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Increased myocardial native T1 and extracellular volume in patients with Duchenne muscular dystrophy.

ABSTRACT: Duchenne muscular dystrophy (DMD) cardiomyopathy is a progressive disease for which there is no cure. Disease-specific therapies are needed that can be initiated before irreversible myocardial damage ensues. In order to evaluate therapeutic efficacy, surrogate endpoints other than ejection fraction must be found. The hypothesis of this study is that T1 and extracellular volume fraction (ECV) mapping using cardiovascular magnetic resonance (CMR) can detect diffuse extracellular matrix expansion in DMD patients with normal left ventricular ejection fraction (LVEF) and without myocardial late gadolinium enhancement (LGE).Thirty-one DMD and 11 healthy control participants were prospectively enrolled. CMR using a modified Look-Locker (MOLLI) sequence was performed in all participants before and after contrast administration. T1 and ECV maps of the mid left ventricular myocardium were generated and regions of interest were contoured using the standard 6-segment AHA model. Global and segmental values were compared between DMD and controls using a Wilcoxon rank-sum test.The DMD participants had significantly higher mean native T1 compared with controls (1045 ms vs. 988 ms, p = 0.001). DMD participants with normal LVEF and without evidence of LGE also demonstrated elevated mean native T1 (1039 ms vs. 988 ms, p = 0.002, and 1038 ms vs. 988 ms, p = 0.011). DMD participants had a significantly greater mean ECV than controls (0.31 vs. 0.24, p < 0.001), even in the settings of normal LVEF (0.28 vs. 0.24, p < 0.001) and negative LGE (0.29 vs. 0.24, p = 0.001).DMD participants have elevated LV myocardial native T1 and ECV, even in the setting of normal LVEF and in the absence of LGE. T1 and ECV mapping in DMD have potential to serve as surrogate cardiomyopathy outcome measures for clinical trials.

SUBMITTER: Soslow JH

PROVIDER: S-EPMC4722665 | biostudies-other | 2016 Jan

REPOSITORIES: biostudies-other

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Project description:AimsTo determine how native myocardial T1 and extracellular volume (ECV) change with age, both to understand aging and to inform on normal reference ranges.Methods and resultsNinety-four healthy volunteers with no a history or symptoms of cardiovascular disease or diabetes underwent cardiovascular magnetic resonance at 1.5 T. Mid-ventricular short axis native and post-contrast T1 maps by Shortened MOdified Look-Locker Inversion-recovery (ShMOLLI), MOdified Look-Locker Inversion Recovery (MOLLI) [pre-contrast: 5s(3s)3s, post-contrast: 4s(1s)3s(1s)2s] and saturation recovery single-shot acquisition (SASHA) were acquired and ECV by these three techniques were derived for the mid anteroseptum. Mean age was 50 ± 14 years (range 20-76), male 52%, with no age difference between genders (males 51 ± 14 years; females 49 ± 15 years, P = 0.55). Quoting respectively ShMOLLI, MOLLI, SASHA throughout, mean myocardial T1 was 957 ± 30 ms, 1025 ± 38 ms, 1144 ± 45 ms (P < 0.0001) and ECV 28.4 ± 3.0% [95% confidence interval (CI) 27.8-29.0], 27.3 ± 2.7 (95% CI 26.8-27.9), 24.1 ± 2.9% (95% CI 23.5-24.7) (P < 0.0001), with all values higher in females for all techniques (T1 +18 ms, +35 ms, +51 ms; ECV +2.7%, +2.6%, +3.4%). Native myocardial T1 reduced slightly with age (R2 = 0.042, P = 0.048; R2 = 0.131, P < 0.0001-on average by 8-11 ms/decade-but not for SASHA (R2 = 0.033 and P = 0.083). ECV did not change with age (R2 = 0.003, P = 0.582; R2 = 0.002, P = 0.689; R2 = 0.003, P = 0.615). Heart rate decreased slightly with age (R2 = 0.075, coefficient = -0.273, P = 0.008), but there was no relationship between age and other blood T1 influences (haematocrit, iron, high density lipoprotein-cholesterol).ConclusionGender influences native T1 and ECV with women having a higher native T1 and ECV. Native T1 measured by MOLLI and ShMOLLI was slightly lower with increasing age but not with SASHA and ECV was independent of age for all techniques.

Project description:BackgroundClinical management of boys with Duchenne muscular dystrophy (DMD) relies on in-depth understanding of cardiac involvement, but right ventricular (RV) structural and functional remodeling remains understudied.PurposeTo evaluate several analysis methods and identify the most reliable one to measure RV pre- and postcontrast T1 (RV-T1) and to characterize myocardial remodeling in the RV of boys with DMD.Study typeProspective.PopulationBoys with DMD (N = 27) and age-/sex-matched healthy controls (N = 17) from two sites.Field strength/sequence3.0 T using balanced steady state free precession, motion-corrected phase sensitive inversion recovery and modified Look-Locker inversion recovery sequences.AssessmentBiventricular mass (Mi), end-diastolic volume (EDVi) and ejection fraction (EF) assessment, tricuspid annular excursion (TAE), late gadolinium enhancement (LGE), pre- and postcontrast myocardial T1 maps. The RV-T1 reliability was assessed by three observers in four different RV regions of interest (ROI) using intraclass correlation (ICC).Statistical testsThe Wilcoxon rank sum test was used to compare RV-T1 differences between DMD boys with negative LGE(-) or positive LGE(+) and healthy controls. Additionally, correlation of precontrast RV-T1 with functional measures was performed. A P-value <0.05 was considered statistically significant.ResultsA 1-pixel thick RV circumferential ROI proved most reliable (ICC > 0.91) for assessing RV-T1. Precontrast RV-T1 was significantly higher in boys with DMD compared to controls. Both LGE(-) and LGE(+) boys had significantly elevated precontrast RV-T1 compared to controls (1543 [1489-1597] msec and 1550 [1402-1699] msec vs. 1436 [1399-1473] msec, respectively). Compared to healthy controls, boys with DMD had preserved RVEF (51.8 [9.9]% vs. 54.2 [7.2]%, P = 0.31) and significantly reduced RVMi (29.8 [9.7] g vs. 48.0 [15.7] g), RVEDVi (69.8 [29.7] mL/m2 vs. 89.1 [21.9] mL/m2 ), and TAE (22.0 [3.2] cm vs. 26.0 [4.7] cm). Significant correlations were found between precontrast RV-T1 and RVEF (β = -0.48%/msec) and between LV-T1 and LVEF (β = -0.51%/msec).Data conclusionPrecontrast RV-T1 is elevated in boys with DMD compared to healthy controls and is negatively correlated with RVEF.Level of evidence1 TECHNICAL EFFICACY: Stage 2.

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Increased myocardial native T1 and extracellular volume in patients with Duchenne muscular dystrophy.

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