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

Abstract

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.

Keywords: arrhythmias, cardiac; autopsy; death, sudden, cardiac; epidemiology; heart arrest; pathology.

Figure I. Identification of WHO-Defined SCDs in the San Francisco Postmortem Systematic invesTigation of Sudden Cardiac Death (POST SCD) Study, February 1, 2011-March 1, 2014

Identification of WHO-defined SCDs via active Medical Examiner surveillance of all out-of-hosptial deaths in San Francisco County 1 February 2011 to 1 March 2014. County death certificates for every death were reviewed for location, circumstances, and cause of death. EMS records and forensic investigator reports were reviewed for all out-of-hospital natural deaths between ages 18-90 years. All OHCA deaths referred for autopsy underwent comprehensive review of medical records and medical examiner records, and those meeting WHO criteria underwent full adjudication. A total of 20,440 deaths occurred in San Francisco County during the 37-month study period (Figure I). Of these, 12,671 out of hospital, ED, and unexpected inpatient deaths were reported to the medical examiner: 2,021 were due to non-natural (e.g., trauma, homicide) causes, 2,012 did not meet age criteria, 3,862 were inpatient, nursing home, or hospice deaths (Supplemental Table I). The medical examiner considered 1,120 reported out of hospital deaths as attended deaths due to active medical care within 3 weeks, thus out of medical examiner jurisdiction and ineligible for autopsy. Of these, 89 (7.9%) met criteria for WHO-defined SCD after comprehensive records review and interviews with the attending or treating physicians who signed the death certificate (Supplemental Table II). Via prospective daily surveillance of the remaining 3,656 unattended out of hospital deaths, we identified 912 OHCA deaths with primary EMS impression of cardiac arrest. Next-of-kin of 16 (2%) OHCA deaths declined autopsy for religious reasons, thus 896 (98%) OHCA deaths underwent the protocol autopsy. At adjudication, 371 OHCA deaths did not meet WHO criteria for SCD, leaving 525 adjudicated autopsied WHO-defined SCDs during the study period. Thus we identified 630 (525 autopsied + 16 declined autopsy + 89 under recent medical care) WHO-defined SCDs over 37, accounting for 3.4% (630/18,443) of total adult mortality. Autopsy rates were 98.2% (896/912) for OHCA deaths and 83.3% (525/630) for WHO-defined SCDs.

Figure II. Adjudicated Etiologies of Autopsied WHO-Defined SCDs

IIA: Adjudicated Etiologies of All Autopsied WHO-Defined SCDs, Adjudicated Etiologies of Autopsied WHO-defined SCDs after review of comprehensive medical records, EMS records, complete autopsy, toxicology, and postmortem chemistries. Autopsy-defined SADs had no identifiable extra-cardiac (e.g., pulmonary embolism, hemorrhage, lethal toxicology) or non-arrhythmic (tamponade, acute HF) cause of death. First % is of total WHO-defined SCDs, second % is of cause of death category. Overall autopsy-defined SADs accounted for 56% of all WHO-defined SCDs, 4% were cardiac non-arrhythmic cause of death, and 40% were non-cardiac cause of death. Autopsy-Defined SAD N = 293​ Acute CAD N = 52​ Acute Coronary Lesions N = 35; Acute MI N = 17 Chronic CAD N = 116​ Chronic Coronary Lesions 41; Healed MI 45; Hypertensive CAD 16; Ischemic CM 14, Cardiomyopathy N = 53, Alcoholic N = 16; Amyloidosis N = 2; ARVD N = 1; Drug-Induced CM N = 3; HIV Cardiomyopathy N = 1; CM w/ Valve Prolapse N = 1; Non-compaction N = 1; Non-ischemic/Dilated/Idiopathic N = 27; Stress CM N = 1 Hypertrophy (Incuding HCM) N = 44​ Hypertensive Heart Disease N = 35; HCM N = 6; Unspecified Hypertrophy N = 3 Primary Electrical Disease N = 7​ Complete Heart Block N = 1; Short QT Syndrome N = 1; Unspecified N = 5 Other Arrhythmic N = 21, Acquired Long QT Syndrome N = 1; Bicupid Aortic Valve N = 1; MINOCA – Acute N = 4; MINOCA - Healed N = 4; CIED Concern N = 3; CIED Failure N = 1; Myocarditis N = 2; Acute AVR Failure N = 1; Mitral Valve Prolapse N = 2; Critical Aortic Stenosis N = 3 Cardiac, Non Arrhythmic N = 22​ Acute MI w/ Pump Failure N = 4; Acute MI w/ Rupture + Tamponade N = 12; Acute on Chronic Heart Failure N = 5; Pericarditis N = 1 Non-Cardiac N = 210​ Acute Renal Failure N = 6​ Aortic Dissection N = 14​ Aspiration/Asphyxia N = 5​ Chemical Overdose N = 71​ Opiates N = 40, Non-Opiates N = 31 GI N = 15​ GI Hemorrhage N = 7; Incarcerated/strangulated hernia N = 4; Bowel Obstruction N = 2; Hepatorenal failure / pancreatitis N = 1; Liver Failure N = 1 Hyperglycemia/DKA N = 9​ Infection N = 23​ Pneumonia N = 12; Sepsis N = 6; Other Infection N = 5 Neurologic N = 29​ Intracranial Hemorrhage N = 18; SUDEP N = 7; Aneurysm Rupture N = 2; Acute CVA N = 1; Other Neuro (Huntington disease) N = 1 Pulmonary Embolism N = 19​ Other Non-Cardiac N = 19​ Acute Alcohol Withdrawal N = 1; Disseminated Cancer N = 1; Hypothermia N = 1; Other Hemorrhage N = 2; Other Trauma N = 4; End-stage COPD N = 4; Obstructive Sleep Apnea N = 1; Aortic Aneurysm Rupture N = 2; Renal Artery Dissection N = 1; Iliac Arterial Dissection N = 1; Pulmonary Artery Dissection N = 1 IIB: Adjudicated Etiologies of Witnessed vs. Unwitnessed WHO-Defined SCDs​ Adjudicated Etiologies of Witnessed vs Unwitnessed WHO-defined SCDs after review of comprehensive medical records, EMS records, complete autopsy, toxicology, and postmortem chemistries. Autopsy-defined SADs accounted for 65% of witnessed and 53% of unwitnessed WHO-defined SCDs, (OR=1.62, 95% CI: 1.06 to 2.48; P=.024). Witnessed: Autopsy-Defined SAD N = 78 (Acute CAD N=16 [20%], Chronic CAD N=35 [45%], Cardiomyopathy N=9 [11%], Hypertrophy N=10 [13%], Primary Electrical Disease N=2 [3%], Other Arrhythmic N=6 [8%]). Unwitnessed: Autopsy-Defined SAD N = 215 (Acute CAD N=36 [17%], Chronic CAD N=81 [38%], Cardiomyopathy N=44 [20%], Hypertrophy N=34 [16%], Primary Electrical Disease N=5 [2%], Other Arrhythmic N=15 [7%]). IIC: Adjudicated Etiologies of WHO-Defined SCDs Age 18-39 vs. Age ≥ 40​ Autopsy-defined SADs accounted for a similar proportion of WHO-Defined SCDs Age 18-39 (19 of 32, 59%) vs. Age ≥ 40 (274 of 493, 56%), P=.68.Age 18-39: Autopsy-Defined SADs N = 19 (Acute CAD N=1 [5%], Chronic CAD N=3 [16%], Cardiomyopathy N=8 [42%], Hypertrophy N=4 [21%], Primary Electrical Disease N=3 [16%]). Age ≥ 40: Autopsy-Defined SADs N = 274 (Acute CAD N=51 [19%], Chronic CAD N=113 [41%], Cardiomyopathy N=45 [16%], Hypertrophy N=40 [15%], Primary Electrical Disease N=4 [1%], Other Arrhythmic N=21 [8%]).

Figure II. Adjudicated Etiologies of Autopsied WHO-Defined SCDs

IIA: Adjudicated Etiologies of All Autopsied WHO-Defined SCDs, Adjudicated Etiologies of Autopsied WHO-defined SCDs after review of comprehensive medical records, EMS records, complete autopsy, toxicology, and postmortem chemistries. Autopsy-defined SADs had no identifiable extra-cardiac (e.g., pulmonary embolism, hemorrhage, lethal toxicology) or non-arrhythmic (tamponade, acute HF) cause of death. First % is of total WHO-defined SCDs, second % is of cause of death category. Overall autopsy-defined SADs accounted for 56% of all WHO-defined SCDs, 4% were cardiac non-arrhythmic cause of death, and 40% were non-cardiac cause of death. Autopsy-Defined SAD N = 293​ Acute CAD N = 52​ Acute Coronary Lesions N = 35; Acute MI N = 17 Chronic CAD N = 116​ Chronic Coronary Lesions 41; Healed MI 45; Hypertensive CAD 16; Ischemic CM 14, Cardiomyopathy N = 53, Alcoholic N = 16; Amyloidosis N = 2; ARVD N = 1; Drug-Induced CM N = 3; HIV Cardiomyopathy N = 1; CM w/ Valve Prolapse N = 1; Non-compaction N = 1; Non-ischemic/Dilated/Idiopathic N = 27; Stress CM N = 1 Hypertrophy (Incuding HCM) N = 44​ Hypertensive Heart Disease N = 35; HCM N = 6; Unspecified Hypertrophy N = 3 Primary Electrical Disease N = 7​ Complete Heart Block N = 1; Short QT Syndrome N = 1; Unspecified N = 5 Other Arrhythmic N = 21, Acquired Long QT Syndrome N = 1; Bicupid Aortic Valve N = 1; MINOCA – Acute N = 4; MINOCA - Healed N = 4; CIED Concern N = 3; CIED Failure N = 1; Myocarditis N = 2; Acute AVR Failure N = 1; Mitral Valve Prolapse N = 2; Critical Aortic Stenosis N = 3 Cardiac, Non Arrhythmic N = 22​ Acute MI w/ Pump Failure N = 4; Acute MI w/ Rupture + Tamponade N = 12; Acute on Chronic Heart Failure N = 5; Pericarditis N = 1 Non-Cardiac N = 210​ Acute Renal Failure N = 6​ Aortic Dissection N = 14​ Aspiration/Asphyxia N = 5​ Chemical Overdose N = 71​ Opiates N = 40, Non-Opiates N = 31 GI N = 15​ GI Hemorrhage N = 7; Incarcerated/strangulated hernia N = 4; Bowel Obstruction N = 2; Hepatorenal failure / pancreatitis N = 1; Liver Failure N = 1 Hyperglycemia/DKA N = 9​ Infection N = 23​ Pneumonia N = 12; Sepsis N = 6; Other Infection N = 5 Neurologic N = 29​ Intracranial Hemorrhage N = 18; SUDEP N = 7; Aneurysm Rupture N = 2; Acute CVA N = 1; Other Neuro (Huntington disease) N = 1 Pulmonary Embolism N = 19​ Other Non-Cardiac N = 19​ Acute Alcohol Withdrawal N = 1; Disseminated Cancer N = 1; Hypothermia N = 1; Other Hemorrhage N = 2; Other Trauma N = 4; End-stage COPD N = 4; Obstructive Sleep Apnea N = 1; Aortic Aneurysm Rupture N = 2; Renal Artery Dissection N = 1; Iliac Arterial Dissection N = 1; Pulmonary Artery Dissection N = 1 IIB: Adjudicated Etiologies of Witnessed vs. Unwitnessed WHO-Defined SCDs​ Adjudicated Etiologies of Witnessed vs Unwitnessed WHO-defined SCDs after review of comprehensive medical records, EMS records, complete autopsy, toxicology, and postmortem chemistries. Autopsy-defined SADs accounted for 65% of witnessed and 53% of unwitnessed WHO-defined SCDs, (OR=1.62, 95% CI: 1.06 to 2.48; P=.024). Witnessed: Autopsy-Defined SAD N = 78 (Acute CAD N=16 [20%], Chronic CAD N=35 [45%], Cardiomyopathy N=9 [11%], Hypertrophy N=10 [13%], Primary Electrical Disease N=2 [3%], Other Arrhythmic N=6 [8%]). Unwitnessed: Autopsy-Defined SAD N = 215 (Acute CAD N=36 [17%], Chronic CAD N=81 [38%], Cardiomyopathy N=44 [20%], Hypertrophy N=34 [16%], Primary Electrical Disease N=5 [2%], Other Arrhythmic N=15 [7%]). IIC: Adjudicated Etiologies of WHO-Defined SCDs Age 18-39 vs. Age ≥ 40​ Autopsy-defined SADs accounted for a similar proportion of WHO-Defined SCDs Age 18-39 (19 of 32, 59%) vs. Age ≥ 40 (274 of 493, 56%), P=.68.Age 18-39: Autopsy-Defined SADs N = 19 (Acute CAD N=1 [5%], Chronic CAD N=3 [16%], Cardiomyopathy N=8 [42%], Hypertrophy N=4 [21%], Primary Electrical Disease N=3 [16%]). Age ≥ 40: Autopsy-Defined SADs N = 274 (Acute CAD N=51 [19%], Chronic CAD N=113 [41%], Cardiomyopathy N=45 [16%], Hypertrophy N=40 [15%], Primary Electrical Disease N=4 [1%], Other Arrhythmic N=21 [8%]).

Figure II. Adjudicated Etiologies of Autopsied WHO-Defined SCDs

IIA: Adjudicated Etiologies of All Autopsied WHO-Defined SCDs, Adjudicated Etiologies of Autopsied WHO-defined SCDs after review of comprehensive medical records, EMS records, complete autopsy, toxicology, and postmortem chemistries. Autopsy-defined SADs had no identifiable extra-cardiac (e.g., pulmonary embolism, hemorrhage, lethal toxicology) or non-arrhythmic (tamponade, acute HF) cause of death. First % is of total WHO-defined SCDs, second % is of cause of death category. Overall autopsy-defined SADs accounted for 56% of all WHO-defined SCDs, 4% were cardiac non-arrhythmic cause of death, and 40% were non-cardiac cause of death. Autopsy-Defined SAD N = 293​ Acute CAD N = 52​ Acute Coronary Lesions N = 35; Acute MI N = 17 Chronic CAD N = 116​ Chronic Coronary Lesions 41; Healed MI 45; Hypertensive CAD 16; Ischemic CM 14, Cardiomyopathy N = 53, Alcoholic N = 16; Amyloidosis N = 2; ARVD N = 1; Drug-Induced CM N = 3; HIV Cardiomyopathy N = 1; CM w/ Valve Prolapse N = 1; Non-compaction N = 1; Non-ischemic/Dilated/Idiopathic N = 27; Stress CM N = 1 Hypertrophy (Incuding HCM) N = 44​ Hypertensive Heart Disease N = 35; HCM N = 6; Unspecified Hypertrophy N = 3 Primary Electrical Disease N = 7​ Complete Heart Block N = 1; Short QT Syndrome N = 1; Unspecified N = 5 Other Arrhythmic N = 21, Acquired Long QT Syndrome N = 1; Bicupid Aortic Valve N = 1; MINOCA – Acute N = 4; MINOCA - Healed N = 4; CIED Concern N = 3; CIED Failure N = 1; Myocarditis N = 2; Acute AVR Failure N = 1; Mitral Valve Prolapse N = 2; Critical Aortic Stenosis N = 3 Cardiac, Non Arrhythmic N = 22​ Acute MI w/ Pump Failure N = 4; Acute MI w/ Rupture + Tamponade N = 12; Acute on Chronic Heart Failure N = 5; Pericarditis N = 1 Non-Cardiac N = 210​ Acute Renal Failure N = 6​ Aortic Dissection N = 14​ Aspiration/Asphyxia N = 5​ Chemical Overdose N = 71​ Opiates N = 40, Non-Opiates N = 31 GI N = 15​ GI Hemorrhage N = 7; Incarcerated/strangulated hernia N = 4; Bowel Obstruction N = 2; Hepatorenal failure / pancreatitis N = 1; Liver Failure N = 1 Hyperglycemia/DKA N = 9​ Infection N = 23​ Pneumonia N = 12; Sepsis N = 6; Other Infection N = 5 Neurologic N = 29​ Intracranial Hemorrhage N = 18; SUDEP N = 7; Aneurysm Rupture N = 2; Acute CVA N = 1; Other Neuro (Huntington disease) N = 1 Pulmonary Embolism N = 19​ Other Non-Cardiac N = 19​ Acute Alcohol Withdrawal N = 1; Disseminated Cancer N = 1; Hypothermia N = 1; Other Hemorrhage N = 2; Other Trauma N = 4; End-stage COPD N = 4; Obstructive Sleep Apnea N = 1; Aortic Aneurysm Rupture N = 2; Renal Artery Dissection N = 1; Iliac Arterial Dissection N = 1; Pulmonary Artery Dissection N = 1 IIB: Adjudicated Etiologies of Witnessed vs. Unwitnessed WHO-Defined SCDs​ Adjudicated Etiologies of Witnessed vs Unwitnessed WHO-defined SCDs after review of comprehensive medical records, EMS records, complete autopsy, toxicology, and postmortem chemistries. Autopsy-defined SADs accounted for 65% of witnessed and 53% of unwitnessed WHO-defined SCDs, (OR=1.62, 95% CI: 1.06 to 2.48; P=.024). Witnessed: Autopsy-Defined SAD N = 78 (Acute CAD N=16 [20%], Chronic CAD N=35 [45%], Cardiomyopathy N=9 [11%], Hypertrophy N=10 [13%], Primary Electrical Disease N=2 [3%], Other Arrhythmic N=6 [8%]). Unwitnessed: Autopsy-Defined SAD N = 215 (Acute CAD N=36 [17%], Chronic CAD N=81 [38%], Cardiomyopathy N=44 [20%], Hypertrophy N=34 [16%], Primary Electrical Disease N=5 [2%], Other Arrhythmic N=15 [7%]). IIC: Adjudicated Etiologies of WHO-Defined SCDs Age 18-39 vs. Age ≥ 40​ Autopsy-defined SADs accounted for a similar proportion of WHO-Defined SCDs Age 18-39 (19 of 32, 59%) vs. Age ≥ 40 (274 of 493, 56%), P=.68.Age 18-39: Autopsy-Defined SADs N = 19 (Acute CAD N=1 [5%], Chronic CAD N=3 [16%], Cardiomyopathy N=8 [42%], Hypertrophy N=4 [21%], Primary Electrical Disease N=3 [16%]). Age ≥ 40: Autopsy-Defined SADs N = 274 (Acute CAD N=51 [19%], Chronic CAD N=113 [41%], Cardiomyopathy N=45 [16%], Hypertrophy N=40 [15%], Primary Electrical Disease N=4 [1%], Other Arrhythmic N=21 [8%]).

Figure III. Adjusted Incidence rates for OHCA Deaths, WHO-defined SCDs, and Autopsy-defined SADs in San Francisco County 1 February 2011 to 1 March 2014

Adjusted incidence rates per 100,000 person-years for all observed OHCA deaths, WHO-defined SCDs, and Autopsy-defined SADs in San Francisco County 1 February 2011 to 1 March 2014. Adult countywide incidence of OHCA death and WHO-defined SCD over 37 months were 46/100,000 and 29.6/100,000 person-years, respectively. OHCA death and WHO-defined SCD incidence rates both include the 89 identified WHO-defined SCDs that were considered attended by the medical examiner (due to recent medical care < 3 weeks prior to death) and 16 OHCA deaths that did not undergo autopsy. After comprehensive records review and adjudication, 371 OHCA deaths initially identified by CARES OHCA criteria were excluded as not meeting WHO SCD criteria at presentation. Sex- and race-specific incidence rate ratios (IRR) for all WHO-defined SCD and weighted autopsy-defined SAD are shown. Weighted countywide incidence of autopsy-defined SAD was 17/100,000 person-years, accounting for the 89 WHO-defined SCDs without autopsy. Autopsy-defined SAD accounted for a weighted proportion of 57.4% all WHO SCDs. Incidence rate ratios for WHO SCD and autopsy-defined SAD were over 2- and 3-fold higher in men vs. women, respectively (P<.0001), and highest in Blacks (P>.0001), lowest in Hispanics (P=.0018). Blacks (45%) and Hispanics (54.6%) had the lowest proportion of WHO-defined SCDs that were autopsy-defined SADs. Other race includes American Indian/Alaskan Natives, Native Hawaiians, and other Pacific Islanders.