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 The role of neurohormonal blockers in the primary prevention of acute-, early-, and late-onset anthracycline-induced cardiotoxicity

2020 ◽  
Vol 72 (1) ◽  
Author(s):  
Ahmed Ayuna ◽  
Nik Abidin
Keyword(s):  
Primary Prevention ◽  
Myocardial Injury ◽  
Troponin I ◽  
Late Onset ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Main Body ◽  
Converting Enzyme Inhibitors ◽  
Ventricular Ejection Fraction

Abstract Background Anthracycline-induced cardiotoxicity has been classified based on its onset into acute, early, and late. It may have a significant burden on the quality and quantity of life of those exposed to this class of medication. Currently, there are several ongoing debates on the role of different measures in the primary prevention of cardiotoxicity in cancer survivors. Our article aims to focus on the role of neurohormonal blockers in the primary prevention of anthracycline-induced cardiotoxicity, whether it is acute, early, or late onset. Main body of the abstract PubMed and Google Scholar database were searched for the relevant articles; we reviewed and appraised 15 RCTs, and we found that angiotensin-converting enzyme inhibitors (ACEI) and B-blockers were the most commonly used agents. Angiotensin II receptor blockers (ARBs) and mineralocorticoid receptor antagonists (MRAs) were used in a few other trials. The follow-up period was on the range of 1–156 weeks (mode 26 weeks). Left ventricular ejection fraction (LVEF), left ventricular diameters, and diastolic function were assessed by either echocardiogram or occasionally by cardiac magnetic resonance imaging (MRI). The occurrence of myocardial injury was assessed by troponin I. It was obvious that neurohormonal blockers reduced the occurrence of LVEF and myocardial injury in 14/15 RCTs. Short conclusion Beta-blockers, especially carvedilol and ACEI, especially enalapril, should be considered for the primary prevention of acute- and early-onset cardiotoxicity. ARB and MRA are suitable alternatives when patients are intolerant to ACE-I and B-blockers. We recommend further studies to explore and establish the role of neurohormonal blockers in the primary prevention of the acute-, early-, and late-onset cardiotoxicity.

Nicorandil reduces myocardial injury and improves cardiac function in valve replacement surgery.

2019 ◽  
Vol 1 (4) ◽  
pp. 120-126
Author(s):  
Wael Elfeky ◽  
Mohamed Aboelnasr ◽  
Ayman Sallam ◽  
Wael Haseeb ◽  
Dalia R El-Afify
Keyword(s):  
Valve Replacement ◽  
Myocardial Protection ◽  
Myocardial Injury ◽  
Troponin I ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Replacement Surgery ◽  
Tnf Α ◽  
Valve Replacement Surgery

Background: Myocardial injury during cardiac surgery is associated with increased morbidity and mortality, and proper myocardial protection improves surgical outcomes. We aimed to study the role of preoperative nicorandil in myocardial protection during valve replacement surgery. Methods: The study included 40 patients who were randomized into two groups: control group, and nicorandil group. Preoperative, intraoperative, and postoperative data were collected. Creatine kinase- MB (CK-MB), troponin I, malondialdehyde (MDA), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were measured 24-hours before surgery then 4, 12 and 48 hours after aortic cross-clamp removal. Results: Nicorandil significantly decreased MDA (p=0.005 and 0.036), TNF-α (p< 0.001), IL-6 (p<0.001 and 0.003) 4 and 12 hours following the removal of aortic clamp compared to the control group. Additionally, It significantly reduced CK-MB (p< 0.0001 and 0.0002) and troponin-I (p= 0.0002 and < 0.0001) 4 and 12 hours after the removal of the aortic clamp, respectively. However, there was no significant difference in MDA, TNF-α, IL-6, CK-MB, and troponin-I levels between the nicorandil and the control group after 48 hours following the removal of aortic clamping (p= 0.084; 0.64; 0.12; 0.12; 0.75; respectively). Conclusions: Nicorandil reduced myocardial injury significantly in valve replacement surgery. Nicorandil decreased CK-MB and troponin I and improved postoperative left ventricular ejection fraction.

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.

Evidence for lack of myocardial injury in children with acute rheumatic carditis

2002 ◽  
Vol 12 (6) ◽  
pp. 519-523 ◽  
Author(s):  
Richard V. Williams ◽  
L. LuAnn Minich ◽  
Robert E. Shaddy ◽  
L. George Veasy ◽  
Lloyd Y. Tani
Keyword(s):  
Mitral Regurgitation ◽  
Cardiac Troponin ◽  
Myocardial Injury ◽  
Troponin I ◽  
Left Ventricular ◽  
Cardiac Troponin I ◽  
Left Ventricular Ejection ◽  
Myocardial Inflammation ◽  
Rheumatic Carditis ◽  
Ventricular Ejection Fraction

Despite pathologic evidence of myocardial inflammation, the significance of myocarditis in children with acute rheumatic carditis remains controversial. Elevations in cardiac troponin I have been demonstrated in other forms of myocarditis. The purpose of our study was to determine if levels of cardiac troponin I are elevated, suggesting myocardial injury, in patients with acute rheumatic carditis. We identified all those patients with acute rheumatic fever, presenting between July 1998 and December 2000, who had clinical evidence of carditis, such as a new murmur of mitral or aortic regurgitation, and who had an echocardiogram, measurements of levels of cardiac troponin I, erythrocyte sedimentation rate, and/or C-reactive protein performed at the time of presentation. Their charts were reviewed for demographic and clinical data. Echocardiograms were reviewed for severity of aortic and mitral regurgitation, and measurements made of left ventricular ejection fraction, fractional shortening, and end-diastolic dimension. We found 16 patients with acute rheumatic carditis, ranging in age from 2.0 to 16.1 years, with just over one-third having symptoms of congestive heart failure. All patients had evidence of acute inflammation. There was a significant relationship between symptoms and severity of mitral regurgitation. No patient had elevated levels of cardiac troponin I level. The fact that levels of cardiac troponin I are not elevated in the serum of children with acute rheumatic carditis suggests that there is minimal myocytic necrosis in this setting. This supports the concept that acute valvar regurgitation is the major hemodynamic abnormality in these patients.

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 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.

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