Microvascular Rarefaction and Myocardial Fibrosis in Hypertrophic Obstructive Cardiomyopathy: A Histopathological Comparison of Pediatric and Adult Patients

Abstract

Background: Hypertrophic obstructive cardiomyopathy (HOCM) is a genetic cardiomyopathy characterized by microvascular ischemia and myocardial fibrosis. Microvessels play an important role in myocardial fibrosis in HOCM. However, the changes of myocardial microvessels and myocardial fibrosis in pediatric and adult patients with HOCM remain unclear. This study was to investigate the changes in myocardial microvessel density (MVD) and myocardial fibrosis in pediatric and adult patients with HOCM. Methods: We analyzed the changes in MVD and myocardial fibrosis in myectomy left ventricular (LV) septal wall specimens in 12 adult patients and five pediatric patients with HOCM. Control myocardium from the LV septal wall was collected at autopsy of 5 adults and 4 pediatric individuals, who died of non-cardiac causes. Results: There was no significant difference in MVD between pediatric HOCM patients and control subjects (706.4±187.5 vs. 940.2±491.1, P > 0.05), but the myocardial fibrosis area ratio was significantly increased in HOCM than in control subjects (10.6±3.5 vs. 4.9±1.2, P < 0.01). MVD was significantly reduced, and myocardial fibrosis area ratio was significantly higher in adult HOCM patients than in control subjects (i.e. 523.3± 209.4 vs. 845.7±260.7, P < 0.05; 12.8±5.1 vs. 4.4±1.3, P < 0.05). There was no significant difference in MVD and myocardial fibrosis between pediatric and adult HOCM patients (706.4±187.5 vs. 523.3±209.4, P > 0.05; 10.6±3.5 vs. 12.8±5.1, P > 0.05). Conclusions: Pediatric and adult patients with HOCM have high myocardial fibrosis. The present findings suggest that myocardial microvascular density lesions contribute to myocardial fibrosis during childhood.

The role of SMAD signaling in hypertrophic obstructive cardiomyopathy: an immunohistopathological study in pediatric and adult patients

“…Therefore, activated SMAD signaling may be the direct cause of the fibrotic outcome of HOCM. And in our previous study, we found that patients with HOCM had reduced microvascular density and impaired myocardial perfusion 4 . The main role of MMP is to degrade type I and III collagen, and its elevated activity can cause increased fibrillar collagen degradation, extracellular matrix remodeling, and ventricular dilation 28 .…”

“…Some studies confirmed the high burden of myocardial fibrosis in both young patients who suffered sudden cardiac death 2 or older patients with HOCM suffering from advanced heart failure 3 . Our previous histopathological study demonstrated that pediatric patients with HOCM may present with severe myocardial fibrosis and reduced microvascular density 4 .…”

Mechanisms and prognostic impact of myocardial ischaemia in hypertrophic cardiomyopathy

“…Numerous studies have measured the density of small vessels in hypertrophied HCM septal/LV tissue samples and have found this to be 21–44% lower than in control patients [ 54 , 56 , 57 , 60 – 63 ]. With no convincing association with genotype [ 61 ], reductions in small vessel density may be linked to hypertrophy in HCM and are more severe in end-stage disease patients, such as those undergoing heart transplantation, than in patients referred for myectomy [ 62 ].…”