Original ArticleBackground-Inherited long-QT syndrome (LQTS) is associated with risk of sudden death. We assessed the clinical course and the fulfillment of current treatment strategies in molecularly defined pediatric LQTS type 1 and (LQT1)

BackgroundLong QT syndrome (LQTS) is an inherited cardiac disorder predisposing to sudden cardiac death (SCD). We studied factors affecting the clinical course of genetically confirmed patients, in particular those not receiving β-blocker treatment. In addition, an attempt was made to associate risk of events to specific types of KCNQ1 and KCNH2 mutations.MethodsA follow-up study covering a mean of 18.6 ± 6.1 years was conducted in 867 genetically confirmed LQT1 and LQT2 patients and 654 non-carrier relatives aged 18–40 years. Cox regression models were used to evaluate the contribution of clinical and genetic risk factors to cardiac events.ResultsIn mutation carriers, risk factors for cardiac events before initiation of β-blocker included LQT2 genotype (hazard ratio [HR] = 2.1, p = 0.002), female gender (HR = 3.2, p < 0.001), a cardiac event before the age of 18 years (HR = 5.9, p < 0.001), and QTc ≥500 ms (vs < 470 ms, HR = 2.7, p = 0.001). LQT1 patients carrying the KCNQ1 D317N mutation were at higher risk (HR = 3.0–3.9, p < 0.001–0.03) compared to G589D, c.1129-2A > G and other KCNQ1 mutation carriers after adjusting for gender, QTc duration, and cardiac events before age 18. KCNH2 c.453delC, L552S and R176W mutations associated with lower risk (HR = 0.11–0.23, p < 0.001) than other KCNH2 mutations.ConclusionsLQT2 (compared to LQT1), female gender, a cardiac event before age 18, and long QT interval increased the risk of cardiac events in LQTS patients aged 18 to 40 years. The nature of the underlying mutation may be associated with risk variation in both LQT1 and LQT2. The identification of high-risk and low-risk mutations may enhance risk stratification.Electronic supplementary materialThe online version of this article (10.1186/s12881-018-0574-0) contains supplementary material, which is available to authorized users.

Background Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a severe inherited arrhythmic disease associated with a risk of syncope and sudden cardiac death (SCD). Aims We aimed at identifying RYR2 P2328S founder mutation carriers and describing the clinical course associated with the mutation. Methods The study population was drawn from the Finnish Inherited Cardiac Disorder Research Registry, and from the present genealogical study. Kaplan-Meier graphs, log-rank test and Cox regression model were used to evaluate the clinical course. Results Genealogical study revealed a common ancestor couple living in the late 17th century. A total of 1837 living descendants were tested for RYR2 P2328S mutation unveiling 62 mutation carriers aged mean 39±23 years old. No arrhythmic deaths were documented among genotyped subjects, but 11 SCDs were detected in non-genotyped family members since 1970. Three genotyped patients (5%) suffered an aborted cardiac arrest (ACA), and 15 (25%) had a syncope triggered by exercise or stress. Rate of cardiac events was higher among patients who in exercise stress test showed a maximum rate of premature ventricular contractions >30/min (68% vs 17%, p<0.01; hazard ratio = 7.1, p = 0.02), in comparison to patients without the respective finding. A cardioverter-defibrillator (ICD) was implanted to 13 (22%) patients, with an appropriate ICD shock in four (31%) subjects. All ICD shocks, one ACA, and one syncope occurred during β-blocker medication. Conclusions Previously undiagnosed CPVT patients may be identified by well-conducted genealogical studies. The RYR2 P2328S mutation causes a potentially severe phenotype, but its expression is variable, thus calling for additional studies on modifying factors.