Strategy Lowers Sudden Death Risk in Myotonic Dystrophy

Megan Brooks

March 27, 2012

March 27, 2012 — In a retrospective study of adults with myotonic dystrophy type 1 (DM1) and major infranodal conduction delays, an invasive strategy based on electrophysiologic study and prophylactic permanent pacing was associated with a lower incidence of sudden death and a higher survival rate at 9 years, compared with a strategy based solely on noninvasive follow-up.

"Clinicians who identify conduction defects on the [electrocardiogram (ECG)] of their patients with DM1 should probably propose that they undergo electrophysiological testing, eventually followed by the implantation of a pacemaker (in primary prevention) if the HV interval is >70 ms," Karim Wahbi, MD, from the Department of Cardiology, Cochin Hospital, Paris, France, told Medscape Medical News.

Dr. Karim Wahbi

"This strategy was associated with a lower incidence of sudden death and a longer survival than a strategy solely based on noninvasive follow-up," he added.

The study was published in the March 28 issue of JAMA.

Longer Survival

With an incidence of 1 in 8000, DM1 is the most common inherited neuromuscular disease in adults. Manifestations include muscle weakness, myotonia, multiple endocrine disorders, respiratory insufficiency, and cardiac abnormalities, most commonly, rhythm disturbances.

The prevention of sudden death, which occurs in up to one third of patients with DM1, is "central to patient management," the authors note. Progression of conduction system disease to complete atrioventricular block is the presumed cause of sudden death in many of these patients.

Thus, permanent pacing has been recommended by the American College of Cardiology and the American Heart Association when complete atrioventricular block or advanced high-degree atrioventricular block are detected or as prophylaxis for patients with first-degree atrioventricular or fascicular block on the ECG. However, the benefit of prophylactic pacing on sudden death remains largely unknown.

Dr. Wahbi's team conducted a retrospective observational study of patients with genetically confirmed DM1 admitted to the Neurological Unit of the Myology Institute of Pitié-Salpêtrière Hospital in Paris between January 2000 and December 2009.

Among 486 patients whose ECG showed a PR interval greater than 200 ms, a QRS duration greater than 100 ms, or both, they compared the outcome of 341 patients (70.2%) who underwent the invasive strategy with 145 (29.8%) treated noninvasively.

During a median follow-up of 7.4 years (range, 0-9.9 years), 80 patients died (50 in the invasive group and 30 in the noninvasive group), corresponding to a 9-year survival of 74.4% (95% confidence interval [CI] 69.2% to 79.9%).

The investigators say, regardless of the method used to adjust for between-group differences in baseline characteristics, the invasive strategy was associated with a longer survival.

Table 1. Risk for Death in the Invasive Compared with Noninvasive Group

Analysis Method Hazard Ratio (95% CI)
Unadjusted 0.74 (0.47 - 1.16)
Adjusted 0.61 (0.38 - 0.98)
Propensity matched 0.55 (0.31 - 0.96)
Propensity matched plus covariates 0.47 (0.26 - 0.84)

CI = confidence interval

Careful Follow-up

The survival advantage in the invasive group was mainly because of a lower incidence of sudden death, which occurred in 10 patients in the invasive strategy group and 16 in the noninvasive strategy group. The risk for sudden death was about 75% lower in the invasive strategy group, regardless of the analytical method applied, the investigators report.

Table 2. Risk for Sudden Death in the Invasive Compared with Noninvasive Group

Analysis Method Hazard Ratio (95% CI)
Unadjusted 0.28 (0.13 - 0.61)
Adjusted 0.26 (0.11 - 0.61)
Propensity matched 0.26 (0.09 - 0.73)
Propensity matched plus covariates 0.24 (0.08 - 0.69)

CI = confidence interval

"We expected a lower incidence of sudden death in patients who underwent the invasive strategy," Dr. Wahbi said. "However, we were surprised by the importance of this benefit, which allowed a significant effect on overall survival."

"While other studies are needed to confirm these findings, consideration of this strategy may be prudent in this population at higher-than-average risk for sudden death," the investigators write. "All patients carrying the DM1 mutation with conduction defects on the ECG, even without cardiac symptoms," are candidates for this strategy, Dr. Wahbi added.

Reached for comment, William J. Groh, MD, MPH, a cardiac electrophysiologist from the Krannert Institute of Cardiology at Indiana University, in Indianapolis, told Medscape Medical News that the evidence suggests the procedure is "beneficial."

As reported by Medscape Medical News in 2008 in the New England Journal of Medicine, Dr. Groh and colleagues reported results of a large observational study confirming that adults with DM1 are at high risk for arrhythmias and death and they identified independent risk factors for sudden death in this population, including severe abnormalities on the surface ECG and a clinical diagnosis of atrial tachyarrhythmia.

"The current JAMA paper and our research have been working to determine how to stratify patients for risk of arrhythmias that can lead to sudden death," said Dr. Groh commented. "The French researchers are well-respected. Our research and their research are the largest most carefully constructed work looking at heart involvement in myotonic dystrophy," he added.

"The strength of the study is the large number of patients included and the long duration of follow-up. The investigators should be recognized for their careful follow-up of such a large number of patients.

"The limitations of the work was that it was an observational (not randomized) study, that it was uncertain how the groups were chosen for the noninvasive strategy or the invasive strategy, and exactly how the propensity analysis was done that gave a statistically significant result. It remains observational data supporting a position," Dr. Groh said.

The study was funded by grants from the French Alliance Against Myopathies. Dr. Wahbi and Dr. Groh have disclosed no relevant financial relationships. A complete list of author disclosures is listed with the original article.

JAMA 2012;307:1292-1301.