Electrophysiological and histological abnormalities of the heart in myotonic dystrophy

Uemura, Nobuhiro; Tanaka, Hiromitsu; Niimura, Tatsuru; Hashiguchi, Nobuo; Yoshimura, Masahiro; Terashi, Shin-ichi; Kanehisa, Takuya

doi:10.1016/0002-8703(73)90338-4

Cited by 60 publications

(20 citation statements)

References 20 publications

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“…A high frequency of mitral valve prolapse has been reported in myo tonic dystrophy [20] but the existence of a causal relation has recently been questioned [7]. Histopathological studies of the heart are limited and the reported findings nonspe cific and vary from normal structure to atro phy of myocardial muscle, diffuse myocar dial fibrosis, fatty infiltration and focal myo carditis [21][22][23]. Information on the course of the heart disease in myotonic dystrophy and its relation to the severity of neuromus cular symptoms are still limited.…”

Section: Discussionmentioning

confidence: 99%

24-Hour Electrocardiographic Study in Myotonic Dystrophy

Forsberg¹,

Andersson²,

Henriksson³

et al. 1988

Cardiology

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Thirty-eight consecutive adult patients with myotonic dystrophy were included in a study with electrocardiography at rest and 24-hour ambulatory electrocardiography. The patients were subdivided into three groups according to the severity of the disease. The prevalence of abnormal electrocardiograms at rest was 31, 50 and 100% in patients with mild, moderate and severe disease, respectively. The main characteristics observed at ambulatory electrocardiography were a high frequency of sinus bradycardia (58%) and intermittent atrioventricular block II (8 %). These bradyarrhythmias were not correlated to the severity of the disease. Sustained atrial fibrillation or flutter was found in 3 patients (8%), all with the most severe form of the disease. Ambulatory electrocardiography should be used deliberately in the evaluation of patients with myotonic dystrophy and symptoms compatible with cardiac arrhythmias.

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Section: Discussionmentioning

confidence: 99%

24-Hour Electrocardiographic Study in Myotonic Dystrophy

Forsberg¹,

Andersson²,

Henriksson³

et al. 1988

Cardiology

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“…The second phenotype is mechanical, in which both diastolic and systolic dysfunction can progress to combined systolic and diastolic heart failure (11). Conduction defects include prolonged PR interval, altered QRS complex, and prolonged His to ventricle interval on ECG analysis (1,12,13). Light microscopy revealed infiltration of fatty tissue and fibrosis in the myocardium, whereas electron microscopy revealed vacuolation and disorganization of sarcoplasmic reticulum and accumulation of mitochondria (12,14,15).…”

Section: Introductionmentioning

confidence: 99%

“…Conduction defects include prolonged PR interval, altered QRS complex, and prolonged His to ventricle interval on ECG analysis (1,12,13). Light microscopy revealed infiltration of fatty tissue and fibrosis in the myocardium, whereas electron microscopy revealed vacuolation and disorganization of sarcoplasmic reticulum and accumulation of mitochondria (12,14,15). The molecular mechanisms causing abnormalities in electric conduction or contractility in DM1 have not yet been identified.…”

Section: Introductionmentioning

confidence: 99%

Elevation of RNA-binding protein CUGBP1 is an early event in an inducible heart-specific mouse model of myotonic dystrophy

et al. 2007

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Myotonic dystrophy type 1 (DM1) is caused by a CTG trinucleotide expansion in the 3′ untranslated region (3′ UTR) of DM protein kinase (DMPK). The key feature of DM1 pathogenesis is nuclear accumulation of RNA, which causes aberrant alternative splicing of specific pre-mRNAs by altering the functions of CUG-binding proteins (CUGBPs). Cardiac involvement occurs in more than 80% of individuals with DM1 and is responsible for up to 30% of disease-related deaths. We have generated an inducible and heart-specific DM1 mouse model expressing expanded CUG RNA in the context of DMPK 3′ UTR that recapitulated pathological and molecular features of DM1 including dilated cardiomyopathy, arrhythmias, systolic and diastolic dysfunction, and misregulated alternative splicing. Combined in situ hybridization and immunofluorescent staining for CUGBP1 and CUGBP2, the 2 CUGBP1 and ETR-3 like factor (CELF) proteins expressed in heart, demonstrated elevated protein levels specifically in nuclei containing foci of CUG repeat RNA. A time-course study demonstrated that colocalization of MBNL1 with RNA foci and increased CUGBP1 occurred within hours of induced expression of CUG repeat RNA and coincided with reversion to embryonic splicing patterns. These results indicate that CUGBP1 upregulation is an early and primary response to expression of CUG repeat RNA.

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“…lymphocytic infiltrates, can be commonly observed in patients with myotonic dystrophy [1,21,22], even in the absence of cardiac symptoms and at an early stage in the disease process [22], Similar changes of the myocardium have been shown to be associated with abnormal Doppler indexes of diastolic function in various conditions such as heart transplant rejection [23], myocarditis [24], ankylos ing spondylitis [25], systemic lupus erythematosus [26], progressive systemic sclerosis [27] and rheumatoid arthri tis [28]. Therefore, it is interesting to speculate that myo cardial lesions in myotonic dystrophy, while causing no clinically overt impairment of left ventricular myocardial function, may be sufficient to alter the relaxation process and affect calcium movement within the cells.…”

Section: Discussionmentioning

confidence: 99%

Doppler Echocardiographic Assessment of Left Ventricular Diastolic Function in Myotonic Dystrophy

Fragola

Calò²,

Luzi

et al. 1997

Cardiology

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We utilized Doppler echocardiography to characterize left ventricular diastolic function in 42 patients with myotonic dystrophy (mean age 37 ± 12 years, 64% male) who had no symptoms of heart failure and had normal left ventricular systolic function. Data were compared with those in 41 normal control subjects of similar age and gender. Heart rate, systemic blood pressure, and cardiac dimensions (wall thickness, left atrial and left ventricular cavity dimensions) were similar and not significantly different in patients and controls. As a group, patients showed significantly increased deceleration time and decreased rate of decline of flow velocity in early diastole (p < 0.0001 and p < 0.01, respectively) when compared to controls. Individual patient analysis showed that 10 (24%) of the 42 patients with myotonic dystrophy had 2 or more abnormal Doppler indexes of diastolic function consistent with a pattern of impaired left ventricular relaxation. The most common abnormalities were increased deceleration time ( > 224 ms; 9 patients), prolonged isovolumic relaxation time ( > 103 ms; 8 patients) and reduced rate of decline of flow velocity in early diastole ( < 2.1 m/s²; 5 patients). In addition, peak early diastolic flow velocity was reduced ( < 43 cm/s) in 3 patients and early to atrial peak flow velocity ratio was reduced ( < 1) in 2 patients. Comparison of subgroups of patients with and without abnormal Doppler indexes showed no significant differences with regard to age, gender, heart rate, systemic blood pressure, severity of neuromuscular disease, and cardiac dimensions. After study, patients were clinically followed up for a mean period of 20 ± 7 months (range 12-35). During observation no patients died and none experienced symptoms of heart failure. This Doppler echocardiographic analysis demonstrates that diastolic abnormalities may be present in patients with myotonic dystrophy, even in the absence of symptoms of cardiac failure or left ventricular systolic dysfunction. These diastolic abnormalities suggest an intrinsic myocardial abnormality in patients with myotonic dystrophy; however, whether they represent a preclinical phase of myocardial involvement or an intrinsic feature of the primary myocardial disease process in myotonic dystrophy remains to be elucidated.

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Electrophysiological and histological abnormalities of the heart in myotonic dystrophy

Cited by 60 publications

References 20 publications

24-Hour Electrocardiographic Study in Myotonic Dystrophy

24-Hour Electrocardiographic Study in Myotonic Dystrophy

Elevation of RNA-binding protein CUGBP1 is an early event in an inducible heart-specific mouse model of myotonic dystrophy

Doppler Echocardiographic Assessment of Left Ventricular Diastolic Function in Myotonic Dystrophy

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