Search

Background: We sought to evaluate the diagnostic accuracy of post-mortem cardiac magnetic resonance (PMCMR) of explanted hearts to detect the cardiac causes of sudden death. Methods: PMCMR was performed in formalin-fixed explanted hearts of 115 cases of sudden death. Histological sampling of myocardium was performed using two different approaches: (1) guideline-based sampling; (2) guideline-based plus PMCMR-driven sampling. Results: Forensic diagnosis of cardiac cause of death was ascertained in 72 (63%) patients. When the guideline-driven histological sampling was used, the PMCMR interpretation matched with final forensic diagnosis in 93 out of 115 cases (81%) with sensitivity of 88% (79–95%), specificity of 65% (47–80%), PPV of 84% (78–90%), NPV of 73% (58–84%), accuracy of 81% (72–88%), and AUC of 0.77 (0.68–0.84). When a PMCMR-driven approach was added to the guideline-based one, the matching increased to 102 (89%) cases with a PMCMR sensitivity of 89% (80–94%), a specificity of 86% (67–96%), PPV of 95% (89–98%), NPV of 73% (59–83%), accuracy of 89% (81–93%), and AUC of 0.88 (0.80–0.93). Conclusions: PMCMR has high accuracy to identify the cardiac cause of sudden death and may be considered a valid auxilium for forensic diagnosis. PMCMR could improve histological diagnosis in conditions with focal myocardial involvement or demonstrating signs of myocardial ischemia.

The authors wish to make the following corrections to this paper [...]

MicroRNAs (miRNAs) are a class of non-coding RNAs of about 20 nucleotides in length, involved in the regulation of many biochemical pathways in the human body. The level of miRNAs in tissues and circulation can be deregulated because of altered pathophysiological mechanisms; thus, they can be employed as biomarkers for different pathological conditions, such as cardiac diseases. This review summarizes published findings of these molecular biomarkers in the three most common structural cardiomyopathies: human dilated, arrhythmogenic and hypertrophic cardiomyopathy.

Molecular autopsy is the process of investigating sudden death through genetic analysis. It is particularly useful in cases where traditional autopsy is negative or only shows non-diagnostic features, i.e., in sudden unexplained deaths (SUDs), which are often due to an underlying inherited arrhythmogenic cardiac disease. The final goal of molecular autopsy in SUD cases is to aid medico-legal inquiries and to guide cascade genetic screening of the victim’s relatives. Early attempts of molecular autopsy relied on Sanger sequencing, which, despite being accurate and easy to use, has a low throughput and can only be employed to analyse a small panel of genes. Conversely, the recent adoption of next-generation sequencing (NGS) technologies has allowed exome/genome wide examination, providing an increase in detection of pathogenic variants and the discovery of newer genotype-phenotype associations. NGS has nonetheless brought new challenges to molecular autopsy, especially regarding the clinical interpretation of the large number of variants of unknown significance detected in each individual.

MicroRNAs (miRNAs) are a class of non-coding RNAs containing 18–24 nucleotides that are involved in the regulation of many biochemical mechanisms in the human body. The level of miRNAs in body fluids and tissues increases because of altered pathophysiological mechanisms, thus they are employed as biomarkers for various diseases and conditions. In recent years, miRNAs obtained a great interest in many fields of forensic medicine given their stability and specificity. Several specific miRNAs have been studied in body fluid identification, in wound vitality in time of death determination, in drowning, in the anti-doping field, and other forensic fields. However, the major problems are (1) lack of universal protocols for diagnostic expression testing and (2) low reproducibility of independent studies. This review is an update on the application of these molecular markers in forensic biology.

Background: Post-mortem cardiac magnetic resonance (PMCMR) is an emerging tool supporting forensic medicine for the identification of the causes of cardiac death, such as hypertrophic cardiomyopathy (HCM). We proposed a new method of PMCMR to diagnose HCM despite myocardial rigor mortis. Methods: We performed CMR in 49 HCM patients, 30 non-HCM hypertrophy, and 32 healthy controls. In cine images, rigor mortis was simulated by the analysis of the cardiac phase corresponding to 25% of diastole. Left ventricular mass, mean, and standard deviation (SD) of WT, maximal WT, minimal WT, and their difference were compared for the identification of HCM. These parameters were validated at PMCMR, evaluating eight hearts with HCM, 10 with coronary artery disease, and 10 with non-cardiac death. Results: The SD of WT with a cut-off of &gt, 2.4 had the highest accuracy to identify HCM (AUC 0.95, 95% CI = 0.89&ndash, 0.98). This was particularly evident in the female population of HCM (AUC=0.998), with 100% specificity (95% CI = 85&ndash, 100%) and 96% sensitivity (95% CI = 79&ndash, 99%). Using this parameter, at PMCMR, all of the eight patients with HCM were correctly identified with no false positives. Conclusions: PMCMR allows identification of HCM as the cause of sudden death using the SD of WT &gt, 2.4 as the diagnostic parameter.

Background Sudden unexplained death (SUD) refers to cases of sudden death where autopsy fails to identify any cardiac or extracardiac underlying cause. Guideline‐directed standard genetic testing identifies a disease‐causing mutation in less than one‐third of cases of SUD. Conversely, whole exome sequencing (WES) may provide the key to solve most cases of SUD even after several years from the subject's death. Methods We report on a case of sudden unexpected death of a 37‐year‐old male, with inconclusive autopsy conducted 14 years ago. A recent reevaluation through WES was performed on DNA extracted from left ventricular samples. A multiple step process including several “in silico” tools was applied to identify potentially pathogenic variants. Data analysis was based on a 562 gene panel, including 234 candidate genes associated with sudden cardiac death or heart diseases, with the addition of 328 genes highly expressed in the heart. WebGestalt algorithms were used for association enrichment analysis of all genes with detected putative pathogenic variants. Results WES analysis identified four potentially pathogenic variants: RYR2:c.12168G>T, TTN:c.11821C>T (rs397517804), MYBPC3:c.1255C>T (rs368770848), and ACADVL:c.848T>C (rs113994167). WebGestalt algorithms indicated that their combination holds an unfavorable arrhythmic susceptibility which conceivably caused the occurrence of the events leading to our subject's sudden death. Conclusion Associating WES technique with online prediction algorithms may allow the recognition of genetic mutations potentially responsible for otherwise unexplained deaths., We report on a case of sudden unexpected death of a 37‐year‐old male, with inconclusive autopsy conducted 14 years ago, where recent reevaluation through whole exome sequencing (WES) and WebGestalt algorithms allowed the recognition of four genetic mutations (RYR2‐K4056N, TTN‐R3941C, MYBPC3‐R419C, and ACADVL‐V283A) potentially responsible for the subject's sudden death.