IMPORTANCEUnexplained sudden cardiac death (SCD) describes SCD with no cause identified. Genetic testing helps to diagnose inherited cardiac diseases in unexplained SCD; however, the associations between pathogenic or likely pathogenic (P/LP) variants of inherited cardiomyopathies (CMs) and arrhythmia syndromes and the risk of unexplained SCD in both White and African American adults living the United States has never been systematically examined.OBJECTIVE To investigate cases of unexplained SCD to determine the frequency of P/LP genetic variants of inherited CMs and arrhythmia syndromes. DESIGN, SETTING, AND PARTICIPANTSThis genetic association study included 683 African American and White adults who died of unexplained SCD and were included in an autopsy registry. Overall, 413 individuals had DNA of acceptable quality for genetic sequencing. Data were collected from January 1995 to December 2015. A total of 30 CM genes and 38 arrhythmia genes were sequenced, and variants in these genes, curated as P/LP, were examined to study their frequency. Data analysis was performed from June 2018 to March 2021. MAIN OUTCOMES AND MEASURESThe frequency of P/LP variants for CM or arrhythmia in individuals with unexplained SCD. RESULTSThe median (interquartile range) age at death of the 413 included individuals was 41 (29-48) years, 259 (62.7%) were men, and 208 (50.4%) were African American adults. A total of 76 patients (18.4%) with unexplained SCD carried variants considered P/LP for CM and arrhythmia genes. In total, 52 patients (12.6%) had 49 P/LP variants for CM, 22 (5.3%) carried 23 P/LP variants for arrhythmia, and 2 (0.5%) had P/LP variants for both CM and arrhythmia. Overall, 41 P/LP variants for hypertrophic CM were found in 45 patients (10.9%), 9 P/LP variants for dilated CM were found in 11 patients (2.7%), and 10 P/LP variants for long QT syndrome were found in 11 patients (2.7%). No significant difference was found in clinical and heart characteristics between individuals with or without P/LP variants. African American and White patients were equally likely to harbor P/LP variants. CONCLUSIONS AND RELEVANCEIn this large genetic association study of community cases of unexplained SCD, nearly 20% of patients carried P/LP variants, suggesting that genetics may contribute to a significant number of cases of unexplained SCD. Our findings regarding both the association of unexplained SCD with CM genes and race-specific genetic variants suggest new avenues of study for this poorly understood entity.

Forensic pathologists are commonly tasked with identifying human remains. Although DNA analysis remains the gold standard in identification, time and cost make it particularly prohibitive. Radiological examination, more specifically analog imaging, is more cost‐effective and has been widely used in the medical examiner setting as a means of identification. In the United States, CT imaging is a fairly new imaging modality in the forensic setting, but in more recent years, offices are acquiring CT scans or collaborating with local hospitals to utilize the technology. To broaden the spectrum of potential identifying characteristics, we collected 20 cases with antemortem and postmortem CT images. The results were qualitatively assessed by a forensic pathologist and a nonmedically trained intern, and all cases were correctly identified. This study demonstrates that identification of human remains using visual comparison could be performed with ease by a forensic pathologist with limited CT experience.

Background: Unexplained-sudden cardiac death (SCD) describes SCD with no cause identified after a comprehensive autopsy and toxicologic examination. Genetic testing helps to diagnose inherited cardiac diseases in unexplained-SCD, however, the relationship between pathogenic or likely pathogenic (P/LP) variants of inherited cardiomyopathies and primary electrical disorders (PED) and risk of unexplained-SCD in adults living the United States has never been systematically examined. Methods: We performed sequencing of 29 cardiomyopathy and 39 arrhythmia genes in 413 African-Americans and Caucasians (>18 years-old) who died of unexplained-SCD (median age; 41 years-old, 37% females, 50% African-Americans) and whose hearts were found to have no gross pathological finding upon referral to our institution for pathologic consultation from the State of Maryland Medical Examiner. We examined P/LP variants in these genes to study the association between presence of these variants and unexplained-SCD. Results: 143/413 (34.6%) subjects had variants considered P/LP for cardiomyopathy and/or PED (i.e. Brugada Syndrome (BrS), long QT syndrome (LQTS), and arrhythmogenic right ventricular dysplasia (ARVD)). In total, 102 (24.7%) subjects harbored 86 P/LP variants for cardiomyopathies and 60 (14.5%) subjects carried 76 P/LP variants for PED. The following pathogenic variants were identified: 68 P/LP variants for hypertrophic cardiomyopathy (HCM) in 79/413 (19.1%) subjects, 18 P/LP variants for dilated cardiomyopathy (DCM) in 22/413 subjects (5.3%), and 76 P/LP variants in 60/413 (14.5%) for PED. There were greater than 121.0- and 138.5- fold median enrichments (431.4- and 200.0- fold cumulative enrichments) in these cardiomyopathy and arrhythmia variants in victims of unexplained SCD versus the general population, respectively. Among these P/LP positive carriers, combinations of conditions were found, including 14/413 (2.4%) having both HCM and PED variants, and 5/413 (1.2%) with DCM and PED variants. African Americans (AA) and Caucasians were equally likely to harbor P/LP variants (32.7% versus 36.6%, p=0.5), but AA had a higher frequent variants of unknown significance. Conclusions: This study represents the largest examination reported on the association between cardiomyopathy and arrhythmia P/LP genetic variants and unexplained-SCD in adults with no gross abnormality on rigorous pathological examination. Nearly one-third of those with unexplained-SCD were carriers of P/LP variants. Our findings with respect to both the association of unexplained SCD with cardiomyopathy genes and race-specific genetic variants suggest new avenues of study for this poorly understood entity.