Sudden arrhythmia death syndrome in young victims: a five-year retrospective review and two-year prospective molecular autopsy study by next-generation sequencing and clinical evaluation of their first-degree relatives.

OBJECTIVE: Sudden arrhythmia death syndrome (SADS) accounts for about 30% of causes of sudden cardiac death (SCD) in young people. In Hong Kong, there are scarce data on SADS and a lack of experience in molecular autopsy. We aimed to investigate the value of molecular autopsy techniques for detecting SADS in an East Asian population. METHODS: This was a two-part study. First, we conducted a retrospective 5-year review of autopsies performed in public mortuaries on young SCD victims. Second, we conducted a prospective 2-year study combining conventional autopsy investigations, molecular autopsy, and cardiac evaluation of the first-degree relatives of SCD victims. A panel of 35 genes implicated in SADS was analysed by next-generation sequencing. RESULTS: There were 289 SCD victims included in the 5-year review. Coronary artery disease was the major cause of death (35%); 40% were structural heart diseases and 25% were unexplained. These unexplained cases could include SADS-related conditions. In the 2-year prospective study, 21 SCD victims were examined: 10% had arrhythmogenic right ventricular cardiomyopathy, 5% had hypertrophic cardiomyopathy, and 85% had negative autopsy. Genetic analysis showed 29% with positive heterozygous genetic variants; six variants were novel. One third of victims had history of syncope, and 14% had family history of SCD. More than half of the 11 first-degree relatives who underwent genetic testing carried related genetic variants, and 10% had SADS-related clinical features. CONCLUSION: This pilot feasibility study shows the value of incorporating cardiac evaluation of surviving relatives and next-generation sequencing molecular autopsy into conventional forensic investigations in diagnosing young SCD victims in East Asian populations. The interpretation of genetic variants in the context of SCD is complicated and we recommend its analysis and reporting by qualified pathologists.

Genetic basis of channelopathies and cardiomyopathies in Hong Kong Chinese patients: a 10-year regional laboratory experience.

INTRODUCTION: Hereditary channelopathies and cardiomyopathies are potentially lethal and are clinically and genetically heterogeneous, involving at least 90 genes. Genetic testing can provide an accurate diagnosis, guide treatment, and enable cascade screening. The genetic basis among the Hong Kong Chinese population is largely unknown. We aimed to report on 28 unrelated patients with positive genetic findings detected from January 2006 to December 2015. METHODS: Sanger sequencing was performed for 28 unrelated patients with a clinical diagnosis of channelopathies or cardiomyopathies, testing for the following genes: KCNQ1,KCNH2,KCNE1,KCNE2, and SCN5A, for long QT syndrome; SCN5A for Brugada syndrome; RYR2 for catecholaminergic polymorphic ventricular tachycardia; MYH7 and MYBPC3 for hypertrophic cardiomyopathy; LMNA for dilated cardiomyopathy; and PKP2 and DSP for arrhythmogenic right ventricular dysplasia/cardiomyopathy. RESULTS: There were 17 males and 11 females; their mean age at diagnosis was 39 years (range, 1-80 years). The major clinical presentations included syncope, palpitations, and abnormal electrocardiography findings. A family history was present in 13 (46%) patients. There were 26 different heterozygous mutations detected, of which six were novel-two in SCN5A (NM_198056.2:c.429del and c.2024-11T>A), two in MYBPC3 (NM_000256.3:c.906-22G>A and c.2105_2106del), and two in LMNA (NM_170707.3:c.73C>A and c.1209_1213dup). CONCLUSIONS: We have characterised the genetic heterogeneity in channelopathies and cardiomyopathies among Hong Kong Chinese patients in a 10-year case series. Correct interpretation of genetic findings is difficult and requires expertise and experience. Caution regarding issues of non-penetrance, variable expressivity, phenotype-genotype correlation, susceptibility risk, and digenic inheritance is necessary for genetic counselling and cascade screening.

Right Parasternal Electrode Configuration Converts a Failed Electrocardiographic Screening to a Pass for Subcutaneous Implantable Cardioverter-Defibrillator Implantation.

BACKGROUND: Pre-operative electrocardiographic (ECG) screening before subcutaneous implantable cardioverter-defibrillator (SICD) implantation is essential to prevent T-wave oversensing and inappropriate shocks. The failure rate of ECG screening was reported to be up to 8% when only two body positions were tested. METHOD: Three subcutaneous ECG vectors represented by lead I, II and III were obtained in standing, supine, sitting and squatting positions. A patient qualified if the ECG in any same lead passed in all four positions. We report a 31-year-old man with idiopathic ventricular fibrillation who failed ECG screening for SICD implantation with the conventional left parasternal electrode (LPS) configuration in all three subcutaneous ECG vectors. Right parasternal electrode (RPS) configuration with left arm and right arm ECG electrodes positioned 1cm lateral to right sternal border was attempted for screening. RESULT: The amplitude of the QRS complex was significantly larger in the RPS compared to the LPS configuration in lead III and the patient passed the ECG screening in four body positions. He underwent successful SICD implantation with RPS approach with appropriate sensing both during the procedure and exercise treadmill test four weeks later. Ventricular fibrillation was successfully converted with 65J standard polarity shock during the procedure and no ICD shock was experienced by the patient on six-month follow-up. CONCLUSION: RPS configuration may be considered in patients who fail the ECG screening with the conventional LPS approach for SICD implantation.

Initial experience of cryoballoon catheter ablation for atrial fibrillation in Hong Kong.

OBJECTIVE. To report the initial experience in using cryoballoon catheter ablation in the treatment of atrial fibrillation in Hong Kong. DESIGN. Single-centre, prospective case series. SETTING. Regional hospital, Hong Kong. PATIENTS. Sixteen patients (mean age, 55 years; standard deviation, 14 years; 11 males) with paroxysmal (n=12) or persistent (n=4) atrial fibrillation. INTERVENTIONS. Pulmonary vein isolation by ablation with a 28-mm cryoballoon catheter. MAIN OUTCOME MEASURES. Safety, effectiveness, and learning curve of this procedure. RESULTS. Of 67 pulmonary veins, 61 (91%) could be successfully isolated with the cryoballoon alone. The remaining pulmonary veins were isolated with additional ablation using an 8-mm tip cryocatheter. One phrenic nerve palsy developed during right middle pulmonary vein ablation, which resolved. Another patient endured a minor guidewire dissection of the right inferior pulmonary vein. The mean (standard deviation) procedural and fluoroscopic times were 231 (32) and 62 (18) minutes, respectively. On comparing the first nine and last seven procedures, there was a significant improvement in procedural time (mean [standard deviation], 244 [32] vs 213 [24] minutes; P=0.04) and in the fluoroscopic time (70 [21] vs 51 [7] minutes; P=0.038). With a median follow-up of 21 months, nine (75%) of the 12 patients with paroxysmal atrial fibrillation and one (25%) of those four with persistent atrial fibrillation had no recurrence, without the use of anti-arrhythmic drugs. CONCLUSIONS. Pulmonary vein isolation by cryoballoon catheter ablation is safe and effective in treating patients with paroxysmal, but not for patients with persistent atrial fibrillation. A relatively short learning curve of around 10 cases was deemed appropriate.

Clopidogrel-induced hepatotoxicity after percutaneous coronary stenting.

Clopidogrel, an adenosine diphosphate receptor blocker, is widely used as an adjunctive antiplatelet therapy in acute coronary syndrome and percutaneous coronary stenting. The occurrence of hepatotoxicity is rare. We describe the occurrence of symptomatic liver disease in a 74-year-old man 5 weeks following commencement of therapy with clopidogrel. The reported cases of clopidogrel-induced hepatotoxicity are reviewed and the clinical significance of this event are discussed.

Clinical profile and genetic basis of Brugada syndrome in the Chinese population.

OBJECTIVE: To study the clinical profile and genetic basis of Brugada syndrome in Chinese patients. DESIGN: Prospective observational study. SETTING: Seven regional public hospitals, Hong Kong. MAIN OUTCOME MEASURES: The clinical and follow-up data of 50 patients (47 men, 3 women; mean age, 53 years) were collected, and genetic data of 36 probands and eight family members of three genotyped probands were analysed. RESULTS: Eight patients survived sudden cardiac death (group A), 12 had syncope of unknown origin but no sudden death (group B), and 30 were asymptomatic before recognition of Brugada syndrome (group C). Programmed electrical stimulation induced sustained ventricular arrhythmias in 88% (7/8), 82% (9/11), and 27% (3/11) of patients in group A, group B, and group C, respectively. New arrhythmic events occurred in 50% (4/8) of patients in group A and 17% (2/12) of patients in group B after a mean follow-up period of 30 (standard deviation, 13) months and 25 (7) months, respectively. All group C patients remained asymptomatic during a mean follow-up period of 25 (standard deviation, 11) months. Five of 36 probands and three of eight family members who underwent genetic testing were found to have a mutation in their SCN5A gene. CONCLUSIONS: Chinese patients with Brugada syndrome who are symptomatic have a high likelihood of arrhythmia recurrence, whereas asymptomatic patients enjoy a good short-term prognosis. The prevalence of SCN5A mutation among probands is 14%. Thus, Chinese patients with Brugada syndrome share with their western counterparts similar clinical and genetic heterogeneity.

Prolonged jaundice following percutaneous coronary intervention and ticlopidine therapy.

Ticlopidine, an adenosine diphosphate receptor blocker, is widely used to prevent subacute stent thrombosis after percutaneous coronary intervention. Along with neutropenia and thrombotic thrombocytopenic purpura, cholestatic hepatitis is one of the most serious potential side-effects of ticlopidine therapy. Four patients with prolonged jaundice after ticlopidine therapy, including one fatal case, are presented. Alternative antithrombotic therapy for subsequent percutaneous coronary intervention is also described. Clopidogrel therapy was found to be safe and effective in two patients with a history of ticlopidine-related cholestatic hepatitis.

Left main coronary artery aneurysm: sealing by stent graft and long-term follow-up.

We describe the implantation of a stent graft to seal off the left main coronary artery aneurysm of a 64-year-old man with guidance by intravascular ultrasound. The aneurysm was successfully sealed off. At 6-month and 1-year follow-up, a small residual aneurysm reappeared, which was treated conservatively. The technical issues in closing this aneurysm and the management of the residual aneurysm are discussed.

Multiple coronary-pulmonary fistulae involving all three coronary arteries: a case report.

Coronary pulmonary fistulae are rare cardiac anomalies. We present the case of a 46-year-old woman with multiple coronary-pulmonary fistulae involving all three coronary arteries. She presented with atypical chest pain and had no obstructive coronary lesion. SPECT thallium study demonstrated no perfusion defect. The fistulae were multiple but small with only a small left to right shunt (Qp:Qs = 1.2). The patient has remained well without intervention.