Myocardial fibrosis by late gadolinium enhancement cardiovascular magnetic resonance in myotonic muscular dystrophy type 1: highly prevalent but not associated with surface conduction abnormality

Abstract

Background Conduction disease and arrhythmias represent a major cause of mortality in myotonic muscular dystrophy type 1 (MMD1). Permanent pacemaker (PPM) implantation is the cornerstone of therapy to reduce cardiovascular mortality in MMD1. Cardiovascular magnetic resonance (CMR) studies demonstrate a high prevalence of myocardial fibrosis in MMD1, however the association between CMR myocardial fibrosis with late gadolinium enhancement (CMR-LGE) and surface conduction abnormality is not well established in MMD1. We investigated whether myocardial fibrosis by CMR-LGE is associated with surface conduction abnormalities meeting criteria for PPM implantation according to current guidelines in a cohort of patients with genetically confirmed MMD1. Methods Patients with genetically confirmed MMD1 were retrospectively evaluated. 12-lead electrocardiography (ECG) performed within 6 months of CMR was necessary for inclusion. The severity and extent of MMD1 was quantified using a validated Muscular Impairment Rating Scale (MIRS). Based on current guidelines for device-based therapy of cardiac rhythm abnormalities, we defined surface conduction abnormality as the presence of ECG alterations meeting criteria for PPM implant (class I or II indications): PR interval > 200 ms (type I atrioventricular (AV) block) and/or mono or bifascicular block (QRS > 120 ms), or evidence of advanced AV block. Balanced steady-state free precession sequences (bSSFP) were used for assessment of left ventricular (LV) volumes and ejection fraction. MOdified Look-Locker Inversion Recovery (MOLLI) acquisition schemes were used to acquire T1 maps. Patients’ charts were reviewed up to 12 months post-CMR for occurrence of PPM implantation. Results Fifty-two patients (38% male, 41 ± 14 years) were included. Overall, 31 (60%) patients had a surface conduction abnormality and 22 (42%) demonstrated midwall myocardial fibrosis by CMR-LGE. After a median of 57 days from CMR exam, 15 patients (29%) underwent PPM implantation. Subjects with vs. without surface conduction abnormality had significantly longer disease length (15.5 vs. 7.8 years, p = 0.015) and higher disease severity on the MIRS scale ( p = 0.041). High prevalence of myocardial fibrosis by CMR-LGE was detected in subjects with and without surface conduction abnormality with no significant difference between the two cohorts (42% vs. 43%, p = 0.999). By multivariate logistic regression analysis, disease length was the only independent variable associated with surface conduction abnormality (OR 1.071, 95%CI 1.003–1.144, p = 0.040); while CMR-LGE was not associated with conduction abnormality (ρ = − 0.009, p = 0.949). Conclusions Myocardial fibrosis by CMR-LGE is highly prevalent in MMD1 but not related to surface conduction abnormality meeting current...

Cardiac Magnetic Resonance Findings and Prognosis in Type 1 Myotonic Dystrophy

“…CMR studies on DM1 have been highly heterogeneous as to the prevalence and patterns of cardiac involvement [21,22,39,40,23,[31][32][33][34][35][36][37]. To some extent, this is also due to the rarity of the disease and the limited availability of the technique -as compared to echocardiography.…”

Cardiac Pathology in Myotonic Dystrophy Type 1

“…The last decade has seen multiple studies documenting cardiac magnetic resonance imaging (CMR) changes in the heart of individuals with DM1. Many investigators commented on the frequency of cardiac fibrosis and the possibility that CMR could be a valuable biomarker for DM1 [ 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 ]. CMR can be used to assess the structural and functional parameters seen by echocardiography, and in addition, it provides a means for assessing fatty infiltration, edema and diffuse and focal fibrosis.…”

“…In a 2019 study, Chimelewski et al reported about 42% of patients with abnormal CMRs with multiple parameters indicative of fibrosis (diffuse and focal), decreased strain and LV-ejection fraction, and found increased prevalence of ECG changes (especially Afib/Afl) in patients with abnormal CMR studies. Cardona et al also found about 40% of patients had abnormal CMR exams with evidence of increased fibrosis, but did not find a correlation with surface ECG findings, again emphasizing the point that CMR evidence of cardiac fibrosis occurred in the absence of standard ECG changes [ 88 ]. Luetkens et al studied a cohort of DM1 patients without known cardiovascular disease and found CMR evidence of diffuse fibrosis (i.e., increased T1 and ECV values; patchy and extensive increased LGE uptake) in about 35–40% of patients, decreased LV-ejection fraction, and decreased myocardial strain measurements [ 91 ].…”

Role of CMR Imaging in Diagnostics and Evaluation of Cardiac Involvement in Muscle Dystrophies

“…Regarding CMR, DM1 is associated with a non-ischemic pattern of LGE enhancement and ECV even in subclinical stages, indicating that the remodeling process is starting at an early age [79][80][81]. In a cohort of 80 patients, Hermans et al found myocardial fibrosis in 13%.…”