Upgrading to biventricular pacing guided by pressure-volume loop analysis during implantation.

INTRODUCTION: cardiac resynchronization therapy (CRT) may improve prognosis in patients with chronic right ventricular (RV) pacing, and optimal lead position can decrease nonresponders. We evaluated the clinical and echocardiographic response to CRT in patients with previous chronic RV pacing, using pressure-volume loop analyses to determine the optimal left ventricular (LV) lead position during implantation. METHODS AND RESULTS: In this single-blinded, randomized, controlled crossover study, 40 patients with chronic RV apical pacing and symptoms of heart failure, decreased LV ejection fraction (LVEF) or dyssynchrony were included. During implantation, stroke work (SW), LVEF, cardiac output, and LV dP/dt(max) were assessed by a conductance catheter. Clinical and echocardiographic response was studied during a 3-month period of RV pacing (RV period, LV lead inactive) and a 3-month period of biventricular pacing (CRT period). At the optimal LV lead position, SW (37 ± 41%), LVEF (16 ± 13%), cardiac output (29 ± 16%), and LV dP/dt(max) increased (11 ± 11%) significantly during biventricular pacing compared to baseline. Additional benefit could be achieved by pressure-volume loop guided selection of the best left-sided pacing location. RV outflow tract pacing did not improve hemodynamics. During follow-up, symptoms improved during CRT, VO(2,max) increased 10% and significant improvements in LVEF, LV volumes, and mitral regurgitation were observed as compared to the RV period. CONCLUSIONS: CRT in patients with chronic RV pacing causes significant improvement of both LV function as measured by pressure-volume loops during implantation and clinical and echocardiographic improvement during follow-up. Pressure-volume loops during implantation may facilitate selection of the most optimal pacing site.

Efficacy of multi-electrode duty-cycled radiofrequency ablation for pulmonary vein disconnection in patients with paroxysmal and persistent atrial fibrillation.

AIM: A novel multi-electrode pulmonary vein ablation catheter (PVAC) combining circular mapping and duty-cycled multi-electrode radiofrequency (RF) energy delivery has been developed to map and isolate the pulmonary veins (PVs). The aim of this study was to assess the efficacy of multi-electrode RF ablation using the PVAC device. METHODS AND RESULTS: A total of 102 consecutive patients, age 57.9 +/- 9.6 years, with paroxysmal or persistent drug refractory atrial fibrillation (AF) were referred for ablation. All patients had documented AF episodes with an AF duration of 9.3 +/- 7.5 years (range 1.5-25). The mean total procedure time was 139.30 +/- 37.72 (median 135, range 115-172). The mean fluoroscopy time required for PVAC ablation was 17 +/- 12 min (median 16, range 12-33) and the total fluoroscopy time was 32.1 +/- 11.3 min (median 29, range 25-39). The mean multi-electrode RF ablation time required to achieve complete PV isolation was 31 +/- 6.7 min (range 16-51). In eight patients with persistent AF, additional ablations were performed to defragment septal and posterior part of the left atrium. In five patients additional RF ablations using conventional catheters were necessary. After multi-electrode duty-cycled RF ablation, 62 of 102 (60.8%) patients were in sustained sinus rhythm without anti-arrhythmic drugs. The mean follow-up duration was 12.2 +/- 3.9 months (range 6-15). CONCLUSION: This novel multi-electrode ablation technique can be used for PV isolation and left atrium ablation with a relatively low medium-term success rate after the first ablation of approximately 61%. Larger studies with longer follow-up are required to evaluate the efficacy and whether multi-electrode RF ablation is associated with a different complication rate compared with standard PV isolation.

Dominant frequency of atrial fibrillation correlates poorly with atrial fibrillation cycle length.

BACKGROUND: Localized sites of high frequency during atrial fibrillation (AF) are used as target sites to eliminate AF. Spectral analysis is used experimentally to determine these sites. The purpose of this study was to compare dominant frequencies (DF) with AF cycle length (AFCL) of unipolar and bipolar recordings. METHODS AND RESULTS: Left and right atrial endocardial electrograms were recorded during AF in 40 patients with lone AF, using two 20-polar catheters. Mean age was 53+/-9.9 years. Unipolar and bipolar electrograms were recorded simultaneously during 16 seconds at 2 right and 4 left atrial sites. AFCLs and DFs were determined. QRS subtraction was performed in unipolar signals. DFs were compared with mean, median, and mode of AFCLs; 4800 unipolar and 2400 bipolar electrograms were analyzed. Intraclass correlation was poor for all spectral analysis protocols. Best correlation was accomplished with DFs from unipolar electrograms compared with median AFCL (intraclass correlation coefficient, 0.67). A gradient in median AFCL of >25% was detected in 16 of 40 patients. In 13 of 16 patients (81%) with a frequency gradient of >25%, the site with highest frequency was located in the left atrium (posterior left atrium in 8 patients). The site with shortest median AFCL and highest DF corresponded in 25% if unipolar and in 31% if bipolar electrograms were analyzed. CONCLUSIONS: DFs from unipolar and bipolar electrograms recorded during AF correlated poorly with mean, median, and mode AFCL. If a frequency gradient >25% existed, the site with highest DF corresponded to the site of shortest median AFCL in only 25% of patients. Because spectral analysis is being used to identify ablation sites, these data may have important clinical implications.

Monitoring of atrial fibrillation burden after surgical ablation: relevancy of end-point criteria after radiofrequency ablation treatment of patients with lone atrial fibrillation.

Studies have shown that continuous rhythm monitoring enables the detection of significantly more atrial fibrillation (AF) episodes than routine follow-up of patients, i.e. based on perception of symptoms or on 24-48 h Holter monitoring. The positive outcome of radiofrequency ablation (RFA) may be easily overestimated, especially in patients with paroxysmal AF. Thirty-three consecutive patients, aged 59.4+/-8.9 years (range 38-75 years) participated in this study. All patients had documented AF episodes with an AF duration of 9.4+/-7.1 years (range 1.5-25 years). A new monitoring device, the AF-Alarm was used to more accurately assess the outcome after surgical isolation of pulmonary veins. The AF-Alarm was applied for a duration of 128+/-42.5 h (range 49-191 h) during a period of 8-15 days. The success rate was 87% based on serial electrocardiograms (ECGs) and 24-48 h Holter monitoring during regular outpatient visits. Combination of ECG, Holter and AF-Alarm data yielded a significantly lower success rate, i.e. at the latest follow-up 69% of the patients were free from AF after surgical ablation (P<0.05). Furthermore, the AF-Alarm device demonstrated a dissociation between symptoms and atrial arrhythmic events and confirmed the occurrence of asymptomatic AF episodes. The most important limitation of the AF-Alarm device was noise detection with oversensing and inappropriate detection of non-existing AF episodes in 9% of patients. Long-term follow-up of the patients seems to be essential as success rates of the initial ablation procedure might vary over time. External recorders like the AF-Alarm may be used as an additional tool to document symptomatic and asymptomatic episodes of atrial arrhythmias in the outpatient setting.

Long-term clinical response of cardiac resynchronization after chronic right ventricular pacing.

Chronic right ventricular (RV) pacing might elicit unpredictably deleterious effects on left ventricular (LV) function similar to that of native left bundle branch block (LBBB). The objective of the present study was to evaluate the clinical and echocardiographic response to cardiac resynchronization therapy after years of chronic RV pacing. In this prospective observational study of 284 consecutive patients, cardiac resynchronization therapy was performed in 194 patients (68%) with a native LBBB and in 90 patients (32%) with a pacing-induced LBBB after chronic RV pacing (upgraded group). Echocardiographic and clinical parameters were evaluated in both groups at baseline and during 2 years of follow-up. The clinical response was defined as survival with improvement of > or =1 in the New York Heart Association class without heart failure hospitalization. Reverse LV remodeling was defined as LV end-systolic volume reduction of > or =15%. At baseline, the New York Heart Association class, quality of life, and exercise capacity were comparable but the LV ejection fraction was significant greater and the LV volumes were significant smaller in the upgraded group. Changes with time in the clinical parameters, echocardiographic parameters, and clinical response were not significantly different between the 2 groups. Reverse LV remodeling was observed in 86% in the upgraded group versus 78% of the native LBBB group after 1 year (p = 0.39). Survival was not significantly different between the 2 groups. In conclusion, comparable clinical and echocardiographic improvement was seen when resynchronization therapy was applied in patients with preceding chronic RV pacing compared with patients with a native LBBB.

Pressure-volume loop analysis during implantation of biventricular pacemaker/cardiac resynchronization therapy device to optimize right and left ventricular pacing sites.

AIMS: To evaluate the clinical utility of pressure-volume loop analyses during pacemaker/implantable cardioverter defibrillator (ICD) implantations to assess the optimal right ventricular (RV) and/or left ventricular (LV) lead position. METHODS AND RESULTS: 29 patients with heart failure and chronic RV apical pacing were studied. Stroke work (SW), LV ejection fraction (LVEF), cardiac output (CO), and LV dP/dt(max) were assessed using a conductance catheter in the LV during RV apical, RV outflow tract, single-site LV, and biventricular pacing at different left-sided pacing locations. Left ventricular ejection fraction was 34.3 +/- 9.8%. Compared with baseline, RV outflow tract pacing showed a small increase of 4.0 +/- 6.4% in LV dP/dt(max) and no improvement in SW, LVEF, or CO. In the optimal biventricular configuration, SW increased 39 +/- 41%, LVEF increased 22 +/- 13%, CO increased 16 +/- 16%, and LV dP/dt(max) increased 10 +/- 11% (all P < 0.05). In 45% of the patients, the optimal LV lead position was found at a different location as the 'first choice' postero-lateral or lateral target vein. CONCLUSION: Pressure-volume loop analysis during pacemaker/ICD implantations facilitates to determine the optimal LV pacing site. Patients with chronic RV pacing showed a significant acute improvement in LV function when LV pacing or biventricular pacing is applied.

Intermediate to long-term results of radiofrequency modified Maze procedure as an adjunct to open-heart surgery.

BACKGROUND: Of patients scheduled for elective open heart surgery, a substantial number of patients have preoperative atrial fibrillation (AF). The cut-and-sew Maze procedure and variant Maze procedures abolish AF in 45% to 95% during short- to intermediate-term follow-up. Limited data are available about maintenance of sinus rhythm during intermediate- to long-term follow-up. The objective of the present study was to assess the association between postoperative rhythm and mortality and stroke. METHODS: From November 1995 to November 2003, 258 patients with structural heart disease and permanent AF with a duration of longer than 12 months were scheduled for elective cardiac surgery and included in a registry. They underwent a radiofrequency modified Maze procedure as an adjunct to the open heart operation. Patients were followed in the outpatient clinic, and follow-up data were obtained from medical correspondence of attending physicians. For this paper, follow-up ended November 2006; however, patients are being followed in an ongoing registry. RESULTS: Two hundred fifty-eight patients (mean age, 68.1 +/- 9.5 years) with permanent AF underwent cardiac surgical procedures and concomitant radiofrequency Maze surgery; 213 patients (82.5%) underwent more than one procedure. Mean duration of permanent AF was 66.6 +/- 69.8 months (range, 16 to 96). Preoperatively, 82.9% of patients were in New York Heart Association class III. In-hospital mortality was 3.9% (10 patients), and during a mean follow-up of 43.7 +/- 25.9 months (range, 27 to 114), 73 patients (28.3%) died. Left ventricular ejection fraction was normal in 44.6%, moderately decreased in 42.5%, and poor in 12.9% of patients. Sustained sinus rhythm, including atrial rhythm or an atrial-based paced rhythm was present in 69% of patients at 1 year, in 56% at 3 years, in 52% at 5 years, and in 57% of patients at the latest follow-up. Antiarrhythmic drugs were used by 64% of survivors who were free of atrial fibrillation. Oral anticoagulation therapy was taken by 99% of patients. Stroke was reported in 4 patients (1.6%). CONCLUSIONS: The RF modified Maze procedure abolishes AF in the majority of patients with structural heart disease and longstanding permanent AF. Postoperative rhythm was not predictive of all-cause mortality, cardiac mortality, and stroke, neither in the whole group nor in the subgroups defined by preoperative left ventricular ejection fraction and New York Heart Association class. The stroke rate was very low in this group with longstanding AF.

Predictive factors of sustained sinus rhythm and recurrent atrial fibrillation after a radiofrequency modified Maze procedure.

BACKGROUND: Preoperative atrial fibrillation (AF) in patients scheduled for elective open-heart surgery is a well-known phenomenon. The cut and sew Maze procedure or variant Maze procedures abolish AF in 45-95% of patients during short- to intermediate-term follow-up. We determined preoperative and postoperative factors predictive of sustained sinus rhythm (SR) and recurrent AF in an elderly cohort of patients with structural heart disease who underwent cardiac surgery. PATIENTS AND METHODS: From November 1995 to November 2003, 285 patients with structural heart disease and permanent AF were scheduled for elective cardiac surgery. All patients underwent a radiofrequency (RF) modified Maze procedure as an adjunct to the open-heart operation. Patients were followed in the outpatient clinic or follow-up data were obtained from attending doctors. Patients are being followed in an ongoing registry; however for the patients who are the subject of this paper follow-up ended November 2006. Preoperative factors predicting recurrent AF postoperatively were assessed, as were factors associated with sustained SR. RESULTS: Two hundred and eighty-five patients (mean age 68.0+/-9.6 years) underwent a total of 655 open-heart procedures and concomitant RF Maze surgery. In-hospital mortality was 4.6% (13 patients). Mean and median duration of AF were 60.9+/-68.7 months and 26 months (range 6-396), respectively. Median follow-up was 36.5 months (range 27-114 months). Sustained SR, including atrial rhythm or an atrial-based paced rhythm was present in 59% of patients at 1 year, in 54.4% at 3 years, in 53.4% at 5 years and in 57.1% of patients at the latest follow-up. Stroke was reported in six patients (2.1%). Factors predictive of postoperative AF recurrence were duration of permanent AF, preoperative atrial fibrillation wave and preoperative left atrial (LA) size. Postoperative angiotensin converting enzyme (ACE) inhibitor therapy was associated with SR during follow-up. LA size decreased during follow-up in patients with sustained SR, whereas LA size increased in case of recurrent AF. CONCLUSIONS: In this group of elderly patients with permanent AF in the setting of structural heart disease who underwent cardiac surgery and a RF Maze procedure as a concomitant procedure, the duration of AF, preoperative atrial fibrillation wave and preoperative LA size were predictive of recurrent AF, whereas left ventricular ejection fraction, left ventricular diameters and invasive hemodynamic parameters were not. Postoperative ACE inhibitor therapy was associated with sustained SR. Furthermore, sustained SR after RF Maze surgery was associated with decreased LA dimensions.

Clinical response of cardiac resynchronization therapy in the elderly.

BACKGROUND: Although prevalence of heart failure increases with age, in most clinical trials of cardiac resynchronization therapy (CRT), older patients are not included. Observational studies of effects of CRT in older patients had a small sample size. In the present study, the clinical and echocardiographic response to CRT in a larger group of elderly (age > 75 years) patients was evaluated. METHODS: In this prospective observational study of 266 consecutive patients, CRT was performed in 107 elderly patients (40%) and 159 (60%) younger patients (age < or = 75 years). Echocardiographic and clinical parameters were evaluated at baseline and at 3, 12, and 24 months. RESULTS: In the elderly group, mean age was 79 years compared with 67 years in patients aged < or = 75 years. Clinical baseline characteristics between the 2 groups were comparable. During follow-up, there was a comparable and sustained improvement in both groups according to New York Heart Association (NYHA) class, quality of life score, and left ventricular (LV) ejection fraction. Clinical response, defined as survival with improvement (> or = 1 score) of NYHA class without hospital admittance for heart failure, was seen in 67% and 69% (group aged < or = 75 years) versus 65% and 60% (group aged > 75 years) after 3 months and 1 year, respectively. Reverse LV remodeling defined as LV end-systolic volume reduction > or = 10% was seen in 79% and 87% (group aged < or = 75 years) versus 71% and 79% (group aged > 75 years) after 3 months and 1 year, respectively. Hospitalization for heart failure decreased significantly in both groups in the year after CRT. A subgroup analysis of 39 octogenarians (> 80 years) also showed a significant improvement in NYHA class and LV ejection fraction in this subgroup. Also, LV reverse remodeling occurred in a similar extent (75% and 84%) after 3 months and 1 year, respectively. CONCLUSIONS: This study shows a clinical and echocardiographic improvement of CRT in patients aged > 75 years and even so in octogenarians.

Comparison of usefulness of cardiac resynchronization therapy in patients with atrial fibrillation and heart failure versus patients with sinus rhythm and heart failure.

The prevalence of atrial fibrillation (AF) in patients with heart failure is high, but data about the effects of cardiac resynchronization therapy (CRT) in patients with chronic AF are scarce. In this prospective observational study of 263 consecutive patients, CRT was performed in 96 patients (37%) with chronic AF and 167 patients (63%) with sinus rhythm (SR). Echocardiographic and clinical parameters were evaluated at baseline and 3 and 12 months. Reverse left ventricular (LV) remodeling is defined as LV end-systolic volume decrease > or =10%. Hospitalization rates for heart failure in the year before and after implantation were compared. Baseline characteristics between patients with and without AF were similar, but the AF group had smaller LV end-systolic and end-diastolic volumes and larger left atrial dimensions. New York Heart Association class, 6-minute walking distance, quality-of-life score, LV ejection fraction, and mitral regurgitation improved significantly at 3 and 12 months in both groups, and the changes were similar. Reverse LV remodeling after 3 and 12 months was 74% and 82% (AF group) versus 77% and 83%, respectively (SR group, p = 0.79). After 1 year, cardioversion had occurred in 25% of patients with AF. In the year after implantation, significant decreases in hospitalizations for heart failure in both groups (84% and 90%) were documented. Long-term mortality was almost equal in both groups. In conclusion, this large-scale study shows that the benefit of CRT in patients with chronic AF and heart failure is similar to that in patients with SR. Patients with chronic AF and heart failure should be considered candidates for CRT.

Successful radiofrequency ablation in patients with previous atrial fibrillation results in a significant decrease in left atrial size.

BACKGROUND: The objective of the present study was to evaluate the relation between freedom from atrial fibrillation (AF) and left atrial (LA) size in patients who underwent circumferential pulmonary vein (PV) isolation and LA ablation. METHODS AND RESULTS: One hundred five consecutive patients with symptomatic and drug-refractory paroxysmal or persistent AF were included in the present study. The mean age was 52+/-9.5 years (range, 27 to 75 years); 74 patients (70%) were male. Paroxysmal AF was present in 52 (49.5%) and persistent AF in 53 (50.5%) patients. Mean AF duration was 6.0+/-5.1 years in the paroxysmal AF group and 7.6+/-6.0 years in the persistent AF group. A 3D electroanatomic map of the LA including the PV ostia was constructed with a nonfluoroscopic navigation system (Carto, Biosense Webster). Left- and right-sided PVs were encircled by continuous radiofrequency ablation lines. We performed 128 ablation procedures in 105 patients, ie, 23 redo procedures. The mean long-term follow-up duration was 14.6+/-4.9 months (range, 6 to 24 months). Sinus rhythm was present in 45 patients (86.5%) in the paroxysmal AF group and in 41 patients (77.3%) in the persistent AF group at the latest follow-up. Six months after ablation, LA dimension in the persistent AF subjects who remained in sinus rhythm decreased from 44.0+/-5.8 to 40+/-4.5 mm (range, 31 to 51 mm). In contrast, in patients with recurrences of AF, LA dimension increased from 45+/-6.5 to 49+/-5.4 mm (range, 32 to 59 mm). In the successfully treated paroxysmal AF group, LA dimension decreased from 40.5+/-4.4 to 37.5+/-3.5 mm (P<0.01). CONCLUSIONS: In radiofrequency ablation of AF using an electroanatomic approach, there is a statistically significant relationship between medium-term procedural success and LA size: persistent sinus rhythm is associated with reduced and recurrent AF with increased LA dimensions.

Magnesium in addition to sotalol does not influence the incidence of postoperative atrial tachyarrhythmias after coronary artery bypass surgery.

OBJECTIVE: Postoperative atrial tachyarrhythmias (POATs) after coronary artery bypass grafting (CABG) are reported in 11% to 40% of patients. Several etiologic factors are mentioned. Prophylactic intervention with sotalol is reported to reduce the incidence of POAT. The authors studied the effect of magnesium chloride (MgCl2) in addition to sotalol in the prevention of POAT. DESIGN: Prospective, randomized, double-blinded, placebo-controlled trial. SETTING: Single center. PARTICIPANTS AND INTERVENTIONS: After institutional approval and written informed consent, patients undergoing CABG with use of cardiopulmonary bypass were included in a prospective, randomized, placebo-controlled double-blind study. In 74 patients, intravenous MgCl2, 50 mmol/24 hours, was continuously administered after the induction of anesthesia during 36 hours; 73 patients received placebo. In both groups, sotalol orally was started 16 to 24 hours after CABG. The incidence and duration of in-hospital POAT were evaluated. MEASUREMENTS AND MAIN RESULTS: A total of 147 patients could be evaluated: in the magnesium-treated group (n = 74), 25 patients developed POAT (34%) and in the placebo group (n = 73) 19 patients (26%) (p = 0.36). There was no statistically significant difference in duration of POAT between the groups. In the magnesium-treated group, 9 patients experienced serious bradyarrhythmias (12%), and in the placebo group no serious bradyarrhythmias were observed (p = 0.003). There was no mortality in either group. CONCLUSIONS: These results show that MgCl(2), in addition to sotalol, is not more effective than sotalol alone in the prevention of tachyarrhythmias after CABG. The data showed that this combination may also induce serious bradyarrhythmias.

Long-term results of irrigated radiofrequency modified maze procedure in 200 patients with concomitant cardiac surgery: six years experience.

BACKGROUND: The Cox maze procedure is considered an effective surgical treatment of atrial fibrillation in patients with and without organic heart disease. Radiofrequency energy offers an alternative to the complex surgical maze procedure. We used the radiofrequency modified maze III procedure in patients with atrial fibrillation undergoing elective concomitant cardiac surgery. This study evaluated the long-term results of the irrigated radiofrequency ablation to create linear lines of conduction block endocardially. METHODS: Between November 1995 and June 2001, 200 patients with mainly structural heart disease and chronic atrial fibrillation underwent intraoperative radiofrequency linear ablation in both atria with concomitant cardiac surgery. RESULTS: The in-hospital mortality rate was 3.5% (7 patients) and during the mean follow-up of 40 months (range, 12 to 80) 27 patients (13.5%) died. Eight patients (4%) were lost from follow-up and complete data were available in 158 survivors. Sinus or atrial rhythm was present in 116 patients (73.4%) and an atrial driven rhythm in 10 patients (6.3%) with an atrioventricular pacemaker. Atrial fibrillation or flutter was documented in 32 patients (20.3%). Antiarrhythmic drugs were used in 49% of survivors who were free of atrial fibrillation or flutter. CONCLUSIONS: Intraoperative radiofrequency endocardial ablation is an effective technique to eliminate atrial fibrillation with promising long-term results.

New strategies in the surgical treatment of atrial fibrillation.

In patients with longstanding atrial fibrillation surgical correction of the underlying cardiac abnormality alone will not abolish the arrhythmia. The Cox's Maze III has proven to be an effective treatment for atrial fibrillation but because of its complexity cardiac surgeons are reluctant to expose their patients to the potential risks of this procedure. Attempts have been made to simplify the Cox's Maze III procedure by using alternative energy sources and modifying the pattern of atrial lines of conduction block. In patients with atrial fibrillation without structural heart disease Maze surgery may be an option as an ultimate therapeutic alternative when atrial fibrillation is drug resistant and very symptomatic. The objective of this article is to outline the different surgical procedures that have formerly been used in the treatment of atrial fibrillation and to give an overview of new and evolving techniques.

Multisite atrial pacing for atrial fibrillation prevention: where to go from here?

Atrial fibrillation (AF) is a common arrhythmia associated with stroke, increased mortality and with a negative impact on quality of life. Pharmacologic treatments for AF have not provided long-term relief from arrhythmia recurrence. Multi-site atrial pacing was introduced by Daubert and colleagues about 10 years ago for the treatment of severe atrial conduction delays in patients with sick sinus syndrome. They found that this type of atrial stimulation reduced or prevented AF. Multi-site atrial pacing results in reduction of intra-atrial and interatrial conduction differences and diminishes heterogeneity of refractoriness, i.e. atrial resynchronization. Acute electrophysiological studies have shown that biatrial stimulation reduced AF inducibility. The Dutch Dual-site Right Atrial Pacing for Prevention of Atrial Fibrillation study was a prospective randomized crossover trial comparing the recurrences of AF in dual-site right atrial and single-site high right atrial pacing in patients with symptomatic medically refractory AF, without or with minimal structural heart disease. Patients were randomized to initial dual-site pacing (Group I n = 18) or initial single-site (Group II n = 22) pacing. After 6 months or after a study endpoint was reached patients were crossed over to the other pacing modality.Although, the arrhythmia free intervals were longer for dual-site pacing during both treatments periods (Group I 162 +/- 12 and Group II 114 +/- 15 days) compared to single-site pacing (Group I 143 +/- 16 and Group II 97 +/- 10 days) the difference was not statistically significant (p = 0.061). However, the sequence of the randomized treatment periods had a significant effect on outcome (p < 0.02). Event free intervals (AF > 48 hours requiring electrical cardioversion) were longer during dual-site pacing in both groups compared to single-site stimulation but the difference was statistically not significant (p = 0.055) because of treatment interaction (P < 0.05). To establish the clinical benefits of multi-site pacing for the treatment of patients with medically refractory symptomatic AF, additional prospective randomized studies are needed. Trials with a parallel design are necessary to avoid carry-over effects of different stimulation protocols.