Molecular diagnostics of cardiovascular diseases in sudden unexplained death

Area of Science:

• Cardiovascular Pathology
• Molecular Diagnostics
• Forensic Pathology

Background:

• Sudden unexplained death (SUD) presents diagnostic challenges, with diverse etiologies beyond the cardiovascular system.
• Cardiac channelopathies and cardiomyopathies are significant contributors to sudden cardiac death.
• Understanding the molecular underpinnings is crucial for accurate post-mortem diagnosis.

Purpose of the Study:

• To provide autopsy pathologists with an actionable guide to SUD.
• To illuminate the clinically relevant molecular basis of cardiac channelopathies and cardiomyopathies.
• To review the evolving landscape of molecular diagnostics in sudden cardiac death investigations.

Main Methods:

• Literature review focusing on molecular mechanisms of cardiac channelopathies and cardiomyopathies.
• Analysis of current diagnostic approaches in forensic pathology.
• Synthesis of information on genetic and molecular testing relevant to SUD.

Main Results:

• Cardiac channelopathies (e.g., Long QT syndrome, Brugada syndrome) arise from ion channel gene mutations.
• Cardiomyopathies (e.g., hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy) involve structural heart muscle abnormalities with genetic links.
• Molecular diagnostics, including next-generation sequencing, are increasingly vital for identifying genetic predispositions.

Conclusions:

• Accurate diagnosis of SUD requires integrating clinical, pathological, and molecular findings.
• Knowledge of molecular pathology aids in identifying at-risk families and preventing future deaths.
• Pathologists must stay abreast of advancements in molecular diagnostics for comprehensive SUD evaluation.