Invasive treatment strategy may increase survival for patients with certain neuromuscular disorder

March 27, 2012

Patients with a cardiac irregularity and myotonic dystrophy type 1 (a severe neuromuscular disorder with a high risk of sudden death) who received an invasive treatment strategy that included testing of their heart's electrical conduction system and if needed, implantation of a device such as a pacemaker, had an associated higher rate of 9-year survival compared to patients treated noninvasively, according to a study in the March 28 issue of JAMA.

Myotonic dystrophy type 1 (DM 1) is the most common inherited neuromuscular disease in adults, with an incidence of 1 in 8,000. "The manifestations of the disease include muscle weakness, myotonia [abnormally long muscular contractions], multiple endocrine disorders, respiratory insufficiency, and cardiac abnormalities. The prevention of sudden death is central to patient management," according to background information in the article. Progression of conduction system (special muscle fibers that conduct electrical impulses throughout the muscle of the heart) disease to complete atrioventricular block (impairment of the conduction between the atria and ventricles of the heart) is the presumed cause of sudden death in a high proportion of patients. Permanent cardiac pacing has been recommended by the American College of Cardiology and the American Heart Association for patients who meet certain criteria. "Up to one-third of patients with myotonic dystrophy type 1 die suddenly. Thus far, no intervention has effectively prevented sudden death," the authors write.

Karim Wahbi, M.D., of the Department of Cardiology, Cochin Hospital, Paris, and colleagues conducted a study to determine the overall survival rates of patients with conduction abnormalities on the electrocardiogram who were managed with a noninvasive strategy and regular surveillance compared with patients managed with an invasive strategy with electrophysiological study (testing of the heart's electrical conduction system) and prophylactic cardiac pacing for patients when the measurement of the conduction time of a specific area of the heart exceeded a certain level. The study, the DM1 Heart Registry, included 914 patients older than 18 years with genetically confirmed myotonic dystrophy type 1 who were admitted to a teaching medical center in Paris, between January 2000 and December 2009. This analysis included 486 patients who presented with minor conduction defects. Among these patients, 341 were assigned to the invasive strategy group and 145 were assigned to the noninvasive strategy group. The median (midpoint) patient follow-up was 7.4 years.

Among the 486 patients, 80 died during follow-up, corresponding to a 9-year survival of 74.4 percent. Of these, 50 patients died in the invasive strategy group and 30 died in the noninvasive strategy group. Analysis indicated that survival in the invasive strategy group was consistently higher than in the noninvasive strategy group, and their respective 9-year survival rates were 76.7 percent and 69.2 percent. After adjustment for various factors, the hazard of dying was nearly 40 percent lower in the invasive strategy group than in the noninvasive strategy group.

The researchers suggest that the survival difference was largely attributable to a lower incidence of sudden death; the 9-year cumulative incidence of sudden death was 4.5 percent in the invasive strategy group and 18.0 percent in the noninvasive strategy group, with the hazard of dying suddenly 75 percent lower in the invasive strategy group than in the noninvasive strategy group.

At 9 years, the cumulative incidence of death from respiratory failure was 11.1 percent in the invasive strategy group and 9.1 percent in the noninvasive strategy group. No significant difference in the rate of respiratory death was observed between the 2 groups.

The authors note that the markedly lower incidence of sudden death in the invasive strategy group suggests that conduction system disease is a major cause of sudden death that appears to be preventable by implementation of an invasive strategy; and that electrophysiological study might have contributed to the identification of malignant ventricular arrhythmias, and might account for some of the observed differences between the invasive strategy group and the noninvasive strategy group.

"In summary, among patients with DM1 with major infranodal conduction delays, management with an invasive strategy based on systematic electrophysiological studies and prophylactic permanent pacing is associated with longer 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."
(JAMA. 2012;307[12]:1292-1301. Available pre-embargo to the media at

Editor's Note: This study was funded by grants from the Association Francaise Contre les Myopathies (French Alliance Against Myopathies). Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

The JAMA Network Journals

Related Disease Articles from Brightsurf:

CLCN6 identified as disease gene for a severe form of lysosomal neurodegenerative disease
A mutation in the CLCN6 gene is associated with a novel, particularly severe neurodegenerative disorder.

Cellular pathway of genetic heart disease similar to neurodegenerative disease
Research on a genetic heart disease has uncovered a new and unexpected mechanism for heart failure.

Mechanism linking gum disease to heart disease, other inflammatory conditions discovered
The link between periodontal (gum) disease and other inflammatory conditions such as heart disease and diabetes has long been established, but the mechanism behind that association has, until now, remained a mystery.

Potential link for Alzheimer's disease and common brain disease that mimics its symptoms
A new study by investigators from Brigham and Women's Hospital uncovered a group of closely related genes that may capture molecular links between Alzheimer's disease and Limbic-predominant Age-related TDP-43 Encephalopathy, or LATE, a recently recognized common brain disorder that can mimic Alzheimer's symptoms.

Antioxidant agent may prevent chronic kidney disease and Parkinson's disease
Researchers from Osaka University developed a novel dietary silicon-based antioxidant agent with renoprotective and neuroprotective effects.

Tools used to study human disease reveal coral disease risk factors
In a study published in Scientific Reports, a team of international researchers led by University of Hawai'i (UH) at Mānoa postdoctoral fellow Jamie Caldwell used a statistical technique typically employed in human epidemiology to determine the ecological risk factors affecting the prevalence of two coral diseases--growth anomalies, abnormalities like coral tumors, and white syndromes, infectious diseases similar to flesh eating bacteria.

Disease-aggravating mutation found in a mouse model of neonatal mitochondrial disease
The new mitochondrial DNA (mtDNA) variant drastically speeds up the disease progression in a mouse model of GRACILE syndrome.

Human longevity largest study of its kind shows early detection of disease & disease risks
Human Longevity, Inc. (HLI) announced the publication of a ground-breaking study in the journal Proceedings of the National Academy of Sciences (PNAS).

30-year study identifies need of disease-modifying therapies for maple syrup urine disease
A new study analyzes 30 years of patient data and details the clinical course of 184 individuals with genetically diverse forms of Maple Syrup Urine Disease (MSUD), which is among the most volatile and dangerous inherited metabolic disorders.

Long-dormant disease becomes most dominant foliar disease in New York onion crops
Until recently, Stemphylium leaf blight has been considered a minor foliar disease as it has not done much damage in New York since the early 1990s.

Read More: Disease News and Disease Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to