Feline Hypertrophic Cardiomyopathy: The Consequence of Cardiomyocyte-Initiated and Macrophage-Driven Remodeling Processes?

Abstract

vHypertrophic cardiomyopathy (HCM) is the most commonly diagnosed cardiac disease in cats. The complex pathophysiology of HCM is still far from clear, but myocardial remodeling is a key process, and cardiomyocyte disarray, interstitial fibrosis, leukocyte infiltration, and vascular dysplasia are described histopathologic features. The present study systematically investigated the pathological processes in HCM, with the aim to shed more light on its pathogenesis. Hearts from 18 HCM cases and 18 cats without cardiac disease (controls) were examined, using light and transmission electron microscopy, immunohistochemistry, and morphometric approaches to identify and quantify the morphological changes. Reverse transcription–quantitative polymerase chain reaction was applied to provide additional mechanistic data on remodeling processes. In HCM, the left and right ventricular free wall and septal myocardium exhibited a significantly reduced overall cellularity, accompanied by a significant increase in interstitial Iba1-positive cells with macrophage morphology. In addition, the myocardium of almost half of the diseased hearts exhibited areas where cardiomyocytes were replaced by cell-rich fibrous tissue with abundant small and medium-sized vessels. HCM hearts also showed significantly higher transcription levels for several inflammatory and profibrotic mediators. Our findings suggest that HCM is the consequence of cardiac remodeling processes that are the result of cardiomyocyte damage and to which macrophages contribute by maintaining an inflammatory and profibrotic environment.

Electrophysiological and Structural Remodeling of the Atria in a Mouse Model of Troponin-I Mutation Linked Hypertrophic Cardiomyopathy: Implications for Atrial Fibrillation

“…Therefore, ICAM-1 levels in our study may be unchanged, as our model did not demonstrate inducible AF. Macrophages are another source of inflammatory cell infiltration, which has previously been shown to drive remodeling in HCM [53]. Likewise, we found increased Iba-1 +ve macrophages in the HCM atria albeit without significant changes in circulating TNFα and ICAM-1 levels.…”

Intrahistiocytic Storage of Clofazimine Crystals in a Cat

“…12 Cats with hypertrophic cardiomyopathy have recently been shown to have increased numbers of macrophages within the myocardial interstitium. 14 Although lacking the classical finding of myocardial disarray, the variably-sized myocardiocytes in this cat, the subjective cardiomegaly with ventricular thickening, and increased cardiac weight (0.78% of body weight) are suggestive of, though not diagnostic for, hypertrophic cardiomyopathy. Alternatively, the increased heart weight may have been the result of infiltration of the myocardium by clofazimine-laden macrophages.…”

Digoxin-specific antibody fragments for the treatment of suspected Nerium oleander toxicosis in a cat

“…16,17 Cardiac necrosis could also be attributed to cardiomyopathy-induced hypoxia; however, fibrosis supportive of chronicity would be expected. 15,18 Congestion of multiple organs is also observed with congestive heart failure, but the presence of gastrointestinal hemorrhage may be more suggestive of toxicity. Oral ulceration from irritating saponin compounds have been observed and may explain the patient’s facial edema.…”