Non-atherosclerotic coronary artery disease in molecular autopsy: a literature review

Non-atherosclerotic coronary artery disease (N-ACAD) is a group of conditions affecting the coronary arteries that can result in sudden cardiac death. This group of conditions can be categorized into structural anomalies, such as collagenopathies, and functional anomalies, such as inflammatory vasculopathies, based on the pathological mechanism. The epidemiology of N-ACAD varies according to the genetic condition involved; however, these disorders are thought to represent a significant proportion of sudden cardiac deaths among young individuals, especially those with a family history of inherited cardiovascular diseases. In collagenopathies, the causes of N-ACAD are genetic, involving pathogenic mutations in several genes responsible for encoding the structural proteins of the vascular wall. Conversely, in vasculitis, etiology is multifactorial, encompassing genetic, immune, environmental, and infectious contributors that influence inflammatory processes. Notably, pathogenic variants may result in arterial dissection, aneurysm formation, rupture, and, ultimately, sudden cardiac death. When the cause of death remains unexplained following a standard post-mortem examination, the case is classified as a sudden unexplained death. In such circumstances, a post-mortem genetic investigation-referred to as a molecular autopsy-is of key importance for identifying potential inherited cardiac conditions and assessing the genetic risk within the deceased’s family, with the aim of preventing future cases of sudden cardiac death. In this literature review, we focus on the role of pathogenic variants in the pathogenesis of non-atherosclerotic coronary artery disease associated with sudden cardiac death in the young.