Tailored treatment strategies: a new approach for modern management of atrial fibrillation.

Atrial fibrillation (AF) is not benign. Cardiovascular diseases and risk factors differ importantly amongst patients. Careful phenotyping with the aim to start tailored therapy may improve outcome and quality of life. Furthermore, structural remodelling plays an important role in initiation and progression of AF. Therapies that interfere in the remodelling processes are promising because they may modify the atrial substrate. However, success is still limited probably due to variations in the underlying substrate in individual patients. The most favourable effects of lifestyle changes on success of rhythm control have been demonstrated in obese patients with AF. Differences in genotype may also play an important role. Common gene variants have been associated with recurrence of AF after electrical cardioversion, antiarrhythmic drug therapy and catheter ablation. Therefore, both phenotyping and genotyping may become useful for patient selection in the future. Beside the choice of rate or rhythm control, and type of rhythm control, prevention of complications associated with AF may also differ depending on genotype and phenotype. Efficacy of stroke prevention has been well established, but bleeding remains a clinically relevant problem. Risk stratification is still cumbersome, especially in low-risk patients and in those with a high bleeding risk. The decision whether to start anticoagulation (and if so which type of anticoagulant) or, alternatively, to implant an occlusion device of the left atrial appendage may also be improved by genotyping and phenotyping. In this review, we will summarize new insights into the roles of phenotype and genotype in generating more tailored treatment strategies in patients with AF and discuss several patient-tailored treatment options.

[Arrhythmias in adult patients with congenital heart disease]. / Le aritmie nei pazienti adulti con cardiopatia congenita.

Arrhythmias are the main cause of morbidity and mortality in adult patients with congenital heart disease. Arrhythmias can be due to the primary anatomical defect or they can be a consequence of the long term effects of haemodynamical defects and surgical repairs. Atrial arrhythmias are the most frequent form and their prevalence varies between 10-60% in different congenital defects. Ventricular tachycardia are less common but they have potentially a dramatic impact on survival. When correcting the haemodynamic defect is not effective in avoiding arrhythmias complications, it is necessary to apply specific therapy. Antiarrhythmic drugs must be used very carefully, there is an increasing application for transcatheter or surgical ablation and device implantation.

Electrophysiological study and catheter ablation of a Mahaim fibre located at the mitral annulus-aorta junction.

Accessory pathways with slow and anterograde decremental conduction (Mahaim fibres) are responsible for a minority of atrioventricular reentrant tachycardias. While usually located along the tricuspid annulus, left-sided Mahaim fibres have been occasionally reported. We here report on a unique case of radiofrequency catheter ablation of a Mahaim pathway located at the supero-septal aspect of the mitral annulus, in a region known as mitral annulus-aorta junction, between the right and left fibrous trigons. Electrophysiological properties and embryological implications of this unusual accessory pathway are discussed.

The intriguing problem of atrial fibrillation in competitive athletes.

Atrial fibrillation (AF) is the most frequent cause of prolonged palpitations in young competitive athletes, even including those performing elite sport activity. This arrhythmia may occasionally affect impair athletes' ability to compete thus leading to non-eligibility at prequalification screening. Competitive sport has a significant impact on the autonomous nervous system. In fact, long-term regular intense physical training determines an increase in vagal tone leading to resting bradycardia. During physical activity, particularly in the setting of competition, a marked release of catecholamines occurs as a result of both the intense physical effort and emotional stress. Both of these adaptive phenomena may precipitate AF. Furthermore, in several athletes with AF an association with sick sinus syndrome has been found, even though the pathophysiological basis of this finding is not clear. This picture is further complicated by the increasingly intake of illicit substances, whose arrhythmogenic effect has been shown both at the ventricular and atrial levels. Moreover, the use of recreational drugs, such as amphetamines, ecstasy, alcohol, cannabinoids, cocaine and so called new drugs in clubs has dramatically increased, with several cases of drug-induced arrhythmic events. These effects are often exacerbated by the combined use of different drugs, especially in situations such as sports competitions, in which the adrenergic system is already hyperactivated. No data have been published on the efficacy of antiarrhythmic therapy in athletes with AF, but it has been reported that athletes are more predisposed to the development of pro-arrhythmic effects induced by antiarrhythmic drugs when compared to general population. Most recently, radiofrequency catheter ablation involving electrical disconnection of the pulmonary veins in athletes with AF limiting their normal training activity and participation in sports competitions has proven highly effective to restore stable sinus rhythm and enable subsequent re-eligibility.

Randomized comparison of antiarrhythmic drug therapy with implantable defibrillators in patients resuscitated from cardiac arrest : the Cardiac Arrest Study Hamburg (CASH).

BACKGROUND: We conducted a prospective, multicenter, randomized comparison of implantable cardioverter-defibrillator (ICD) versus antiarrhythmic drug therapy in survivors of cardiac arrest secondary to documented ventricular arrhythmias. METHODS AND RESULTS: From 1987, eligible patients were randomized to an ICD, amiodarone, propafenone, or metoprolol (ICD versus antiarrhythmic agents randomization ratio 1:3). Assignment to propafenone was discontinued in March 1992, after an interim analysis conducted in 58 patients showed a 61% higher all-cause mortality rate than in 61 ICD patients during a follow-up of 11.3 months. The study continued to recruit 288 patients in the remaining 3 study groups; of these, 99 were assigned to ICDs, 92 to amiodarone, and 97 to metoprolol. The primary end point was all-cause mortality. The study was terminated in March 1998, when all patients had concluded a minimum 2-year follow-up. Over a mean follow-up of 57+/-34 months, the crude death rates were 36.4% (95% CI 26.9% to 46.6%) in the ICD and 44.4% (95% CI 37.2% to 51.8%) in the amiodarone/metoprolol arm. Overall survival was higher, though not significantly, in patients assigned to ICD than in those assigned to drug therapy (1-sided P=0.081, hazard ratio 0.766, [97.5% CI upper bound 1.112]). In ICD patients, the percent reductions in all-cause mortality were 41.9%, 39.3%, 28. 4%, 27.7%, 22.8%, 11.4%, 9.1%, 10.6%, and 24.7% at years 1 to 9 of follow-up. CONCLUSIONS: During long-term follow-up of cardiac arrest survivors, therapy with an ICD is associated with a 23% (nonsignificant) reduction of all-cause mortality rates when compared with treatment with amiodarone/metoprolol. The benefit of ICD therapy is more evident during the first 5 years after the index event.

Modification of the substrate for maintenance of idiopathic human atrial fibrillation: efficacy of radiofrequency ablation using nonfluoroscopic catheter guidance.

BACKGROUND: Catheter ablative techniques to modify the substrate to maintain atrial fibrillation (AF) require the creation of continuous radiofrequency current-induced ablation lines. This study was designed to assess the efficacy and safety of nonfluoroscopic mapping in this setting. METHODS AND RESULTS: A total of 45 consecutive patients with idiopathic AF were studied. The first 13 underwent ablation confined to the left atrium by creating a circular line isolating the pulmonary vein ostia and a second line connecting the former with the mitral annulus. Subsequently, 12 of these patients underwent a procedure confined to the right atrium (RA), where attempts were made to create an isthmus line between the inferior vena cava and the tricuspid annulus, an anterior line connecting the tricuspid annulus with the superior vena cava, and an intercaval line between the ostia of the inferior and superior venae cavae. In the last 32 patients, only the RA approach was performed. Technical difficulties prevented the creation of the intended left atrial line pattern: all patients experienced recurrences. A 100% recurrence rate was also observed after subsequent RA ablation, despite creation of a complete line pattern in 4 of 12 patients. Of the final 32 patients, AF recurred in 94%; a complete ablation line pattern had been achieved in 18 patients (56%), 16 of whom had recurrences. CONCLUSIONS: The electroanatomically-guided creation of extended radiofrequency current lesions is technically feasible only in the RA. However, procedural success in the RA does not suppress recurrences of AF in the majority of patients.

Catheter ablation of paroxysmal atrial fibrillation using a 3D mapping system.

BACKGROUND: We treated paroxysmal recurrent atrial fibrillation (AF) with radiofrequency (RF) catheter ablation by creating long linear lesions in the atria. To achieve line continuity, a 3D electroanatomic nonfluoroscopic mapping system was used. METHODS AND RESULTS: In 27 patients with recurrent AF, a catheter incorporating a passive magnetic field sensor was navigated in both atria to construct a 3D activation map. RF energy was delivered to create continuous linear lesions: 3 lines (intercaval, isthmic, and anteroseptal) in the right atrium and a long line encircling the pulmonary veins in the left atrium. After RF application, the atria were remapped to validate completeness of the block lines, demonstrated by late activation of the areas circumscribed by the lines. The mean procedure duration was 312+/-103 minutes (range, 187 to 495), with mean fluoroscopy time of 107+/-44 minutes (range, 32 to 185 minutes). No acute complications occurred, but 1 patient experienced early prolonged sinus pauses and received a pacemaker. During the first day, 17 patients (63%) had AF episodes, but at discharge, 25 patients were in sinus rhythm. After a follow-up of 6. 0 to 15.3 months (average, 10.5+/-3.0 months), 16 patients are asymptomatic, 3 have an almost complete disappearance of symptoms, 1 patient is improved, and 7 patients have their AF attacks unchanged. CONCLUSIONS: Paroxysmal recurrent drug-refractory AF can be treated by RF catheter ablation. Creation of long continuous linear lesions necessary to compartmentalize the atria is facilitated by a nonfluoroscopic electroanatomic mapping system.

Direct and autonomically mediated effects of oral quinidine on RR/QT relation after an abrupt increase in heart rate.

OBJECTIVES: This study evaluates the direct and autonomically mediated effects of oral quinidine on ventricular repolarization in humans. BACKGROUND: Interactions between quinidine-related vagolytic properties and autonomic modulation on ventricular repolarization are unknown. The relative role of the two components, if present, might improve our understanding of the therapeutic and proarrhythmic mechanisms of quinidine on the ventricular tissue. METHODS: Rate-related changes in the QT interval were investigated after an abrupt increase in heart rate in 15 patients during atrial pacing. In the control study, the QT interval was measured at six paced cycle lengths (600, 540, 500, 460, 430 and 400 ms) both in the basal state and after autonomic blockade (intravenous propranolol, 0.2 mg/kg, and intravenous atropine, 0.04 mg/kg); oral quinidine was then administered at a daily dosage of 1,200 mg for 3 to 4 days, after which the QT duration was reassessed using the same method in a second study. RESULTS: During the control study, the mean slope of the regression curve estimating the correlation between pacing cycle length and QT duration was significantly lower after autonomic blockade (0.14 +/- 0.05) than in the basal state (0.27 +/- 0.10, p < 0.05). Quinidine exhibited a prominent but opposite effect on the mean slope of the regression curves in basal conditions (from 0.27 +/- 0.10 to 0.20 +/- 0.07, p < 0.05) and after withdrawal of autonomic modulation (from 0.14 +/- 0.05 to 0.19 +/- 0.05, p < 0.05), thus annulling the differences observed between the two states in the control study. CONCLUSIONS: A quinidine-induced increase in QT duration as cycle length is prolonged is consistent with a reverse use dependence effect on ventricular repolarization. This effect is not evident in the basal state owing to interaction of quinidine-related vagolytic effect with the autonomic tone. Reverse use dependence and vagolytic activity on ventricular tissue indicate two potentially undesirable effects that could play a role in the lack of efficacy or proarrhythmic effect of quinidine.

Ventricular tachycardia during follow-up in patients resuscitated from ventricular fibrillation: experience from stored electrograms of implantable cardioverter-defibrillators.

OBJECTIVE: The purpose of this study was to use the electrogram storage capabilities of the implantable cardioverter-defibrillator (ICD) to categorize any arrhythmic event during follow-up in a group of patients who had survived an episode of ventricular fibrillation (VF) and to possibly identify clinical predictors of future arrhythmic events. BACKGROUND: Little is known about the electrophysiologic characteristics of ventricular arrhythmias recurring during follow-up in survivors of VF as the sole documented arrhythmia at the time of resuscitation. METHODS: Forty patients (58+/-10 years; 73% men; left ventricular ejection fraction 42+/-18%; 70% with coronary artery disease) who had survived an episode of VF and subsequently received an ICD capable of intracardiac electrogram recording and storage were followed for 23+/-11 months. In all patients, the arrhythmogenic substrate was investigated by means of programmed electrical stimulation (PES). RESULTS: Among the 40 patients, 41 episodes of ventricular arrhythmias were documented in 13 patients (33%): 36 episodes of ventricular tachycardias (VT) were recorded in 11 patients (28%) and 5 episodes of VF were recorded in the remaining 2 patients (5%). Age, gender, cardiac disease and left ventricular ejection fraction failed to distinguish between patients with clinical recurrences and patients without. The sensitivity, specificity and positive accuracy of PES were 29%, 63% and 46%, respectively, for prediction of ventricular arrhythmia recurrence; 45%, 70% and 36%, respectively, for prediction of VT; and 50%, 98% and 50%, respectively, for prediction of VF during follow-up. CONCLUSIONS: In survivors of VF receiving ICD therapy, VT is the most common ventricular arrhythmia recorded on device-incorporated electrograms during follow-up. This finding, associated with the relatively well-preserved ventricular function, may account for the ability of these patients to survive at time of the index arrhythmia; the use of antitachycardia pacing as a modality to treat arrhythmia recurrences may contribute to reduce the incidence of shock during follow-up in these patients.

Efficacy and safety of out-of-hospital self-administered single-dose oral drug treatment in the management of infrequent, well-tolerated paroxysmal supraventricular tachycardia.

OBJECTIVES: We tested the efficacy of two drug treatments, flecainide (F) and the combination ofdiltiazem and propranolol (D/P), administered as a single oral dose for termination of the arrhythmic episodes. BACKGROUND: Both prophylactic drug therapy and catheter ablation are questionable as first-line treatments in patients with infrequent and well-tolerated episodes of paroxysmal supraventricular tachycardia (SVT). METHODS: Among 42 eligible patients (13% of all screened for SVT) with infrequent (< or =5/year), well-tolerated and long-lasting episodes, 37 were enrolled and 33 had SVT inducible during electrophysiological study. In the latter, three treatments (placebo, F, and D/P) were administered in a random order 5 min after SVT induction on three different days. RESULTS: Conversion to sinus rhythm occurred within 2 h in 52%, 61%, and 94% of patients on placebo, F and D/P, respectively (p < 0.001). The conversion time was shorter after D/P (32 +/- 22 min) than after placebo (77 +/- 42 min, p < 0.001) or F (74 +/- 37 min, p < 0.001). Four patients (1 placebo, 1 D/P, and 2 F) had hypotension and four (3 D/P and 1 F) a sinus rate <50 beats/min following SVT interruption. Patients were discharged on a single oral dose of the most effective drug treatment (F or D/P) at time of acute testing. Twenty-six patients were discharged on D/P and five on F. During 17 +/- 12 months follow-up, the treatment was successful in 81% of D/P patients and in 80% of F patients, as all the arrhythmic episodes were interrupted out-of-hospital within 2 h. In the remaining patients, a failure occurred during one or more episodes because of drug ineffectiveness or drug unavailability. One patient had syncope after D/P ingestion. During follow-up, the percentage of patients calling for emergency room assistance was significantly reduced as compared to the year before enrollment (9% vs. 100%, p < 0.0001). CONCLUSIONS: The episodic treatment with oral D/P and F, as assessed during acute testing, appears effective in the management of selected patients with SVT. This therapeutic strategy minimizes the need for emergency room admissions during tachycardia recurrences.

Secondary prevention of sudden death: the Dutch Study, the Antiarrhythmics Versus Implantable Defibrillator Trial, the Cardiac Arrest Study Hamburg, and the Canadian Implantable Defibrillator Study.

Although indisputably effective in the prevention of sudden death, use of implantable cardioverter defibrillator (ICD) therapy may not necessarily affect all-cause mortality, as most patients at risk also present with severely depressed left ventricular dysfunction. Correction of the sudden death risk in these patients creates a new clinical condition in need of a careful assessment. Should all-cause mortality be affected by the expected reduction in sudden death rate associated with ICD therapy, issues of critical importance, such as the time extent of life prolongation and the associated quality of life, still remain to established. To investigate the potential benefit of ICD therapy compared with antiarrhythmic drug treatment, 4 prospective studies--the Dutch trial, the Antiarrhythmics Versus Implantable Defibrillators (AVID) study, the Cardiac Arrest Study Hamburg (CASH), and the Canadian Implantable Defibrillator Study (CIDS)--have been conducted in which patients with documented sustained ventricular arrhythmia were randomized to 1 of these 2 treatment strategies. The enrollment criteria differed in these 4 studies: (1) in the Dutch trial, they included cardiac arrest secondary to a ventricular arrhythmia, old (> 4 weeks) myocardial infarction, and inducible ventricular arrhythmia; (2) in AVID and CIDS, ventricular fibrillation or poorly tolerated ventricular tachycardia; and (3) in CASH, cardiac arrest secondary to a ventricular arrhythmia regardless of the underlying disease. With regard to the antiarrhythmic drugs, the Dutch trial tested class I and III agents, whereas AVID and CIDS compared ICD therapy with class III agents (mostly amiodarone). In CASH, 3 drug subgroups were investigated: propafenone, amiodarone, and metoprolol. All trials used all-cause mortality as the primary endpoint. Data from these trials provide support for ICD as a therapy superior to antiarrhythmic drugs in prolonging survival in patients meeting the entry criteria. This review briefly summarizes the methods, results, limitations, and clinical implications of these 4 studies.

Sympathetic and vagal influences on rate-dependent changes of QT interval in healthy subjects.

Dependence of QT interval duration on cardiac heart rate has been well established and is considered to be an intrinsic property of ventricular myocardium. Conclusive results of autonomic influences on such phenomena are lacking. To evaluate whether rate-dependent changes of QT interval are conditioned by the autonomic nervous system, 28 normal subjects with no heart disease and a normal QT interval were electrophysiologically assessed. The QT interval was calculated at 6 paced cycle lengths (600, 540, 500, 460, 430 and 400 ms) during the basal state, and after beta blockade (propranolol 0.2 mg/kg) and autonomic blockade (propranolol plus atropine 0.04 mg/kg). Because of atrioventricular nodal conduction limits, intrapatient cross-comparisons were performed in 10 subjects (aged 42 +/- 15 years). Single regression lines, evaluated in each subject, showing correlation between pacing cycle length and QT duration at each of the 3 states were analyzed. The mean slope observed after autonomic blockade (b = 0.10 +/- 0.04) was significantly lower than that seen during the basal state (b = 0.22 +/- 0.12, p less than 0.05) and after beta blockade (b = 0.23 +/- 0.08, p less than 0.05); nonsignificant differences were found between slopes during the basal state and after beta blockade. Results showed that vagal tone increased intrinsic dependence of QT at increasing cycle length, whereas sympathetic tone did not seem to interfere significantly. Since (in each subject) beta blockade was performed--or achieved--before atropine administration, the vagal influences are likely to be directly exerted on the ventricular electrophysiologic substrate.

Direct and autonomically mediated effects of oral flecainide.

This study was undertaken to determine if oral flecainide exerts autonomically mediated actions in addition to its direct depressant effect. Electrophysiologic studies were performed twice in each of 15 patients (mean age 59 years) with normal resting and intrinsic heart rate and normal A-H interval. In the first study, the variables of sinus node and atrioventricular node were evaluated both in the basal state and after autonomic blockade (propranolol 0.2 and atropine 0.04 mg/kg). Oral flecainide was administered for 4 to 5 days (200 to 250 mg daily) and the study was then repeated using the same methods. From comparison of data obtained in the 2 studies in the basal state, the overall effect of flecainide was evaluated and by comparing those obtained after autonomic blockade, the direct action of the drug was assessed. The overall effect of flecainide on sinus node was slight; sinus cycle length, corrected sinus node recovery time and sinoatrial conduction time did not change significantly after the drug. In contrast, after autonomic blockade the variables of sinosal automaticity were increased significantly (p less than 0.01). Flecainide significantly prolonged the atrioventricular node variables both in the basal state and after autonomic blockade (p less than 0.01), but the degree of increase was more marked after autonomic blockade (p less than 0.05). These data show dual effects of oral flecainide: a direct depressant action and an autonomically mediated opposing action, likely of vagolytic type.

Significance of newly acquired negative T waves after interruption of paroxysmal reentrant supraventricular tachycardia with narrow QRS complex.

Sixty-three patients with paroxysmal supraventricular tachycardia were studied and 25 patients (39%) showed newly acquired negative T waves after tachycardia termination. Silent coronary artery disease could not be found in about 90% of these patients; moreover, age, sex, organic heart disease, and tachycardia duration and rate did not predict the appearance of negative T waves.

Long-term effects of theophylline in atrial fibrillation with a slow ventricular response.

In 17 patients (aged 78 +/- 9 years) with symptomatic atrial fibrillation and a slow ventricular response not related to drugs, a resting electrocardiogram and 24-hour Holter recording were obtained before and 5 to 6 days after administration of slow-release theophylline (700 mg/day), and successively every 3 months during the long-term phase. Fourteen patients had organic heart disease, and 13 complained of syncope or presyncope, and 4 of asthenia and easy fatigability. At the steady-state evaluation, theophylline significantly increased resting heart rate (HR) by 42%, mean 24-hour HR by 31% and minimal 24-hour HR by 34%. Cardiac pauses > 2,500 ms disappeared or markedly decreased. The daily number of wide QRS complexes increased. Serum theophylline level was 13 +/- 5 ng/ml. During the follow-up period (20 +/- 18 months), the mean daily theophylline dosage was 450 mg and the mean serum theophylline level 9 ng/ml. Seven patients died: 1 because of heart failure, and 6 because of noncardiac death. One patient complained of a syncopal episode during 1 visit. The drug markedly reduced asthenia and easy fatigability. During the long-term phase, HR increased spontaneously in 3 patients, and the treatment was interrupted. In 2 patients, theophylline had to be discontinued because of gastric intolerance. During long-term therapy, HR was similar to that observed at the steady-state evaluation, despite the reduction in daily dosage. The data suggest that theophylline is an effective therapy in most patients with symptomatic atrial fibrillation and a slow ventricular response.

Preliminary results of the Cardiac Arrest Study Hamburg (CASH). CASH Investigators.

Sodium channel blockers and class III antiarrhythmic compounds, as well as beta blockers, have been used in preventing recurrences of sudden cardiac death. In recent years, implantable cardioverter-defibrillators (ICDs) have been used increasingly, but no data from randomized trials comparing antiarrhythmic drug and ICD therapy have been reported in this setting. In 1987, the Cardiac Arrest Study Hamburg (CASH), a prospective, randomized trial, was initiated to compare metoprolol, amiodarone, propafenone, and ICD implantation in patients surviving sudden cardiac death due to documented ventricular tachycardia and/or ventricular fibrillation. The details of the study design and preliminary results are presented herein. The primary endpoint of the study is total mortality. The data reviewed in March 1992, representing a mean follow-up period of 11 months, indicated no significant differences among patients randomized to metoprolol, amiodarone, and ICDs. However, there was a significantly higher total mortality and cardiac arrest recurrence in patients randomized to propafenone compared with those randomized to the ICD treatment limb. The study continues with the deletion of the propafenone treatment limb.

Intrinsic electrophysiologic properties of reentrant supraventricular tachycardia involving bypass tracts.

This study evaluates the effects of autonomic blockade (propranolol, 0.2 mg/kg, and atropine, 0.04 mg/kg) in 20 patients with paroxysmal supraventricular tachycardia (SVT). In 8 patients the SVT circuit involved a concealed atrioventricular bypass for retrograde conduction (group I) and in 12 a concealed atrio-His pathway (group II). Autonomic blockade did not significantly change atrial and ventricular refractory periods, whereas it prolonged atrioventricular nodal refractoriness without varying AH interval. The ventriculoatrial interval did not change in any patient. The H2A2 interval was unchanged in all but 2 group II patients. In both groups, the effective refractory period of the concealed bypass was prolonged by autonomic blockade. In the basal state, SVT was induced in all patients; after autonomic blockade, SVT was induced in 7 patients in group I (87%) and in 7 in group II (58%) (p less than 0.05). Cycle length of SVT was prolonged after autonomic blockade in 11 of these 14 patients. The variations were observed only in the anterograde conduction (Ae-H interval), whereas retrograde conduction (H-Ae interval) was unchanged in all patients. These data indicate that the autonomic system appears to facilitate induction of SVT in patients with concealed atrio-His bypass as well as shorten the cycle length of SVT in both groups of patients.

Role of sinus node artery disease in sick sinus syndrome in inferior wall acute myocardial infarction.

This study was undertaken to evaluate a possible role of sinus node (SN) artery disease in the pathogenesis of sick sinus syndrome (SSS) in patients with an inferior wall acute myocardial infarction (AMI). Coronary angiography and electrophysiologic studies of the SN, both in the basal state and after pharmacologic autonomic blockade, were performed in 23 study patients (mean age 60 years) with SSS and a previous inferior wall AMI and in another 23 control patients (mean age 57 years) with normal sinus rate and a previous inferior AMI. Stenosis of the SN artery (or that proximal to its origin) greater than 50% was present in 13 study patients (56%) and in 8 control patients (34%) (p less than 0.05). In the study group, the intrinsic heart rate was abnormal in 5 of the 6 patients (83%) with severe SN artery stenosis (greater than or equal to 75% narrowing), in 3 of the 7 (43%) with moderate stenosis (50 to 75% narrowing) and in 3 of the 10 (30%) with insignificant stenosis (less than 50% narrowing). In the study group, the correlation between the SN measures (heart rate, corrected SN recovery time and sinoatrial conduction time) and the severity of SN artery stenosis was good after autonomic blockade (r between 0.59 and 0.64) and poor in the basal state. These data provide evidence for a role of SN artery disease in the pathogenesis of SSS in patients with an inferior wall AMI.

Which strategy is "best" after myocardial infarction? The Beta-blocker Strategy plus Implantable Cardioverter Defibrillator Trial: rationale and study design.

The Beta-blocker Strategy plus Implantable Cardioverter Defibrillator (BEST-ICD) Trial is a multicenter prospective randomized trial that started in June 1998, in 95 centers in Italy and Germany. The trial will test the hypothesis whether, in high-risk post myocardial infarction (MI) patients already treated with beta blockers, electrophysiologic study (EPS)-guided therapy (including the prophylactic implantation of implantable cardioverter defibrillator [ICD] in inducible patients) will improve survival compared with conventional therapy. Patients eligible for the study are survivors of recent MI (> or = 5 and < or = 21 days), aged < or = 80 years, with left ventricular ejection fraction < or = 35% and > or = 1 of the following additional risk factors: (1) ventricular premature beats > or = 10/hour; (2) decreased heart rate variability (standard deviation of unusual RR intervals < 70 msec); and (3) presence of ventricular late potentials. Furthermore, all enrolled patients must be able to tolerate at least 25 mg of metoprolol per day. These patients constitute about 9% of all patients with recent MI and are expected to have a 2-year all-cause mortality > 25% of which 50% is anticipated to be from sudden death. The main criteria of exclusion from the study are (1) a history of sustained ventricular arrhythmia; (2) documentation of nonsustained ventricular tachycardia during the screening phase; and (3) the need for myocardial revascularization and contraindications or intolerance to beta-blocker therapy. Eligible patients will be randomized to 2 different therapeutic strategies: conventional strategy or EPS/ICD strategy. Patients allocated to the EPS/ICD strategy will undergo further risk stratification, and electrophysiologically inducible patients (approximately 35%) will receive prophylactic ICDs, in addition to the conventional therapy, whereas noninducible patients will be only conventionally treated. The primary endpoint of the study will be death from all causes. By hypothesizing a 30% reduction in the 2-year mortality (from 20% to 14%) in the EPS/ICD group compared with conventionally treated patients, 1,200 patients will have to be included. A triangular, 2-sided sequential design with preset boundaries, for a 5% significance level and 90% power to detect a reduction in 2-year mortality from 20% to 14%, will be used to permit early termination of the trial if the strategy is found to be efficacious, no difference, or inefficacious.