived to discharge. Arrhythmic cause predicted survival and nearly one-half of nonsurvivors had nonarrhythmic causes, suggesting that SCA survivors are not equivalent to SCDs. Early identification of nonarrhythmic SCAs, such as neurologic emergencies, may be a target to improve OHCA survival.

Sex and Racial Differences in Autopsy-Defined Causes of Presumed Sudden Cardiac Death.

[Figure: see text].

Antemortem and Post-Mortem Characteristics of Lethal Mitral Valve Prolapse Among All Countywide Sudden Deaths.

OBJECTIVES: The goal of this study was to investigate the characteristics of mitral valve prolapse (MVP) in a post-mortem study of consecutive sudden cardiac deaths (SCDs) in subjects up to 90 years of age. BACKGROUND: Up to 2.3% of subjects with MVPs experience SCD, but by convention SCD is rarely confirmed by autopsy. In a post-mortem study of persons <40 years of age, 7% of SCDs were caused by MVP; bileaflet involvement, mitral annular disjunction (MAD), and replacement fibrosis were common. METHODS: In the San Francisco POST SCD (Postmortem Systematic Investigation of Sudden Cardiac Death) study, autopsies have been performed on >1,000 consecutive World Health Organization-defined (presumed) cases of SCD in subjects aged 18 to 90 years since 2011; a total of 603 were adjudicated. Autopsy-defined sudden arrhythmic death (SAD) required absence of nonarrhythmic cause; MVP diagnosis required leaflet billowing. One hundred antemortem echocardiograms were revised to identify additional MVPs missed on autopsy. RESULTS: Among the 603 presumed SCDs, 339 (56%) were autopsy-defined SADs, with MVP identified in 7 (1%). Six additional MVPs were identified by review of echocardiograms, for a prevalence of at least 2% among 603 presumed SCDs and 4% among 339 SADs (vs. 264 non-SADs; p = 0.02). All 6 additional MVPs had monoleaflet rather than bileaflet involvement and mild mitral regurgitation, ruling out hemodynamic cause. Less than one-half had MAD with replacement fibrosis, but all had multisite interstitial fibrosis. CONCLUSIONS: In a countywide post-mortem study of all adult cases of SCD, MVP prevalence was at least 4% of SADs, but one-half were missed on autopsy. Monoleaflet MVP was often underdiagnosed post-mortem. Compared with young cases of SCD, lethal MVP in older cases of SCD did not consistently have bileaflet anatomy, replacement fibrosis, or MAD.

NAloxone CARdiac Arrest Decision Instruments (NACARDI) for targeted antidotal therapy in occult opioid overdose precipitated cardiac arrest.

BACKGROUND: We have recently demonstrated that a significant proportion of fatal out-of-hospital cardiac arrests (OHCAs) are precipitated by occult overdose, which could benefit from antidote therapy administered adjunctively with other cardiac resuscitation measures. We sought to develop simple decision instruments that EMS providers and other first responders can use to rapidly identify occult opioid overdose-associated OHCAs. METHODS: We examined data from February 2011 through December 2017 in the Postmortem Systematic Investigation of Sudden Cardiac Death study, in which San Francisco (California) County EMS-attended OHCA deaths received autopsy and expert panel adjudication of cause of death. Using classification tree analyses, we derived highly sensitive and specific decision instruments that predicted our primary outcome of occult opioid OD-associated OHCA. We then calculated screening performance characteristics of these instruments. RESULTS: Of 767 OHCA deaths, 80 (10.4%) were associated with occult opioid overdose. Of the eight models with 100% sensitivity for opioid overdose-associated cardiac arrest, the highest specificity model (23.4%, 95% confidence interval [CI] 20.3-26.7%) was age < 60 years OR race = black or non-Latinx white OR arrest in public place. The highest specificity instrument (96.3%, 95% CI 94.6-97.5%) consisting of age < 60 years AND race = black or non-Latinx white AND unwitnessed arrest AND female sex had 25% (95% CI 16-35.9%) sensitivity. CONCLUSIONS: We have derived simple decision instruments that can identify patients whose OHCA precipitant was occult opioid overdose. These instruments may be used to guide selective administration of the antidote naloxone in OHCA resuscitations.

Association of QT-Prolonging Medications With Risk of Autopsy-Defined Causes of Sudden Death.

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, 1.47-30.67]; 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 Relevance: These 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.

Refining the World Health Organization Definition: Predicting Autopsy-Defined Sudden Arrhythmic Deaths Among Presumed Sudden Cardiac Deaths in the POST SCD Study.

BACKGROUND: Conventional definitions of sudden cardiac death (SCD) presume cardiac cause. We studied the World Health Organization-defined SCDs autopsied in the POST SCD study (Postmortem Systematic Investigation of SCD) to determine whether premortem characteristics could identify autopsy-defined sudden arrhythmic death (SAD) among presumed SCDs. METHODS: Between January 2, 2011, and January 4, 2016, we prospectively identified all 615 World Health Organization-defined SCDs (144 witnessed) 18 to 90 years in San Francisco County for medical record review and autopsy via medical examiner surveillance. Autopsy-defined SADs had no extracardiac or acute heart failure cause of death. We used 2 nested sets of premortem predictors-an emergency medical system set and a comprehensive set adding medical record data-to develop Least Absolute Selection and Shrinkage Operator models of SAD among witnessed and unwitnessed cohorts. RESULTS: Of 615 presumed SCDs, 348 (57%) were autopsy-defined SAD. For witnessed cases, the emergency medical system model (area under the receiver operator curve 0.75 [0.67-0.82]) included presenting rhythm of ventricular tachycardia/fibrillation and pulseless electrical activity, while the comprehensive (area under the receiver operator curve 0.78 [0.70-0.84]) added depression. If only ventricular tachycardia/fibrillation witnessed cases (n=48) were classified as SAD, sensitivity was 0.46 (0.36-0.57), and specificity was 0.90 (0.79-0.97). For unwitnessed cases, the emergency medical system model (area under the receiver operator curve 0.68 [0.64-0.73]) included black race, male sex, age, and time since last seen normal, while the comprehensive (area under the receiver operator curve 0.75 [0.71-0.79]) added use of ß-blockers, antidepressants, QT-prolonging drugs, opiates, illicit drugs, and dyslipidemia. If only unwitnessed cases <1 hour (n=59) were classified as SAD, sensitivity was 0.18 (0.13-0.22) and specificity was 0.95 (0.90-0.97). CONCLUSIONS: Our models identify premortem characteristics that can better specify autopsy-defined SAD among presumed SCDs and suggest the World Health Organization definition can be improved by restricting witnessed SCDs to ventricular tachycardia/fibrillation or nonpulseless electrical activity rhythms and unwitnessed cases to <1 hour since last normal, at the cost of sensitivity.

Prospective Countywide Surveillance and Autopsy Characterization of Sudden Cardiac Death: POST SCD Study.

BACKGROUND: Studies of out-of-hospital cardiac arrest and sudden cardiac death (SCD) use emergency medical services records, death certificates, or definitions that infer cause of death; thus, the true incidence of SCD is unknown. Over 90% of SCDs occur out-of-hospital; nonforensic autopsies are rarely performed, and therefore causes of death are presumed. We conducted a medical examiner-based investigation to determine the precise incidence and autopsy-defined causes of all SCDs in an entire metropolitan area. We hypothesized that postmortem investigation would identify actual sudden arrhythmic deaths among presumed SCDs. METHODS: Between February 1, 2011, and March 1, 2014, we prospectively identified all incident deaths attributed to out-of-hospital cardiac arrest (emergency medical services primary impression, cardiac arrest) between 18 to 90 years of age in San Francisco County for autopsy, toxicology, and histology via medical examiner surveillance of consecutive out-of-hospital deaths, all reported by law. We obtained comprehensive records to determine whether out-of-hospital cardiac arrest deaths met World Health Organization (WHO) criteria for SCD. We reviewed death certificates filed quarterly for missed SCDs. Autopsy-defined sudden arrhythmic deaths had no extracardiac cause of death or acute heart failure. A multidisciplinary committee adjudicated final cause. RESULTS: All 20 440 deaths were reviewed; 12 671 were unattended and reported to the medical examiner. From these, we identified 912 out-of-hospital cardiac arrest deaths; 541 (59%) met WHO SCD criteria (mean 62.8 years, 69% male) and 525 (97%) were autopsied. Eighty-nine additional WHO-defined SCDs occurred within 3 weeks of active medical care with the death certificate signed by the attending physician, ineligible for autopsy but included in the countywide WHO-defined SCD incidence of 29.6/100 000 person-years, highest in black men (P<0.0001). Of 525 WHO-defined SCDs, 301 (57%) had no cardiac history. Leading causes of death were coronary disease (32%), occult overdose (13.5%), cardiomyopathy (10%), cardiac hypertrophy (8%), and neurological (5.5%). Autopsy-defined sudden arrhythmic deaths were 55.8% (293/525) of overall, 65% (78/120) of witnessed, and 53% (215/405) of unwitnessed WHO-defined SCDs (P=0.024); 286 of 293 (98%) had structural cardiac disease. CONCLUSIONS: 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.

Incidence of cardiac fibrosis in SUDEP and control cases.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Underestimation of sudden deaths among patients with seizures and epilepsy.

OBJECTIVE: To determine the definite and potential frequency of seizures and epilepsy as a cause of death (COD) and how often this goes unrecognized. METHODS: Prospective determination of seizures or epilepsy and final COD for individuals aged 18-90 years with out-of-hospital sudden cardiac deaths (SCDs) from the population-based San Francisco POST SCD Study. We compared prospective seizure or epilepsy diagnosis and final COD as adjudicated by a multidisciplinary committee (pathologists, electrophysiologists, and a vascular neurologist) vs retrospective adjudication by 2 epileptologists with expertise in seizure-related mortality. RESULTS: Of 541 SCDs identified during the 37-month study period (mean age 62.8 years, 69% men), 525 (97%) were autopsied; 39/525 (7.4%) had seizures or epilepsy (mean age: 58 years, range: 27-92; 67% men), comprising 17% of 231 nonarrhythmic sudden deaths. The multidisciplinary team identified 15 cases of epilepsy, 6 sudden unexpected deaths in epilepsy (SUDEPs), and no deaths related to acute symptomatic seizures. The epileptologists identified 25 cases of epilepsy and 8 definite SUDEPs, 10 possible SUDEPs, and 5 potential cases of acute symptomatic seizures as a COD. CONCLUSIONS: Among the 25 patients identified with epilepsy by the epileptologists, they found definite or possible SUDEP in 72% (18/25) vs 24% (6/25) by the multidisciplinary group (6/15 cases they identified with epilepsy). The epileptologists identified acute symptomatic seizures as a potential COD in 5/14 patients with alcohol-related seizures. Epilepsy is underdiagnosed among decedents. Among patients with seizures and epilepsy who die suddenly, seizures and SUDEP often go unrecognized as a potential or definite COD.

Sudden neurologic death masquerading as out-of-hospital sudden cardiac death.

OBJECTIVE: To characterize the frequency of and risk factors for out-of-hospital sudden neurologic deaths. METHODS: During the initial 25 months (February 1, 2011-March 1, 2013) of the San Francisco Postmortem Systematic Investigation of Sudden Cardiac Death Study, we captured incident WHO criteria sudden cardiac deaths (SCDs) through active surveillance of consecutive out-of-hospital deaths, which must be reported to the medical examiner by law. All cases were referred for full autopsy with detailed examination of the heart and cranial vault, toxicology, and histology. A multidisciplinary committee adjudicated a final cause of death. RESULTS: Of 352 incident SCDs, 335 (95%) underwent systematic evaluation including full autopsy. Of these 335 cases, 18 (5.4%) were sudden neurologic deaths (mean age 60.6 years [SD 17.6, range 27-87]; 67.7% female), which accounted for 14.9% of the 121 noncardiac sudden deaths. The risk of sudden neurologic death compared to non-neurologic SCD was lower in male and white participants (p < 0.01). Neurologic causes included intracranial hemorrhage (8), sudden unexpected death in epilepsy (6, including 2 with juvenile myoclonic epilepsy), aneurysmal subarachnoid hemorrhage (2), acute ischemic stroke (1), and aspiration from Huntington disease (1). Most deaths were unwitnessed (16; 89%) with asystole at presentation (17; 94%). Prior stroke/TIA was not associated with risk of stroke (odds ratio [OR] 1.4 [95% confidence interval (CI) 0.18-11.8], p = 0.73), but antithrombotic medication use was (OR 3.9 [95% 1.01-15.5], p = 0.05). CONCLUSIONS: Sudden neurologic death is an important cause of out-of-hospital apparent SCDs. Low prevailing autopsy rates may result in systematic misclassification of apparent SCDs and underestimation of the incidence of sudden neurologic death.