Coronary arterial vasculature in the pathophysiology of hypertrophic cardiomyopathy

Abstract

Alterations in the coronary vascular system are likely associated with a mismatch between energy demand and energy supply and critical in triggering the cascade of events that leads to symptomatic hypertrophic cardiomyopathy. Targeting the early events, particularly vascular remodeling, may be a key approach to developing effective treatments. Improvement in our understanding of hypertrophic cardiomyopathy began with the results of early biophysical studies, proceeded to genetic analyses pinpointing the mutational origin, and now pertains to imaging of the metabolic and flow-related consequences of such mutations. Microvascular dysfunction has been an ongoing hot topic in the imaging of genetic cardiomyopathies marked by its histologically significant remodeling and has proven to be a powerful asset in determining prognosis for these patients as well as enlightening scientists on a potential pathophysiological cascade that may begin early during the developmental process. Here, we discuss questions that continue to remain on the mechanistic processes leading to microvascular dysfunction, its correlation to the morphological changes in the vessels, and its contribution to disease progression.

Dysfunctional network and mutation genes of hypertrophic cardiomyopathy

“…Similar to our analysis results, the differentially expressed genes are also related to epidermis development in the dilated cardiomyopathy (37). In addition, the mechanism of metabolism has an important in uence on the pathophysiological process of HCM (38). Studies have shown that the decrease of left ventricular systolic function in female HCM mice is related to the decrease of activities of fatty acid transporter (CD 36) and AMP activated protein kinase (AMPK) (39).…”

Phenotyping hypertrophic cardiomyopathy using cardiac diffusion magnetic resonance imaging: the relationship between microvascular dysfunction and microstructural changes

“…Various histological studies have demonstrated subendocardial arterioles in HCM patients to have smaller cross-sectional lumen area 29 and greater coronary flow resistance 30 than controls, and authors have speculated whether this could be due to compressive effects of regional hypertrophy. 31,32 This hypothesis is supported by our finding of an inverse correlation between subendocardial MD and MPR, however histological corroboration of this is still lacking. The incremental increase in MD in segments with hypertrophy and scarring in our cohort correlates with an increase in ECV and LGE; and would seem to be more attributable to a gradual interstitial fibrotic process that ensues in these segments, as other authors have observed.…”

Histopathological comparison of intramural coronary artery remodeling and myocardial fibrosis in obstructive versus end-stage hypertrophic cardiomyopathy

“…Functional studies have reinforced this concept as impaired myocardial blood flow measured with PET has been found in areas with delayed gadolinium enhancement at MRI, generally associated with myocardial scarring [5]. Interestingly, early microvascular abnormalities and dysfunction in HCM have been found to precede myocardial alterations such as myocyte hypertrophy [14]. Long-term, intramural coronary dysfunction has been identified as a predictor of LV remodeling (including the end-stage phase), characterized by extensive progression of replacement fibrosis, as well as heart failurerelated outcome [6,7].…”