Abstract 12450: Myocardial Fibrosis Burden Predicts Left Ventricular Ejection Fraction and is Modified by Age and Steroid Treatment Duration in Duchenne Muscular Dystrophy

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Animesh Tandon ◽  
Chet R Villa ◽  
Kan N Hor ◽  
John L Jefferies ◽  
Zhiqian Gao ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Myocardial Fibrosis ◽  
Cardiac Dysfunction ◽  
Treatment Duration ◽  
Left Ventricular ◽  
Steroid Treatment ◽  
Left Ventricular Ejection ◽  
Patient Age ◽  
Patient Âgé

Background: Patients with Duchenne muscular dystrophy (DMD) typically exhibit progressive cardiac and skeletal muscle dysfunction, and are commonly treated with corticosteroids to prolong ambulation. Myocardial fibrosis and steroid treatment may modulate the progression of cardiac dysfunction in DMD patients. We aimed to longitudinally characterize the impact of myocardial fibrosis and steroid treatment on the progression of cardiac dysfunction using cardiac magnetic resonance (CMR) in a large DMD cohort. Methods: Serial CMR studies performed on DMD patients were reviewed for LVEF and late gadolinium enhancement (LGE) status, a marker for myocardial fibrosis. LVEF was modeled by examining effects of patient age, steroid treatment duration, LGE status, and myocardial fibrosis burden, as assessed by the number of LGE positive (LGE+) LV segments. Results: We analyzed 469 CMR studies from 99 DMD patients with ≥4 CMRs. Patient age at time of CMR ranged from 6.6 to 29.4 (median 12.3) years. There were 146 (31.1%) LGE+ studies and 59 studies (12.6%) that demonstrated depressed LVEF (LVEF<55%). An age-only model demonstrated that LVEF declined 0.58±0.10%/yr (p<0.0001, r 2 =0.067). Univariate modeling showed significant associations between LVEF and steroid treatment duration, presence of LGE, and number of LGE+ LV segments; multivariate modeling showed that LVEF declined by 0.93±0.09% for each LGE+ LV segment (p<0.0001, r 2 =0.171), while age and steroid treatment duration were no longer significant. The number of LGE+ LV segments increased with age by 1.2 segments/year (95% confidence interval 1.1-1.2), and steroid treatment partially mitigated this increase (interaction term β=-0.01±0.005, p=0.010). Conclusions: Progressive myocardial fibrosis, as imaged by LGE on CMR, is a strong marker for the decline in LVEF in DMD patients. Steroid treatment partially attenuates the age-related increase in myocardial fibrosis burden.

scholarly journals Cardiac Dysfunction in Duchenne Muscular Dystrophy Is Less Frequent in Patients With Mutations in the Dystrophin Dp116 Coding Region Than in Other Regions

2018 ◽  
Vol 11 (1) ◽  
Author(s):  
Tetsushi Yamamoto ◽  
Hiroyuki Awano ◽  
Zhujun Zhang ◽  
Mio Sakuma ◽  
Shoko Kitaaki ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Left Ventricular Ejection Fraction ◽  
Muscular Dystrophy ◽  
Ejection Fraction ◽  
Cardiac Dysfunction ◽  
Cardiac Involvement ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Coding Region ◽  
Ventricular Ejection Fraction

Background Duchenne muscular dystrophy (DMD), the most common inherited muscular disease in childhood, is caused by dystrophin deficiency because of mutations in the DMD gene. Although DMD is characterized by fatal progressive muscle wasting, cardiomyopathy is the most important nonmuscle symptom threatening the life of patients with DMD. The relationship between cardiac involvement and dystrophin isoforms has not been analyzed. Methods and Results The results of 1109 echocardiograms obtained from 181 Japanese DMD patients with confirmed mutations in the DMD gene were retrospectively analyzed. Patients showed an age-related decline in left ventricular ejection fraction. Patients were divided by patterns of dystrophin isoform deficiency into 5 groups. The cardiac dysfunction-free survival was significantly higher in the group with mutations in the Dp116 coding region than the others, whereas no significant differences in the other 3 groups. At age 25 years, the cardiac dysfunction-free rate was 0.6 in the Dp116 group, but only 0.1 in others. PCR amplification of Dp116 transcript in human cardiac muscle indicated promoter activation. Conclusions Left ventricular ejection fraction in DMD declined stepwise with age. Cardiac dysfunction was less frequent in Dp116-deficient than other patients with DMD. Dp116 transcript was identified in human cardiac muscle for the first time. These results indicate that Dp116 is associated with cardiac involvement in DMD.

scholarly journals Non-contrast cardiovascular magnetic resonance detection of myocardial fibrosis in Duchenne muscular dystrophy

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Frank J. Raucci ◽  
Meng Xu ◽  
Kristen George-Durrett ◽  
Kimberly Crum ◽  
James C. Slaughter ◽  
...  
Keyword(s):  
Cardiovascular Magnetic Resonance ◽  
Duchenne Muscular Dystrophy ◽  
Magnetic Resonance ◽  
Muscular Dystrophy ◽  
Myocardial Fibrosis ◽  
Severity Score ◽  
T1 Mapping ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Native T1

Abstract Background Duchenne muscular dystrophy (DMD) leads to progressive cardiomyopathy. Detection of myocardial fibrosis with late gadolinium enhancement (LGE) by cardiovascular magnetic resonance (CMR) is critical for clinical management. Due to concerns of brain deposition of gadolinium, non-contrast methods for detecting and monitoring myocardial fibrosis would be beneficial. Objectives We hypothesized that native T1 mapping and/or circumferential (εcc) and longitudinal (εls) strain can detect myocardial fibrosis. Methods 156 CMRs with gadolinium were performed in 66 DMD boys and included: (1) left ventricular ejection fraction (LVEF), (2) LGE, (3) native T1 mapping and myocardial tagging (εcc-tag measured using harmonic phase analysis). LGE was graded as: (1) presence/absence by segment, slice, and globally; (2) global severity from 0 (no LGE) to 4 (severe); (3) percent LGE using full width half maximum (FWHM). εls and εcc measured using feature tracking. Regression models to predict LGE included native T1 and either εcc-tag or εls and εcc measured at each segment, slice, and globally. Results Mean age and LVEF at first CMR were 14 years and 54%, respectively. Global εls and εcc strongly predicted presence or absence of LGE (OR 2.6 [1.1, 6.0], p = 0.029, and OR 2.3 [1.0, 5.1], p = 0.049, respectively) while global native T1 did not. Global εcc, εls, and native T1 predicted global severity score (OR 2.6 [1.4, 4.8], p = 0.002, OR 2.6 [1.4, 6.0], p = 0.002, and OR 1.8 [1.1, 3.1], p = 0.025, respectively). εls correlated with change in LGE by severity score (n = 33, 3.8 [1.0, 14.2], p = 0.048) and εcc-tag correlated with change in percent LGE by FWHM (n = 34, OR 0.2 [0.1, 0.9], p = 0.01). Conclusions Pre-contrast sequences predict presence and severity of LGE, with εls and εcc being more predictive in most models, but there was not an observable advantage over using LVEF as a predictor. Change in LGE was predicted by εls (global severity score) and εcc-tag (FWHM). While statistically significant, our results suggest these sequences are currently not a replacement for LGE and may only have utility in a very limited subset of DMD patients.

Abstract 17250: Serum vs. Imaging Biomarkers of Myocardial Injury in Duchenne Muscular Dystrophy: Findings from the E-SCAR DMD Trial

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Subha V Raman ◽  
Kan N Hor ◽  
Wojciech Mazur ◽  
Nancy Halnon ◽  
Tam Tran ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Myocardial Injury ◽  
Troponin I ◽  
Left Ventricular ◽  
Serum Biomarkers ◽  
Left Ventricular Ejection ◽  
Imaging Biomarkers ◽  
Mineralocorticoid Receptor Antagonist ◽  
Lge Cmr

Introduction: Cardiomyopathy has become a leading cause of death in Duchenne muscular dystrophy (DMD). We previously showed that early mineralocorticoid receptor antagonist therapy reduces myocardial damage in a preclinical model of DMD. The Eplerenone for Subclinical Cardiomyopathy in DMD (E-SCAR DMD, NCT01521546) is a multicenter randomized placebo-controlled clinical trial evaluating eplerenone in boys with preserved left ventricular ejection fraction (LVEF) and evident myocardial injury by late gadolinium enhancement cardiac magnetic resonance (LGE-CMR). Hypothesis: To better define biomarkers of early disease, we hypothesized that LGE has greater sensitivity vs. serum biomarkers for myocardial injury in DMD cardiomyopathy. Methods: Boys with DMD age ≥ 7 years were enrolled across 3 centers. LGE-CMR images were acquired using comparable techniques across 3T scanners, and core laboratory LGE quantification was performed blinded to laboratory findings as a percentage of LV mass using software based on the full-width half-maximum technique. Troponin-I, creatine kinase (CK) and CK isoenzymes were measured from blood samples obtained at the time of CMR examination using standardized clinical assays. Results: 42 boys age 16 ± 7 years had preserved LVEF (57 ± 6%), and LGE-positive regions averaged 5.0 ± 2.6% of LV myocardium. While 100% had evident myocardial injury by LGE, 43% had measurable CK-MB and only 18% had detectable troponin-I in serum (Figure). %LGE was higher (5.4 ± 2.7 vs. 3.3 ± 1.8%, p<0.05) and LVEF was lower (55.4 ± 4.9 vs. 59.0 ± 7.1%, p < 0.01) in boys with detectable vs. those with undetectable troponin-I, whereas detectable CK-MB did not predict higher %LGE or lower LVEF. Conclusion: DMD patients with abnormal myocardium by LGE-CMR may have no detectable abnormalities by serum biomarkers, underscoring the importance of myocardial injury imaging in identifying patients with subclinical cardiomyopathy who may benefit from early treatment.

scholarly journals Real-world outcomes of long-term prednisone and deflazacort use in patients with Duchenne muscular dystrophy: experience at a single, large care center

2020 ◽  
Vol 9 (3) ◽  
pp. 177-189
Author(s):  
Jessica R Marden ◽  
Jonathan Freimark ◽  
Zhiwen Yao ◽  
James Signorovitch ◽  
Cuixia Tian ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Real World ◽  
Medical Center ◽  
Care Center ◽  
Left Ventricular ◽  
Whole Body ◽  
Left Ventricular Ejection ◽  
Mineral Density ◽  
Ventricular Ejection Fraction

Aim: To assess outcomes among patients with Duchenne muscular dystrophy receiving deflazacort or prednisone in real-world practice. Methods: Clinical data for 435 boys with Duchenne muscular dystrophy from Cincinnati Children’s Hospital Medical Center were studied retrospectively using time-to-event and regression analyses. Results: Median ages at loss of ambulation were 15.6 and 13.5 years among deflazacort- and prednisone-initiated patients, respectively. Deflazacort was also associated with a lower risk of scoliosis and better ambulatory function, greater % lean body mass, shorter stature and lower weight, after adjusting for age and steroid duration. No differences were observed in whole body bone mineral density or left ventricular ejection fraction. Conclusion: This single center study adds to the real-world evidence associating deflazacort with improved clinical outcomes.

scholarly journals Participation of the C-terminal propeptide procollagen type I in the formation of cardiofibrosis in patients with myocardial infarction with preserved left ventricular ejection fraction

2021 ◽  
Vol 26 (2) ◽  
pp. 4137
Author(s):  
A. V. Osokina ◽  
V. N. Karetnikova ◽  
O. M. Polikutina ◽  
A. V. Ivanova ◽  
T. B. Pecherina ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Ejection Fraction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Type I ◽  
Patient Age ◽  
Procollagen Type ◽  
Patient Âgé ◽  
Procollagen Type I ◽  
One Year

Aim. To study the dynamics of procollagen type I carboxy-terminal propeptide (PICP) with an assessment of potential associations with cardiac fibrosis (CF) and diastolic dysfunction (DD) of the left ventricle (LV) during the hospitalization and one year after ST segment elevation myocardial infarction (STEMI).Material and methods. The study included 120 patients with STEMI. There were following inclusion criteria: diagnosis of STEMI (2015 European Society of Cardiology guidelines); Killip £III acute heart failure (AHF); signed informed consent; patient age >18 years old. There were following exclusion criteria: STEMI due to percutaneous coronary intervention or coronary artery bypass grafting; Killip IV AHF; patient age >80 years; clinically significant comorbidities; death of the patient during the first day of hospitalization. On the 1st, 12th day of the disease and after a year all patients underwent echocardiography and the PICP concentration was determined. One year after myocardial infarction, contrast-enhanced cardiac magnetic resonance imaging was performed to assess CF. In the analyzed group of patients, on day 1 of STEMI, mean values of LV ejection fraction (EF) in the range of 40-49% were observed in 3 (2,5%) patients, LVEF <40% — in 31 (26%), LVEF ≥50% — in 86 (71,7%). The final analysis was performed on a sample of patients with preserved LVEF (n=86) (71,7%).Results. On the first day of myocardial infarction, signs of DD were noted in 25 (29,1%) patients, while after 1 year, their number increased by 9 (10%) and amounted to 34 (39,5%) patients. In 15 (17,6%) people, worsening of myocardial systolic dysfunction was noted. Patients with a CF ³16% had the highest PICP expression on the first day of the disease. CF ≥16% one year after STEMI with preserved EF is associated with PICP concentration on day 1 of the disease. In addition, multidirectional correlations were revealed between the CF ≥16% and parameters of LV diastolic function (e’, mean pulmonary artery pressure, E/e’).Conclusion. Determination of the PICP concentration on the 1st day of myocardial infarction will allow early identification of patients at risk of CF one year after STEMI with preserved EF.

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