Letter to the Editor

Cardiac fibrosis, arrhythmia and sudden death in myotonic dystrophy type 1: Could TGF-ß1 improve the predictive accuracy of patients at risk, opening new therapeutic challenges?

Myotonic dystrophy type 1 (DM1) is a multisystem disease in which cardiac involvement is common. The aim of this study was to identify early changes in left atrial (LA) mechanics and left ventricular (LV) systolic function in patients with myotonic dystrophy type 1 using three-dimensional (3D) speckle tracking echocardiography (3D-STE).

This observational study included 25 patients with DM1 and 25 healthy volunteers. We assessed LA and LV global strain parameters using 3D-STE.

Patients with DM1 showed significantly lower longitudinal LA strain (22.85%±5.06 vs. 26.82%±5.15; p=0.008 in univariate analysis and p=0.026 in multivariate analysis) and global LV longitudinal strain (-13.55%±1.82 vs. -16.11%±1.33; p<0.001 in univariate analysis and p<0.001 in multivariate analysis), which was not observed with LA area tracking (p=0.412) or LV global circumferential strain (p=0.879), global radial strain (p=0.058), area tracking (p=0.092) or twist (p=0.992).

LA and LV global longitudinal strain is significantly decreased in patients with DM1, which may be an early marker of subclinical dysfunction in these patients.

A distrofia miotónica do tipo 1 é uma doença multissistémica com o envolvimento cardíaco a ser comum. O objetivo deste estudo foi identificar alterações precoces no strain da aurícula esquerda e função sistólica do ventrículo esquerdo em doentes com distrofia miotónica tipo 1, com o uso da tecnologia 3D speckle tracking.

Estudo observacional, que incluiu 25 doentes com distrofia miotónica do tipo 1 e 25 voluntários saudáveis. Foram avaliados os parâmetros de deformação global da aurícula esquerda e do ventrículo com o uso de 3D speckle tracking.

Os doentes com distrofia miotónica do tipo 1 apresentaram strain longitudinal da aurícula esquerda (22,85%±5,06 versus 26,82%±5,15; p=0,008 na análise univariada e p=0,026 na análise multivariada) e strain global longitudinal do ventrículo esquerdo (-13,55%±1,82 versus -16,11%±1,33, p<0,001 na análise univariada e p<0,001 na análise multivariada) significativamente menores, o que não se verificou com a area tracking da aurícula esquerda (p=0,412) ou com o strain global circunferencial (p=0,879), strain global radial (p=0,058), area tracking (p=0,092) e twist (p=0,992) do ventrículo esquerdo.

O strain longitudinal global do ventrículo esquerdo e da aurícula esquerda encontra-se significativamente diminuído em doentes com distrofia miotónica do tipo 1, pode ser um marcador precoce de disfunção subclínica nesaes doentes.

The heart is frequently affected in neuromuscular disorders (NMDs). Some of these patients even experience sudden cardiac death (SCD). In the following review, we summarize recent findings concerning epidemiology, risk stratification, and prevention of SCD in NMDs.

Review of publications about SCD and NMDs by search of MEDLINE applying appropriate search terms.

NMDs in which SCD was most frequently reported include myotonic dystrophy type 1, mitochondrial disorders, laminopathy, desminopathy, Danon disease, and amyotrophic lateral sclerosis. Risk factors for developing SCD vary considerably between NMDs and include positive family history for SCD, palpitations, arterial hypertension, ECG-abnormalities (bundle branch block, bifascicular block, QT-prolongation, increased QT-variability, early repolarization, T-wave alternans, ventricular tachycardia), late gadolinium enhancement as an equivalent of myocardial fibrosis, and noncompaction. NMD patients at risk for SCD require a thorough history, long-term ECG recordings, and cardiac MRI with contrast medium. In case a propensity for ventricular arrhythmias is documented, implantation of an implantable cardioverter defibrillator should be considered.

SCD is the cause of death in various NMDs why these patients need to be thoroughly screened for risk factors of SCD. Verification of risk factors for SCD in NMDs requires appropriate management.

The myotonic dystrophies share dominant inheritance of myotonia, cataracts, and muscle weakness, and have variable multisystem manifestations affecting brain, cardiopulmonary, smooth muscle, gastrointestinal, hepatic, immune, and endocrine systems. Myotonic dystrophy type 1 (DM1) results from an unstable trinucleotide repeat expansion (CTG) in the 3′ untranslated region of the dystrophia myotonica-protein kinase gene (DMPK gene) on chromosome 19q13.3. Myotonic dystrophy type 2 (DM2) results from an unstable four-nucleotide repeat expansion (CCTG) in intron 1 of the CNBP/ZNF9 gene. DM2 patients have similar, sometimes less severe, multisystem manifestations compared to DM1, as well as greater proximal than distal weakness and less muscle wasting. There are no congenital or early childhood forms of DM2. Current treatment for DM1 and DM2 is symptomatic and supportive. Research suggests that certain disease manifestations in adults with DM1 and DM2 may result primarily from abnormal regulation of alternative splicing in mature tissues. Experimental therapies to correct this abnormality in mouse models of DM1 show promising results and plans are in progress to translate these findings into therapeutic trials in patients.