Humans ; Diagnosis, Differential ; Long QT Syndrome/genetics* ; Syncope/diagnosis* ; Epilepsy/diagnosis* ; Electrocardiography

Humans ; Mutation, Missense ; KCNQ1 Potassium Channel/genetics* ; Long QT Syndrome/genetics* ; Phenotype ; Mutation ; Pedigree

Humans ; Mutation, Missense ; KCNQ1 Potassium Channel/genetics* ; Long QT Syndrome/genetics* ; Phenotype ; Mutation ; Pedigree

Andersen Syndrome/genetics* ; Humans ; Syncope ; Tachycardia, Ventricular

Objective: To investigate the long-term efficacy and safety of left cardiac sympathetic denervation(LCSD) for long QT syndrome(LQTS) patients with either recurrence on drug therapy intolerance/refusal. Methods: This study was a retrospective cohort study. The cases selected from 193 patients with LQTS who were enrolled in the Chinese Channelopathy Registry Study from November 1999 to November 2012. This study selected 28 LQTS patients with either recurrence on drug therapy intolerance/refusal and underwent LCSD surgery in the Peking University People's Hospital or Beijing Tongren Hospital. The patients were allocated into 3 groups: high-risk group(n=13, baseline QTc ≥550 ms or symptomatic in the first year of life or highly malignant genetics); intermediate-risk group(n=10, 500 ms≤baseline QTc<550 ms, symptomatic after the first year and without highly malignant genetics); low-risk group(n=5, baseline QTc<500 ms, symptomatic after the first year and without highly malignant genetics). LCSD was performed with the traditional supraclavicular approach or video assisted thoracoscopic surgery (VATS). Patients were regularly followed up until 20 years after the surgery. Data were collected before and 1 year after surgery and at the last follow-up. Patients' electrocardiograph(ECG), cardiac events and surgery-related complications were recorded. Kaplan-Meier survival analysis was used to determine the cardiac event-free survival based on different risk stratification and genotypes. Results: A total of 28 LQTS patients, aged 20.5 (15.0, 37.5) and underwent LCSD surgery, were enrolled in this study, including 23(82.1%) women. There were 11(39.3%) patients treated with traditional approach while 17(60.7%) with VATS-LCSD. There were 19(67.9%) patients had positive genetic test results, including 4 LQT1, 12 LQT2, 1 LQT1/LQT2 mixed type, and 2 Jervell-Lange-Nielsen (JLN) syndrome. The median follow-up period was 189.3(138.7, 204.9) months. The dropout rate was 10.7%(3/28) while 3 patients in the intermediate-risk group were lost to follow-up. Horner syndrome occurred in 1 patient (in the high-risk group). Sudden cardiac deaths were observed in 3 (12.0%) patients (all in the high-risk group), and 12 patients (48.0%) had syncope recurrences (2 in low-risk group, 3 in intermediate-risk group and 7 in high-risk group). A significant reduction in the mean yearly episodes of cardiac events was observed, from (3.5±3.3) before LCSD to(0.2±0.1) at one year after LCSD and (0.5±0.8) at last follow up(P<0.001). The mean QTc was shortened from (545.7±51.2)ms before the surgery to (489.0±40.1)ms at the last follow-up (P<0.001). Among the 20 patients with basic QTc ≥500 ms and completing the follow-up, the QTc intervals of 11(55.0%) patients were shortened to below 500 ms. The event free survival rates for any cardiac events after LCSD decreased sequentially in the low-, intermediate- and high-risk groups, and the difference was statistically significant (χ²=7.24, log-rank P=0.026). No difference was found in the event free survival rates among LQT1, LQT2 and undefined gene patients (χ²=5.20, log-rank P>0.05). Conclusions: LCSD surgery can reduce the incidence of cardiac events and shorten the QTc interval in patients with LQTS after the long-term follow-up. LCSD surgery is effective and safe for patients with LQTS ineffective or intolerant to drug therapy. However, high-risk patients are still at a high risk of sudden death after surgery and should be actively monitored and protected by combined therapies.
Electrocardiography ; Female ; Heart ; Humans ; Long QT Syndrome ; Male ; Retrospective Studies ; Sympathectomy/methods*

Early recognition and treatment for early warning electrocardiogram (ECG) of sudden death are very important to prevent and treat malignant arrhythmia and sudden death. Previous studies have found that R-on-T and T wave alternation, and QT interval prolongation are closely related to malignant arrhythmia or sudden death, which are included in the critical value of ECG.By analyzing the ECG characteristics of 4 patients with sudden death, we found that although the causes of the patients were different, there were transient prolongation of QT interval after premature contraction in 12 lead ECG, followed by malignant arrhythmia or sudden death. Thus, we thought that the transient prolongation of QT interval after premature contraction had a high value for warning malignant arrhythmia or sudden death. This phenomenon should be paid enough attention to reduce the risk of sudden death.
Arrhythmias, Cardiac/diagnosis* ; Death, Sudden ; Death, Sudden, Cardiac ; Electrocardiography ; Humans ; Long QT Syndrome/diagnosis*

Objective: To evaluate the main triggers of recurrent cardiac events in patients with symptomatic congenital long QT syndrome (cLQTS). Methods: In this retrospective case analysis study, clinical characteristics were reviewed from 38 patients with recurrent cardiac events after first visit out of 66 symptomatic cLQTS patients. General clinical data such as gender, age, clinical presentation, family history and treatment were collected, auxiliary examination results such as electrocardiogram and gene detection were analyzed. LQTS-related cardiac events were defined as arrhythmogenic syncope, implantable cardioverter defibrillator (ICD) shock, inappropriate ICD shock, aborted cardiac arrest, sudden cardiac death or ventricular tachycardia. Results: A total of 38 patients with recurrent symptoms were enrolled in this study, including 30 females (79%) and 14 children (37%). The average age of onset was (15.6±14.6) years, and the recurrence time was (3.6±3.5) years. Subtype analysis showed that there were 11 cases (29%) of LQT1 (including 2 cases of jervel-Lange Nielson syndrome), 19 cases (50%) of LQT2, 5 cases (13%) of LQT3 and 3 cases (8%) of other rare subtypes (1 LQT5, 1 LQT7 and 1 LQT11) in this patient cohort. LQT1 patients experienced recurrent cardiac event due to drug withdrawal (6 (55%)), specific triggers (exercise and emotional excitement) (4 (36%)) and medication adjustment (1 (9%)). For LQT2 patients, main triggers for cardiac events were drug withdrawal (16 (84%)), specific triggers (shock, sound stimulation, waking up (6 (32%)). One patient (5%) had recurrent syncope after pregnancy. One patient (20%) had inappropriate ICD shock. For LQT3 patients, 4 (80%) patients developed syncope during resting state, and 1 (20%) developed ventricular tachycardia during exercise test. One LQT5 patients experienced syncope and ICD shock under specific triggers (emotional excitement). One LQT11 patient had repeated ICD shocks under specific inducement (fatigue). One LQT7 patient experienced inappropriate ICD shock. Left cardiac sympathetic denervation (LCSD) significantly alleviated the symptoms in 2 children with Jervell-Lange Nielson syndrome (JLNS) post ineffective β-blocker medication. Nadolol succeeded in eliminating cardiac events in one patient with LQT2 post ineffective metoprolol medication. Mexiletine significantly improved symptoms in 2 patients with LQT2 post ineffective β-blocker medication. Conclusions: Medication withdrawal is an important trigger of the recurrence of cardiac events among patients with symptomatic congenital long QT syndrome.
Adolescent ; Adult ; Child ; Child, Preschool ; Death, Sudden, Cardiac ; Electrocardiography ; Female ; Heart ; Humans ; Infant ; Long QT Syndrome ; Retrospective Studies ; Young Adult

OBJECTIVES: To investigate the effect of taurine magnesium coordination compound (TMCC) on torsades de pointes (TdP) in isolated guinea pig hearts. METHODS: Healthy male guinea pigs weighting 250~300 g were randomly divided into 4 groups:①TdP model group (=7):Isolated hearts were perfused by normal K-H solution 20 minutes, then perfused by slowly activated delayed rectifier potassium current(IKs) blocker 10mol/L Chromanol 293B under hypokalemic solution(1.8 mmol/L) to establish TdP model;②~④ TdP model + TMCC group (=6):Isolated hearts were perfused by normal K-H solution for 20 minutes, then perfused by IKs blocker 10mol/L Chromanol 293B under hypokalemic solution(1.8 mmol/L) for 60 minutes, at the same time TMCC which concentration was 1, 2, 4 mmol/L was administered respectively by Langendorff retrograde aortic perfusion method. Cardiac surface electrocardiogram of guinea pigs was collected and recorded by Biopac electrophysiological recorder. Incidence of TdP, transmural dispersion of repolarization (TDR), instability of QT interval were acquired from Lead Ⅱ electrocardiograph (ECG) wave forms to describe the effect of TMCC on TdP model. Datas were acquired at the time of 20 min and pre-TdP, in case there was no TdP observed, a value of 60 min was entered for calculation purpose. RESULTS: Incidence of TdP in TdP model group was 6/7. TdP incidence could be decreased significantly by 1, 2, 4 mmol/L TMCC, and was 5/6, 1/6, 0/6 respectively. Compared with the pre-drug, Chromanol 293B under hypokalemic solution in TdP model group increased TDR(corrected) evidently(<0.01). Compared with the pre-drug, 1, 2, 4 mmol/L TMCC in TdP model + TMCC group could decrease the increased TDR(corrected) induced by Chromanol 293B under hypokalemic solution(>0.05). Compared with the TdP model group, 2, 4 mmol/L TMCC could evidently decrease the instability of QT interval induced by Chromanol 293B under hypokalemic solution(<0.05). During the establishment of TdP model, P waves in more than one cardiac cycle continuously were disappeared in ECG. However, P wave could always be seen independent in ECG acquired from TdP model + TMCC group. CONCLUSIONS TMCC can play the role against TdP through decreasing TDR and instability of QT interval, and inhibiting early after depolarization(EAD).
Animals ; Anti-Arrhythmia Agents ; pharmacology ; Electrocardiography ; Guinea Pigs ; In Vitro Techniques ; Long QT Syndrome ; Magnesium ; pharmacology ; Male ; Random Allocation ; Taurine ; pharmacology ; Torsades de Pointes ; drug therapy

Biological sex (being female or male) significantly influences the course of disease. This simple fact must be considered in all cardiovascular diagnosis and therapy. However, major gaps in knowledge about and awareness of cardiovascular disease in women still impede the implementation of sex-specific strategies. Among the gaps are a lack of understanding of the pathophysiology of women-biased coronary artery disease syndromes (spasms, dissections, Takotsubo syndrome), sex differences in cardiomyopathies and heart failure, a higher prevalence of cardiomyopathies with sarcomeric mutations in men, a higher prevalence of heart failure with preserved ejection fraction in women, and sex-specific disease mechanisms, as well as sex differences in sudden cardiac arrest and long QT syndrome. Basic research strategies must do more to include female-specific aspects of disease such as the genetic imbalance of 2 versus one X chromosome and the effects of sex hormones. Drug therapy in women also needs more attention. Furthermore, pregnancy-associated cardiovascular disease must be considered a potential risk factor in women, including pregnancy-related coronary artery dissection, preeclampsia, and peripartum cardiomyopathy. Finally, the sociocultural dimension of gender should be included in research efforts. The organization of gender medicine must be established as a cross-sectional discipline but also as a centered structure with its own research resources, methods, and questions.
Cardiomyopathies ; Cardiovascular Diseases ; Coronary Artery Disease ; Coronary Vessels ; Death, Sudden, Cardiac ; Diagnosis ; Drug Therapy ; Female ; Gonadal Steroid Hormones ; Heart Failure ; Humans ; Long QT Syndrome ; Male ; Peripartum Period ; Pre-Eclampsia ; Prevalence ; Risk Factors ; Sex Characteristics ; X Chromosome

Long QT syndrome (LQTS) is an inherited cardiac disease characterized by a prolonged heart rate-corrected QT (QTc) interval. We investigated the genetic causes in patients with prolonged QTc intervals who were negative for pathogenic variants in three major LQTS-related genes (KCNQ1, KCNH2, and SCN5A). Molecular genetic testing was performed using a panel including 13 LQTS-related genes and 67 additional genes implicated in other cardiac diseases. Overall, putative genetic causes of prolonged QTc interval were identified in three of the 30 patients (10%). Among the LQTS-related genes, we detected a previously reported pathogenic variant, CACNA1C c.1552C>T, responsible for cardiac-only Timothy syndrome. Among the genes related to other cardiac diseases, a likely pathogenic variant, RYR2 c.11995A>G, was identified in a patient with catecholaminergic polymorphic ventricular tachycardia. Another patient who developed dilated cardiomyopathy with prolonged QTc interval was found to carry a likely pathogenic variant, TAZ c.718G>A, associated with infantile dilated cardiomyopathy. Comprehensive screening of genetic variants using multigene panel sequencing enables detection of genetic variants with a possible involvement in QTc interval prolongation, thus uncovering unknown molecular mechanisms underlying LQTS.
Cardiomyopathy, Dilated ; Heart ; Heart Diseases ; Humans ; Long QT Syndrome ; Mass Screening ; Molecular Biology ; Ryanodine Receptor Calcium Release Channel ; Tachycardia, Ventricular