Genetic characterization of KCNQ1 variants improves risk stratification in type 1 long QT syndrome patients.

AIMS: KCNQ1 mutations cause QTc prolongation increasing life-threatening arrhythmias risks. Heterozygous mutations [type 1 long QT syndrome (LQT1)] are common. Homozygous KCNQ1 mutations cause type 1 Jervell and Lange-Nielsen syndrome (JLNS) with deafness and higher sudden cardiac death risk. KCNQ1 variants causing JLNS or LQT1 might have distinct phenotypic expressions in heterozygous patients. The aim of this study is to evaluate QTc duration and incidence of long QT syndrome-related cardiac events according to genetic presentation. METHODS AND RESULTS: We enrolled LQT1 or JLNS patients with class IV/V KCNQ1 variants from our inherited arrhythmia clinic (September 1993 to January 2023). Medical history, ECG, and follow-up were collected. Additionally, we conducted a thorough literature review for JLNS variants. Survival curves were compared between groups, and multivariate Cox regression models identified genetic and clinical risk factors. Among the 789 KCNQ1 variant carriers, 3 groups were identified: 30 JLNS, 161 heterozygous carriers of JLNS variants (HTZ-JLNS), and 550 LQT1 heterozygous carriers of non-JLNS variants (HTZ-Non-JLNS). At diagnosis, mean age was 3.4 ± 4.7 years for JLNS, 26.7 ± 21 years for HTZ-JLNS, and 26 ± 21 years for HTZ-non-JLNS; 55.3% were female; and the mean QTc was 551 ± 54 ms for JLNS, 441 ± 32 ms for HTZ-JLNS, and 467 ± 36 ms for HTZ-Non-JLNS. Patients with heterozygous JLNS mutations (HTZ-JLNS) represented 22% of heterozygous KCNQ1 variant carriers and had a lower risk of cardiac events than heterozygous non-JLNS variant carriers (HTZ-Non-JLNS) [hazard ratio (HR) = 0.34 (0.22-0.54); P < 0.01]. After multivariate analysis, four genetic parameters were independently associated with events: haploinsufficiency [HR = 0.60 (0.37-0.97); P = 0.04], pore localization [HR = 1.61 (1.14-1.2.26); P < 0.01], C-terminal localization [HR = 0.67 (0.46-0.98); P = 0.04], and group [HR = 0.43 (0.27-0.69); P < 0.01]. CONCLUSION: Heterozygous carriers of JLNS variants have a lower risk of cardiac arrhythmic events than other LQT1 patients.

How to improve medical students' ECG interpretation skills ? Multicenter survey and results of a comparative study evaluating a new educational approach.

BACKGROUND: Learning to interpret electrocardiograms (ECGs) is a crucial objective in medical education. Despite its importance, errors in ECGs interpretation are common, and the optimal teaching methods have not yet been clearly established. OBJECTIVES: To evaluate students' confidence in ECGs analysis and their opinion on current teaching methods, and to assess the effectiveness of a new ECG educational approach. METHODS: First, we conducted a survey on ECG learning among fourth to sixth-year medical students. Second, a 5-week multicenter comparative study was conducted with fourth-year medical students during their cardiology internship. Two different teaching methods were used, assigned by center. The first group participated in 5-minutes workshops 4 times a week using a "reversed classroom" method, supervised by a cardiologist, where students took turns selecting, presenting and discussing ECGs. The control group attended a single 2-hour face-to-face ECG course. All participants completed a 30-minute ECGs analysis test at baseline and after 5 weeks. RESULTS: Out of 401 survey respondents, the confidence levels in ECG interpretation were 3/5 (IQR 2-3) for routine situations and 2/5 (IQR 1-3) for emergency situations. Satisfaction with ECG teaching was low (2/5, IQR 1-3) and 96.3% of respondents favored more extensive ECG training. In the comparative study, 52 students from 3 medical schools were enrolled (control group: n = 27; workshop group: n = 25). Both groups showed significant improvement in exam scores from baseline to 5-week (33/100 ± 12/100 to 44/100 ± 12/100, p < 0.0001 for the control group and 36/100 ± 13/100 to 62/100 ± 12/100, p < 0.0001 for the workshop group). The improvement was significantly greater in the workshop group compared to the control group (+ 26 ± 11 vs. + 11 ± 6, p < 0.001). CONCLUSIONS: Among French medical students who initially reported low confidence and insufficient skills in ECG interpretation, the workshop approach using a "reversed classroom" method was found to be more effective than conventional lecture-based teaching during cardiology internship.

Impact of resident training on cardiac electrophysiological procedures.

BACKGROUND: Modern management of cardiac arrhythmias often requires interventions in which young physicians must acquire a high level of expertise. However, concerns have been raised about the increase in side effects during procedures performed with resident involvement. AIM: This study aims to identify the effects of resident training on cardiac electrophysiological procedures within a university centre. METHODS: In a single-centre study, cardiac arrhythmia procedures were reviewed retrospectively, and resident involvement was scrutinized. Univariate and multivariable models were built for the following outcomes: fluoroscopy time; operative time; length of hospitalization after procedure; and adverse events. RESULTS: We reviewed 991 procedures, 574 without and 417 with resident involvement (650 cardiac pacemakers or defibrillators, 120 generator replacements, 188 electrophysiological studies and 153 radiofrequency ablations). Resident involvement was associated with an increase in fluoroscopy time: +1.7±0.4minutes (P<0.01) for pacemaker implantation; and +2.5±0.9minutes (P=0.01) for electrophysiological studies. Operative time was longer for electrophysiological studies (+10.8±4.9minutes; P=0.03) and pacing implantation (+8.4±2.2minutes; P<0.01). There was no significant association between resident training and adverse events (7.67 vs. 9.83%; P=0.28). CONCLUSIONS: Cardiac electrophysiological procedures performed with resident involvement have a good safety profile. However, resident training modestly, but significantly, prolongs fluoroscopy time and operative time.

Type 3 long QT syndrome: Is the effectiveness of treatment with beta-blockers population-specific?

BACKGROUND: The efficacy of beta-blocker treatment in type 3 long QT syndrome (LQT3) remains debated. OBJECTIVES: The purpose of this study was to test the hypothesis that beta-blocker use is associated with cardiac events (CEs) in a French cohort of LQT3 patients. METHODS: All patients with a likely pathogenic/pathogenic variant in the SCN5A gene (linked to LQT3) were included and followed-up. Documented ventricular tachycardia/ventricular fibrillation, torsades de pointes, aborted cardiac arrest, sudden death, and appropriate shocks were considered as severe cardiac events (SCEs). CEs also included syncope. RESULTS: We included 147 patients from 54 families carrying 23 variants. Six of the patients developed symptoms before the age of 1 year and were analyzed separately. The 141 remaining patients (52.5% male; median age at diagnosis 24.0 years) were followed-up for a median of 11 years. The probabilities of a CE and an SCE from birth to the age of 40 were 20.5% and 9.9%, respectively. QTc prolongation (hazard ratio [HR] 1.12 [1.0-1.2]; P = .005]) and proband status (HR 4.07 [1.9-8.9]; P <.001) were independently associated with the occurrence of CEs. Proband status (HR 8.13 [1.7-38.8]; P = .009) was found to be independently associated with SCEs, whereas QTc prolongation (HR 1.11 [1.0-1.3]; P = .108) did not reach statistical significance. The cumulative probability of the age at first CE/SCE was not lower in patients treated with a beta-blocker. CONCLUSION: In agreement with the literature, proband status and lengthened QTc were associated with a higher risk of CEs. Our data do not show a protective effect of beta-blocker treatment.