Does cytosine-thymine-guanine (CTG) expansion size predict cardiac events and electrocardiographic progression in myotonic dystrophy?

Abstract

Objective-To assess whether the size of the cytosine-thymine-guanine (CTG) expansion mutation in myotonic dystrophy predicts progression of conduction system disease and cardiac events. Design-Longitudinal study involving ECG and clinical follow up over (mean (SD)) 4.8 (1.8) and 6.2 (1.9) years, respectively, of patients stratified by CTG expansion size (E0 to E4). Patients-73 adult patients under annual review in a regional myotonic dystrophy clinic. Patients were grouped into E0/E1 (n = 25), E2 (n = 34), and E3/E4 (n = 14). Results-The proportion of patients with a QRS complex > 100 ms at baseline increased with the size of the CTG expansion (EO/E1, 4%; E2, 12%; E3/E4, 36%; p = 0.02). This trend was more pronounced at follow up (E0/E1, 4%; E2, 21%; E3/E4, 57%; p = 0.0004). The rate of widening of the QRS complex (ms/year) was similarly related to the size of the mutation (EO/E1, 0.4 (1.3); E2, 1.4 (2.5); E3/E4, 1.5 (1.6); p = 0.04). First degree atrioventricular block was present in 23% of patients at baseline and 34% at follow up, with no significant relation to expansion size. Seven patients suVered a cardiac event during follow up (sudden death in two, permanent pacemaker insertion in three, chronic atrial arrhythmia in two), of whom six were in CTG expansion group E2 or greater. Patients who experienced a cardiac event during follow up had more rapid rates of PR interval increase (9.9 (11.1) v 1.6 (2.9) ms/year; p = 0.008) and a trend to greater QRS complex widening (3.6 (4.5) v 0.9 (1.5) ms/year; p = 0.06) than those who did not. Conclusions-Larger CTG expansions are associated with a higher rate of conduction disease progression and a trend to increased risk of cardiac events in myotonic dystrophy. (Heart 2001;86:411-416)

Usefulness of clinical and electrocardiographic data for predicting adverse cardiac events in patients with myotonic dystrophy

“…Although such a correlation between the extent of CTG repeats and the degree of cardiac involvement has been described in some series, others have shown conflicting results (9,17,18,25,(34)(35)(36)(37)(38)(39). Of note is the study by Lazarus et al (17); using precise invasive electrophysiological measurements, the study was unable to show such a relationship between conduction delays and the extent of CTG repeats.…”

Cardiac manifestations of myotonic dystrophy type 1

“…Eleven follow up studies (n = 1365) reported data on the incidence of SCD in MD1-patients [4,10,[13][14][15][18][19][20][21][22][23]. The studies reported 70 SCDs during a total of 12414 follow up years.…”

Endocrine function in 97 patients with myotonic dystrophy type 1

“…This causes the multisystemic affections of the disease: Myotonia, muscular dystrophy with primarily distal and facial muscle weakness and wasting, cataracts, cardiac involvement, hypogonadism, hypersomnia, cognitive impairment, and frontal balding [1,3] with symptoms ranging from very mild (cataracts at middle age) to very severe (neonatal lethal hypotonia and death) [4]. The size of the CTG expansion has been reported to correlate with disease severity and age of onset [5], intellectual impairment [6], cardiac involvement [7,8], impaired cardiac and brain glucose metabolism [9], radiologic pharyngoesophageal alterations [10], and muscle strength [11]. Furthermore, a study in a small cohort has shown a correlation between the degree of abnormal calcium metabolism and number of CTG repeats [12].…”