Dataset Information

Effects of myocardial fibrosis assessed by MRI on dynamic left ventricular outflow tract obstruction in patients with hypertrophic cardiomyopathy: a retrospective database analysis.

ABSTRACT:

Background

While implications of myocardial fibrosis on left ventricular (LV) function at rest have been studied in hypertrophic cardiomyopathy (HCM), the pathophysiological consequences on dynamic LV outflow tract (LVOT) gradient have so far not been investigated in detail.

Objective

To evaluate the influence of myocardial fibrosis, detected by MRI as late-gadolinium enhancement (LGE), on LVOT gradient in HCM.

Design

Retrospective database analysis.

Setting

A single Italian cardiomyopathies referral centre.

Patients

Seventy-six HCM patients with normal ejection fraction at rest.

Interventions

Patients underwent cardiac MR and performed bicycle exercise echocardiogram within a month.

Results

LGE was present in 54 patients (71%), ranging from 0.2% to 32.4% of LV mass. There was a weak correlation between the amount of fibrosis and LVOT gradient variation during exercise in the overall population (r=-0.243, p=0.034) and a stronger correlation in patients with obstructive HCM at rest (r=-0.524, p=0.021). Patients with an LVOT gradient increase ?50 mm Hg during exercise had a significantly lesser extent of fibrosis than those with an increase <50 mm Hg (0.7% (IQR 0-2.4) vs 3.2% (IQR 0.2-7.4), p=0.006). The extent of fibrosis was significantly lower among the highest quartiles of LVOT gradient increase (p=0.009).

Conclusions

In patients with HCM and normal ejection fraction at rest, myocardial fibrosis was associated with a lower increase in LVOT gradient during exercise, probably due to a lesser degree of myocardial contractility recruitment. This negative association was more evident in patients with an obstructive form at rest.

SUBMITTER: Biagini E

PROVIDER: S-EPMC3488754 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

Effects of myocardial fibrosis assessed by MRI on dynamic left ventricular outflow tract obstruction in patients with hypertrophic cardiomyopathy: a retrospective database analysis.

Biagini Elena E Lorenzini Massimiliano M Olivotto Iacopo I Rocchi Guido G Lovato Luigi L Lai Francesco F Rosmini Stefania S Pazzi Chiara C Pasquale Ferdinando F Reggiani Maria Letizia Bacchi ML Fattori Rossella R Rapezzi Claudio C

BMJ open 20121011 5

<h4>Background</h4>While implications of myocardial fibrosis on left ventricular (LV) function at rest have been studied in hypertrophic cardiomyopathy (HCM), the pathophysiological consequences on dynamic LV outflow tract (LVOT) gradient have so far not been investigated in detail.<h4>Objective</h4>To evaluate the influence of myocardial fibrosis, detected by MRI as late-gadolinium enhancement (LGE), on LVOT gradient in HCM.<h4>Design</h4>Retrospective database analysis.<h4>Setting</h4>A single ...[more]

PMID: 23065447

Similar Datasets

Project description:Hypertrophic cardiomyopathy (HCM) is an inherited disease of the heart muscle characterized by otherwise unexplained thickening of the left ventricle. Left ventricular outflow tract (LVOT) obstruction is present in approximately two-thirds of patients and substantially increases the risk of disease complications. Invasive treatment with septal myectomy or alcohol septal ablation can improve symptoms and functional status, but currently available drugs for reducing obstruction have pleiotropic effects and variable therapeutic responses. New medical treatments with more targeted pharmacology are needed, but the lack of preclinical animal models for HCM with LVOT obstruction has limited their development. HCM is a common cause of heart failure in cats, and a subset exhibit systolic anterior motion of the mitral valve leading to LVOT obstruction. MYK-461 is a recently-described, mechanistically novel small molecule that acts at the sarcomere to specifically inhibit contractility that has been proposed as a treatment for HCM. Here, we use MYK-461 to test whether direct reduction in contractility is sufficient to relieve LVOT obstruction in feline HCM. We evaluated mixed-breed cats in a research colony derived from a Maine Coon/mixed-breed founder with naturally-occurring HCM. By echocardiography, we identified five cats that developed systolic anterior motion of the mitral valve and LVOT obstruction both at rest and under anesthesia when provoked with an adrenergic agonist. An IV MYK-461 infusion and echocardiography protocol was developed to serially assess contractility and LVOT gradient at multiple MYK-461 concentrations. Treatment with MYK-461 reduced contractility, eliminated systolic anterior motion of the mitral valve and relieved LVOT pressure gradients in an exposure-dependent manner. Our findings provide proof of principle that acute reduction in contractility with MYK-461 is sufficient to relieve LVOT obstruction. Further, these studies suggest that feline HCM will be a valuable translational model for the study of disease pathology, particularly LVOT obstruction.

Project description:BACKGROUND:Cardiovascular magnetic resonance (CMR) imaging in patients with hypertrophic cardiomyopathy (HCM) enables the assessment of not only left ventricular (LV) hypertrophy and scarring but also the severity of mitral regurgitation. CMR assessment of mitral regurgitation is primarily based on the difference between LV stroke volume (LVSV) and aortic forward flow (Ao) measured using the phase-contrast (PC) technique. However, LV outflow tract (LVOT) obstruction causing turbulent, non-laminar flow in the ascending aorta may impact the accuracy of aortic flow quantification, leading to false conclusions regarding mitral regurgitation severity. Thus, we decided to quantify mitral regurgitation in patients with HCM using Ao or, alternatively, main pulmonary artery forward flow (MPA) for mitral regurgitation volume (MRvol) calculations. METHODS:The analysis included 143 prospectively recruited subjects with HCM and 15 controls. MRvol was calculated as the difference between LVSV computed with either the inclusion (LVSVincl) or exclusion (LVSVexcl) of papillary muscles and trabeculations from the blood pool and either Ao (MRvolAoi or MRvolAoe) or MPA (MRvolMPAi or MRvolMPAe). The presence or absence of LVOT obstruction was determined based on Doppler echocardiography findings. RESULTS:MRvolAoi was higher than MRvolMPAi in HCM patients with LVOT obstruction [47.0 ml, interquartile range (IQR)?=?31.5-60.0 vs. 35.5 ml, IQR?=?26.0-51.0; p <?0.0001] but not in non-obstructive HCM patients (23.0 ml, IQR?=?16.0-32.0 vs. 24.0 ml, IQR?=?15.3-32.0; p?=?0.26) or controls (18.0 ml, IQR?=?14.3-21.8 vs. 20.0 ml, IQR?=?14.3-22.0; p?=?0.89). In contrast to controls and HCM patients without LVOT obstruction, in HCM patients with LVOT obstruction, aortic flow-based MRvol (MRvolAoi) was higher than pulmonary-based findings (MRvolMPAi) (bias?=?9.5 ml; limits of agreement: -11.7-30.7 with a difference of 47 ml in the extreme case). The differences between aortic-based and pulmonary-based MRvol values calculated using LVSVexcl mirrored those derived using LVSVincl. However, MRvol values calculated using LVSVexcl were lower in all the groups analyzed (HCM with LVOT obstruction, HCM without LVOT obstruction, and controls) and with all methods of MRvol quantification used (p???0.0001 for all comparisons). CONCLUSIONS:In HCM patients, LVOT obstruction significantly affects the estimation of aortic flow, leading to its underestimation and, consequently, to higher MRvol values than those obtained with MPA-based MRvol calculations.

Dataset Information

Effects of myocardial fibrosis assessed by MRI on dynamic left ventricular outflow tract obstruction in patients with hypertrophic cardiomyopathy: a retrospective database analysis.

Background

Objective

Design

Setting

Patients

Interventions

Results

Conclusions

Publications

Effects of myocardial fibrosis assessed by MRI on dynamic left ventricular outflow tract obstruction in patients with hypertrophic cardiomyopathy: a retrospective database analysis.

Similar Datasets

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