Long-term prognosis of patients diagnosed with Brugada syndrome: Results from the FINGER Brugada Syndrome Registry.

BACKGROUND: Brugada syndrome is characterized by ST-segment elevation in the right precordial leads and an increased risk of sudden cardiac death (SCD). Fundamental questions remain on the best strategy for assessing the real disease-associated arrhythmic risk, especially in asymptomatic patients. The aim of the present study was to evaluate the prognosis and risk factors of SCD in Brugada syndrome patients in the FINGER (France, Italy, Netherlands, Germany) Brugada syndrome registry. METHODS AND RESULTS: Patients were recruited in 11 tertiary centers in 4 European countries. Inclusion criteria consisted of a type 1 ECG present either at baseline or after drug challenge, after exclusion of diseases that mimic Brugada syndrome. The registry included 1029 consecutive individuals (745 men; 72%) with a median age of 45 (35 to 55) years. Diagnosis was based on (1) aborted SCD (6%); (2) syncope, otherwise unexplained (30%); and (3) asymptomatic patients (64%). During a median follow-up of 31.9 (14 to 54.4) months, 51 cardiac events (5%) occurred (44 patients experienced appropriate implantable cardioverter-defibrillator shocks, and 7 died suddenly). The cardiac event rate per year was 7.7% in patients with aborted SCD, 1.9% in patients with syncope, and 0.5% in asymptomatic patients. Symptoms and spontaneous type 1 ECG were predictors of arrhythmic events, whereas gender, familial history of SCD, inducibility of ventricular tachyarrhythmias during electrophysiological study, and the presence of an SCN5A mutation were not predictive of arrhythmic events. CONCLUSIONS: In the largest series of Brugada syndrome patients thus far, event rates in asymptomatic patients were low. Inducibility of ventricular tachyarrhythmia and family history of SCD were not predictors of cardiac events.

Long-term follow-up of right ventricular monomorphic extrasystoles.

OBJECTIVES: The purpose of this study was to verify in a long-term follow-up whether frequent monomorphic right ventricle extrasystoles may progress to arrhythmogenic right ventricular dysplasia (ARVD). BACKGROUND: Frequent monomorphic right ventricle extrasystoles are generally considered benign. However, in patients with this pattern, cardiac magnetic resonance (MR) has recently shown anatomical and functional abnormalities of the right ventricle. METHODS: Sixty-one patients who had been classified by noninvasive examinations as having frequent idiopathic right ventricle ectopy were contacted after 15 +/- 2 years (12 to 20) and submitted to clinical examination, electrocardiogram (ECG), Holter monitoring, stress test, signal averaged ECG, echocardiography and, in 11 patients, cardiac MR. The primary end point was to ascertain the presence of cases of sudden death or progression to ARVD. RESULTS: At the end of the follow-up, 55 patients were alive; six died, none of sudden death; eight stated to be well but refused further examinations. The 47 patients examined had normal ECG; in 24 patients (51%), extrasystoles were no longer present at Holter monitoring; late potentials were present in up to 15% of the patients; the right ventricle was normal at echocardiography. In 8 of 11 patients (73%), cardiac MR showed focal fatty replacement and other abnormalities of the right ventricle. CONCLUSIONS: In this long-term follow-up study, no patient died of sudden death nor developed ARVD; two-thirds of the patients were asymptomatic, and, in half of the patients, ectopy had disappeared. Focal fatty replacement in the right ventricle was present in most.

Atrial electrophysiological features in patients with Wolff-Parkinson-White and atrial fibrillation: absence of rate adaptation of intraatrial conduction time parameters.

Clinical electrophysiology has not yet clearly defined atrial features that can predict spontaneous occurrence of atrial fibrillation (AF). The aim of this work was to identify atrial electrophysiological features that can distinguish Wolff-Parkinson-White patients with spontaneous AF from those without this arrhythmia. Sixty-nine patients with Wolff-Parkinson-White were divided into three groups: group I (16 patients) with spontaneous AF; group II (35 patients) with reciprocating tachycardia but not AF; and group III (18 patients) asymptomatic without documented arrhythmias. Atrial effective refractory periods (ERPs) and intraatrial conduction times in response to premature extrastimuli were analyzed. The latter were evaluated as the A1A2 interval minus the correspondent S1S2 interval (A1A2-S1S2), S1A2 and the interval A1A2 following the shortest S1S2 producing atrial activation (FRP'). All the parameters have been evaluated in two atrial sites and at two atrial pacing cycle lengths (600 and 400 ms). For all the parameters, the difference ("gradient") was calculated between the values of the same parameter measured at the atrial pacing cycle length of 600 ms and that found at the atrial pacing cycle length of 400 ms in the same recording site in each patient was calculated. Atrial ERP did not differ significantly in the three groups. Intraatrial conduction parameters, evaluated in the high right atrium (HRA), were longer when measured at an atrial pacing of 400 ms and showed a lack of rate adaptation in patients with spontaneous AF. In group I patients in particular, FRP' became longer with the increase of atrial rate, while in groups 2 and 3, it usually shortened. The mean gradient of HRA FRP' was -15.0 +/- 19 ms in group I as compared to 5.7 +/- 13 ms in group II and 6.4 +/- 13 ms in group III (P < 0.001); sensitivity, specificity, and negative predictive value of a negative gradient in the identification of patients with spontaneous AF, were, respectively, 83%, 75%, and 93%. Patients from groups 2 and 3 did not differ in any of the analyzed parameters. Patients with Wolff-Parkinson-White and spontaneous AF showed prolonged intraatrial conduction times and a different behavior in response to modification of heart rate.

[Idiopathic ventricular tachycardia with onset in the verapamil-sensitive left ventricle: the clinical characteristics and long-term follow-up of 37 patients]. / Tachicardia ventricolare idiopatica ad insorgenza dal ventricolo sinistro sensibile al verapamil: caratteristiche cliniche e follow-up a lungo termine di 37 pazienti.

BACKGROUND: Idiopathic verapamil-responsive left ventricular tachycardia (IVRLVT) is a rare, well known form of ventricular tachycardia. Issues concerning long-term prognosis, drug prophylaxis and non-pharmacological therapy are rarely reported in the literature. We report the long-term follow-up, the efficacy of various drugs in the prophylaxis and the role of catheter ablation in a large group of patients with IVRLVT. METHODS AND RESULTS: This retrospective study involves 37 patients with a mean age of 28.3 +/- 14.8 years at first IVRLVT episode. The tachycardia morphology was typically with a right bundle-branch block configuration in all cases, with left axis deviation in 33 and right axis deviation in 5 (one patient had the 2 morphologies). Four patients had a mitral valve prolapse; the remaining 33 patients had neither clinical nor echocardiographic signs of heart disease. Only sporadic ventricular extrasystoles were detected at Holter monitoring in 73% of cases; 30% of patients had positive criteria for the presence of late potentials at signal averaged ECG. During electrophysiologic study, the tachycardia could be easily induced in 91% of patients. Mean follow-up is 7.3 +/- 4.7 years; all patients are alive at the end of follow-up. A mean of 2.3 +/- 1.2 drugs was prescribed in 35 patients (94.6%); betablockers were effective in 66% of the cases, verapamil in 20%, class I drugs in 22%, class III drugs in 15%. Both the 2 patients, who never received prophylaxis, and the 4 who stopped medication, utilize verapamil in case of recurrences. Eight patients were submitted to catheter ablation, with DC shock the first 2 patients, with RF energy from the third on; all but one (with DC shock) were successfully cured. CONCLUSIONS: Long-term follow-up confirmed the good prognosis of this form of ventricular tachycardia; a new insight that has been addressed about prophylaxis is the high efficacy of betablockers in preventing relapse and the poor efficacy of verapamil per os in chronic prophylaxis. Radiofrequency catheter ablation is effective and safe, using the earliest ventricular potential and the pace-mapping reproducing the same morphology of the tachycardia in all the 12 leads as a marker to identify the site of RF application, and may be proposed to all patients suffering from frequent episodes of IVRLVT.

Catheter ablation of permanent junctional reciprocating tachycardia with radiofrequency current.

OBJECTIVES: This study evaluated accessory pathway location, its relation to retrograde P wave polarity on the surface electrocardiogram and radiofrequency ablation efficacy and safety in a large group of patients with permanent junctional reciprocating tachycardia. BACKGROUND: Permanent junctional reciprocating tachycardia is an uncommon form of reciprocating tachycardia, almost incessant from infancy and usually refractory to drug therapy. It is characterized by RP > PR interval and usually by negative P waves in leads II, III, aVF and V4 to V6. Retrograde conduction occurs through an accessory pathway with slow and decremental properties. Although this accessory pathway has been classically located in the posteroseptal zone, other locations have been recently reported. METHODS: The study included 32 patients (20 men, 12 women, mean [+/- SD] age 29 +/- 15 years) with a diagnosis of permanent junctional reciprocating tachycardia confirmed at electrophysiologic study. Seven patients had depressed left ventricular function. Radiofrequency energy was applied at the site of the earliest retrograde atrial activation during tachycardia. RESULTS: There were 33 accessory pathways. The site of the earliest retrograde atrial activation was posteroseptal in 25 patients (76%), midseptal in 4 (12%), right posterior in 1 (3%), right lateral in 1 (3%), left posterior in 1 (3%) and left lateral in 1 (3%). Thirty pathways were ablated with a right approach; in 11 patients with posteroseptal pathway the ablation was performed through the coronary sinus. Three pathways were ablated with a left approach. Positive retrograde P wave in lead I suggested that ablation could be performed from the right side; if negative, it did not exclude ablation from this approach. All the accessory pathways were successfully ablated, with a median of 3 and a mean of 5.6 +/- 5 radiofrequency applications of 70 +/- 26 s in duration. In two patients with the accessory pathway in the midseptal zone, a transient second- and third-degree atrioventricular block, respectively, was observed after ablation. At a mean follow-up of 18 +/- 12 months, 31 patients (97%) are asymptomatic without antiarrhythmic therapy (95% confidence interval [CI] 84% to 99%). Recurrences were observed in four patients (13%) (95% CI 4% to 29%), three of whom had the accessory pathway ablated successfully at a second session. All patients with depressed left ventricular function showed a marked improvement after successful ablation. CONCLUSIONS: In our experience, most of the patients with permanent junctional reciprocating tachycardia had posteroseptal pathways; all these pathways were ablated from the right side. P wave configuration may be helpful in suggesting the approach to the site of ablation. Catheter ablation using radiofrequency energy is an effective therapy for permanent junctional reciprocating tachycardia.

Idiopathic verapamil-responsive left ventricular tachycardia: clinical characteristics and long-term follow-up of 33 patients.

Long-term prognosis, pharmacological prophylaxis and transcatheter ablation in a large group of patients with idiopathic verapamil-responsive left ventricular tachycardia (IVRLVT) are reported in this study. Thirty-three patients with a mean age of 27 +/- 16 years at their first IVRLVT episode, were studied retrospectively. Ventricular tachycardia was of the right bundle branch block morphology in all cases, with left axis deviation in 29 and right axis deviation in five (one patient had the two morphologies). Mitral valve prolapse was present in four patients; no heart disease was found in the remaining 29. Ventricular tachycardia could be electrophysiologically induced in 90% of the patients; Holter monitoring showed only sporadic ventricular extrasystoles in 76%; late potentials were found in 33% of the cases. At the end of a follow-up of 5.7 +/- 4.7 years, no patient had died. Thirty-one patients (94%) received a mean of 2.5 +/- 1.2 drugs; beta-blockers were effective in 71% of the cases, verapamil in 25%, class 1 drugs in 22%, class 3 drugs in 18%. Two patients who never received prophylaxis and four in whom it was stopped, were controlled with verapamil in case of recurrence. Six patients underwent catheter ablation; two with DC shock in whom it was successful in one, and four with radiofrequency energy, with a total success rate. The good prognosis of IVRLVT has been confirmed in a long-term follow-up; a new finding is the high efficacy of beta-blockers for prophylaxis. Radiofrequency transcatheter ablation is an effective and safe therapy for patients with symptoms not controlled by drug treatment.

Associated cardiac lesions in patients with radiation-induced complete heart block.

We investigated the clinical, electrophysiological, haemodynamic and angiographic aspects of four patients (two men and two women, aged 31-46 years) who developed complete heart block 13-20 years after therapeutic irradiation of the chest for Hodgkin's disease. The initial cardiac symptom was syncope in three, effort intolerance in one. The electrocardiogram recorded third-degree atrioventricular block in three patients, right bundle branch block and posterior fascicular block in one. The electrophysiological study, performed in three cases, showed that the block was infranodal in two. Three patients had significant coronary arterial stenoses, that involved the ostia in two. All patients had mild-to-moderate aortic and mitral regurgitation. One patient had haemodynamic signs of constriction. Another patient had recurrent pericardial effusions. All had echocardiographic evidence of a thickened pericardium. Cardiac involvement can be extensive in patient with radiation-induced heart block. Because coronary artery disease can be particularly severe, coronary angiography appears to be warranted in such patients.

Catheter ablation of accessory pathways in patients with Wolff-Parkinson-White syndrome.

PATIENTS: Fifty-two patients with Wolff-Parkinson-White syndrome underwent transcatheter ablation. All patients were symptomatic. Eighteen had documented episodes of atrial fibrillation, 14 of which also had reentrant tachycardias; the remaining 34 had only episodes of reentrant tachycardias. Forty-nine patients had both anterograde and retrograde conduction through the accessory pathway; 3 had retrograde conduction alone; 2 patients had 2 accessory pathways and 1 had 3. All patients were resistant or intolerant to at least 2 antiarrhythmic drugs. METHODS: All patients were treated with radiofrequency current. Ablation was considered successful if the anterograde and retrograde conduction were completely abolished. Ablation was considered unsuccessful if ablation of only 1 pathway in patients with 2 or more accessory pathways and/or modification of the accessory pathway conduction without interruption was achieved. RESULTS: Accessory pathway ablation was successfully performed in 46 out of 52 patients (88%). Fifty out of 56 accessory pathways were effectively ablated (89%). Thirty-eight required a single session of ablation and 8 additional patients were successfully ablated during a second session. The number of radiofrequency current applications ranged from 2 to 13 (mean 4.1 +/- 2.5). The mean duration of the sessions was 4.30 +/- 1.50 hours (range 2.30 to 9). The mean radiation exposure for session was 55 +/- 25 minutes (range 20 minutes to 2.30 hours). Complications were observed in 2 out of 52 patients. One patient had a transient II degree type 1 atrioventricular block; another patient with severe arterial hypertension had a mild hemorrhagic stroke with complete neurological remission. FOLLOW-UP. Forty-five out of the 46 patients in whom ablation was successful were asymptomatic for arrhythmias during a mean follow-up of 8 months (range 4 to 16), without antiarrhythmic treatment, and without reappearance of preexcitation. One patient showed reappearance of preexcitation at electrocardiogram one month after the ablation, followed by an episode of reentrant tachycardia; this patient underwent a second successful ablation session. CONCLUSIONS: Our results show that ablation techniques have high success rates with no serious complications.

Wolff-Parkinson-White syndrome. Identification and management.

Patients with Wolff-Parkinson-White (WPW) pattern of ventricular pre-excitation may develop paroxysmal re-entrant tachyarrhythmias through the Kent bundle and, less commonly, atrial fibrillation. WPW patients are at risk of sudden death when a rapid ventricular response occurs during atrial fibrillation due to conduction through the accessory pathway. Conduction properties of the accessory pathway and atrial vulnerability, which is the propensity to develop atrial fibrillation, are important parameters for evaluation in these patients. The former can be assessed by means of noninvasive tests, such as stress and pharmacological tests, and with electrophysiological study; the latter only by electrophysiological study. There is no indication for treatment of asymptomatic patients. Antiarrhythmic prophylaxis is required in patients with previous episodes of atrial fibrillation with rapid ventricular response, in patients with paroxysmal re-entrant tachycardias and rapid conduction through the accessory pathway, and in patients with frequent episodes of re-entrant tachycardias of long duration. Vaughan-Williams class IC anti-arrhythmic drugs (propafenone, flecainide) are the first choice for drugs in patients with rapid anterograde conduction through the accessory pathway due to their high efficacy and low incidence of adverse effects, while beta-blockers (atenolol, nadolol) are indicated for patients with re-entrant tachycardias and low conduction capacity through the bypass tract. When pharmacological therapy is ineffective, surgical or catheter ablation of the accessory pathway may be considered.

[Nonpharmacological therapy of supraventricular arrhythmia]. / Terapia non farmacologica delle aritmie sopraventricolari.

Between 1985 and 1990, 1242 patients with supraventricular arrhythmias were followed-up at our Institution. Six hundred and twenty patients had atrial fibrillation or flutter; 7 of them (1%) underwent modulation of atrioventricular conduction. Four hundred and twenty-eight patients had ventricular preexcitation; in 23 (5%) surgical or transcatheter ablation of an accessory pathway were performed. Atrioventricular node reentrant tachycardias were diagnosed in 111 patients; 8 patients (7%) underwent antitachycardia pacemaker implantation. Surgical and catheter ablative techniques eliminate the substrate of the tachycardia; death and complete A-V block (paraseptal pathways) are at this moment rarely reported. Antitachycardia pacemakers do not offer a definitive therapy. For their safeness and effectiveness they are still indicated in patients with A-V node reentrant tachycardias, until technological development will reduce the risks of ablative techniques.

Relation between spontaneous atrial fibrillation and atrial vulnerability in patients with Wolff-Parkinson-White pattern.

An intracavitary electrophysiological study was carried out on 103 patients with Wolff-Parkinson-White (WPW), 23 symptomatic patients had documented episodes of atrial fibrillation, 54 symptomatic patients had atrioventricular reentrant tachycardias, and 26 asymptomatic. Patients were examined for the relation between spontaneous atrial fibrillation and atrial vulnerability, defined as the possibility to induce sustained (greater than 1 minute) episodes of atrial fibrillation with a stimulation protocol excluding atrial bursts. Atrail fibrillation induction was attempted by single and double atrial extrastimuli during pacing at two different cycle lengths and incremental atrial pacing. Sustained atrail fibrillation was induced in 65% of the patients with spontaneous atrial fibrillation, and in 13% of the symptomatic patients with documented episodes of atrioventricular reentrant tachycardias and in 15% of the asymptomatic patients (P less than 0.0005). Atrial vulnerability was higher in patients with spontaneous atrial fibrillation than in patients without this arrhythmia. No significant difference was observed between symptomatic without atrial fibrillation and asymptomatic patients.

[Induction of atrial tachyarrhythmia in patients with Wolff-Parkinson-White syndrome with and without spontaneous atrial fibrillation]. / Induzione di tachiaritmie atriali in pazienti con Wolff-Parkinson-White con e senza fibrillazione atriale spontanea.

The purpose of this study was to examine the relation between spontaneous atrial fibrillation and the induction of atrial tachyarrhythmias during electrophysiologic study in patients with Wolff-Parkinson-White, with and without atrial fibrillation. Intracavitary electrophysiologic study was performed on 115 patients, 27 with spontaneous atrial fibrillation (group 1), 57 symptomatic due to AV re-entrant tachycardias, without spontaneous atrial fibrillation (group 2) and 31 asymptomatic (group 3). Induction of atrial fibrillation was attempted by using single and double atrial extrastimuli during atrial pacing at 2 different cycle lengths and by incremental atrial pacing (protocol A). When atrial fibrillation was not obtained, atrial bursts were added (protocol B). Atrial fibrillation or flutter were induced in 81% of group 1.54% of group 2 and 55% of group 3 patients (p less than 0.05), using protocol A. They were induced in 100, 75 and 71%, respectively (p = 0.01), with protocol B. Considering only sustained (greater than 1 minute) episodes, atrial fibrillation or flutter were induced in the three groups with protocol A in 74, 33 and 32% of the patients, respectively (p less than 0.001). The difference in the three groups was even greater when atrial fibrillation was considered separately from atrial flutter. The reason for this was that atrial fibrillation was induced in two thirds of group 1 patients, while only about 15% of patients without spontaneous atrial fibrillation had this arrhythmia induced. Our results suggest that the induction of sustained atrial fibrillation is a useful parameter to separate Wolff-Parkinson-White patients with from those without spontaneous atrial fibrillation. Due to the low specificity of the analysis of the shortest R-R interval during induced atrial fibrillation for the identification of the patients at risk of sudden death, the induction of sustained atrial fibrillation could be proposed as an additional parameter. This would improve the specificity of electrophysiologic study.

[Torsade de pointes during an atropine sulfate test in a patient with congenital long QT syndrome]. / Torsione di punta durante test con atropina solfato in paziente con QT lungo congenito.

After a brief revision about the long QT syndrome, we report the case of a 52 year old man admitted to hospital for a syncopal attack. His electrocardiogram was considered normal: sinus bradycardia and U waves were recorded. The echocardiogram revealed anterior mitral leaflet redundancy and possible tricuspid prolapse. During the atropine test, after a normal increment of sinus frequency, 2 runs of self-limited torsade de pointes appeared. The electrocardiogram showed lesion wave at first, and then prolonged QT. During the intracavitary study, premature ventricular stimulation caused torsade de pointes. After propranolol iv it was no more possible to induce major ventricular arrhythmias anymore. Coronarography was normal. Nadolol therapy was begun. On 6 months follow-up the patient is asymptomatic.

Stress and pharmacologic tests as methods to identify patients with Wolff-Parkinson-White syndrome at risk of sudden death.

Noninvasive stress and pharmacologic tests with procainamide and propafenone were studied as methods to identify patients with Wolff-Parkinson-White syndrome (WPW) who would otherwise be judged at risk of sudden death on the basis of electrophysiologic criteria: the shortest RR interval during induced atrial fibrillation less than or equal to 250 ms or accessory pathway anterograde effective refractory period less than or equal to 250 ms. Sixty-five patients were studied. Twenty-four patients fulfilled the electrophysiologic risk criteria (group A) and 41 patients fulfilled none of these criteria (group B). Persistence of preexcitation during stress test showed a sensitivity of 96% and a specificity of 17% to identify group A patients; its positive predictive value was 40% and negative predictive value 88%. With both procainamide and propafenone tests persistence of preexcitation identified group A patients with a sensitivity of 96% and a specificity of 51%; their positive and negative predictive value were, respectively, 53 and 95%. Stress and pharmacologic tests have good sensitivity and negative predictive value, but low specificity and positive predictive value.

Pericardial effusion mimicking left atrial thrombus after coronary bypass surgery.

This report describes a patient in whom pericardial effusion, two months after coronary bypass surgery, mimicked the presence of a left atrial mass on both echocardiography and cardiac angiography.

[Electrophysiologic study in supine and upright positions in patients with Wolff-Parkinson-White syndrome]. / Studio elettrofisiologico in clino- ed in ortostatismo dei pazienti con Wolff-Parkinson-White.

It is well known that in patients with Wolff-Parkinson-White (W.P.W.) adrenergic activity stimulation induced by exercise or isoproterenol I.V. infusion shortens the anterograde effective refractory period (E.R.P.) of the accessory pathway. Our purpose was to evaluate whether the upright position produces similar changes on the electrophysiologic properties of the accessory pathway and influences reciprocating tachycardias induction. In 18 patients, with W.P.W. syndrome, who underwent electrophysiologic study, we determined the anterograde E.R.P. of the accessory pathway and attempted to induce a reciprocating tachycardia in the supine and in the upright position. In 13 patients (72%) the anterograde E.R.P. of the accessory pathway shortened in the upright position (303 +/- 104 msec vs 331 +/- 123 msec; p less than 0.001); in 4 patients (22%) it was unchanged; in 1 patient was not defined, being inferior to the atrium E.R.P. We were able to induce a reciprocating tachycardia in 3 patients in the supine position, in 6 patients in the upright position. Electrophysiologic testing in the upright position improves the evaluation of the accessory pathway electrophysiologic properties.