Multifocal Myocardial Necrosis and Fibrosis in Pancreatic Diseases of Children

Abstract

From a review of 2,000 autopsies of children, 16 cases of extensive necrosis and scarring fibrosis of the myocardium were found. These lesions involved mainly the left ventricle and spared the endocardium, the pericardium, and the coronary vessels. These necrotic or fibrotic heart lesions were found to be closely associated with various pancreatic diseases: cystic fibrosis (11 cases), pancreatic lipomatosis (2 cases), extensive small bowel resection (3 cases, 2 of which were associated with acute interstitial pancreatitis). To explain these unexpected associations, two hypotheses can be put forth: (1) The lack of absorption of some presently undetermined substances indispensable for the correct trophicity of the myocardium, and (2) the release in the blood of proteolytic enzymes with consecutive activation of phlogistic substances such as kinins.

Fibrosis: A General Feature in Cystic Fibrosis?

“…She had severe pancreatic disease, and low vitamin E serum concentrations were noted at 6 weeks (4.8 mg/L; normal, 5–16 mg/L), as were low vitamin A serum concentrations at 4 months of age (0.02 mg/L; normal, 0.2–1.2 mg/L). However, as seen from a previously described 1‐day‐old neonate with meconium ileus, myocardial fibrosis may also occur before pancreatic disease and without malnutrition (14).…”

“…As mentioned above, intrinsically increased fibrogenesis has repeatedly been hypothesised for patients with CF, contributing to lung disease, myocardial fibrosis, liver cirrhosis, and bowel fibrosis (6,9,12–14,16). Interestingly, patient 3, who showed the most severe gastrointestinal symptoms, simultaneously had and died of myocardial fibrosis.…”

“…Interestingly, patient 3, who showed the most severe gastrointestinal symptoms, simultaneously had and died of myocardial fibrosis. Increased susceptibility of the CF myocardial cells to exogenous noxious agents because of the CFTR-channel defect may cause this rare complication (14,15). A deficiency of nutrients, antioxidants, and vitamins, and release of pancreatic enzymes in the course of pancreatic disease, may account for these exogenous noxae.…”

“…Ultrasonographic investigations also have revealed thickening of the bowel wall in CF independent of pancreatic enzyme therapy (10,11), and ultrastructural investigations of the liver and bile ducts have suggested that hitherto unidentified toxic or biochemical agents, or CF transmembrane regulator-related factors may contribute to liver cirrhosis (12,13). Finally, myocardial fibrosis is a rare but typical complication in CF (14,15), and one histopathologic study revealed congenital submucosal fibrosis in the rectum of a neonate with meconium ileus and CF (16). Hypothesizing that intrinsically increased fibrogenesis should lead to microscopic changes detectable at birth, we conducted the following study.…”

Nontransmural Myocardial Infarction as a Complication of Untreated Cystic Fibrosis

“…Less frequently, the development of primary cardiomyopathy due to cardiac fibrosis has been described (7). At autopsy, patchy fibrosis with or without extensive necrosis of mainly the left ventricle has been observed in a number of cases of cystic fibrosis (8,9). The hypothesis has been put forward that a disturbance of the cardiac lymph circulation, leading to edematous sclerosis, might be the underlying cause of this condition (7).…”