Update on cardiomyopathies and sudden cardiac death

Abstract

Sudden cardiac death (SCD) remains a leading mode of death in western countries. Since SCD can be the first and last clinical presentation of the underlying disease, autopsy could be the only medical examination available for early diagnosis and it should be performed according to the guidelines of the Association for European Cardiovascular Pathology. Although the vast majority of SCD are due to coronary artery disease, non-ischemic causes of SCD do exist and are prevalent in young people with structural (i.e. arrhythmogenic, hypertrophic and inflammatory cardiomyopathy) and non-structural (ion channel diseases) cardiomyopathies, accounting for up to one half of cases. A standardized autopsy protocol, in combination with blood sampling to ensure feasibility of postmortem molecular testing if needed, is mandatory. The pathologist is called to provide the correct diagnosis and to advice the relatives on the need of a cascade clinical and genetic screening in the presence of a heredo-familial disease.

Keywords: Forensic sciences; autopsy; cardiomyopathies; forensic pathology; genetics; sudden death.

Figure 1.

Causes of sudden death in Veneto Region Northeast Italy, time interval 1980–2013. CAD: coronary artery disease; ACM: arrhythmogenic cardiomyopathy; HCM: hypertrophic cardiomyopathy; MVP: mitral valve prolapse; cong: congenital anomalies of the coronary arteries; DCM: dilated cardiomyopathy; CHD: congenital heart disease; PE: pulmonary embolism.

Figure 2.

Arrhythmic sudden death in a 23-year-old man due to hypertrophic cardiomyopathy [24]. (A) Long axis view of the left ventricular outflow tract: the bulging of septal hypertrophy creates subaortic stenosis, which is aggravated by a fibrous plaque superimposed to the septal endocardium facing the anterior leaflet of the mitral valve; (B) Mid-apical cross-section of the same heart: note the asymmetric septal hypertrophy with reduced left ventricular cavity and the presence of white scars in the septum; (C) Fascicular disarray of the myocardium (Trichrome Heidenhain, ×120); (D) Disarray of single myocytes (Trichrome Heidenhain, ×30).

Figure 3.

Arrhythmic sudden death on effort in a 14-year-old boy due to hypertrophic cardiomyopathy. (A) Cross-section of the heart shows a large focus of fibrosis in the postero-septal wall of left ventricle. Note the intramyocardial course of the left anterior descending coronary artery; (B) Histological examination of the ventricular septum confirms the large area of replacement-type fibrous tissue, most probably the result of previous ischaemic injury (Trichrome Heidenhain, ×3).

Figure 4.

Arrhythmic sudden death due to arrhythmogenic cardiomyopathy (segmental form) in a 26-year-old athlete. (A) Anterior view of the right ventricular outflow tract which appears mildly dilated; (B) Cross-section of the heart showing the absence of right ventricular free wall aneurysms: note the spotty involvement of the posterior right ventricular free wall; (C) Histology of the right ventricular outflow tract: note the regional loss of myocardium with fibro-fatty replacement (Trichrome Heidenhain, ×2.5); (D) Histology of the posterior right ventricular free wall: note the fibro-fatty replacement of the myocardium in the absence of wall thinning (Trichrome Heidenhain, ×5).

Figure 5.

Arrhythmic sudden death due to arrhythmogenic cardiomyopathy (diffuse form) in a 14-year-old boy, during a soccer play. (A) Cross-section of the heart showing the presence of anterior and posterior aneurysms as well as patchy involvement of the left ventricular free wall, postero-lateral region; (B) Histology of the aneurysmal postero-inferior wall: note the loss of myocardium with fibro-fatty replacement (Trichrome Heidenhain, ×2.5); (C) Histology of the left ventricular free wall in the areas of fibro-fatty replacement (Trichrome Heidenhain, ×5); (D) Adipogenesis in areas of myocyte injury (HE, ×200).

Figure 6.

Arrhythmic SD due to lymphocytic myocarditis. (A) Focus of inflammatory infiltrates associated with myocyte necrosis (HE stain, ×200); (B) At immunohistochemistry, the inflammatory infiltrate is rich in T-lymphocytes (CD3 immunostaining, ×200); (C) PCR-proved lymphocytic myocarditis due to enterovirus infection.