Modulating effects of age and gender on the clinical course of long QT syndrome by genotype

Abstract

During childhood, the risk of cardiac events was significantly higher in LQT1 males than in LQT1 females (hazard ratio [HR] = 1.72), whereas there was no significant gender-related difference in the risk of cardiac events among LQT2 and LQT3 carriers. During adulthood, LQT2 females (HR = 3.71) and LQT1 females (HR = 3.35) had a significantly higher risk of cardiac events than respective males. The lethality of cardiac events was highest in LQT3 males and females (19% and 18%), and higher in LQT1 and LQT2 males (5% and 6%) than in LQT1 and LQT2 females (2% for both). CONCLUSIONS; Age and gender have different, genotype-specific modulating effects on the probability of cardiac events and electrocardiographic presentation in LQT1 and LQT2 patients.

Gender Disparities in Cardiac Cellular Electrophysiology and Arrhythmia Susceptibility in Human Failing Ventricular Myocytes

“…This result corresponds with experimental findings in healthy animals 16,17) and supports the clinical observation that female gender is an independent risk factor for TdP. 2,9,10) Several cellular mechanisms have been implicated in EAD formation in ventricular muscle, including I Ca,L reactivation, Na-Ca exchange current enhancement, and I na reactivation. 11,26) In human VMs, we previously demonstrated that VMs with longer APs are predisposed to develop EADs.…”

“…[6][7][8] Mirroring these gender disparities in ECG variables, there are striking gender disparities in the incidence of cardiac arrhythmias. 1,2) Among the most notable examples are inherited 9) and acquired (eg, secondary to drug use) 10) long QT syndrome (LQTS), where women are far more likely than men to sustain torsade de pointes (TdP) ventricular tachycardia.…”

The long QT syndrome family of cardiac ion channelopathies: A HuGE review

“…15 Demographic characteristics among patient groups, such as sex, age at first event, and mean age first seen in clinic for the event, tend to vary by genotype (Table 2). 14,15,26 The frequency of cardiac events (syncope, aborted cardiac arrest and sudden death) tends to be higher in individuals with LQT2 mutations than in those with LQT1 or LQT3 mutations. However, a higher percentage of lethal events by age 40 is associated with the LQT3 genotype.…”

“…However, a higher percentage of lethal events by age 40 is associated with the LQT3 genotype. 26 Inheritance patterns and complexity of disease presentation Inherited LQTS manifests in two different forms. The more common familial form, referred to as the Romano-Ward syndrome (RWS), displays the cardiac electrophysiologic abnormalities of LQTS and normal hearing.…”

“…Research pointing to a hormonal influence has demonstrated gender differences through time in risk and severity of cardiac events according to genotype. 26 Androgenic protective effects, as well as relative progesterone and estrogen levels in females may be involved. Sex modulates response to QT-prolonging drugs and has been postulated as a modifier of gene expression (e.g., QTc in HERG K897T polymorphisms).…”