By reconstructing family trees dating back to 1811, researchers identified age ranges during which risk for mortality is highest in those with untreated arrhythmia disorders.
In recent years, researchers have discovered the molecular genetic substrate of various inherited arrhythmia disorders, which allows the identification of mutation carriers before they develop symptoms. Nevertheless, a number of questions remain, especially regarding whether all asymptomatic carriers of disease-causing genes should be treated, at what age should treatment be initiated and from what age onward can treatment be safely withheld in asymptomatic patients.
“In symptomatic untreated patients, the risk of sudden cardiac death is substantial,” researcher Eline A. Nannenberg, MD, clinical geneticist at the Academic Medical Centre in Amsterdam, the Netherlands, and colleagues wrote in a study published in Circulation: Cardiovascular Genetics. “However, in asymptomatic mutation carriers, the risk is ill-defined. Preventive lifestyle advice may be given, and pharmacological and/or invasive treatment offered. However, such therapies may have side effects and a significant impact on the quality of life.”
Mortality risk
For their study, the researchers targeted six inherited arrhythmia disorders caused by specific mutations: long QT syndrome types 1, 2 and 3; SCN5a-overlap syndrome; catecholaminergic polymorphic ventricular tachycardia; and Brugada syndrome. Using Dutch archives, they reconstructed family trees for patients with different conditions and compared death statistics in 266 people who carried a mutation of a gene associated with arrhythmia, 904 family members with a 50% chance of having the mutation and the general population.
Results revealed the following for mutation carriers:
- For long QT syndrome type 1, mortality risk was severely increased throughout childhood (ages 1 to 19 years), particularly the first 10 years of life (standardized mortality ratio [SMR]=2.9; 95% CI, 1.5-5.1).
- For long QT syndrome type 2, increased mortality risk begins at age 15 years, with data showing statistical significance for those aged 30 to 39 years (SMR=4; 95% CI, 1.1-10).
- For long QT syndrome type 3, risk is increased for those aged 15 to 19 years (SMR=5.8; 95% CI, 1.2-16.9).
- For SCN5a-overlap syndrome, data indicated excess mortality for those aged 10 to 59 years, with a peak for those aged 20 to 39 years (SMR=3.8; 95% CI, 2.5-5.7).
- For catecholaminergic polymorphic ventricular tachycardia, risk for death was highest for those aged 20 to 39 years (SMR=3; 95% CI, 1.3-6).
- For Brugada syndrome, excess mortality was observed for those aged 40 to 59 years (SMR=1.79; 95% CI, 1.2-2.4), especially in men.
“This information can help doctors know when to treat and screen families with arrhythmia syndromes caused by different gene mutations,” Nannenberg said in a press release.
Interpretations
The researchers said it is too early to begin basing clinical decisions on their findings.
“We have to be careful not to draw conclusions for families with arrhythmias caused by different mutations,” Nannenberg said. “However, this new data can guide screening. In long QT syndrome type 1, we advise starting genetic and heart screening of first-degree family members, such as children, siblings and parents, at a very young age.”
For more information: Nannenberg EA. Circ Cardiovasc Genet. 2012;doi:10.1161/CIRCGENETICS.111.961102.
SOURCE: Cardiology Today