Wenling Liu

Surgical left cardiac sympathetic denervation for long QT syndrome: effects on QT interval and heart rate.

The primary aim of the present study was to investigate the short-term effects of surgical left cardiac sympathetic denervation (LCSD) on the QT interval and heart rate in patients with congenital long QT syndrome (LQTS). Left cardiac sympathetic denervation was performed in five LQTS patients who had a history of syncope. The patients’ 12-lead and 24-h Holter monitoring ECG was recorded 24u2009h before and 24u2009h after LCSD. Treadmill exercise tests were also performed before and 6 days after surgery to assess changes in heart rate and the QT interval after surgery. Left cardiac sympathetic denervation was successful in all patients. The mean value of the corrected QT interval (QTc) in the five patients decreased from 0.59 ± 0.05 to 0.48 ± 0.04u2009s (P = 0.006) immediately after the procedure and remained short (0.47 ± 0.04, P < 0.05) after a 21-month follow-up. The mean value of QTc on the 24-h Holter monitoring ECG also decreased in all patients (0.67 ± 0.07 vs 0.60 ± 0.05u2009s, P < 0.01). The mean, maximum, and minimum heart rate on the 24-h ECG remained unchanged (P > 0.05). The maximum heart rate during the exercise tests decreased from 162 ± 4 beats/min before surgery to 129 ± 10 beats/min (P < 0.01). The exercise-induced increase in QTc remained unchanged after the surgery (P > 0.05). Although four of the five patients were syncope-free until 21 months postoperatively, the remaining patient had a recurrence of syncope, requiring an increased dose of β blocker. These findings indicate that LCSD shortens QTc and diminishes the exercise-induced increase in heart rate whereas the resting heart rate and exercise-induced increase in QTc remain unchanged. These results may have implications for the effectiveness and limitations of LCSD.

Mutations of Plakophilin-2 in Chinese With Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited heart muscle disease associated with increased risks of sudden death, particularly in young, otherwise healthy, patients. The pathologic features are progressive myocardial atrophy and fibrofatty replacement. Plakophilin-2 (PKP2) is reported as the most common ARVD/C-causing gene in Western countries. In this study we aimed to determine the prevalence of PKP2 mutations in Chinese patients with ARVD/C and their phenotype characteristics. Genotype and phenotype were investigated in a cohort of 18 unrelated Chinese patients with a clinical diagnosis of ARVD/C. Direct sequencing of PKP2 led to the identification of 5 novel heterozygous mutations (R158K, Q211X, L419S, A793D, and N852fsX930) in 39% of patients (7 of 18) with ARVD/C. Among them, N852fsX930 was found in 3 unrelated young patients who presented with symptomatic ventricular tachyarrhythmia. Nevertheless, no significant difference could be detected between patients with ARVD/C with (n = 7) and without (n = 11) PKP2 mutations with regard to the phenotype characteristics and clinical outcomes. Decreased penetrance was prominent in family members. In conclusion, 5 novel PKP2 mutations were identified in a cohort of symptomatic Chinese patients with ARVD/C. N852fsX930 appeared to be a hot-spot mutation in which patients presented with a severe ARVD/C phenotype, and 2/3 had early onset of arrhythmic events. No significant difference was found in phenotype characteristics between patients with ARVD/C with and without PKP2 mutations. The decreased penetrance indicated that an ARVD/C diagnosis cannot solely rely on genotyping results.

Genetic analysis of Brugada syndrome and congenital long-QT syndrome type 3 in the Chinese

Background: Brugada syndrome and congenital long-QT syndrome (LQTS) type 3 (LQT3) are 2 inherited conditions of abnormal cardiac excitability characterized clinically by an increased risk of ventricular tachyarrhythmias. SCN5A gene that encodes the cardiac sodium channel α subunit is responsible for the 2 diseases, and more work is needed to improve correlations between SCN5A genotypes and associated clinical syndromes. Methods and Results: Four patients diagnosed as having Brugada syndrome, 9 patients suspected to have Brugada syndrome, and 3 LQTS patients suspected to be LQT3 without mutations in KCNQ1 and HERG participated in the study. DNA samples from these patients were analyzed using direct sequencing. One patient with Brugada syndrome had 2 novel mutations, V95I and A1649V. The former was identified in the N-terminus of SCN5A and the latter was in the DIVS4/S5 linker of SCN5A. One patient suspected to have Brugada syndrome had a mutation, delF1617, in the DIIIS3/S4 linker of SCN5A. A novel mutation in the C-terminus of SCN5A, delD1790, was found in a patient with LQT3. No other mutations of SCN5A were found in the remaining patients. These 4 mutations were not detected in 50 unrelated control subjects. Conclusions: Two novel and a reported SCN5A mutations were found in Chinese patients with Brugada syndrome, and a novel SCN5A mutation was found in a Chinese patient with LQT3.

Clinical features and management of congenital long QT syndrome: a report on 54 patients from a national registry.

To assess the clinical features and the management of congenital long QT syndrome (LQTS) in China, we collected the clinical data of 54 LQTS patients (14 males and 40 females) from our newly established national registry. All patients were symptomatic, with syncope being the most common symptom. The average age when the first symptoms occurred was 17.9 ± 15.6 (range, 0.5–62) years; 55.6% of them had the first symptoms before the age of 20. The most common triggers of the symptoms were physical exercise or emotional stress. The average corrected QT interval was 0.55 ± 0.08u2009s. Using ECG criteria, there were 14 (25.9%) LQT1 patients, 28 (51.9%) LQT2, and 2 (3.7%) LQT3. Thirty (55.6%) patients were treated with Β-blockers at the time of enrollment, with propranolol being the most commonly used drug, with an average daily dose of 57.5 ± 39.1u2009mg. Four patients underwent left cardiac sympathectomy. After an average follow-up of 24.9 ± 13.2 months, 3.1% (1/32) of patients with antiadrenergic therapy and 9.1% (2/22) without antiadrengergic therapy died of sudden cardiac death (P ≪ 0.05). We concluded that LQT2 might be the most common subtype in these patients. Antiadrenergic treatment was underused, raising the urgent need for educating both physicians and patients on the nature of the disease and its optimal antiadrenergic therapy.

Patient with obstructive sleep apnea-hypopnea syndrome and SCN5A mutation (R1193Q polymorphism) associated with Brugada type 2 electrocardiographic pattern

We describe a 45-year-old Asian man with Brugada-type 2 electrocardiogram and probable nocturnal agonal respiration. After genetic screening, drug challenge test and polysomnography examination, we ruled out Brugada syndrome and identified obstructive sleep apnea-hypopnea syndrome. Therefore, obstructive sleep apnea-hypopnea syndrome should be considered as a rare differential diagnosis for Brugada syndrome.