Systolic and diastolic myocardial mechanics in hypertrophic cardiomyopathy and their link to the extent of hypertrophy, replacement fibrosis and interstitial fibrosis

Abstract

Aim of the present study was to investigate the relations between myocardial mechanics and the extent of hypertrophy and fibrosis in hypertrophic cardiomyopathy (HCM). Forty-five consecutive patients with HCM and 15 subjects without structural heart disease were included. Cardiac magnetic resonance with late gadolinium enhancement (LGE) imaging was performed to evaluate biventricular function, LV mass index and presence/extent of LGE, expression of replacement fibrosis. Myocardial T1 relaxation, a surrogate of interstitial fibrosis, was measured from Look-Locker sequence. Feature-tracking analysis was applied to LV basal, mid and apical short-axis images to assess systolic and diastolic global LV circumferential strain (CS) and strain rate (CSr). Peak systolic CS and CSr were significantly higher among HCM patients as compared to control subjects (p = 0.015 and p = 0.007, respectively). The ratio of peak CSr during early filling to peak systolic CSr was significantly lower among HCM patients (p = 0.002). At multivariate linear regression analysis, LV mass index (p < 0.001) and %LV LGE (p = 0.011) were significantly and independently related to peak systolic CS; LV mass index (p < 0.001) and %LV LGE (p = 0.023) were significantly and independently related to peak systolic CSr; %LV LGE (p = 0.021) and T1 ratio (p = 0.006) were significantly and independently related to the ratio of peak CSr during early filling to peak systolic CSr. LV systolic mechanics are enhanced and LV diastolic mechanics are impaired in HCM. Extent of hypertrophy and replacement fibrosis influence the LV systolic mechanics while extent of replacement fibrosis and interstitial fibrosis influence the LV diastolic mechanics.

Myofilament protein dynamics modulate EAD formation in human hypertrophic cardiomyopathy

“…Our results show that sarcomeric mutations, which disrupt the regulation of the thin filament (decreased perm 50 , decreased k offH , increased k on ) in a way that has a downstream effect of increasing Ca 2+ sensitivity, increase the degree of repolarization reserve reduction necessary for EADs to emerge and decreases the frequency of EAD occurrence. Combined with the observations from the previous studies, this suggests that the enhanced arrhythmogenicity seen in HCM is not due to altered Ca 2+ sensitivity, but rather due to HCM-induced ionic remodeling as suggested by Coppini et al (Coppini et al, 2013) or from secondary effects of myofilament remodeling at the tissue level, such as hypertrophy and fibrosis (Chan et al, 2014; Nucifora et al, 2015). …”

Strain imaging using cardiac magnetic resonance

“…The analysis of myocardial strain offers new insight into disease’s mechanisms: intramural functional abnormalities have been shown to extend beyond the presence of late gadolinium enhancement (LGE) in patients with hypertrophic cardiomyopathy (HCM), as intramural systolic strain is abnormal in hypertrophied segments as compared to segments without hypertrophy, irrespective of the presence of LGE [60]. However, a linear correlation between myocardial strain and the amount of LGE has been shown in different studies [15, 61, 62], both at the global and segmental levels, so that it has been inferred that strain analysis might be considered in the future to indirectly detect the presence of scar, without need of contrast agent [62]. …”

Reverse remodeling after percutaneous transluminal septal myocardial ablation in severe but asymptomatic LVOT obstruction (RASTA) study: Rationale and design of transcatheter septal reduction in asymptomatic patients with severe hypertrophic obstructive cardiomyopathy

“…The severity of LVOT obstruction is an important pathognomonic factor in disease progression and clinical outcome 1,2 . Histological and imaging studies have identified replacement and interstitial fibrosis as the pathological basis for systolic and diastolic dysfunction, respectively 15,16 . The extent of hypertrophy is inversely associated with regional systolic function and correlates positively with myocardial scarring, even in asymptomatic patients 17,18 .…”