Risk for arrhythmic events in long QT syndrome (LQTS) patients can vary by genotype and variant site, as well as age and sex, according to a new report. The disease is characterized by QT interval prolongation and electrocardiogram results that show syncope or sudden cardiac death in young individuals. The cause is most attributed to ion channel genes, most commonly LQTS type 1 (LQT1), LQT2, and LQT3.
Investigators from Japan retrospectively observed 1124 genotype-positive patients with long QT syndrome in order to determine if there was a sex-specific component to risk of long QT syndrome. The investigators identified these patients through a LQTS genetic registry study in Asia, which, to their knowledge, is the largest such registry.
The patients were pooled from 11 Japanese institutions between March 2006 and February 2013. There were 616 probands and 508 family members in the study which included LQT1, LQT2, and LQT3 patients. The investigators also said that the patients had KCNQ1 (521 patients), KCNH2 (487) and SCN5A (116) genes.
Previous studies have shown that variants of LQ syndrome do not fully support a genotype-phenotype correlation. For example, female sex after adolescence is linked to higher risk of arrhythmic events in congenital LQT3, but the link between sex and genotype-based risk of LQTS remains unclear, the study authors wrote.
When the patients were younger than age 15, the study authors learned, there was no sex difference observed in regards to risk for arrhythmic events. However, female sex was associated with a higher risk for LQT1 and LQT2 among those older than 15 years, they wrote.
For LQT1 patients, the specific variant site was linked to a higher risk of arrhythmic events than a different site, but the investigators said the location of the site mattered only in female patients. For LQT2 patients, the location of the site mattered in relation to the arrhythmic risk in both male and female patients.
Being female itself was a risk for arrhythmic events for LQT2 patients after puberty, the study authors said.
“Pathogenic variants in the pore areas of the channels were associated with higher risk of arrhythmic events than were other variants in each genotype, while sex-associated differences were observed in patients with LQT1 and LQT2 but not in those with LQT3,” the study authors wrote. “The findings of this study suggest that risk for cardiac events in LQTS varies according to genotype, variant site, age, and sex.”
In a related editorial
, Wojciech Zareba, MD, PhD, from the University of Rochester Medical Center wrote that refining risk stratification among LQTS patients is important to identify those who might benefit from pharmacologic or implantable devices.
“History of cardiac arrest leaves no doubt regarding the use of implantable cardioverter defibrillators to prevent sudden cardiac death in patients with LQTS,” Zareba wrote. “However, decisions regarding most patients with LQTS who have not experienced cardiac arrest must rely on risk-stratification methods. These risk-stratification strategies are constantly being refined, combining information on age, sex, history of syncope, genotype, and mutation location, and their interaction is further optimized by accounting for race/ethnicity.”
The paper, “Association of Genetic and Clinical Aspects of Congenital Long QT Syndrome With Life-Threatening Arrhythmias in Japanese Patients
,” was published in JAMA Cardiology