Predictors of clinical efficacy of 'Ablate and Pace' therapy in patients with permanent atrial fibrillation.

OBJECTIVE: To evaluate the 2-year clinical improvement after 'Ablate and Pace' therapy and to identify the variables able to influence the efficacy of this therapy in patients with permanent atrial fibrillation (AF). Design Prospective multicentre observational study. Setting Cardiology departments of 19 general hospitals in Italy, Spain and Greece. PATIENTS: 171 patients with drug-refractory severely symptomatic permanent AF considered for AV junction ablation. Interventions Patients underwent AV junction ablation, received a right ventricular (RV) pacing or echo-guided cardiac resynchronisation (CRT) pacing and were followed-up to 24 months. Main outcome measures Non-responders to Ablate and Pace therapy were defined those patients who, during the follow-up period had clinical failure (defined as death or hospitalisation due to heart failure, or worsening heart failure) or showed no improvement in their clinical condition. RESULTS: Responders were 63% of RV-paced patients and 83% of CRT-paced patients. Another 27% showed no clinical improvement (7%) or worsened (20%) (non-responders group). On multivariable Cox regression analysis, CRT mode and echo-optimised CRT were the only independent protective factors against non-response (HR=0.24, 95% CI 0.10-0.58, p=0.001 and HR=0.22, 95% CI 0.07-0.77, p=0.018 respectively). On comparing freedom from non-response, a trend in favour of echo-optimised CRT versus simultaneous biventricular pacing (p=0.077) was seen. CONCLUSIONS: In patients affected by severely symptomatic permanent AF, Ablate and Pace therapy yielded a clinical benefit in 63% of RV-paced patients and 83% of CRT-paced patients. CRT pacing and echo-optimised CRT were the only independent predictor of clinical benefit.

An evaluation of the strategy of maintenance of sinus rhythm by antiarrhythmic drug therapy after ablation and pacing therapy in patients with paroxysmal atrial fibrillation.

AIMS: Permanent atrial fibrillation develops in many patients after ablation and pacing therapy. We compared a strategy that initially allowed patients to remain in atrial fibrillation with a strategy that initially attempted to restore and maintain sinus rhythm. METHODS AND RESULTS: In this multicentre randomized controlled trial, 68 patients affected by severely symptomatic paroxysmal atrial fibrillation were assigned, after successful atrioventricular junction ablation and pacing treatment, to antiarrhythmic drug therapy with amiodarone, propafenone, flecainide or sotalol and were compared with 69 patients assigned, after successful AV junction ablation and pacing treatment, to no antiarrhythmic drug therapy. The patients were followed-up for 12 to 24 months (mean 16+/-4). The drug arm patients had a 57% reduction in the risk of developing permanent atrial fibrillation (21% vs 37%, P=0.02). Evaluation after 12 months revealed similar quality of life scores and echocardiographic parameters in the two groups, but the drug arm patients had more episodes of heart failure and hospitalizations (P=0.05). The outcome was similar between the 40 patients who developed permanent atrial fibrillation and the 97 who did not. CONCLUSION: Conventional antiarrhythmic therapy reduces the risk of development of permanent atrial fibrillation after ablation and pacing therapy. The present data do not support the concept that the development of permanent atrial fibrillation is related to an adverse outcome when a perfect control of heart rate is obtained by ablation and pacing.

Impact of consistent atrial pacing algorithm on premature atrial complexe number and paroxysmal atrial fibrillation recurrences in brady-tachy syndrome: a randomized prospective cross over study.

AIM OF THE STUDY: The Consistent Atrial Pacing (CAP) algorithm has been designed to achieve a high percentage of atrial pacing to suppress paroxysmal atrial fibrillation. The aim of our study was to compare the impact of DDDR+CAP versus DDDR pacing on paroxysmal atrial fibrillation recurrences and triggers in patients with Brady-Tachy Syndrome. METHODS: 61 patients, 23 M and 38 F, mean age 75+/-9 y, affected by Brady-Tachy Syndrome, implanted with a DDDR pacemaker, were randomized to DDDR or DDDR+CAP pacing with cross over of pacing modality after 1 month. RESULTS: 78 % of patients in DDDR pacing and 73 % in DDDR + CAP pacing (p=n.s.) were free from symptomatic paroxysmal atrial fibrillation recurrences. During DDDR+CAP pacing, the atrial pacing percentage increased from 77+/-29 % to 96+/-7 % (p<0.0001). Automatic mode switch episodes/day were 0.73+/-1.09 in DDDR and 0.79+/-1.14 (p=n.s.) in DDDR+CAP. In patients with less than 50 % of atrial pacing during DDDR, automaticmode switch episodes/day decreased during DDDR+CAP from 1.13+/-1.59 to 0.23+/-0.32 (p<0.05) and in patients with less than 90 % from 1.23+/-1.27 to 0.75+/-1.10 (p<0.001). The number of premature atrial complexes per day decreased during DDDR + CAP from 2665+/-4468 to 556+/-704 (p<0.02). CONCLUSION: CAP algorithm allowed continuous overdrive atrial pacing without major side effects. Triggers of paroxysmal atrial fibrillation induction, such as premature atrial complexes, were critically decreased. Paroxysmal atrial fibrillation episodes were reduced in patients with atrial pacing percentage lower than 90 % during DDDR pacing.

Pregnancy with an ICD and a documented ICD discharge.

We report a successful pregnancy in a patient affected by idiopathic ventricular fibrillation 3 years after insertion of an ICD, with a documented defibrillator discharge.

External cardioversion of atrial fibrillation: role of paddle position on technical efficacy and energy requirements.

AIM: To define the effect of defibrillator paddle position on technical success and dc shock energy requirements of external cardioversion of atrial fibrillation. METHODS: 301 patients (mean (SD) age 62 (11) years) with stable atrial fibrillation were randomly assigned to elective external cardioversion using anterolateral paddle position (ventricular apex-right infraclavicular area; group AL (151 patients)) or anteroposterior paddle position (sternal body-angle of the left scapula; group AP (150 patients)). A step up protocol was used, delivering a 3 J/kg body weight dc shock, then a 4 J/kg shock (maximum 360 J), and finally a second 4 J/kg shock using the alternative paddle location. RESULTS: The two groups were comparable for the all clinical variables evaluated. The cumulative percentage of patients successfully converted to sinus rhythm was 58% in group AL and 67% in group AP with low energy dc shock (NS); this rose to 76% in group AL and to 87% in group AP with high energy dc shock (p = 0.013). Thirty seven patients in group AL and 19 in group AP experienced dc shock with the alternative paddle position; atrial fibrillation persisted in 10/37 in group AL and in 10/19 in group AP. Mean dc shock energy requirements were lower for group AP patients than for group AL patients, at 383 (235) v 451 (287) J, p = 0.025. Arrhythmia duration was the only factor that affected the technical success of external cardioversion (successful: 281 patients, 80 (109) days; unsuccessful: 20 patients, 193 (229) days; p < 0.0001). The success rate was lower if atrial fibrillation persisted for > 6 months: 29 of 37 (78%) v 252 of 264 (95%); p = 0.0001. CONCLUSIONS: An anteroposterior defibrillator paddle position is superior to an anterolateral location with regard to technical success in external cardioversion of stable atrial fibrillation, and permits lower dc shock energy requirements. Arrhythmia duration is the only clinical variable that can limit the restoration of sinus rhythm.

Modulation of ventricular rate in permanent atrial fibrillation: randomized, crossover study of the effects of slow-release formulations of gallopamil, diltiazem, or verapamil.

BACKGROUND: The management of permanent atrial fibrillation (PAF) consists primarily of long-term anticoagulation with either aspirin or warfarin to prevent systemic embolization, and modulation of ventricular rate (VR) to improve cardiac function by prolonging the ventricular diastolic filling time. HYPOTHESIS: The effects of slow-release formulations of gallopamil (100 mg b.i.d.), diltiazem (120 mg b.i.d.), or verapamil (120 mg b.i.d.) on VR were evaluated in 18 patients with PAF without organic heart disease. METHODS: In all patients, each treatment was administered randomly, was compared with oral digoxin, and was assessed by 24-h Holter monitoring during daily life and by a 6-min walking test. RESULTS: There were no significant differences in mean and minimum VR recorded during 24-h Holter monitoring among the four treatments. Peak heart rates recorded during the 6-min walking test with digoxin treatment was 167 +/- 12 beats/min. This was significantly reduced by gallopamil (149 +/- 23 beats/min, p = 0.01), diltiazem (142 +/- 24 beats/min, p < 0.001), and verapamil (137 +/- 30 beats/min, p < 0.001). There were no significant differences in peak VR during the walking test among the three calcium antagonists. Pauses of > 3 s were observed in 3 of 18 (17%) patients who received digoxin (max 3.4 s) and in 5 of 18 (28%) patients who received diltiazem (max 3.4 s); p = NS. Periods of bradycardia < 30 beats/min were observed in 5 of 18 (28%) patients during digoxin treatment, and in 3 of 18 (17%) patients during treatment with gallopamil, diltiazem, and verapamil; p = NS. CONCLUSION: Gallopamil, diltiazem, or verapamil are superior to digoxin in controlling VR during mild exercise in patients with PAF without organic heart disease. The reduction of peak VR is obtainable without further slowing of resting VR. However, gallopamil appears to be the least effective calcium blocker at controlling resting and exercise VR; thus, there are no advantages over the other calcium blockers in its use in the clinical setting.

Oral loading with propafenone: a placebo-controlled study in elderly and nonelderly patients with recent onset atrial fibrillation.

UNLABELLED: The efficacy and safety of propafenone as an oral loading dose (600-mg single oral dose) in converting recent-onset atrial fibrillation (< or = 7 days duration) to sinus rhythm were evaluated in a single-blind, placebo-controlled study according to patients' age. Overall, 240 hospitalized patients, NYHA Class < or = 2 without signs or symptoms of heart failure were enrolled: among patients aged < or = 60 years, 55 were allocated to propafenone treatment and 59 to placebo, respectively, and among patients aged > 60 years, 64 were allocated to propafenone treatment and 62 to placebo, respectively. RESULTS: In each age group, the likelihood of conversion to sinus rhythm was significantly greater after propafenone compared with placebo at 3 and 8 hours. For patients aged < or = 60 years, corresponding odd ratios were 3.78 (95% CI = 1.80-7.92, P = 0.04) at 3 hours and 4.74 (95% CI = 2.12-10.54, P = 0.02) at 8 hours; for patients aged > 60 years odd ratios were 5.03 (95% CI = 2.08-12.12, P = 0.02) at 3 hours and 6.75 (95% CI = 3.28-73.86, P = 0.01) at 8 hours, respectively. Logistic regression analysis showed that conversion to sinus rhythm within 3 hours was predicted by age < or = 60 years (P = 0.0064) and by propafenone treatment (P < 0.0001), and conversion to sinus rhythm within 8 hours was predicted by age < or = 60 years (P = 0.0467) and by propafenone treatment (P < 0.0001). The occurrence of adverse effects was observed in 14%-16% of propafenone treated patients and in 8% of placebo treated patients without significant differences according to age. In conclusion, in patients with recent-onset atrial fibrillation without signs of heart failure, propafenone as a single oral loading dose is effective. It is also effective in selected elderly subjects with a favorable safety profile. Moreover, spontaneous conversion to sinus rhythm appears to occur less frequently in elderly patients.

Randomized, crossover, controlled comparison of oral loading versus intravenous infusion of propafenone in recent-onset atrial fibrillation.

A population of 123 patients with recent-onset (< 72 hours) atrial fibrillation (AF) without heart failure was randomly treated with propafenone (PFN) intravenously (i.v.) (2 mg/kg bolus followed by 0.0078 mg/kg/min infusion) or in a single oral dose (o.s.) (600 mg), or with placebo (PLA) (phase 1). If AF persisted 8 hours later, patients on active drugs received the alternative formulation (crossover), and patients receiving PLA remained on PLA (phase 2). A 24-hour Holter monitoring was performed and conversion to sinus rhythm (SR) at 1, 4, and 8 hours of each phase was used as the criterion of efficacy. Conversion to SR occurred within 1 hour in 48% of patients with i.v.-PFN, 15% with o.s.-PFN, and in 17% with PLA (both P < 0.05 vs i.v.-PFN). Oral PFN was superior to PLA at 4 hours (71% vs 33%, P = 0.001) and 8 hours (78% vs 48%, P < 0.01), and 1 at 8 hours also superior to i.v.-PFN (53%, P < 0.03). The mean conversion time within 4 hours was shorter with i.v.-PFN (25 +/- 15') than with o.s.-PFN (167 +/- 166', P < 0.001) or with PLA (156 +/- 107', P < 0.001). The rates of conversion to SR with i.v.-PFN after o.s.-PFN failure were comparable to PLA at any observation time, whereas nonresponders to i.v.-PFN who received o.s.-PFN had significantly higher conversion rates than with placebo at both 4 hours (65% vs 19%) and 8 hours (76% vs 24%; both P < 0.045). Neither serious adverse effects nor episodes of regular tachycardia with 1:1 AV conduction were noted. PFN administered intravenously or in a single oral loading dose was safe and efficacious in converting recent-onset AF to SR. The rates of conversion were different with different routes of administration: i.v.-PFN was superior to o.s.-PFN over a short observation period, while the overall efficacy of o.s.-PFN was superior at 8 hours.

Oral propafenone to convert recent-onset atrial fibrillation in patients with and without underlying heart disease. A randomized, controlled trial.

BACKGROUND: The effectiveness of oral propafenone in converting recent-onset atrial fibrillation to sinus rhythm has been established by controlled trials. However, it is not clear whether the effectiveness of propafenone is affected by the presence or absence of underlying heart disease. OBJECTIVES: To investigate the safety and effectiveness of oral propafenone and the role of underlying heart disease. DESIGN: Randomized, single-blind, controlled study. SETTING: 3 teaching hospitals. PATIENTS: 240 hospitalized patients with recent-onset atrial fibrillation. INTERVENTION: Propafenone (one 500-mg oral dose) or placebo. MEASUREMENTS: Conversion rates at 3 and 8 hours. RESULTS: Propafenone was more effective than placebo for converting atrial fibrillation to sinus rhythm at 3 hours: Fifty-four of 119 patients (45%) receiving propafenone and 22 of 121 patients (18%) receiving placebo had conversion (P < 0.001). It was also more effective at 8 hours: Ninety-one of 119 patients (76%) receiving propafenone and 45 of 121 patients (37%) receiving placebo had conversion (P < 0.001). Subgroup analysis showed that among patients without heart disease, 78% of those receiving propafenone and 56% of those receiving placebo converted to sinus rhythm within 8 hours (P = 0.02). In those with hypertension, the rate was 70% for those receiving propafenone and 27% for those receiving placebo (P < 0.001); in patients with structural heart disease, the rate was 81% for those receiving propafenone and 17% for those receiving placebo (P < 0.001). CONCLUSIONS: Oral loading of propafenone was more effective than placebo for conversion to sinus rhythm within 8 hours and had a favorable safety profile. The rate of spontaneous conversion to sinus rhythm was higher in patients without structural heart disease; this finding has important implications for the assessment of drug effectiveness in recent-onset atrial fibrillation.

Conversion of recent onset atrial fibrillation to sinus rhythm using a single oral loading dose of propafenone: comparison of two regimens.

A population of 105 patients with recent onset (< 72 h) atrial fibrillation was randomly treated with propafenone as a single oral loading dose of 450 mg (Regimen A) or 600 mg (Regimen B) or with placebo. A 24-h Holter was performed. Criteria of efficacy were conversion to sinus rhythm at 2, 4 and 8 h compared to placebo and also significant reduction of mean ventricular rate in persistent atrial fibrillation. After 2 h, regimen B was more effective than either regimen A (43% vs. 8%; p = 0.001) or placebo (11%; p = 0.004). At 4 h, both the active treatments were more effective than placebo (17% vs. 46% regimen A and 57% vs. regimen B; p < 0.04 and p < 0.001, respectively). Sinus rhythm resumed within 24 h in 71%, 80% and 69% of the patients with regimen A, B and placebo, respectively (p = not significant). The mean ventricular rate reduction after 1 h was 8%, 11% and 4% for regimen A, B and placebo, respectively (p < 0.005 vs. regimen B), and 17%, 25% and 6% respectively (p < 0.001 placebo vs. regimen A and B, p < 0.05 regimen B vs. A) at 2 h. No major adverse effect occurred. Atrial flutter with 1:1 atrioventricular conduction only in one case who received placebo. Propafenone acute oral administration is more effective than placebo in rapidly converting recent-onset atrial fibrillation to sinus rhythm and may be the treatment of choice in this setting limiting hospitalization and contributing to improved quality of life.

Conversion of recent onset atrial fibrillation with single loading oral dose of propafenone: is in-hospital admission absolutely necessary?

A population of 283 patients with recent onset (< 72 hours) AF, without heart failure, who received a single 450- or 600-mg oral dose of propafenone, or digoxin 1 mg, or placebo for conversion to sinus rhythm (SR), was studied to determine whether a routine admission to the hospital for drug administration is justified. Previous bradyarrhythmias or sick sinus syndrome (SSS), and concomitant use of antiarrhythmic drugs were exclusion criteria. None of the 283 patients studied experienced VT or VF and none of them needed implantation of a temporary pacemaker. Periods of atrial tachyarrhythmias with regularization of atrial waves and 1:1 AV conduction were observed in only two cases, both receiving placebo. No predictor of proarrhythmia was found among the clinical variables considered (age, etiology, arrhythmia duration, atrial dimension, and blood potassium). No serious hemodynamic adverse effects were noted in either group. The rates of conversion to SR after 4 hours were: 80 (57%) of 141 patients who received propafenone and 35 (25%) of 142 patients who received digoxin or placebo (P < 0.001). Acute oral treatment with propafenone is simple and effective for the conversion of recent onset AF to SR in patients without clinical signs of heart failure. The routine admission of these patients to the hospital is not necessary. Home-based administration of oral propafenone to a selected group of patients could significantly increase the cost effectiveness of this treatment.

Regular ventricular rhythms before conversion of recent onset atrial fibrillation to sinus rhythm.

The incidence of fast atrial tachycardias with regular ventricular rhythm was assessed in a population of 243 patients with recent onset (< 72 hours) atrial fibrillation (AF), without heart failure, randomly treated with single loading oral dose of propafenone (600 mg), flecainide (300 mg), digoxin (1 mg), or placebo for acute conversion to sinus rhythm (SR). Fast atrial arrhythmias developed in 14 (6%) patients: 6/92 treated with propafenone, 3/34 treated with flecainide, 1/25 treated with digoxin, and 4/92 who received placebo (P = NS). Heart rate > 175 beats/min with 1:1 AV conduction ensued in 4 cases: 2 treated with flecainide and 2 treated with placebo; in the other cases 2:1 AV conduction was observed. Widening of QRS during regular tachycardia was observed in 4 patients; 3 who received propafenone and 1 who received flecainide. Conversion to SR within 4 hours was achieved in 55/92 (60%) patients treated with propafenone, 20/34 (59%) patients treated with flecainide, 7/25 (28%) patients treated with digoxin, and 19/92 (20%) treated with placebo (P < 0.001 propafenone vs placebo and flecainide vs placebo; P < 0.05 propafenone vs digoxin and flecainide vs digoxin). Periods of regular tachycardia are expected in recent onset AF and may not necessarily represent a proarrhythmic effect of Class 1C drugs, rather than mark the transition from AF to SR. Class 1C agents are probably responsible for widening of the QRS complex seen during these tachycardias. Propafenone and flecainide appear equally effective in converting recent onset AF.