Submit Manuscript    >>    Login | Register

Role of atrio-ventricular junction ablation in symptomatic atrial fibrillation for optimization of cardiac resynchronization therapy




Role of Atrio-Ventricular Junction Ablation in Symptomatic Atrial Fibrillation for Optimization of Cardiac Resynchronization Therapy
Paul J. Garabelli, MD, Stavros Stavrakis, MD, PhD
Department of Medicine, Cardiovascular Section, University of Oklahoma Health Sciences Center, Oklahoma City, OK

Abstract
Cardiac resynchronization (CRT) therapy is indicated in patients with at least mildly symptomatic heart failure, left ventricular ejection fraction ≤35% and wide QRS, and has been associated with decreased morbidity and mortality. Unfortunately, approximately 30% of the patients appropriately selected for therapy do not respond to CRT. Among the reasons for non-response, atrial fibrillation (AF) plays a prominent role. AF limits the degree of biventricular pacing during CRT, not only when the ventricular rate is fast and highly irregular, but also during periods of of relatively constant rate, by causing fusion and pseudo-fusion complexes. Importantly, achievement of nearly 100% biventricular pacing is necessary to derive benefit from CRT. A simple, albeit irreversible, method to maximize biventricular pacing in patients with AF who are otherwise eligible for CRT is atrioventricular junction (AVJ) ablation. In this review, we discuss the role of AVJ ablation in CRT optimization in patients with AF. The available evidence from observational non-randomized studies suggests that AVJ ablation in patients with AF qualifying for CRT may offer improvement in heart failure symptoms, better survival, and better cardiac function. In light of the inherent limitations of non-randomized studies, further randomized studies are needed to support this treatment option.

Corresponding Address : Stavros Stavrakis, MD, PhD, University of Oklahoma Health Sciences Center, 1200 Everett Dr 6E103, Oklahoma City, OK 73104.

Introduction
Heart failure (HF) is a significant cause of mortality and morbidity in the United States. In 2010, the estimated prevalence in adults over 18 years of age was 2.8%, and by 2030 the prevalence is projected to grow by 25% 1 While optimal pharmacologic therapy has been shown to reduce HF symptoms and mortality, many patients still remain symptomatic and need additional interventions.2 In patients with at least mildly symptomatic HF (New York Heart Association [NYHA] class II to IV), left ventricular (LV) ejection fraction ≤35%, wide QRS with a left bundle branch block (LBBB) morphology and sinus rhythm, cardiac resynchronization therapy (CRT) is indicated3 CRT has been shown to improve functional status, increase exercise capacity, decrease hospitalizations, and reduce mortality in HF patients that meet implant criteria. 4-8
Unfortunately, about 30% of patients who are appropriately selected for therapy, do not respond to CRT.9 Several predictors of non-response havebeen identified, including male gender, ischemic cardiomyopathy, QRS duration <150ms and non-LBBB pattern.10-13 Other studies have identified apical LV lead position,14 presence of lateral LV scar15 and impaired renal function16 as reasons for a lack of response to CRT. Atrial fibrillation (AF) is another possible cause of poor response to CRT,17as patients with AF do not derive as large a benefit as patients with sinus rhythm do. This is unfortunate for several reasons. First, at least 25% of patients eligible for CRT have AF.18,19 Furthermore, since HF and AF share similar risk factors, about 40% of patients with AF or HF will develop the other condition 1, and the prevalence of AF is related to worsening NYHA class.18 The lack of a definitive benefit of CRT in patients with AF is reflected in the current ACCF/AHA/HRS guidelines, which require the presence of sinus rhythm for a class I indication.3
Atrial Fibrillation and CRT Response
Achievement of nearly 100% biventricular pacing has been the holy grail of CRT. In a study of more than 36,000 patients (most of whom were in sinus rhythm) who underwent CRT implantation and were enrolled in a remote monitoring program, there was a direct relationship between the percentage of biventricular pacing and mortality, with incremental increases in mortality benefit observed with an increasing percentage of biventricular pacing, whereas AF limited the degree of biventricular pacing.20 In another study, the presence of atrial arrhythmias was associated with a less-than-optimal degree of biventricular pacing, which in turn limits the efficacy of CRT.21 AF limits the degree of biventricular pacing, not only when the rate is fast and highly irregular, but also during periods of relatively constant rate, by causing fusion and pseudo-fusion complexes.22 While slower ventricular rates help increase the degree of biventricular pacing, even modest increases in ventricular rates have been shown to reduce the benefit of CRT.23 Moreover, the absence of regular, organized atrial activity, and the loss of atrioventricular synchrony in the presence of AF, may adversely influence the response to CRT.17,23
Most of the randomized controlled CRT trials included only patients with sinus rhythm.3 Therefore, evidence for the benefit of CRT in patients with AF has been derived from mostly observational studies,24-32 whereas only two randomized controlled trials included patients with AF.5,33 An acute hemodynamic study of biventricular pacing in patients with HF and LBBB, in either sinus rhythm or AF, revealed a similar degree of improvement in pulmonary capillary wedge pressure, V-wave amplitude and systolic blood pressure in both groups, suggesting that biventricular pacing may be beneficial in patients with HF regardless of whether or not they are in sinus rhythm.34 A few small preliminary studies indicated that CRT may improve symptoms and exercise tolerance 35,36 and induce reverse LV remodeling 36 at 1 year in patients with HF and wide QRS, regardless of the presence of AF. However, despite aggressive rate control to ensure adequate biventricular pacing, reverse LV remodeling was less prominent in the AF group in the latter study,36 whereas in the former study, atrioventricular junction (AVJ) ablation was performed systematically in all patients with AF, in order to achieve complete and permanent biventricular pacing 35. Of note, AF was associated with an increased risk of death at follow-up in both studies .35,36
In the first randomized controlled trial to include patients with AF, the Multisite Stimulation in Cardiomyopathy (MUSTIC) study, the benefit of CRT in surrogate markers, including exercise tolerance, peak oxygen uptake, quality of life and NYHA class was observed equally in the AF and sinus rhythm groups at 12 months follow up.33 However this study did not offer definitive evidence as the sample size was small and it was not powered to examine differences between subgroups. In a pre-specified secondary analysis of the Resynchronization/Defibrillation for Ambulatory Heart Failure Trial (RAFT), the effect of CRT was examined in a subgroup of patients with permanent atrial fibrillation who received either an implantable cardioverter defibrillator (ICD) or CRT-ICD. In this analysis, there was no clear improvement in any clinical or surrogate outcome in the CRT-ICD group compared to the ICD group. AF was associated with a higher risk of death, but there was a trend towards reduced HF hospitalizations in the CRT-ICD group.37 However, the trial was underpowered to detect moderate treatment effect differences, and only one third of patients received more than 95% biventricular pacing, suggesting that the effect of CRT was not maximized.
To summarize the available evidence on the efficacy of CRT in patients with AF compared to those in SR, Wilton et al.38 conducted a meta-analysis on 23 observational studies, including 7,495 CRT recipients (25.5% with AF). In five of the included studies, clinical response was defined as improvement in one functional class and survival over 6 to 12 months. The remainder of the studies used a 10% improvement in 6-minute walk distance or a 15% improvement in quality of life score. Patients with AF had a significantly higher risk of non-response to CRT and all-cause mortality compared to those in sinus rhythm.38 Likewise, AF was associated with an attenuated improvement in 6 minute walk distance, quality of life and LV end-systolic volume. Importantly, among patients with AF, AVJ ablation was associated with a lower risk of CRT non-response, as well as improved survival. In another meta-analysis of prospective cohort studies, Upadhyay et al.39 examined the differential impact of CRT for patients in AF and sinus rhythm. Five studies met their inclusion criteria, four of which were prospective cohort studies and one was a subgroup of a randomized clinical trial. The use of AVJ ablation in this meta-analysis varied from 22% 24 to 100%.35 Only two of the studies mentioned biventricular capture rates. Specifically, Gasparini et al.28 reported a 75% biventricular capture rate and Molhoek et al.31 reported 82% capture rate. They concluded that while patients with AF derive benefit from CRT, they have smaller functional improvements compared to thise in sinus rhythm. Specifically, while both groups had improvement in the 6-minute walk test, those in sinus rhythm patients walked 11.6 m farther on average. Similarly, both groups showed improvement in the quality of life as measured by the Minnesota Living with HF questionnaire, but those in in sinus rhythm showed more relative improvement. In summary, the presence of AF is associated with an attenuated response to CRT, in part because of the inability to achieve almost complete biventricular pacing. A simple, albeit irreversible, method to maximize biventricular pacing is AVJ ablation.
AVJ Ablation to Maximize CRT Response In Patients with AF
The importance of biventricular capture in patients with CRT cannot be overstated. Current evidence suggests that a high degree of biventricular pacing is necessary in order to derive benefit from CRT.Analysis of the LATITUDE remote monitoring network ,which followed more than 36,000 CRT patients, showed a 27% reduction in mortality compared to all other groups when biventricular pacing was achieved in excess of 98%.20 Most of these patients, however, were predominantly in sinus rhythm. In a subgroup analysis of patients with atrial arrhythmias from the RENEWAL and REFLEX trials, those with biventricular pacing percentages more than 92% had a reduced hazard ratio of heart failure events compared to those with less than 92% biventricular pacing.21
As described above, fast and irregular AF poses a significant challenge to achieving effective CRT by reducing the degree of biventricular pacing. Another challenge, which is often overlooked, arises when the percentage of biventricular pacing taken directly from the device counter does not accurately represent effective CRT. Kamath et al.40 placed Holter monitors on AF patients with CRT devices. In this analysis, a high percentage of pseudo-fusion and fusion beats in patients with AF were seen that the device counters labeled as biventricular paced beats. These beats likely do not deliver the true mechanical benefit of a biventricular paced beat, which further advocates for more complete resynchronization in AF patients with CRT.
AVJ ablation was reported as a successful procedure with a low incidence of complications in 1991 by Yeun-Lai-Wah et al. 41 for the treatment of supraventricular tachycardias, around the same time that radiofrequency catheter ablation started to be used for mapping and ablation of Wolff-Parkinson-White syndrome.42 AVJ ablation continues to be used for the maintenance of appropriate ventricular rate control in AF patients, but usually only as a final option,43-45 mostly because of the irreversible nature of the procedure and the possible long-term consequences. Inappropriate ICD therapies may not be resolved completely after AVJ ablation, but since inappropriate therapies compose about 30% of all ICD interventions, this secondary benefit may have more long term quality of life improvements.46
A recent meta-analysis by Ganesan et al.47 systematically examined the role of AVJ ablation inpatients with coexistent AF and HF undergoing CRT. Six observational non-randomized cohort studies, including 768 patients (339 patients who underwent AVJ ablation and 429 who received medical therapy aimed at rate control alone) were included in the analysis. AVJ ablation was associated with a significant reduction in all-cause and cardiovascular mortality, as well as improvement in NYHA Class when compared to medical management alone.47 In another meta-analysis, Wilton et al. reviewed five studies comparing CRT outcomes by use of AVJ ablation in AF patients with HF, low LV ejection fraction (<35%) and wide QRS (>120ms). In these studies, patients were selected for AVJ ablation based on inability to achieve at least 85% to 90% biventricular pacing, while the timing of AVJ ablation varied from either before or after CRT implantation. AVJ ablation was associated with a lower risk of CRT non-response. Moreover, improved survival with AVJ ablation was seen in two studies, independent of other factors .38
Notwithstanding the limitations of non-randomized trials, these analyses suggest that AVJ ablation is associated with improved outcomes in patients with AF who otherwise meet criteria for CRT. Further randomized trials are warranted to confirm these findings. Importantly, the degree of biventricular pacing in the two groups should be systematically assessed and correlated with clinical outcomes in a pre-specified analysis. Evidence from non-randomized trials supports the notion that the benefit of CRT may be equal in patients with sinus rhythm and those with AF who undergo AVJ ablation. Tolosana et al.19 performed an observational prospective multicenter study in 202 patients who received CRT for symptomatic heart failure despite optimal drug therapy, LV ejection fraction less than 35%, and a QRS duration more than 120ms. Patients were grouped according to their intrinsic rhythm. If biventricular pacing was ≤85% in the first 2 months, AVJ ablation was recommended for patients in AF. In the group of patients with AF, 28% required AVJ ablation after maximizing negative chronotropic drug therapy. After one year of therapy, the percentage of biventricular pacing was similar in all three groups (sinus rhythm, AF, AF/AVJ ablation). , Importantly, there was no difference in the percentage of response,defined as ≥ 10% reduction in left ventricular end-systolic volume at 12 months between patients in sinus rhythm and AF. Nonetheless, the mortality was higher in patients with AF.19 These results are consistent with those of a previous trial, in whichCRT resulted in a similar benefit among patients with sinus rhythm and AF, when AVJ ablation was performed systematically in all patients in the latter group, in order to maximize biventricular pacing.35
The above information taken together seems to suggest that the benefit of AVJ ablation by maximizing effective CRT outweighs the risk of pacemaker dependency. Hopefully, continued advancements in bipolar pacing strategies will reduce this fear in patients who may benefit the most from this strategy. The importance of effective delivery of CRT in patients with AF is reflected in the current ACCF/AHA/HRS guidelines, which indicate that CRT can be useful in patients with AF and low LV ejection fraction who otherwise meet CRT criteria, only if AVJ ablation or pharmacologic rate control will allow near 100% ventricular pacing with CRT (class IIa).3
CRT Use After AVJ Ablation For Refactory AF
As previously mentioned, AVJ ablation with permanent pacing has been used in patients with symptomatic AF with difficult to control high ventricular rates. The optimal pacing modality in these patients is still a matter of debate. In this subgroup of patients, a few studies have compared RV pacing versus CRT in patients undergoing AVJ ablation for refractory AF.48-52 Some studies suggested that CRT might be more beneficial than RV pacing in such patients,48,50-52 whereas some failed to show an additional benefit of CRT beyond that conferred by rate regularization.49 Since most studies evaluated surrogate endpoints and were underpowered to evaluate major clinical endpoints, the optimal pacing modality after AVJ ablation remains unclear.
Our group performed a meta-analysis on this subject and found 5 randomized controlled trials 48-52 meeting our inclusion criteria.53 The majority of the patients included in these studies had at least mildly depressed LV ejection fraction (<45%) and 50% had a QRS duration of >120ms. Our results suggested that CRT for permanent AF after AVJ ablation may be superior to RV pacing. Specifically, CRT decreased hospitalization for heart failure and provided a favorable, albeit non-significant, trend in mortality, compared to RV pacing. Based on this meta-analysis, we hypothesized that the beneficial effect of CRT was a result of reverse LV remodeling, as indicated by the significant improvement in LV ejection fraction, LV end-systolic and end-diastolic diameters compared to RV pacing. These findings are consistent with previous studies, showing that the beneficial effects of CRT are associated with improvement of cardiac structure and function through reverse LV remodeling 54,55 Although these results are encouraging, they cannot be considered definitive. Importantly, the evidence supporting use of CRT after AVJ ablation in patients with normal LV ejection fraction is sparse, even though the benefit of CRT was seen irrespective of LV ejection fraction or NYHA class in one study.52 Therefore, a randomized clinical trial, adequately powered to detect clinical outcomes and specifically examining patients with normalLV ejection fraction, is urgently needed. Based on our calculations, a sample size of 1310 patients would need to be recruited over a 3-year period with a total study duration of 5 years (minimum of 2 years follow-up for all patients) to provide adequate power to detect a difference in mortality between the two groups.53
Conclusions
CRT is a well-studied non-pharmacologic treatment for HF, a disease that is only increasing in prevalence. Atrial fibrillation, among other factors, may have a negative impact on the clinical benefit of CRT by reducing the degree of biventricular pacing. Based on the knowledge that maximizing biventricular pacing reduces mortality, AVJ ablation may be an important treatment in this patient population. Based on the available evidence, werecommend the following algorithm for the use of AVJ ablation in patients with AF for optimization of CRT (Figure 1). In patients who otherwise meet criteria for CRT (NYHA class II to IV, LV ejection fraction ≤35%, QRS duration ≥150ms with left bundle branch morphology) ,3aggressive medical therapy to achieve rate control may be tried first. If the degree of biventricular pacing is <95% at follow-up, we recommend considering AVJ ablation to maximize the response to CRT. In patients with symptomatic AF, in whom a decision was made to perform AVJ ablation, the decision to implant a CRT device may be reserved for those who have HF with a low LV ejection fraction ≤35%. Given the uncertainty of the value of CRT in patients with normal ejection fraction and without HF, no firm recommendations can be made at this time and the decision to implant a CRT in these patients should be individualized.
Figure 1. Recommended strategy for atrioventricular junction (AVJ) ablation in patients with atrial fibrillation (AF) for optimization of cardiac resynchronization therapy (CRT) based on available evidence.



In conclusion, the available evidence from observational non-randomized studies suggests that AVJ ablation in patients with AF qualifying for CRT may offer improvement in HF symptoms, better survival, and better cardiac function. In light of the inherent limitations of non-randomized studies, further randomized studies are needed to support this treatment option.
Disclosures
No disclosures relevant to this article were made by the authors.
References
  • Roger Véronique L , Go Alan S , Lloyd-Jones Donald M , Benjamin Emelia J , Berry Jarett D , Borden William B , Bravata Dawn M , Dai Shifan , Ford Earl S , Fox Caroline S , Fullerton Heather J , Gillespie Cathleen , Hailpern Susan M , Heit John A , Howard Virginia J , Kissela Brett M , Kittner Steven J , Lackland Daniel T , Lichtman Judith H , Lisabeth Lynda D , Makuc Diane M , Marcus Gregory M , Marelli Ariane , Matchar David B , Moy Claudia S , Mozaffarian Dariush , Mussolino Michael E , Nichol Graham , Paynter Nina P , Soliman Elsayed Z , Sorlie Paul D , Sotoodehnia Nona , Turan Tanya N , Virani Salim S , Wong Nathan D , Woo Daniel , Turner Melanie B .Heart disease and stroke statistics--2012 update: a report from the American Heart Association. Circulation . 2012; 125 (1):e2–e220. [ PubMed]
  • Cleland John , Tageldien Ahmed , Khaleva Olga , Hobson Neil , Clark Andrew L .Should patients who have persistent severe symptoms receive a left ventricular assist device or cardiac resynchronization therapy as the next step? Heart Fail Clin . 2007; 3 (3):267–73. [ PubMed]
  • Tracy Cynthia M , Epstein Andrew E , Darbar Dawood , DiMarco John P , Dunbar Sandra B , Estes N A Mark , Ferguson T Bruce , Hammill Stephen C , Karasik Pamela E , Link Mark S , Marine Joseph E , Schoenfeld Mark H , Shanker Amit J , Silka Michael J , Stevenson Lynne Warner , Stevenson William G , Varosy Paul D , Ellenbogen Kenneth A , Freedman Roger A , Gettes Leonard S , Gillinov A Marc , Gregoratos Gabriel , Hayes David L , Page Richard L , Stevenson Lynne Warner , Sweeney Michael O .2012 ACCF/AHA/HRS focused update of the 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. [corrected]. Circulation . 2012; 126 (14):1784–800. [ PubMed]
  • McAlister Finlay A , Ezekowitz Justin , Hooton Nicola , Vandermeer Ben , Spooner Carol , Dryden Donna M , Page Richard L , Hlatky Mark A , Rowe Brian H .Cardiac resynchronization therapy for patients with left ventricular systolic dysfunction: a systematic review. JAMA . 2007; 297 (22):2502–14. [ PubMed]
  • Tang Anthony S L , Wells George A , Talajic Mario , Arnold Malcolm O , Sheldon Robert , Connolly Stuart , Hohnloser Stefan H , Nichol Graham , Birnie David H , Sapp John L , Yee Raymond , Healey Jeffrey S , Rouleau Jean L .Cardiac-resynchronization therapy for mild-to-moderate heart failure. N. Engl. J. Med. . 2010; 363 (25):2385–95. [ PubMed]
  • Moss Arthur J , Hall W Jackson , Cannom David S , Klein Helmut , Brown Mary W , Daubert James P , Estes N A Mark , Foster Elyse , Greenberg Henry , Higgins Steven L , Pfeffer Marc A , Solomon Scott D , Wilber David , Zareba Wojciech .Cardiac-resynchronization therapy for the prevention of heart-failure events. N. Engl. J. Med. . 2009; 361 (14):1329–38. [ PubMed]
  • Cleland John G F , Daubert Jean-Claude , Erdmann Erland , Freemantle Nick , Gras Daniel , Kappenberger Lukas , Tavazzi Luigi .The effect of cardiac resynchronization on morbidity and mortality in heart failure. N. Engl. J. Med. . 2005; 352 (15):1539–49. [ PubMed]
  • Bristow Michael R , Saxon Leslie A , Boehmer John , Krueger Steven , Kass David A , De Marco Teresa , Carson Peter , DiCarlo Lorenzo , DeMets David , White Bill G , DeVries Dale W , Feldman Arthur M .Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N. Engl. J. Med. . 2004; 350 (21):2140–50. [ PubMed]
  • Kass David A .An epidemic of dyssynchrony: but what does it mean? J. Am. Coll. Cardiol. . 2008; 51 (1):12–7. [ PubMed]
  • Goldenberg Ilan , Moss Arthur J , Hall W Jackson , Foster Elyse , Goldberger Jeffrey J , Santucci Peter , Shinn Timothy , Solomon Scott , Steinberg Jonathan S , Wilber David , Barsheshet Alon , McNitt Scott , Zareba Wojciech , Klein Helmut .Predictors of response to cardiac resynchronization therapy in the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT). Circulation . 2011; 124 (14):1527–36. [ PubMed]
  • Sipahi Ilke , Carrigan Thomas P , Rowland Douglas Y , Stambler Bruce S , Fang James C .Impact of QRS duration on clinical event reduction with cardiac resynchronization therapy: meta-analysis of randomized controlled trials. Arch. Intern. Med. . 2011; 171 (16):1454–62. [ PubMed]
  • Sipahi Ilke , Chou Josephine C , Hyden Marshall , Rowland Douglas Y , Simon Daniel I , Fang James C .Effect of QRS morphology on clinical event reduction with cardiac resynchronization therapy: meta-analysis of randomized controlled trials. Am. Heart J. . 2012; 163 (2):260–7.e3. [ PubMed]
  • Stavrakis Stavros , Lazzara Ralph , Thadani Udho .The benefit of cardiac resynchronization therapy and QRS duration: a meta-analysis. J. Cardiovasc. Electrophysiol. . 2012; 23 (2):163–8. [ PubMed]
  • Singh Jagmeet P , Klein Helmut U , Huang David T , Reek Sven , Kuniss Malte , Quesada Aurelio , Barsheshet Alon , Cannom David , Goldenberg Ilan , McNitt Scott , Daubert James P , Zareba Wojciech , Moss Arthur J .Left ventricular lead position and clinical outcome in the multicenter automatic defibrillator implantation trial-cardiac resynchronization therapy (MADIT-CRT) trial. Circulation . 2011; 123 (11):1159–66. [ PubMed]
  • Birnie David , DeKemp Rob A , Ruddy Terence D , Tang Anthony S , Guo Ann , Williams Kathryn , Wassenar Richard , Lalonde Michel , Beanlands Rob S .Effect of lateral wall scar on reverse remodeling with cardiac resynchronization therapy. Heart Rhythm . 2009; 6 (12):1721–6. [ PubMed]
  • Van Bommel Rutger J , Mollema Sjoerd A , Borleffs C Jan Willem , Bertini Matteo , Ypenburg Claudia , Marsan Nina Ajmone , Delgado Victoria , Van Der Wall Ernst E , Schalij Martin J , Bax Jeroen J .Impaired renal function is associated with echocardiographic nonresponse and poor prognosis after cardiac resynchronization therapy. J. Am. Coll. Cardiol. . 2011; 57 (5):549–55. [ PubMed]
  • Steinberg Jonathan S .Desperately seeking a randomized clinical trial of resynchronization therapy for patients with heart failure and atrial fibrillation. J. Am. Coll. Cardiol. . 2006; 48 (4):744–6. [ PubMed]
  • Maisel William H , Stevenson Lynne Warner .Atrial fibrillation in heart failure: epidemiology, pathophysiology, and rationale for therapy. Am. J. Cardiol. . 2003; 91 (6A):2D–8D. [ PubMed]
  • Tolosana José María , Arnau Ana Martín , Madrid Antonio Hernández , Macias Alfonso , Lozano Ignacio Fernández , Osca Joaquín , Quesada Aurelio , Toquero Jorge , Francés Roberto Matia , Bolao Ignacio García , Berruezo Antonio , Sitges Marta , Alcalá Mónica Gimenez , Brugada Josep , Mont Lluís .Cardiac resynchronization therapy in patients with permanent atrial fibrillation. Is it mandatory to ablate the atrioventricular junction to obtain a good response? Eur. J. Heart Fail. . 2012; 14 (6):635–41. [ PubMed]
  • Hayes David L , Boehmer John P , Day John D , Gilliam F R , Heidenreich Paul A , Seth Milan , Jones Paul W , Saxon Leslie A .Cardiac resynchronization therapy and the relationship of percent biventricular pacing to symptoms and survival. Heart Rhythm . 2011; 8 (9):1469–75. [ PubMed]
  • Koplan Bruce A , Kaplan Andrew J , Weiner Stan , Jones Paul W , Seth Milan , Christman Shelly A .Heart failure decompensation and all-cause mortality in relation to percent biventricular pacing in patients with heart failure: is a goal of 100% biventricular pacing necessary? J. Am. Coll. Cardiol. . 2009; 53 (4):355–60. [ PubMed]
  • Gasparini Maurizio , Regoli François , Galimberti Paola , Ceriotti Carlo , Cappelleri Alessio .Cardiac resynchronization therapy in heart failure patients with atrial fibrillation. Europace . 2009; 11 Suppl 5 ():v82–6. [ PubMed]
  • Mullens Wilfried , Grimm Richard A , Verga Tanya , Dresing Thomas , Starling Randall C , Wilkoff Bruce L , Tang W H Wilson .Insights from a cardiac resynchronization optimization clinic as part of a heart failure disease management program. J. Am. Coll. Cardiol. . 2009; 53 (9):765–73. [ PubMed]
  • Delnoy Peter Paul H M , Ottervanger Jan Paul , Luttikhuis Henk Oude , Elvan Arif , Misier Anand R Ramdat , Beukema Willem P , van Hemel Norbert M .Comparison of usefulness of cardiac resynchronization therapy in patients with atrial fibrillation and heart failure versus patients with sinus rhythm and heart failure. Am. J. Cardiol. . 2007; 99 (9):1252–7. [ PubMed]
  • Dong Kan , Shen Win-Kuang , Powell Brian D , Dong Ying-Xu , Rea Robert F , Friedman Paul A , Hodge David O , Wiste Heather J , Webster Tracy , Hayes David L , Cha Yong-Mei .Atrioventricular nodal ablation predicts survival benefit in patients with atrial fibrillation receiving cardiac resynchronization therapy. Heart Rhythm . 2010; 7 (9):1240–5. [ PubMed]
  • Ferreira António M , Adragão Pedro , Cavaco Diogo M , Candeias Rui , Morgado Francisco B , Santos Katya R , Santos Emília , Silva José A .Benefit of cardiac resynchronization therapy in atrial fibrillation patients vs. patients in sinus rhythm: the role of atrioventricular junction ablation. Europace . 2008; 10 (7):809–15. [ PubMed]
  • Gasparini Maurizio , Auricchio Angelo , Metra Marco , Regoli François , Fantoni Cecilia , Lamp Barbara , Curnis Antonio , Vogt Juergen , Klersy Catherine .Long-term survival in patients undergoing cardiac resynchronization therapy: the importance of performing atrio-ventricular junction ablation in patients with permanent atrial fibrillation. Eur. Heart J. . 2008; 29 (13):1644–52. [ PubMed]
  • Gasparini Maurizio , Auricchio Angelo , Regoli François , Fantoni Cecilia , Kawabata Mihoko , Galimberti Paola , Pini Daniela , Ceriotti Carlo , Gronda Edoardo , Klersy Catherine , Fratini Simona , Klein Helmut H .Four-year efficacy of cardiac resynchronization therapy on exercise tolerance and disease progression: the importance of performing atrioventricular junction ablation in patients with atrial fibrillation. J. Am. Coll. Cardiol. . 2006; 48 (4):734–43. [ PubMed]
  • Khadjooi K , Foley P W , Chalil S , Anthony J , Smith R E A , Frenneaux M P , Leyva F .Long-term effects of cardiac resynchronisation therapy in patients with atrial fibrillation. Heart . 2008; 94 (7):879–83. [ PubMed]
  • Kiès P , Leclercq C , Bleeker G B , Crocq C , Molhoek S G , Poulain C , van Erven L , Bootsma M , Zeppenfeld K , van der Wall E E , Daubert J-C , Schalij M J , Bax J J .Cardiac resynchronisation therapy in chronic atrial fibrillation: impact on left atrial size and reversal to sinus rhythm. Heart . 2006; 92 (4):490–4. [ PubMed]
  • Molhoek Sander G , Bax Jeroen J , van Erven Lieselot , Bootsma Marianne , Boersma Eric , Steendijk Paul , van der Wall Ernst E , Schalij Martin J .Comparison of benefits from cardiac resynchronization therapy in patients with ischemic cardiomyopathy versus idiopathic dilated cardiomyopathy. Am. J. Cardiol. . 2004; 93 (7):860–3. [ PubMed]
  • Tolosana Jose Maria , Hernandez Madrid Antonio , Brugada Josep , Sitges Marta , Garcia Bolao Ignacio , Fernandez Lozano Ignacio , Martinez Ferrer Jose , Quesada Aurelio , Macias Alfonso , Marin Walter , Escudier Juan Manuel , Gomez Antonio Alonso , Gimenez Alcala Mónica , Tamborero David , Berruezo Antonio , Mont Lluís .Comparison of benefits and mortality in cardiac resynchronization therapy in patients with atrial fibrillation versus patients in sinus rhythm (Results of the Spanish Atrial Fibrillation and Resynchronization [SPARE] Study). Am. J. Cardiol. . 2008; 102 (4):444–9. [ PubMed]
  • Linde Cecilia , Leclercq Christophe , Rex Steve , Garrigue Stephane , Lavergne Thomas , Cazeau Serge , McKenna William , Fitzgerald Melissa , Deharo Jean-Claude , Alonso Christine , Walker Stuart , Braunschweig Frieder , Bailleul Christophe , Daubert Jean-Claude .Long-term benefits of biventricular pacing in congestive heart failure: results from the MUltisite STimulation in cardiomyopathy (MUSTIC) study. J. Am. Coll. Cardiol. . 2002; 40 (1):111–8. [ PubMed]
  • Etienne Y , Mansourati J , Gilard M , Valls-Bertault V , Boschat J , Benditt D G , Lurie K G , Blanc J J .Evaluation of left ventricular based pacing in patients with congestive heart failure and atrial fibrillation. Am. J. Cardiol. . 1999; 83 (7):1138–40, A9. [ PubMed]
  • Leclercq C , Victor F , Alonso C , Pavin D , Revault d'Allones G , Bansard J Y , Mabo P , Daubert C .Comparative effects of permanent biventricular pacing for refractory heart failure in patients with stable sinus rhythm or chronic atrial fibrillation. Am. J. Cardiol. . 2000; 85 (9):1154–6, A9. [ PubMed]
  • Wilton Stephen B , Kavanagh Katherine M , Aggarwal Sandeep G , Philippon François , Yee Raymond , Cowan Karen , Exner Derek V .Association of rate-controlled persistent atrial fibrillation with clinical outcome and ventricular remodelling in recipients of cardiac resynchronization therapy. Can J Cardiol . 2011; 27 (6):787–93. [ PubMed]
  • Healey Jeff S , Hohnloser Stefan H , Exner Derek V , Birnie David H , Parkash Ratika , Connolly Stuart J , Krahn Andrew D , Simpson Chris S , Thibault Bernard , Basta Magdy , Philippon Francois , Dorian Paul , Nair Girish M , Sivakumaran Soori , Yetisir Elizabeth , Wells George A , Tang Anthony S L .Cardiac resynchronization therapy in patients with permanent atrial fibrillation: results from the Resynchronization for Ambulatory Heart Failure Trial (RAFT). Circ Heart Fail . 2012; 5 (5):566–70. [ PubMed]
  • Wilton Stephen B , Leung Alexander A , Ghali William A , Faris Peter , Exner Derek V .Outcomes of cardiac resynchronization therapy in patients with versus those without atrial fibrillation: a systematic review and meta-analysis. Heart Rhythm . 2011; 8 (7):1088–94. [ PubMed]
  • Upadhyay Gaurav A , Choudhry Niteesh K , Auricchio Angelo , Ruskin Jeremy , Singh Jagmeet P .Cardiac resynchronization in patients with atrial fibrillation: a meta-analysis of prospective cohort studies. J. Am. Coll. Cardiol. . 2008; 52 (15):1239–46. [ PubMed]
  • Kamath Ganesh S , Cotiga Delia , Koneru Jayanthi N , Arshad Aysha , Pierce Walter , Aziz Emad F , Mandava Anisha , Mittal Suneet , Steinberg Jonathan S .The utility of 12-lead Holter monitoring in patients with permanent atrial fibrillation for the identification of nonresponders after cardiac resynchronization therapy. J. Am. Coll. Cardiol. . 2009; 53 (12):1050–5. [ PubMed]
  • Yeung-Lai-Wah J A , Alison J F , Lonergan L , Mohama R , Leather R , Kerr C R .High success rate of atrioventricular node ablation with radiofrequency energy. J. Am. Coll. Cardiol. . 1991; 18 (7):1753–8. [ PubMed]
  • Jackman W M , Wang X Z , Friday K J , Roman C A , Moulton K P , Beckman K J , McClelland J H , Twidale N , Hazlitt H A , Prior M I .Catheter ablation of accessory atrioventricular pathways (Wolff-Parkinson-White syndrome) by radiofrequency current. N. Engl. J. Med. . 1991; 324 (23):1605–11. [ PubMed]
  • Brignole M , Menozzi C , Gianfranchi L , Musso G , Mureddu R , Bottoni N , Lolli G .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 (10):953–60. [ PubMed]
  • Natale A , Zimerman L , Tomassoni G , Newby K , Leonelli F , Fanelli R , Beheiry S , Pisano E .AV node ablation and pacemaker implantation after withdrawal of effective rate-control medications for chronic atrial fibrillation: effect on quality of life and exercise performance. Pacing Clin Electrophysiol . 1999; 22 (11):1634–9. [ PubMed]
  • Ozcan C , Jahangir A , Friedman P A , Patel P J , Munger T M , Rea R F , Lloyd M A , Packer D L , Hodge D O , Gersh B J , Hammill S C , Shen W K .Long-term survival after ablation of the atrioventricular node and implantation of a permanent pacemaker in patients with atrial fibrillation. N. Engl. J. Med. . 2001; 344 (14):1043–51. [ PubMed]
  • Sweeney Michael O , Wathen Mark S , Volosin Kent , Abdalla Ismaile , DeGroot Paul J , Otterness Mary F , Stark Alice J .Appropriate and inappropriate ventricular therapies, quality of life, and mortality among primary and secondary prevention implantable cardioverter defibrillator patients: results from the Pacing Fast VT REduces Shock ThErapies (PainFREE Rx II) trial. Circulation . 2005; 111 (22):2898–905. [ PubMed]
  • Ganesan Anand N , Brooks Anthony G , Roberts-Thomson Kurt C , Lau Dennis H , Kalman Jonathan M , Sanders Prashanthan .Role of AV nodal ablation in cardiac resynchronization in patients with coexistent atrial fibrillation and heart failure a systematic review. J. Am. Coll. Cardiol. . 2012; 59 (8):719–26. [ PubMed]
  • Leclercq C , Walker S , Linde C , Clementy J , Marshall A J , Ritter P , Djiane P , Mabo P , Levy T , Gadler F , Bailleul C , Daubert J-C .Comparative effects of permanent biventricular and right-univentricular pacing in heart failure patients with chronic atrial fibrillation. Eur. Heart J. . 2002; 23 (22):1780–7. [ PubMed]
  • Brignole M , Gammage M , Puggioni E , Alboni P , Raviele A , Sutton R , Vardas P , Bongiorni M G , Bergfeldt L , Menozzi C , Musso G .Comparative assessment of right, left, and biventricular pacing in patients with permanent atrial fibrillation. Eur. Heart J. . 2005; 26 (7):712–22. [ PubMed]
  • Doshi Rahul N , Daoud Emile G , Fellows Christopher , Turk Kyong , Duran Aurelio , Hamdan Mohamed H , Pires Luis A .Left ventricular-based cardiac stimulation post AV nodal ablation evaluation (the PAVE study). J. Cardiovasc. Electrophysiol. . 2005; 16 (11):1160–5. [ PubMed]
  • Orlov Michael V , Gardin Julius M , Slawsky Mara , Bess Renee L , Cohen Gerald , Bailey William , Plumb Vance , Flathmann Horst , de Metz Katerina .Biventricular pacing improves cardiac function and prevents further left atrial remodeling in patients with symptomatic atrial fibrillation after atrioventricular node ablation. Am. Heart J. . 2010; 159 (2):264–70. [ PubMed]
  • Brignole Michele , Botto Gianluca , Mont Lluis , Iacopino Saverio , De Marchi Giuseppe , Oddone Daniele , Luzi Mario , Tolosana Jose M , Navazio Alessandro , Menozzi Carlo .Cardiac resynchronization therapy in patients undergoing atrioventricular junction ablation for permanent atrial fibrillation: a randomized trial. Eur. Heart J. . 2011; 32 (19):2420–9. [ PubMed]
  • Stavrakis Stavros , Garabelli Paul , Reynolds Dwight W .Cardiac resynchronization therapy after atrioventricular junction ablation for symptomatic atrial fibrillation: a meta-analysis. Europace . 2012; 14 (10):1490–7. [ PubMed]
  • Solomon Scott D , Foster Elyse , Bourgoun Mikhail , Shah Amil , Viloria Esperanza , Brown Mary W , Hall W Jackson , Pfeffer Marc A , Moss Arthur J .Effect of cardiac resynchronization therapy on reverse remodeling and relation to outcome: multicenter automatic defibrillator implantation trial: cardiac resynchronization therapy. Circulation . 2010; 122 (10):985–92. [ PubMed]
  • Yu Cheuk-Man , Bleeker Gabe B , Fung Jeffrey Wing-Hong , Schalij Martin J , Zhang Qing , van der Wall Ernst E , Chan Yat-Sun , Kong Shun-Ling , Bax Jeroen J .Left ventricular reverse remodeling but not clinical improvement predicts long-term survival after cardiac resynchronization therapy. Circulation . 2005; 112 (11):1580–6. [ PubMed]



Biosense Webster
event date
Introduction to AFib
Ablation Specialist

View Ablation Specialists