Carlos H Rassi

Myocardial Fibrosis Progression in Duchenne and Becker Muscular Dystrophy: A Randomized Clinical Trial

Importance In Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD), interventions reducing the progression of myocardial disease could affect survival. Objective To assess the effect of early angiotensin-converting enzyme (ACE) inhibitor therapy in patients with normal left ventricular function on the progression of myocardial fibrosis (MF) identified on cardiovascular magnetic resonance (CMR). Design, Setting, and Participants A randomized clinical trial conducted in 2 centers included 76 male patients with DMD or BMD undergoing 2 CMR studies with a 2-year interval for ventricular function and MF assessment. In a non–intent-to-treat trial, 42 patients with MF and normal left ventricular ejection fraction (LVEF) were randomized (1:1) to receive or not receive ACE inhibitor therapy. The study was conducted from June 26, 2009, to June 30, 2012. Data analysis was performed from June 30, 2013, to October 3, 2016. Interventions Randomization (1:1) to receive or not receive ACE inhibitor therapy. Main Outcomes and Measures Primary outcome was MF progression from baseline to the 2-year CMR study. Results Of the 76 male patients included in the study, 70 had DMD (92%) and 6 had BMD (8%); mean (SD) age at baseline was 13.1 (4.4) years. Myocardial fibrosis was present in 55 patients (72%) and LV systolic dysfunction was identified in 13 patients (24%). Myocardial fibrosis at baseline was an independent indicator of lower LVEF at follow-up (coefficient [SE], −0.16 [0.07]; P = .03). Among patients with MF and preserved LVEF (42 [55%]), those randomized (21 patients in each arm) to receive ACE inhibitors demonstrated slower MF progression compared with the untreated group (mean [SD] increase of 3.1% [7.4%] vs 10.0% [6.2%] as a percentage of LV mass; P = .001). In multivariate analysis, ACE inhibitor therapy was an independent indicator of decreased MF progression (coefficient [SE], −4.51 [2.11]; P = .04). Patients with MF noted on CMR had a higher probability of cardiovascular events (event rate, 10 of 55 [18.2%] vs 0 of 21 [0%]; log-rank P = .04). Conclusions and Relevance In this 2-year, follow-up, randomized clinical trial of patients with Duchenne or Becker muscular dystrophy whose LVEF was preserved and MF was present as determined on CMR, ACE inhibitor therapy was associated with significantly slower progression of MF. The presence of MF was associated with worse patient prognosis. Trial Registration clinicaltrials.org Identifier: NCT02432885

Detection of myocardial inflammation in Chagas' disease by cardiac magnetic resonance

Methods Fifty-four patients with CD were analyzed, 16 patients in the indeterminate form (IND), 17 patients with the cardiac form without systolic dysfunction (CF), and 21 patients with the cardiac form with systolic dysfunction (CFSD). All patients underwent 1.5-T cardiac magnetic resonance (CMR) using three pulse sequences, previously described as useful for the diagnosis of viral myocarditis: the myocardial delayed enhancement (MDE) technique, Triple-IR FSE T2-weighted sequence and the T1 weighted global enhancement acquired before and after contrast injection, to identify fibrosis, edema and hyperemia of the myocardium, respectively. The parameters for all sequences followed precisely the recommendations for acute myocarditis published on JACC White Paper (Friedrich et al. J Am Coll Cardiol. 2009 Apr 28;53(17):1475-87).

Progression of myocardial fibrosis by magnetic resonance imaging in patients with Duchenne and Becker muscular dystrophy and preserved left ventricular ejection fraction - a randomized clinical trial for treatment with ACE inhibitors.

Background Duchenne (DMD) and Becker (BMD) muscular dystrophies ( MD) are inherited X-linked diseases characterized by absence or decrease of dystrophin, a sarcolemal protein that is essential for maintenance of the muscular membrane integrity during muscular contraction. Cardiac involvement is as high, it can be clinically silent, but is often complicated by severe heart failure and high mortality. Angiotensin-converting enzyme inhibitors (ACEI) is recommended for patients with left ventricular dysfunction. We previously described that CMR can identify myocardial fibrosis (MF) even in the early stages of cardiomyopathy in MD before overt LV dysfunction (J Am Coll Cardiol 2007;49:1874-9). The impact of treatment with ACE inhibitors in the progression of fibrosis in patients with MD and preserved LV function is still unknown.

Late percutaneous coronary intervention for an occluded infarct-related artery in patients with preserved infarct zone viability: A pooled analysis of cardiovascular magnetic resonance studies

BACKGROUND The results of clinical trials assessing the effect of late opening of infarct-related artery (IRA) on left ventricular ejection fraction (LVEF) and size in stable patients are equivocal, which may be related to the fact that the presence of viability was not a requirement for randomization in these trials. The aim of the study was to assess the influence of late percutaneous coronary intervention (PCI) with optimal medical therapy (OMT) vs. OMT alone on cardiac function and remodeling in patients presenting infarct zone with preserved viability on cardiovascular magnetic resonance (CMR). METHODS The analysis included pooled data of 43 patients from 3 randomized studies. All patients underwent CMR before randomization, but only in 1 previously unpublished study was preserved viability required for randomization to treatment. Follow-up CMR was performed after 6-12 months. RESULTS Late PCI with OMT led to improved LVEF (+5 ± 7% vs. -1 ± 6%, p = 0.005), decreased left ventricular end-systolic volume (-11 ± 19 mL vs. 12 ± 40 mL, p = 0.02) and a trend towards a decrease in end-diastolic volume (-7 ± 27 mL vs. 15 ± 47 mL, p = 0.07) in comparison to OMT alone. Increased LVEF and decreased left ventricular volumes were observed after the analysis was restricted to patients with left anterior descending artery (LAD) occlusion. CONCLUSIONS In patients with the presence of infarct zone viability, OMT with late PCI for an occluded IRA (particularly LAD) is associated with improvement of left ventricular systolic function and size over OMT alone.

Age-related creatinophosphokinase and myocardial fibrosis changes in patients with muscular dystrophy

Background Duchenne (DMD) and Becker (BMD) muscular dystrophy (MD) are characterized by progressive peripheral muscular damage. The cardiac involvement is high and often complicated by severe heart failure and high mortality. Cardiovascular magnetic resonance (CMR) can identify early stages of cardiomyopathy, as presence of myocardial fibrosis (MF). Several studies have shown negative correlation between creatinophosphokinase (CPK) levels and worst stages of peripheral muscular dystrophy, but have not evaluated their possible association with myocardial damage. Our objective was to investigate CPK levels and magnitude of myocardial damage in patients with MD. Methods

Association between specific dystrophin gene mutations and myocardial fibrosis by cardiovascular magnetic resonance imaging in patients with Duchenne and Becker muscular dystrophy.

Background Duchenne (DMD) and Becker (BMD) muscular dystrophies (MD) are allelic X-linked recessive disorders, caused by mutation of the dystrophin gene located at locus Xp21 that consists of 79 exons, characterized by progressive skeletal muscle degeneration and replacement by fibro fatty tissue. Dystrophin is a sarcolemal protein that links the cytoskeleton to the basal lamina and is essential for maintenance of the muscular membrane integrity during muscular contraction. Cardiac involvement is frequent, 70 - 80% of patients, and often develops clinically silent, without any evident early clinical signs. CMR can identify myocardial fibrosis (MF) and may be useful for detecting the early stages of cardiomyopathy in MD. In a previous study, DNA analyses in 47 pts with DMD revealed significant association between dilated cardiomyopathy (DCM) and specific exons and possible protection against DCM by other exons. The association between specific exons mutation of the dystrophin gene and myocardial fibrosis is until unknown.