The management of atrial fibrillation (AF) remains problematic. While a significant array of individual pharmacologic and non-pharmacologic therapies have been evaluated for rhythm control, recurrence of AF is common with virtually all monotherapies. Antiarrhythmic drugs have had modest long-term results in AF prevention. These agents were associated with an increased rate of cardiovascular hospitalizations compared to rate control in the AFFIRM trial.1 Recent reports note the very modest long-term efficacy of a single catheter ablation procedure in prevention of recurrent AF.2,3 Furthermore, these procedures are generally unsuitable for patients with advanced heart disease, the elderly, and may have increased risks in women. Single site right atrial overdrive pacing showed no improvement in prevention of symptomatic AF recurrences in drug refractory patients.4,5
An ablate and pace rate control strategy has been widely advocated formanagement of persistent and permanent AF.6,7 However, this approach has several disadvantages. It results in pacemaker dependency. The strategy does not improve the AF substrate itself and could even promote progression to permanent AF due to loss of AV synchrony. In our center, efforts have focused on a novel “hybrid therapy” approach to improve efficacy and reduce risks associated with a rhythm control strategy. The strategy has several potential benefits in its rationale, as shown in Table 1.
Early clinical experiences demonstrate reduction in CV hospitalizations, improved efficacy in AF suppression documented by full disclosure pacemaker datalogs. In our initial clinical trial experience, the hybrid strategy of “pace and ablate” was associated with a significant reduction in AF-related hospitalizations and need for cardioversion therapy.
Hybrid therapy of AF employing right atrial linear ablation for compartmentalization and dual site RA pacing is useful in patients with drug refractory persistent or recurrent paroxysmal atrial fibrillation and bradycardia (both primary and drug induced). Bradycardia-tachycardia syndrome has been reported in over 25% of patients with sick sinus syndrome or implanted pacemakers. Sinus node dysfunction is observed in over one-third of patients with persistent AF. We have also employed this method with similar success in patients without bradycardias, reflecting increasing evidence that these antiarrhythmic effects are unrelated to bradycardia prevention.
AF is primarily a disease of the elderly, and this approach is well suited for this majority of the AF population. Elderly patients and those with refractory AF have an increased risk of complications from left atrial ablation and anticoagulation, and could be ideal candidates for hybrid therapy. Female patients are also at increased risk of complications from ablation.8 The detailed selection of patients for the hybrid strategy is shown in Figure 1.
Technique of “Ablate and Pace” for Rhythm Control
Right atrial compartmentalization with a MAZE procedure (Figures 2A, 2B and 2C). Multipolar electrode catheters are placed in the right atrium (RA), at the His bundle, and coronary sinus. We use an endocardial balloon catheter electrode (EnSite, St. Jude Medical, St. Paul, MN) to perform mapping, catheter navigation and to validate right atrial compartmentalization. Initially it is introduced into the RA and a three-dimensional contour in the RA is created. Beat-to-beat analysis of spontaneous atrial premature beats, onset arrhythmias and sustained AF can also be performed. Linear lesions are created using the navigation capabilities of the system from the superior to inferior vena cava along the lateral right atrium (inter-caval line), inferior vena cava to tricuspid valve annulus and coronary sinus (isthmus line), and a coronary sinus to fossa ovalis to superior vena cava orifice (septal line). The lesion set produces two atrial compartments, an anterior atrial chamber and a posterior atrial chamber. Linear lesion and compartment integrity is confirmed by pacing in each compartment and on each side of each line and evaluating wavefront propagation on non-contact mapping (Figures 3A–3C).
Atrial resynchronization pacing using dual site right atrial pacing. Standard techniques for insertion of a dual-chamber pacemaker system and right ventricular pacing are used. For dual right atrial pacing, active fixation leads are preferred, especially at the coronary sinus ostium. The first atrial pacing electrode is positioned using a curved stilette with primary and secondary curvatures. Initially, the lead is passed into the coronary sinus ostium under fluoroscopy and the lead position verified by sensed electrograms and paced electrocardiographic (EGG) configuration. The lead is withdrawn to the coronary sinus ostium, and a secondary tip curvature of the stilette is used to lodge it at the rim of the ostium, generally inferior and posterior to the ostium. The lead is fixed at this site, and pacing and sensing thresholds are obtained. Paced P wave configuration is consistent with ostial pacing in this location (inverted P waves in leads II, III and aVF with a shorter PR interval than sinus rhythm). The second atrial lead is then passed and fixed in the anterior compartment in the high right atrium, usually in the right atrial appendage under fluoroscopic control. In postoperative surgical patients with an amputated appendage, it is fixed in the high lateral right atrium. Bipolar pacing thresholds are obtained for both leads. The two atrial lead tip electrodes are cross connected to form a bipole using a Y connector with the high right atrial lead as the cathodal electrode and the coronary sinus lead as the anodal electrode. The in-line bipolar lead from the Y connector is inserted into the atrial port of the pacemaker. The pulse generator is then placed in a prepectoral pocket and the pocket is closed using standard techniques. The fluoroscopic image (Figure 4A) shows the anterior and posterior orientation of the two electrodes. Atrial resynchronization has been demonstrated by tissue Doppler studies (Figure 4B).
In our early clinical experience, 47 patients (66 ± 10 years) with symptomatic persistent (N=26) or permanent (N=21) AF underwent “hybrid therapy” and were followed for 24 ± 15 months. All patients underwent linear right atrial ablation and implantation of pacemaker with previously ineffective antiarrhythmic drug therapy for AF prevention. Device datalogs were used to monitor AF recurrences. Freedom from permanent AF was 97, 90, and 83% at 6 months, 2 and 3 years, respectively. Sixteen patients (34%) had no recurrent AF after “hybrid therapy.” Thirty-one patients (66%) had a total of 55 AF recurrences (mean 1.8 per patient).
There was a significant reduction in the mean AF-related hospitalizations (from 3.5 ± 2.8 to 0.57 ± 1.1 per patient), cardioversion hospitalizations (from 3.5 ± 2.2 to 0.38 ± 0.5 per patient) and DC cardioversions (from 3.1 ± 3.9 to 0.7 ± 0.5 per patient) after hybrid therapy compared to event rates before therapy (p < 0.05 for all) (Figure 5). Rhythm control significantly improved with hybrid therapy in patients with persistent and permanent AF refractory to drugs and cardioversion therapy.9 This improvement is associated with a significant reduction in AF-related hospitalizations and need for cardioversion therapy. A recent review also confirmed the efficacy of hybrid therapy with right atrial ablation, AAD with cardioversion, and pacing in reducing atrial fibrillation burden.10
We are also currently undertaking a pilot multicenter clinical trial, the Hybrid Therapy In Prevention of Atrial Fibrillation (HIPPAF) study, in patients with persistent AF to expand the clinical investigation of this approach. We hope to provide a large majority of the AF population, especially the elderly and those with concomitant bradycardias and/or heart failure, with another therapeuticstrategy to achieve effective rhythm control.
- Slee A, Saksena S. Impact of a Composite Outcome Analysis (CV Hospitalization and Mortality) in Evaluating Atrial Fibrillation Treatment Strategies: A reassessment of the AFFIRM study. Poster presentation at the American Heart Association in Orlando, USA, November 2009.
- Cheema A, Vasamreddy CR, Dalal D, et al. Long-term single procedure efficacy of catheter ablation of atrial fibrillation. J Interv Card Electrophysiol 2006;15:145–155.
- Weerasooriya R, Khairy P, Litalien J, et al. Catheter ablation for atrial fibrillation: are results maintained at 5 years of follow-up? J Am Coll Cardiol 2011;57:160–166.
- Saksena S, Prakash A, Ziegler P, et al. Improved suppression of recurrent atrial fibrillation with dual-site right atrial pacing and antiarrhythmic drug therapy. J Am Coll Cardiol 2002;40:1140–1150.
- Padeletti L, Purerfellner H, Adler SW, et al. Combined efficacy of atrial septal lead placement and atrial pacing algorithms for prevention of paroxysmal atrial tachyarrhythmia. J Cardiovasc Electrophysiol 2003;14:1189–1195.
- Brignole M, Menozzi C, Gianfranchi L, et al. Assessment of atrioventricular junction ablation and VVIR pacemaker versus pharmacological treatment in patients with heart failure and chronic atrial fibrillation: A randomized, controlled study. Circulation 1998;98:953–960.
- Khan MN, Jaïs P, Cummings J, et al., PABA-CHF Investigators. Pulmonary-vein isolation for atrial fibrillation in patients with heart failure. N Engl J Med 2008;359:1778–1785.
- Spragg DD, Dalal D, Cheema A, et al. Complications of catheter ablation for atrial fibrillation: Incidence and predictors. J Cardiovasc Electrophysiol 2008;19:627–631.
- Rao H, Saksena S. Impact of “hybrid therapy” on long-term rhythm control and arrhythmia related hospitalizations in patients with drug-refractory persistent and permanent atrial fibrillation. J Interv Card Electrophysiol 2007;18:127–136.
- Chakravarthy S, Chatterjee S. Efficacy of hybrid therapy in the form of right atrial ablation and adjunctive therapy in refractory atrial fibrillation in symptomatic patients. Am J Ther 2010 Aug 17. (Epub ahead of print).