Progressive myocardial injury in myotonic dystrophy type II and facioscapulohumeral muscular dystrophy 1: a cardiovascular magnetic resonance follow-up study.

AIM: Muscular dystrophy (MD) is a progressive disease with predominantly muscular symptoms. Myotonic dystrophy type II (MD2) and facioscapulohumeral muscular dystrophy type 1 (FSHD1) are gaining an increasing awareness, but data on cardiac involvement are conflicting. The aim of this study was to determine a progression of cardiac remodeling in both entities by applying cardiovascular magnetic resonance (CMR) and evaluate its potential relation to arrhythmias as well as to conduction abnormalities. METHODS AND RESULTS: 83 MD2 and FSHD1 patients were followed. The participation was 87% in MD2 and 80% in FSHD1. 1.5 T CMR was performed to assess functional parameters as well as myocardial tissue characterization applying T1 and T2 mapping, fat/water-separated imaging and late gadolinium enhancement. Focal fibrosis was detected in 23% of MD2) and 33% of FSHD1 subjects and fat infiltration in 32% of MD2 and 28% of FSHD1 subjects, respectively. The incidence of all focal findings was higher at follow-up. T2 decreased, whereas native T1 remained stable. Global extracellular volume fraction (ECV) decreased similarly to the fibrosis volume while the total cell volume remained unchanged. All patients with focal fibrosis showed a significant increase in left ventricular (LV) and right ventricular (RV) volumes. An increase of arrhythmic events was observed. All patients with ventricular arrhythmias had focal myocardial changes and an increased volume of both ventricles (LV end-diastolic volume (EDV) p = 0.003, RVEDV p = 0.031). Patients with supraventricular tachycardias had a significantly higher left atrial volume (p = 0.047). CONCLUSION: We observed a remarkably fast and progressive decline of cardiac morphology and function as well as a progression of rhythm disturbances, even in asymptomatic patients with a potential association between an increase in arrhythmias and progression of myocardial tissue damage, such as focal fibrosis and fat infiltration, exists. These results suggest that MD2 and FSHD1 patients should be carefully followed-up to identify early development of remodeling and potential risks for the development of further cardiac events even in the absence of symptoms. Trial registration ISRCTN, ID ISRCTN16491505. Registered 29 November 2017 - Retrospectively registered, http://www.isrctn.com/ISRCTN16491505.

Correction to: Subclinical myocardial injury in patients with Facioscapulohumeral muscular dystrophy 1 and preserved ejection fraction - assessment by cardiovascular magnetic resonance.

In the original version of this article [1], published on 29 April 2019, there is 1 error in the 'Method' section of the article.

Subclinical myocardial injury in patients with Facioscapulohumeral muscular dystrophy 1 and preserved ejection fraction - assessment by cardiovascular magnetic resonance.

BACKGROUND: Facioscapulohumeral muscular dystrophy type 1 (FSHD1) is an autosomal dominant and the third most common inherited muscle disease. Cardiac involvement is currently described in several muscular dystrophies (MD), but there are conflicting reports in FSHD1. Mostly, FSHD1 is recognized as MD with infrequent cardiac involvement, but sudden cardiac deaths are reported in single cases. The aim of this study is to investigate whether subclinical cardiac involvement in FSHD1 patients is detectable in preserved left ventricular systolic function applying cardiovascular magnetic resonance (CMR). METHODS: We prospectively included patients with genetically confirmed FSHD1 (n = 52, 48 ± 15 years) and compared them with 29 healthy age-matched controls using a 1.5 T CMR scanner. Myocardial tissue differentiation was performed qualitatively using focal fibrosis imaging (late gadolinium enhancement (LGE)), fat imaging (multi-echo sequence for fat/water-separation) and parametric T2- and T1-mapping for quantifying inflammation and diffuse fibrosis. Extracellular volume fraction was calculated. A 12-lead electrocardiogram and 24-h Holter were performed for the assessment of MD-specific Groh-criteria and arrhythmia. RESULTS: Focal fibrosis by LGE was present in 13 patients (25%,10 men), fat infiltration in 7 patients (13%,5 men). T2 values did not differ between FSHD1 and healthy controls. Native T1 mapping revealed significantly higher values in patients (global native myocardial T1 values basal: FSHD1: 1012 ± 26 ms vs. controls: 985 ± 28 ms, p < 0.01, medial FSHD1: 994 ± 37 ms vs. controls: 982 ± 28 ms, p = 0.028). This was also evident in regions adjacent to focal fibrosis, indicating diffuse fibrosis. Groh-criteria were positive in 1 patient. In Holter, arrhythmic events were recorded in 10/43 subjects (23%). CONCLUSIONS: Patients with FSHD1 and preserved left ventricular ejection fraction present focal and diffuse myocardial injury. Longitudinal multi-center trials are needed to define the impact of myocardial changes as well as a relation between myocardial injury and arrhythmias on long-term prognosis and therapeutic decision-making. TRIAL REGISTRATION: ISRCTN registry with study ID ISRCTN13744381 .

Influence of spatial resolution and contrast agent dosage on myocardial T1 relaxation times.

OBJECTIVE: Our aim was to study the influence of small variations in spatial resolution and contrast agent dosage on myocardial T1 relaxation time. MATERIALS AND METHODS: Twenty-nine healthy volunteers underwent cardiovascular magnetic resonance at 3T twice, including a modified look-locker inversion recovery (MOLLI) technique-3(3)3(3)5-for T1 mapping. Native T1 was assessed in three spatial resolutions (voxel size 1.4 × 1.4 × 6, 1.6 × 1.6 × 6, 1.7 × 1.7 × 6 mm3), and postcontrast T1 after 0.1 and 0.2 mmol/kg gadobutrol. Partition coefficient was calculated based on myocardial and blood T1. T1 analysis was done per segment, per slice, and for the whole heart. RESULTS: Native T1 values did not differ with varying spatial resolution per segment (p = 0.116-0.980), per slice (basal: p = 0.772; middle: p = 0.639; apex: p = 0.276), and globally (p = 0.191). Postcontrast T1 values were significantly lower with higher contrast agent dosage (p < 0.001). The global partition coefficient was 0.43 ± 0.3 for 0.2 and 0.1 mmol gadobutrol (p = 0.079). CONCLUSION: Related to the tested MOLLI technique at 3T, very small variations in spatial resolution (voxel sizes between 1.4 × 1.4 × 6 and 1.7 × 1.7 × 6 mm3) remained without effect on the native T1 relaxation times. Postcontrast T1 values were naturally shorter with higher contrast agent dosage while the partition coefficient remained constant. Further studies are necessary to test whether these conclusions hold true for larger matrix sizes and in larger cohorts.

Cardiac Involvement in Myotonic Dystrophy Type 2 Patients With Preserved Ejection Fraction: Detection by Cardiovascular Magnetic Resonance.

BACKGROUND: Myotonic dystrophy type 2 (DM2) is a genetic disorder characterized by skeletal muscle symptoms, metabolic changes, and cardiac involvement. Histopathologic alterations of the skeletal muscle include fibrosis and fatty infiltration. The aim of this study was to investigate whether subclinical cardiac involvement in DM2 is already detectable in preserved left ventricular function by cardiovascular magnetic resonance. METHODS AND RESULTS: Twenty-seven patients (mean age, 54±10 years; 20 females) with a genetically confirmed diagnosis of DM2 were compared with 17 healthy age- and sex-matched controls using a 1.5 T magnetic resonance imaging. For myocardial tissue differentiation, T1 and T2 mapping, fat/water-separated imaging, focal fibrosis imaging (late gadolinium enhancement [LGE]), and (1)H magnetic resonance spectroscopy were performed. Extracellular volume fraction was calculated. Conduction abnormalities were diagnosed based on Groh criteria. LGE located subepicardial basal inferolateral was detectable in 22% of the patients. Extracellular volume was increased in this region and in the adjacent medial inferolateral segment (P=0.03 compared with healthy controls). In 21% of patients with DM2, fat deposits were detectable (all women). The control group showed no abnormalities. Myocardial triglycerides were not different in LGE-positive and LGE-negative subjects (P=0.47). Six patients had indicators for conduction disease (60% of LGE-positive patients and 12.5% of LGE-negative patients). CONCLUSIONS: In DM2, subclinical myocardial injury was already detectable in preserved left ventricular ejection fraction. Extracellular volume was also increased in regions with no focal fibrosis. Myocardial fibrosis was related to conduction abnormalities.

Cardiac Fibrosis in Aortic Stenosis and Hypertensive Heart Disease Assessed by Magnetic Resonance T1 Mapping.

BACKGROUND: Continuous pressure overload may lead to subclinical myocardial tissue changes in patients with hypertensive heart disease (HHD) and aortic stenosis (AS). The study aim was to detect interstitial fibrosis using quantitative cardiovascular magnetic resonance. METHODS: Fifteen patients with HHD (arterial hypertension + septal wall thickness ≥13 mm), 33 with AS (eight mild, 15 moderate, 10 severe), and 60 healthy controls were enrolled. Native T1 maps (modified Look-Locker inversion recovery) were obtained in a basal, mid-ventricular, and apical shortaxis slice of the left ventricle to assess cardiac fibrosis. Focal fibrosis was assessed with late gadolinium enhancement (LGE). RESULTS: Patients with HHD and controls did not differ regarding the native myocardial T1 values, both per slice and per segment. In AS patients, apical native T1 values were lower than in controls, and there was a trend towards higher T1 values in the septum in severe AS (1172.6 ± 62.0 ms versus 1152.9 ± 43.9 ms). Five HHD patients and 11 AS patients had non-ischemic fibrosis in LGE images. Native T1 times did not differ between LGE-positive and LGEnegative groups (both with inclusion and exclusion of segments with LGE). CONCLUSIONS: T1 mapping did not reveal any evidence of abnormal interstitial fibrosis in HHD subjects with mild hypertrophy. In severe AS, a trend towards more interstitial fibrosis was present, but absolute differences were small for decision making.