FT-based assessment of epsilon(cc) correlates highly with epsilon(cc) derived from tagged images in a large DMD patient population with a wide range of cardiac dysfunction and can be performed without additional imaging.

Summary Background Cardiomyopathy is a leading cause of death in patients with Duchenne muscular dystrophy and myocardial damage precedes decline in left ventricular systolic function. We tested the efficacy of eplerenone on top of background therapy in patients with Duchenne muscular dystrophy with early myocardial disease. Methods In this randomised, double-blind, placebo-controlled trial, boys from three centres in the USA aged 7 years or older with Duchenne muscular dystrophy, myocardial damage by late gadolinium enhancement cardiac MRI and preserved ejection fraction received either eplerenone 25 mg or placebo orally, every other day for the first month and once daily thereafter, in addition to background clinician-directed therapy with either angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB). Computer-generated randomisation was done centrally using block sizes of four and six, and only the study statistician and the investigational pharmacy had the preset randomisation assignments. The primary outcome was change in left ventricular circumferential strain (Ecc) at 12 months, a measure of contractile dysfunction. Safety was established through serial serum potassium levels and measurement of cystatin C, a non-creatinine measure of kidney function. This trial is registered with ClinicalTrials.gov, number NCT01521546. Findings Between Jan 26, 2012, and July 3, 2013, 188 boys were screened and 42 were enrolled. 20 were randomly assigned to receive eplerenone and 22 to receive placebo, of whom 20 in the eplerenone group and 20 in the placebo group completed baseline, 6-month, and 12-month visits. After 12 months, decline in left ventricular circumferential strain was less in those who received eplerenone than in those who received placebo (median ΔEcc 1.0 [IQR 0.3–2.2]vs2.2 [1.3–3.1]; p=0.020). Cystatin C concentrations remained normal in both groups, and all non-haemolysed blood samples showed normal potassium concentrations. One 23-year-old patient in the placebo group died of fat embolism, and another patient in the placebo group withdrew from the trial to address long-standing digestive issues. All other adverse events were mild: short-lived headaches coincident with seasonal allergies occurred in one patient given eplerenone, flushing occurred in one patient given placebo, and anxiety occurred in another patient given placebo. Interpretation In boys with Duchenne muscular dystrophy and preserved ejection fraction, addition of eplerenone to background ACEI or ARB therapy attenuates the progressive decline in left ventricular systolic function. Early use of available drugs warrants consideration in this population at high risk of cardiac death, but further studies are needed to determine the effect of combination cardioprotective therapy on event-free survival in Duchenne muscular dystrophy. Funding BallouSkies, Parent Project for Muscular Dystrophy, US National Center for Advancing Translational Sciences, and US National Institutes of Health.

Objectives This study sought to evaluate the natural history of occult cardiac dysfunction in Duchenne Muscular Dystrophy (DMD). Background DMD is characterized by progressive cardiac dysfunction and myocardial fibrosis late in the disease process. We hypothesized that left ventricular myocardial peak circumferential strain (εcc) would decrease in DMD prior to global systolic functional abnormalities regardless of age or ventricular ejection fraction (EF). Methods We evaluated cardiac magnetic resonance image (CMR) data from 70 DMD patients and 16 aged-matched control subjects. Standard imaging data included steady-state free precession (SSFP) short-axis cine stack images, cine myocardial tagged images and myocardial delayed enhancement (MDE, an indicator of myocardial fibrosis) sequences. Analysis was performed using QMASS® and HARP® softwares. DMD patient data was subdivided by age (< 10 years or > 10 years), EF (> 55% or <55%) and the presence or absence of MDE. Results DMD patients with normal EF had reduced εcc at an early age (<10 years) compared to control subjects (p< 0.01). DMD patients >10 years with normal EF had further decline in εcc compared to younger DMD patients (p<0.01). There was further decline in εcc with age in patients with reduced EF (p<0.01) without MDE. The oldest patients, with both reduced EF and positive MDE, exhibited the lowest εcc. None of the patients had ventricular hypertrophy. Conclusions Myocardial strain abnormalities are prevalent in young DMD patients despite normal EF, and these strain values continue to decline with advancing age. Strain analysis in combination with standard CMR and MDE imaging provides a means to stratify DMD cardiomyopathy.

changes within the RV that are associated with adverse surgical outcomes and poorer prognosis following mitral valve surgery. Future studies are needed to confirm whether LGE is a new imaging biomarker that can be used to risk stratify severe asymptomatic MR patients for surgery. Abstract 110 Table 1 Features of patients with and without gadolinium enhancement Late gadolinium enhancement Number of patients MR fraction (%) Systolic RV volume (ml/ m 2) RV ejection fraction (%) Peak VO 2 (ml/ kg/min) VE/ VCO 2 None 43 32±12 28.5±7.7 61±8 24.6±6.9 31.1 ±5.0 RV insertion gadolinium 8 46±17* 31.4±7.6* 55±6* 23.1±8.7 33.2 ±3.2* LV myocardial gadolinium 10 42±19* 35.1±11.1* 55±8* 23.0±5.9 36.7 ±6.9* *denotes statistical significance of P0.05 compared to non-gadolinium cohort on Independent samples 2 tailed T-Test Abstract 110 Figure 1 Late gadolinium enhancement of the basal inferolateral LV

Purpose: An accurate and practical method to measure parameters like strain in myocardial tissue is of great clinical value, since it has been shown, that strain is a more sensitive and earlier marker for contractile dysfunction than the frequently used parameter EF. Current technologies for CMR are time consuming and difficult to implement in clinical practice. Feature tracking is a technology that can lead to more automization and robustness of quantitative analysis of medical images with less time consumption than comparable methods.Methods: An automatic or manual input in a single phase serves as an initialization from which the system starts to track the displacement of individual patterns representing anatomical structures over time. The specialty of this method is that the images do not need to be manipulated in any way beforehand like e.g. tagging of CMR images.Results: The method is very well suited for tracking muscular tissue and with this allowing quantitative elaboration of myocardium and also blood flow.Conclusions: This new method offers a robust and time saving procedure to quantify myocardial tissue and blood with displacement, velocity and deformation parameters on regular sequences of CMR imaging. It therefore can be implemented in clinical practice.

Background Patients with Duchenne muscular dystrophy exhibit progressive cardiac and skeletal muscle dysfunction. Based on prior data, cardiac dysfunction in Duchenne muscular dystrophy patients may be influenced by myocardial fibrosis and steroid therapy. We examined the longitudinal relationship of myocardial fibrosis and ventricular dysfunction using cardiac magnetic resonance in a large Duchenne muscular dystrophy cohort. Methods and Results We reviewed 465 serial cardiac magnetic resonance studies (98 Duchenne muscular dystrophy patients with ≥4 cardiac magnetic resonance studies) for left ventricular ejection fraction (LVEF) and presence of late gadolinium enhancement (LGE), a marker for myocardial fibrosis. LVEF was modeled by examining LGE status, myocardial fibrosis burden (as assessed by the number of LGE‐positive left ventricular segments), patient age, and steroid treatment duration. An age‐only model demonstrated that LVEF declined 0.58±0.10% per year. In patients with both LGE‐negative and LGE‐positive studies (n=51), LVEF did not decline significantly over time if LGE was absent but declined 2.2±0.31% per year when LGE was present. Univariate modeling showed significant associations between LVEF and steroid treatment duration, presence of LGE, and number of LGE‐positive left ventricular segments; multivariate modeling showed that LVEF declined by 0.93±0.09% for each LGE‐positive left ventricular segment, whereas age and steroid treatment duration were not significant. The number of LGE‐positive left ventricular segments increased with age, and longer steroid treatment duration was associated with lower age‐related increases. Conclusion Progressive myocardial fibrosis, as detected by LGE, was strongly correlated with the LVEF decline in Duchenne muscular dystrophy patients. Longer steroid treatment duration was associated with a lower age‐related increase in myocardial fibrosis burden.

BackgroundDuchenne muscular dystrophy (DMD), an X-linked disorder affects approximately 1 in 5000 males, is universally associated with heart disease. We previously identified myocardial disease by late gadolinium enhancement (LGE) in DMD subjects at various stages of disease, but the true prevalence is unclear. Cardiovascular magnetic resonance (CMR) is well established for both assessment of ventricular function and myocardial fibrosis by LGE. We sought to establish i) prevalence and distribution of LGE in a large DMD population and ii) relationship among LGE, age, LVEF by CMR and current living status.MethodsCurrent living status, demographic and CMR data including ventricular volumes, LVEF and LGE from 314 DMD patients undergoing evaluation at a single large tertiary referral center were analyzed.Results113 of 314 (36%) of DMD subjects showed LGE positivity with prevalence increasing from 17% of patients <10 years to 34% of those aged 10–15 years and 59% of those >15 years-old. Patients with LVEF ≥55% were LGE positive in 30% of cases; this increased to 84% for LVEF <55%. LGE was more prevalent in the free wall (531/1243, 42.7%) vs. septal segments (30/565, 5.3%). Patients with septal involvement were significantly older and had lower LVEF than those with isolated free wall LGE. Ten percent (11/113) patients who had LGE died 10.8 months after CMR. Only one patient from the LGE negative group died. Patients who died had higher heart rate, larger left ventricular volume and mass, greater number of positive LGE segment and increase incident of septal LGE compared to those who remained alive.ConclusionIn DMD patients, LGE occurs early, is progressive and increases with both age and decreasing LVEF. Segmentally, the incidence of the number of positive LGE segments increase with age and lower LVEF. Older patients and those who died during the study period had more septal LGE involvement. The current studies suggest that the time course and distribution of LGE-positivity may be an important clinical biomarker to aid in the management of DMD-associated cardiac disease.

Aims The aim of our study was to establish normal ranges for left atrial (LA) strain and strain rate using cardiac magnetic resonance feature tracking (CMR-FT), LA sphericity index, and to compare LA strain using CMR-FT with 2D-speckle tracking echocardiography (STE) in a healthy population. Methods and results A total of 112 volunteers (45 male, 67 female) had adequate tracking for analysis on CMR-FT (Circle Cardiovascular Imaging, Calgary, Canada). The median age was 42 years (range 19–79 years, interquartile range 30–53 years). LA reservoir, conduit, booster strain, strain rate using CMR-FT, and sphericity index were evaluated. Of the 112 volunteers, 91 patients had adequate tracking on 2D-STE using three commonly applied zero-baseline time reference methods: R-R gating, P-P gating, and volume gating (defining end-systole at the LA maximum and end-diastole at the LA minimum). The LA strain, strain rate using CMR-FT, and sphericity index were reported and comparable between both genders (P > 0.05 for all). The LA booster function including strain and strain rate increased significantly with age (P < 0.001 for all), while the LA conduit function gradually decreased. In comparison with STE, the LA reservoir strain was comparable between CMR and volume-gating methods (38.48 ± 9.31 vs. 36.77 ± 6.46; P = 0.13) but not with R-R and P-P gating methods (P < 0.001 for all). LA strain, strain rate, and sphericity index using CMR-FT had good intraobserver and interobserver reproducibility. Conclusion LA strain, strain rate using CMR-FT, and sphericity index can be quickly assessed with good intraobserver and interobserver reproducibility.