Regional Stress-Induced Ischemia in Non-fibrotic Hypertrophied Myocardium in Young HCM Patients

Abstract

The relationship between hypertrophy, perfusion abnormalities and fibrosis is unknown in young patients with hypertrophic cardiomyopathy (HCM). Since mounting evidence suggests causal relationship between myocardial ischemia and major adverse cardiac events, we sought to investigate whether (1) regional myocardial perfusion is decreased in young HCM patients and in individuals at risk of HCM, and (2) hypoperfused areas are larger than areas with fibrosis. HCM patients (n = 12), HCM-risk subjects (n = 15) and controls (n = 9) were imaged on a 1.5 T MRI scanner. Myocardial hypertrophy was assessed on cine images. Perfusion images were acquired during adenosine hyperemia and at rest. Maximum upslope ratios of perfusion (stress/rest) were used for semiquantitative analysis. Fibrosis was assessed by late gadolinium enhancement (LGE). Results are presented as median and range. Perfusion in HCM-risk subjects and in non-hypertrophied segments in HCM patients showed no difference compared to controls (P = ns). Hypertrophic segments in HCM patients without LGE showed decreased perfusion compared to segments without hypertrophy [1.5 (1.1–2.3) vs. 2.0 (1.8–2.6), P < 0.001], and hypertrophic segments with LGE showed even lower perfusion using a segmental analysis [0.9 (0.6–1.8), P < 0.05]. The extent of hypoperfused myocardium in HCM patients during adenosine exceeded the extent of fibrosis on LGE [20 (0–48) vs. 4 (0–7) % slice area, P < 0.05] and hypoperfused areas at rest (P < 0.001). Regional perfusion is decreased in hypertrophied compared to non-hypertrophied myocardium and is lowest in fibrotic myocardium in young HCM patients but does not discriminate HCM-risk subjects from controls. The stress-induced hypoperfused regions exceed regions with LGE, indicating that hypoperfusion precedes fibrosis and may be a more sensitive marker of diseased myocardium in HCM.

Evaluation of myocardial microcirculation using intravoxel incoherent motion imaging

“…The results of our study indicate that the myocardial perfusion of patients with HCM, diabetes, or hypertension is abnormally lower than that of healthy individuals. This is in accord with other recent values reported in the literature …”

“…Earlier studies using PET/SPECT, first‐pass MR, or late gadolinium enhancement showed abnormal myocardial microcirculation, myocardial replacement fibrosis in HCM, diabetes, and hypertension, even if without obstruction of epicardial coronary arteries . It is very important to evaluate myocardial microcirculation for these diseases.…”

Serum Biomarkers of Myocardial Remodeling and Coronary Dysfunction in Early Stages of Hypertrophic Cardiomyopathy in the Young

“…However, when using mitral E/e´ > 8 as a cut-off for LV diastolic dysfunction, we found higher levels of ICTP ( p = 0.02) in the HCM group, a finding that could suggest alterations in ECM prior to development of fibrosis. As recently reported [ 31 ], the degree of myocardial fibrosis was assessed using CMR -LGE, and the association between regional hypoperfusion and fibrosis [ 39 ] in young patients with HCM. In line with previous studies showing a certain correlation between the magnitude of fibrosis and the degree of hypertrophy [ 2 , 7 – 9 ], fibrosis was predominantly found in myocardial segments with advanced hypertrophy [ 39 ] and also indicating a pathology beyond LVH and LGE by showing greater extent of areas with impaired myocardial perfusion even in non-fibrotic myocardium during adenosine hyperemia indicating regional hypoxemia, suggesting an important relationship of myocardial hypoperfusion with fibrosis occurrence in HCM [ 39 ].…”

Coronary arterial vasculature in the pathophysiology of hypertrophic cardiomyopathy

“…Whether these markers are evidence for early fibrosis, early endothelial dysfunction, or myocyte remodeling process, is still questionable and should be more extensively investigated. Although energy impairment may be the initial catalyst, the degree of hypertrophy correlates directly with stress-induced or vasodilator-induced ischemia, whereas energy impairment does not [29, 49, 61]. Ischemia can also be seen in regions of non-hypertrophied myocardium, potentially heralding extension of remodeling in those regions as well [26, 109].…”