Bhuripanyo K

Arrhythmogenic Marker for the Sudden Unexplained Death Syndrome in Thai Men

BACKGROUND Between 1981 and 1988, the Centers for Disease Control and Prevention reported a very high incidence of sudden death among young male Southeast Asians who died unexpectedly during sleep. The pattern of death has long been prevalent in Southeast Asia. We carried out a study to identify the clinical markers for patients at high risk of developing sudden unexplained death syndrome (SUDS) and long-term outcomes. METHODS AND RESULTS We studied 27 Thai men (mean age, 39.7+/-11 years) referred because they had cardiac arrest due to ventricular fibrillation, usually occurring at night while asleep (n=17), or were suspected to have had symptoms similar to the clinical presentation of SUDS (n=10). We performed cardiac testing, including EPS and cardiac catheterization. The patients were then followed at approximately 3-month intervals; our primary end points were death, ventricular fibrillation, or cardiac arrest. A distinct ECG abnormality divided our patients who had no structural heart disease (except 3 patients with mild left ventricular hypertrophy) into two groups: group 1 (n=16) patients had right bundle-branch block and ST-segment elevation in V1 through V3, and group 2 (n=11) had a normal ECG. Group 1 patients had well-defined electrophysiological abnormalities: group 1 had an abnormally prolonged His-Purkinje conduction time (HV interval, 63+/-11 versus 49+/-6 ms; P=.007). Group 1 had a higher incidence of inducible ventricular fibrillation (93% for group 1 versus 11% for group 2; P=.0002) and a positive signal-averaged ECG (92% for group 1 versus 11% for group 2; P=.002), which was associated with a higher incidence of ventricular fibrillation or death (P=.047). The life-table analysis showed that the group 1 patients had a much greater risk of dying suddenly (P=.05). CONCLUSIONS Right bundle-branch block and precordial injury pattern in V1 through V3 is common in SUDS patients and represents an arrhythmogenic marker that identifies patients who face an inordinate risk of ventricular fibrillation or sudden death.

Prevention of Ventricular Fibrillation Episodes in Brugada Syndrome by Catheter Ablation Over the Anterior Right Ventricular Outflow Tract Epicardium

Background— The underlying electrophysiological mechanism that causes an abnormal ECG pattern and ventricular tachycardia/ventricular fibrillation (VT/VF) in patients with the Brugada syndrome (BrS) remains unelucidated. However, several studies have indicated that the right ventricular outflow tract (RVOT) is likely to be the site of electrophysiological substrate. We hypothesized that in patients with BrS who have frequent recurrent VF episodes, the substrate site is the RVOT, either over the epicardium or endocardium; abnormal electrograms would be identified at this location, which would serve as the target site for catheter ablation. Methods and Results— We studied 9 symptomatic patients with the BrS (all men; median age 38 years) who had recurrent VF episodes (median 4 episodes) per month, necessitating implantable cardioverter defibrillator discharge. Electroanatomic mapping of the right ventricle, both endocardially and epicardially, and epicardial mapping of the left ventricle were performed in all patients during sinus rhythm. All patients had typical type 1 Brugada ECG pattern and inducible VT/VF; they were found to have unique abnormal low voltage (0.94±0.79 mV), prolonged duration (132±48 ms), and fractionated late potentials (96±47 ms beyond QRS complex) clustering exclusively in the anterior aspect of the RVOT epicardium. Ablation at these sites rendered VT/VF noninducible (7 of 9 patients [78%]; 95% confidence interval, 0.40 to 0.97, P=0.015) and normalization of the Brugada ECG pattern in 89% (95% confidence interval, 0.52 to 0.99; P=0.008). Long-term outcomes (20±6 months) were excellent, with no recurrent VT/VF in all patients off medication (except 1 patient on amiodarone). Conclusions— The underlying electrophysiological mechanism in patients with BrS is delayed depolarization over the anterior aspect of the RVOT epicardium. Catheter ablation over this abnormal area results in normalization of the Brugada ECG pattern and prevents VT/VF, both during electrophysiological studies as well as spontaneous recurrent VT/VF episodes in patients with BrS.

Randomized double-blind, placebo-controlled trial of oral atenolol in patients with unexplained syncope and positive upright tilt table test results.

The objective of this investigation was the assessment of the response rate of oral atenolol in patients with vasovagal syncope after 1 month of treatment. We randomized into two groups all patients referred to our unit who had had at least one episode of syncope or two episodes of presyncope 1 month before presentation and had a positive isuprel Tilt Table Test (TTT). Group 1 (Gr 1) received oral atenolol, and group 2 (Gr 2) received placebo medication. After a 1-month period patients were reassessed for degree of their symptoms and underwent repeated TTT. Forty-two patients were enrolled in the study. Gr 1 and Gr 2 were comparable in age (38 +/- 13 years vs 43 +/- 14 years, p = 0.216 and sex (male/female = 6:15 vs 10:11, p = 0.204). The severity of attack was similar in both groups. Eight patients in Gr 1 and six patients in Gr 2 had mitral valve prolapse (p = 0.5). No significant differences were seen in systolic blood pressure (122 +/- 17 vs 117 +/- 16 mmHg, p = 0.334), diastolic blood pressure (70 +/- 11 vs 72 +/- 11 mm Hg, p = 0.677), and heart rate (79 +/- 12 vs 79 +/- 13, p = 0.98) between the two groups. The response rates (negative TTT) after 1 month of treatment were 62% versus 5% (p = 0.0004) in the atenolol and control group, respectively. Moreover, patients who received atenolol reported feeling better compared with those who received placebo (71% vs 29%, p = 0.02). In conclusion, atenolol significantly improved symptoms of patients with vasovagal syncope.(ABSTRACT TRUNCATED AT 250 WORDS)

Defibrillator Versus β-Blockers for Unexplained Death in Thailand (DEBUT) A Randomized Clinical Trial

Background—Sudden Unexplained Death Syndrome (SUDS) is the leading cause of death in young, healthy, Southeast Asian men. The role of an implantable cardioverter defibrillator (ICD) for mortality reduction in these patients remains unclear. Methods and Results—The Defibrillator Versus &bgr;-Blockers for Unexplained Death in Thailand (DEBUT) study is a randomized, clinical trial conducted in 2 phases (pilot study followed by the main trial) to compare the annual all-cause mortality rates among SUDS patients treated with &bgr;-blockers versus that among those treated with an ICD. A total of 86 patients who were SUDS survivors and probable SUDS survivors were randomized to receive an ICD or propranolol (20 patients were in the pilot study and 66 were in the main trial). The primary end point was death from all causes. The secondary end point was recurrent ventricular tachycardia/ventricular fibrillation (VF) or cardiac arrest. During the 3-year follow-up period of the main trial, there were 4 deaths; all occurred in the &bgr;-blocker group (P =0.02). Seven subjects in the ICD arm had recurrent VF, and all were effectively treated by the ICD. On the basis of the main trial results, the Data Safety Monitoring Board stopped the study. In total (both from the Pilot study and the main trial), there were 7 deaths (18%) in the &bgr;-blocker group and no deaths in the ICD group, but there were a total of 12 ICD patients receiving ICD discharges due to recurrent VF. Conclusions—ICD treatment provides full protection from death related to primary VF in a SUDS population and is superior to &bgr;-blockade treatment.

One-year outcome after radiofrequency catheter ablation of symptomatic ventricular arrhythmia from right ventricular outflow tract

Although ventricular premature complexes (VPCs) in patients without structural heart disease are benign, many patients experience disabling symptoms. Many patients need long-term medication, which is often ineffective and may have adverse effects. Radiofrequency catheter ablation (RFCA) may be an alternative treatment. RFCA was performed in 33 patients with severely symptomatic VPCs that were refractory to medication. Mean VPCs were 23,987 +/- 2,077 beats/24 hours. Twenty-four-hour ambulatory electrocardiographic monitoring, quality of life, and symptoms were assessed at a screening visit and 1 and 12 months after RFCA. RFCA was successfully performed in 32 patients (97%). This resulted in a significant improvement in symptoms, severity of ventricular arrhythmia, and quality of life at 1 and 12 months after the procedure. There were no major complications related to the procedure. Eight patients (24%) had residual arrhythmia. Five of them underwent repeated ablation with successful results. Thus, catheter ablation is a safe and effective treatment for symptomatic ventricular arrhythmia from the right ventricular outflow tract. It also improves the quality of life. Catheter ablation is a viable alternative to drugs in the presence of disabling symptoms.