1. Chapter 6 Chapter 6 Pathophysiology of Cardiomyopathies © 2014, Elsevier Inc., Willis, et.al., Cellular and Molecular Pathobiology of Cardiovascular Disease

2. 2 FIGURE 6.1 Gross appearance of a dilated heart. DCM is characterized by impaired left ventricular function. Examination of the heart with DCM is representative of all disease states that cause DCM. The characteristic decrease in the ventricular wall thickness masks the overall increase in left ventricular mass, due to myocyte hypertrophy and extracellular fibrosis.

3. 3 © 2014, Elsevier Inc., Willis, et.al., Cellular and Molecular Pathobiology of Cardiovascular Disease FIGURE 6.2 Chronic changes in Chagas cardiomyopathy. Gross heart specimen (left) with left ventricular dilatation in a patient with chronic Chagas disease, with histological evidence of extensive mononuclear infiltration of the myocardium (right) as visualized using H&E stain.

4. 4 © 2014, Elsevier Inc., Willis, et.al., Cellular and Molecular Pathobiology of Cardiovascular Disease FIGURE 6.3 Gross and histologic appearance of hypertrophic cardiomyopathy. (A) Gross section reveals hypertrophy of the left ventricle, with increased septal thickening. (B) Arrow highlights fibrosis of left ventricular outflow tract. (C) H&E histology of interventricular septum with interstitial fibrosis and enlarged myocytes showing disarray. (Reproduced with permission from Binder WD, Fifer MA, King ME, Stone JR. A 48-year-old man with sudden loss of consciousness while jogging. N Engl J Med 2005;353; 824–32).

5. 5 © 2014, Elsevier Inc., Willis, et.al., Cellular and Molecular Pathobiology of Cardiovascular Disease FIGURE 6.4 Cardiomyopathy secondary to storage disease. (A, B) Intracytoplasmic hemosiderin granules in the myocardium of a patient with hemochromatosis as visualized by Perle blue staining. (C, D) Hypertrophied myocytes, containing vacuoles rich with globotriaosylceramide are characteristic of cardiomyopathy associated with Anderson-Fabry’s disease. (E, F) Pompe’s disease is characterized by the presence of myocytes with glycogen deposits as visualized by PAS staining and electron microscopy. (Reproduced with permission from Leone O, Veinot JP, Angelini A, et al. 2011 consensus statement on endomyocardial biopsy from the Association for European Cardiovascular Pathology and the Society for Cardiovascular Pathology. Cardiovasc Pathol 2012;21:245–74).

6. 6 © 2014, Elsevier Inc., Willis, et.al., Cellular and Molecular Pathobiology of Cardiovascular Disease FIGURE 6.5 Gross, histological and electrographic patterns of arrhythmogenic cardiomyopathy (ARVC). The characteristic paper-thin right ventricular wall with no visible myocardium (A, B). Histologically, infiltration with fatty deposition is pathognomonic, giving rise to non-contractile right ventricle and predisposes to ventricular tachyarrhythmias. (Reproduced with permission from Thiene G. Arrhythmogenic cardiomyopathy: from autopsy to genes and transgenic mice. Cardiovasc Pathol 2012;21:229–39).

7. 7 © 2014, Elsevier Inc., Willis, et.al., Cellular and Molecular Pathobiology of Cardiovascular Disease FIGURE 6.6 Characteristic pattern of LV non-compaction cardiomyopathy. Microscopically, on hematoxylin-&- eosin-stained sections, the endocardium is relatively normal, but has alternating trabeculations with deep irregular invaginations forming staghorn-like recesses that line the endocardial spaces (A). A fibrous band separating the spongy and compact portion of the myocardium is visible on trichrome stain (B). Replacement of papillary muscles with interlacing muscle bundles that form anastomosing trabeculae give a spongy characteristic appearance to the heart grossly (C). (Reproduced with permission from Burke A, Mont E, Kutys R, Virmani R. Left ventricular noncompaction: a pathologic study of 14 cases. Human Pathol 2005;36:403–11).