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

Abstract

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 β-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.

Keywords: arrhythmias; autopsy; sudden cardiac death; ventricular fibrillation.

Figure 1:

EMS model for Autopsy-defined SAD Among Unwitnessed WHO-Defined SCDs: sensitivity and specificity curves with predicted probabilities of selected scenarios. Sensitivity (black, blue) and specificity (orange, red) curves are displayed for a range of probability thresholds for classifying WHO-defined SCDs as autopsy-adjudicated SAD in the unwitnessed EMS model. Dashed lines highlight probability thresholds associated with clinically relevant scenarios (A-E) and corresponding test characteristics. CI, confidence interval; EMS, emergency medical system; SAD, sudden arrhythmic death; WHO, World Health Organization.

Figure 2:

Comprehensive model for Autopsy-defined SAD Among Unwitnessed WHO-Defined SCDs: sensitivity and specificity curves with predicted probabilities of selected scenarios. Sensitivity (black, blue) and specificity (orange, red) curves for a range of probability thresholds for classifying WHO-defined SCDs as autopsy-adjudicated SAD in the unwitnessed EMS model. Dashed lines highlight probability thresholds associated with clinically relevant scenarios (A-E) and corresponding test characteristics. CI, confidence interval; EMS, emergency medical system; SAD, sudden arrhythmic death; SSRI, selective serotonin reuptake inhibitor; QTp, QT-prolonging; WHO, World Health Organization.

Figure 3:

Demo of unwitnessed EMS calculator for probability of autopsy-defined SAD. This figure demonstrates the functionality of the calculator. For a given patient, an investigator will enter the status of all variables (green column) included in the applicable model (a calculator has been built for each of the four models produced – this figure demonstrates the unwitnessed EMS calculator). The calculator will then output the associated predicted probability of autopsy-defined SAD (red box). In addition, the calculator demonstrates the equation used to calculate the predicted probability such that it can be readily extrapolated to the entire cohort of interest. The full calculator also demonstrates the test characteristics (sensitivity and specificity) associated with different probability thresholds such that the investigator can select the threshold most appropriate for their intended purpose.