2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement on optimal implantable cardioverter-defibrillator programming and testing

Document Reviewers: Giuseppe Boriani, MD, PhD (Italy); Michele Brignole, MD, FESC (Italy); Alan Cheng, MD, FHRS (USA); Thomas C. Crawford, MD, FACC, FHRS (USA); Luigi Di Biase, MD, PhD, FACC, FHRS (USA); Kevin Donahue, MD (USA); Andrew E. Epstein, MD, FAHA, FACC, FHRS (USA); Michael E. Field, MD, FACC, FHRS (USA); Bulent Gorenek, MD, FACC, FESC (Turkey); Jin-Long Huang, MD, PhD (China); Julia H. Indik, MD, PhD, FACC, FAHA, FHRS (USA); Carsten W. Israel, MD (Germany); Mariell L. Jessup MD, FACC, FAHA, FESC (USA); Christophe Leclercq, MD, PhD (France); Robert J. MacFadyen, MD, PhD (UK); Christopher Madias, MD, FHRS (USA); Manlio F. Marquez, MD, FACC (Mexico); Brian Olshansky, MD, FACC, FAHA, FHRS (USA); Kristen K. Patton, MD (USA); Marwan M. Refaat, MD, mMBA, FACC, FAHA, FHRS, FASE, FESC, FACP, FAAMA (USA); Cynthia M. Tracy, MD, FACC, FAHA (USA); Gaurav A. Upadhyay, MD (USA); Diego Vanegas, MD, FHRS (Colombia); Paul J. Wang, MD, FHRS, CCDS (USA) Implantable cardioverter-defibrillator (ICD) therapy is clearly an effective therapy for selected patients in definable populations. The benefits and risks of ICD therapy are directly impacted by programming and surgical decisions. This flexibility is both a great strength and a weakness, for which there has been no prior official discussion or guidance. It is the consensus of the 4 continental electrophysiology societies that there are 4 important clinical issues for which there are sufficient ICD clinical and trial data to provide evidence-based expert guidance. This document systematically describes the greater than 80% (83%–100%, mean 96%) required consensus achieved for each recommendation by official balloting in regard to the programming of (1) bradycardia mode and rate, (2) tachycardia detection, (3) tachycardia therapy, and (4) the intraprocedural testing of defibrillation efficacy. Representatives nominated by the Heart Rhythm Society (HRS), European Heart Rhythm Association (EHRA), Asian Pacific Heart Rhythm Society (APHRS), and the Sociedad Latinoamericana de Estimulacion Cardiaca y Electrofisiologia (SOLAECE-Latin American Society of Cardiac Pacing and Electrophysiology) participated in the project definition, the literature review, the recommendation development, the writing of the document, and its approval. The 32 recommendations were balloted by the 35 writing committee members and were approved by an average of 96%. The classification of the recommendations and the level of evidence follow the recently updated ACC/AHA standard.1Jacobs A.K. Anderson J.L. Halperin J.L. et al.The evolution and future of ACC/AHA clinical practice guidelines: a 30-year journey: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines.Circulation. Sep 30 2014; 130: 1208-1217Crossref PubMed Scopus (21) Google Scholar, 2Anderson J.L. Evolution of the ACC/AHA Clinical Practice Guidelines in Perspective.J Am Coll Cardiol. 2015; 65: 2735-2738Abstract Full Text Full Text PDF PubMed Google Scholar Class I is a strong recommendation, denoting a benefit greatly exceeding risk. Class IIa is a somewhat weaker recommendation, with a benefit probably exceeding risk, and Class IIb denotes a benefit equivalent to or possibly exceeding risk. Class III is a recommendation against a specific treatment because either there is no net benefit or there is net harm. Level of Evidence A denotes the highest level of evidence from more than 1 high-quality randomized clinical trial (RCT), a meta-analysis of high-quality RCTs, or RCTs corroborated by high-quality registry studies. Level of evidence B indicates moderate-quality evidence from either RCTs with a meta-analysis (B-R) or well-executed nonrandomized trials with a meta-analysis (B-NR). Level of evidence C indicates randomized or nonrandomized observational or registry studies with limited data (C-LD) or from expert opinions (C-EO) based on clinical experience in the absence of credible published evidence. These recommendations were also subject to a 1-month public comment period. Each society then officially reviewed, commented, edited, and endorsed the final document and recommendations. All author and peer reviewer disclosure information is provided in Appendix A. The care of individual patients must be provided in context of their specific clinical condition and the data available on that patient. Although the recommendations in this document provide guidance for a strategic approach to ICD programming, as an individual patient’s condition changes or progresses and additional clinical considerations become apparent, the programming of their ICDs must reflect those changes. Remote and in-person interrogations of the ICD and clinical monitoring must continue to inform the programming choices made for each patient. The recommendations in this document specifically target adult patients and might not be applicable to pediatric patients, particularly when programming rate criteria. Please consider that each ICD has specific programmable options that might not be specifically addressed by the 32 distinctive recommendations in this document. Appendix B, published online (http://www.hrsonline.org/appendix-b), contains the writing committee’s translations specific to each manufacturer and is intended to best approximate the recommended behaviors for each available ICD model. Because the ICD is primarily indicated for tachycardia therapy, there might be some uncertainty regarding optimal bradycardia management for ICD patients. Data from clinical studies adequately address only the programmed mode rather than the number of leads implanted, the number of chambers stimulated, or how frequently the patients required bradycardia support. It is of note that most information on pacing modes has been collected from pacemaker patients, and these patients are clinically distinct from ICD recipients. Dual-chamber pacing (atrial and ventricular) has been compared with single-chamber pacing (atrial or ventricular) in patients with bradycardia in 5 multicenter, parallel, randomized trials, in 1 meta-analysis of randomized trials, and in 1 systematic review that also included 30 randomized crossover comparisons and 4 economic analyses.3Nielsen J.C. Thomsen P.E.B. Hojberg S. et al.A comparison of single-lead atrial pacing with dual-chamber pacing in sick sinus syndrome.Eur Heart J. 2011; 32: 686-696Crossref PubMed Scopus (91) Google Scholar, 4Connolly S.J. Kerr C.R. Gent M. et al.Effects of Physiologic Pacing versus Ventricular Pacing on the Risk of Stroke and Death Due to Cardiovascular Causes.N Engl J Med. 2000; 342: 1385-1391Crossref PubMed Scopus (514) Google Scholar, 5Lamas G.A. Lee K.L. Sweeney M.O. et al.Ventricular Pacing or Dual-Chamber Pacing for Sinus-Node Dysfunction.N Engl J Med. 2002; 346: 1854-1862Crossref PubMed Scopus (579) Google Scholar, 6Lamas G.A. Orav E.J. Stambler B.S. et al.Quality of Life and Clinical Outcomes in Elderly Patients Treated with Ventricular Pacing as Compared with Dual-Chamber Pacing.N Engl J Med. 1998; 338: 1097-1104Crossref PubMed Scopus (429) Google Scholar, 7Toff W.D. Camm A.J. Skehan J.D. Single-Chamber versus Dual-Chamber Pacing for High-Grade Atrioventricular Block.N Engl J Med. 2005; 353: 145-155Crossref PubMed Scopus (204) Google Scholar, 8Healey J.S. Cardiovascular Outcomes With Atrial-Based Pacing Compared With Ventricular Pacing: Meta-Analysis of Randomized Trials, Using Individual Patient Data.Circulation. 2006; 114: 11-17Crossref PubMed Scopus (123) Google Scholar, 9Castelnuovo E. Stein K. Pitt M. Garside R. Payne E. The effectiveness and cost-effectiveness of dual-chamber pacemakers compared with single-chamber pacemakers for bradycardia due to atrioventricular block or sick sinus syndrome: systematic review and economic evaluation.Health Technol. Assess. Nov 2005; 9 (iii, xi-xiii): 1-246Crossref Google Scholar Meta analyses comparing dual-chamber to single-chamber ICDs did not evaluate pacing modes.10Theuns D.A. Klootwijk A.P. Goedhart D.M. Jordaens L.J. Prevention of inappropriate therapy in implantable cardioverter-defibrillators: results of a prospective, randomized study of tachyarrhythmia detection algorithms.J Am Coll Cardiol. Dec 21 2004; 44: 2362-2367Abstract Full Text Full Text PDF PubMed Scopus (117) Google Scholar, 11Chen B.W. Liu Q. Wang X. Dang A.M. Are dual-chamber implantable cardioverter-defibrillators really better than single-chamber ones? A systematic review and meta-analysis.J Interv Card Electrophysiol. Apr 2014; 39: 273-280Crossref PubMed Google Scholar Compared with single-chamber pacing, dual-chamber pacing results in small but potentially significant benefits in patients with sinus node disease and/or atrioventricular block. No difference in mortality has been observed between ventricular pacing modes and dual-chamber pacing modes. Dual-chamber pacing was associated with a lower rate of atrial fibrillation (AF) and stroke.12Wilkoff B.L. Cook J.R. Epstein A.E. et al.Dual-chamber pacing or ventricular backup pacing in patients with an implantable defibrillator: the Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial.JAMA. Dec 25 2002; 288: 3115-3123Crossref PubMed Scopus (1250) Google Scholar The benefit in terms of AF prevention was more marked in trials comprised of patients with sinus node disease. Although trends in favor of dual-chamber pacing have been observed in some trials, there was no benefit in terms of heart failure (HF). In patients without symptomatic bradycardia, however, the Dual Chamber and VVI Implantable Defibrillator (DAVID) trial in ICD recipients showed that one specific choice of dual-chamber rate-responsive (DDDR) programming parameters led to poorer outcomes than VVI backup pacing, most likely secondary to unnecessary right ventricular (RV) pacing. The fact that RV stimulation was responsible was reinforced in the DAVID II trial, in which AAI pacing was demonstrated to be noninferior to VVI backup pacing.13Wilkoff B.L. Kudenchuk P.J. Buxton A.E. et al.The DAVID (Dual Chamber and VVI Implantable Defibrillator) II trial.J Am Coll Cardiol. Mar 10 2009; 53: 872-880Abstract Full Text Full Text PDF PubMed Scopus (58) Google Scholar Approximately a quarter of patients with either sinus node disease or atrioventricular block develop “pacemaker syndrome” with VVI pacing usually associated with retrograde (ventricular to atrial) conduction, which in turn is associated with a reduction in the quality of life.14Castelnuovo E. Stein K. Pitt M. Garside R. Payne E. The effectiveness and cost-effectiveness of dual-chamber pacemakers compared with single-chamber pacemakers for bradycardia due to atrioventricular block or sick sinus syndrome: systematic review and economic evaluation.Health Technol. Assess. 2005/11. 2005; 9Google Scholar In crossover trials, symptoms of pacemaker syndrome (dyspnea, dizziness, palpitations, pulsations, and chest pain) were reduced by reprogramming to a dual-chamber mode.14Castelnuovo E. Stein K. Pitt M. Garside R. Payne E. The effectiveness and cost-effectiveness of dual-chamber pacemakers compared with single-chamber pacemakers for bradycardia due to atrioventricular block or sick sinus syndrome: systematic review and economic evaluation.Health Technol. Assess. 2005/11. 2005; 9Google Scholar Dual-chamber pacing is associated with better exercise performance compared with single-chamber VVI pacing without rate adaptation, but produces similar exercise performance when compared with rate-responsive VVIR pacing. Because of the additional lead, dual-chamber devices involve longer implantation times, have a higher risk of complications, and are more expensive. However, because of the additional clinical consequences of pacemaker syndrome and AF (and its sequelae), the overall cost difference between single- and dual-pacing systems is moderated. In patients with persistent sinus bradycardia, atrial rather than ventricular dual-chamber pacing is the pacing mode of choice. There is evidence for superiority of atrial-based pacing over ventricular pacing for patients who require pacing for a significant proportion of the day. The evidence is stronger for patients with sinus node disease, in whom dual-chamber pacing confers a modest reduction in AF and stroke, but not in hospitalization for HF or death compared with ventricular pacing. In patients with acquired atrioventricular block, large randomized parallel trials were unable to demonstrate the superiority of dual-chamber pacing over ventricular pacing with regard to hard clinical endpoints of mortality and morbidity.4Connolly S.J. Kerr C.R. Gent M. et al.Effects of Physiologic Pacing versus Ventricular Pacing on the Risk of Stroke and Death Due to Cardiovascular Causes.N Engl J Med. 2000; 342: 1385-1391Crossref PubMed Scopus (514) Google Scholar, 6Lamas G.A. Orav E.J. Stambler B.S. et al.Quality of Life and Clinical Outcomes in Elderly Patients Treated with Ventricular Pacing as Compared with Dual-Chamber Pacing.N Engl J Med. 1998; 338: 1097-1104Crossref PubMed Scopus (429) Google Scholar, 7Toff W.D. Camm A.J. Skehan J.D. Single-Chamber versus Dual-Chamber Pacing for High-Grade Atrioventricular Block.N Engl J Med. 2005; 353: 145-155Crossref PubMed Scopus (204) Google Scholar, 8Healey J.S. Cardiovascular Outcomes With Atrial-Based Pacing Compared With Ventricular Pacing: Meta-Analysis of Randomized Trials, Using Individual Patient Data.Circulation. 2006; 114: 11-17Crossref PubMed Scopus (123) Google Scholar The benefit of dual-chamber over ventricular pacing is primarily due to the avoidance of pacemaker syndrome and to improved exercise capacity.14Castelnuovo E. Stein K. Pitt M. Garside R. Payne E. The effectiveness and cost-effectiveness of dual-chamber pacemakers compared with single-chamber pacemakers for bradycardia due to atrioventricular block or sick sinus syndrome: systematic review and economic evaluation.Health Technol. Assess. 2005/11. 2005; 9Google Scholar Even if it is a softer endpoint, pacemaker syndrome is associated with a reduction in quality of life that justifies the preference for dual-chamber pacing when reasonable; thus, there is strong evidence for the superiority of dual-chamber pacing over ventricular pacing that is limited to symptom improvement. Conversely, there is strong evidence of nonsuperiority with regard to survival and morbidity. The net result is that the indications for programming the dual-chamber modes are weaker and the choice regarding the pacing mode should be individualized, taking into consideration the increased complication risk and costs of dual-chamber devices. Because ICD patients usually do not require bradycardia support, with the exception of patients who require cardiac resynchronization, programming choices should avoid pacing and in particular avoid single ventricular pacing, if possible.15Magrì D. Corrà U. Di Lenarda A. et al.Cardiovascular mortality and chronotropic incompetence in systolic heart failure: the importance of a reappraisal of current cut-off criteria.Eur J Heart Fail. 2013/2017; 16: 201-209Crossref PubMed Scopus (0) Google Scholar, 16Sims D.B. Mignatti A. Colombo P.C. et al.Rate responsive pacing using cardiac resynchronization therapy in patients with chronotropic incompetence and chronic heart failure.Europace. 2011; 13: 1459-1463Crossref PubMed Scopus (10) Google Scholar The benefit of rate response programming has been evaluated in patients with bradycardia in 5 multicenter, randomized trials and in 1 systematic review that also included 7 single-center studies.17Padeletti L. Pieragnoli P. Di Biase L. et al.Is a Dual-Sensor Pacemaker Appropriate in Patients with Sino-Atrial Disease? Results from the DUSISLOG Study.Pacing Clin Electrophysiol. 2006; 29: 34-40Crossref PubMed Scopus (0) Google Scholar, 18Sulke N. Chambers J. Dritsas A. Sowton E. A randomized double-blind crossover comparison of four rate-responsive pacing modes.J Am Coll Cardiol. 1991; 17: 696-706Abstract Full Text PDF PubMed Google Scholar, 19Lamas G.A. Knight J.D. Sweeney M.O. et al.Impact of rate-modulated pacing on quality of life and exercise capacity—Evidence from the Advanced Elements of Pacing Randomized Controlled Trial (ADEPT).Heart Rhythm. 2007; 4: 1125-1132Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar, 20Lau C.P. Rushby J. Leigh-Jones M. et al.Symptomatology and quality of life in patients with rate-responsive pacemakers: A double-blind, randomized, crossover study.Clin Cardiol. 1989; 12: 505-512Crossref PubMed Google Scholar, 21Oto M.A. Muderrisoglu H. Ozin M.B. et al.Quality of Life in Patients with Rate Responsive Pacemakers: A Randomized, Cross-Over Study.Pacing Clin Electrophysiol. 1991; 14: 800-806Crossref PubMed Google Scholar, 22Dell’Orto S. Valli P. Greco E.M. Sensors for rate responsive pacing.Indian Pacing Electrophysiol J. 2004; 4: 137-145PubMed Google Scholar Most of these data were obtained from pacemaker studies and must be interpreted in that light. Although there is evidence of the superiority of VVIR pacing compared with VVI pacing in improving quality of life and exercise capacity, improvements in exercise capacity with DDDR compared with DDD have been inconsistent. In 2 small studies on patients with chronotropic incompetence comparing DDD and DDDR pacing, the latter had improved quality of life and exercise capacity; however, a larger, multicenter randomized trial (Advanced Elements of Pacing Randomized Controlled Trial [ADEPT]) failed to show a difference in patients with a modest blunted heart rate response to exercise.17Padeletti L. Pieragnoli P. Di Biase L. et al.Is a Dual-Sensor Pacemaker Appropriate in Patients with Sino-Atrial Disease? Results from the DUSISLOG Study.Pacing Clin Electrophysiol. 2006; 29: 34-40Crossref PubMed Scopus (0) Google Scholar, 18Sulke N. Chambers J. Dritsas A. Sowton E. A randomized double-blind crossover comparison of four rate-responsive pacing modes.J Am Coll Cardiol. 1991; 17: 696-706Abstract Full Text PDF PubMed Google Scholar, 19Lamas G.A. Knight J.D. Sweeney M.O. et al.Impact of rate-modulated pacing on quality of life and exercise capacity—Evidence from the Advanced Elements of Pacing Randomized Controlled Trial (ADEPT).Heart Rhythm. 2007; 4: 1125-1132Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar In addition, DDDR programming in cardiac resynchronization therapy (CRT) patients has the potential to impair AV synchrony and timing. It should be noted that trials evaluating CRT generally did not use rate-responsive pacing, and many in fact avoided atrial stimulation using atrial sensed and ventricular paced pacing modes with a lower base rate. However, the Pacing Evaluation-Atrial Support Study in Cardiac Resynchronization Therapy (PEGASUS CRT) trial is the exception and did not demonstrate adverse impact on mortality and HF events.23Martin D.O. Day J.D. Lai P.Y. et al.Atrial support pacing in heart failure: results from the multicenter PEGASUS CRT trial.J Cardiovasc Electrophysiol. Dec 2012; 23: 1317-1325Crossref PubMed Scopus (14) Google Scholar In patients with persistent or intermittent sinus node dysfunction or chronotropic incompetence, the first choice is DDDR with algorithms responding to intermittent atrioventricular conduction. There is sufficient evidence for the superiority of VVIR compared with VVI in improving quality of life and exercise capacity. The evidence is much weaker in dual-chamber pacing (DDDR vs DDD). Although only an issue when there is some concomitant AV block, the upper rate limit should be programmed higher than the fastest spontaneous sinus rhythm to avoid upper rate limit behavior. To avoid symptomatic bradycardia, the lower rate should be programmed on an individual basis, according to the clinical characteristics and the underlying cardiac substrate of the patient. Patients with permanent AF and either spontaneous or AV junctional ablation-induced high-degree atrioventricular block have little to no chronotropic response to exercise; thus, VVIR pacing is associated with better exercise performance, improved daily activities, improved quality of life, and decreased symptoms of shortness of breath, chest pain, and heart palpitations, compared with VVI.20Lau C.P. Rushby J. Leigh-Jones M. et al.Symptomatology and quality of life in patients with rate-responsive pacemakers: A double-blind, randomized, crossover study.Clin Cardiol. 1989; 12: 505-512Crossref PubMed Google Scholar, 21Oto M.A. Muderrisoglu H. Ozin M.B. et al.Quality of Life in Patients with Rate Responsive Pacemakers: A Randomized, Cross-Over Study.Pacing Clin Electrophysiol. 1991; 14: 800-806Crossref PubMed Google Scholar, 22Dell’Orto S. Valli P. Greco E.M. Sensors for rate responsive pacing.Indian Pacing Electrophysiol J. 2004; 4: 137-145PubMed Google Scholar, 24Leung S.-K. Lau C.-P. Developments in sensor-driven pacing.Cardiol Clin. 2000; 18: 133-155Abstract Full Text Full Text PDF Google Scholar, 25Van Campen LCMC De Cock CC Visser F.C. Visser C.A. The effect of rate responsive pacing in patients with angina pectoris on the extent of ischemia on 201-thallium exercise scintigraphy.Pacing Clin Electrophysiol. 2002; 25: 430-434Crossref PubMed Google Scholar, 26Brignole M. Auricchio A. Baron-Esquivias G. et al.2013 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy: The Task Force on cardiac pacing and resynchronization therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA).Eur Heart J. 2013; 34: 2281-2329Crossref PubMed Scopus (370) Google Scholar Therefore, rate-adaptive pacing is the first choice of pacing mode; fixed-rate VVI pacing should be abandoned in patients with permanent AF and atrioventricular block. It is the experts’ opinion that the minimum rate can be programmed higher (e.g., 70 bpm) than for sinus rhythm patients, in an attempt to compensate for the loss of active atrial filling. In addition, the maximum sensor rate should be programmed restrictively (e.g., 110–120 bpm) to avoid “overpacing” (i.e., pacing with a heart rate faster than necessary), which can be symptomatic, particularly in patients with coronary artery disease. In a small study, however, it was found that rate-responsive pacing could be safe and effective in patients with angina pectoris, without an increase in subjective or objective signs of ischemia.25Van Campen LCMC De Cock CC Visser F.C. Visser C.A. The effect of rate responsive pacing in patients with angina pectoris on the extent of ischemia on 201-thallium exercise scintigraphy.Pacing Clin Electrophysiol. 2002; 25: 430-434Crossref PubMed Google Scholar The lower rate should be programmed on an individual basis, according to the clinical characteristics and the underlying cardiac substrate of the patient. The clinical benefit of programming a lower resting rate at night based on internal clocks has not been evaluated in ICD patients. There is some concern that atrioventricular junction ablation and permanent ventricular pacing might predispose the patient to an increased risk of sudden cardiac death (SCD) related to a bradycardia-dependent prolongation of the QT interval. This risk might be overcome by setting the ventricular pacing rate to a minimum of 80 or 90 bpm for the first 1–2 months following the atrioventricular junction ablation, then reducing it to a conventional 60–70 bpm.27Geelen P. Brugada J. Andries E. Brugada P. Ventricular Fibrillation and Sudden Death After Radiofrequency Catheter Ablation of the Atrioventricular Junction.Pacing Clin Electrophysiol. 1997; 20: 343-348Crossref PubMed Scopus (107) Google Scholar, 28Nowinski K. Gadler F. Jensen-Urstad M. Bergfeldt L. Transient proarrhythmic state following atrioventricular junction radiofrequency ablation: pathophysiologic mechanisms and recommendations for management.The American Journal of Medicine. 2002; 113: 596-602Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar Not all patients with AF and milder forms of atrioventricular block will require a high percentage of ventricular pacing or have a wide QRS. Physicians should consider the risk of increasing preexisting left ventricular (LV) dysfunction with RV pacing vs improved chronotropic responsiveness and the potential value of CRT. The results of a number of large-scale, prospective randomized trials demonstrated a significant reduction in AF in pacemaker patients with atrial-based pacing (AAI or DDD) compared with patients with ventricular-based pacing.4Connolly S.J. Kerr C.R. Gent M. et al.Effects of Physiologic Pacing versus Ventricular Pacing on the Risk of Stroke and Death Due to Cardiovascular Causes.N Engl J Med. 2000; 342: 1385-1391Crossref PubMed Scopus (514) Google Scholar, 8Healey J.S. Cardiovascular Outcomes With Atrial-Based Pacing Compared With Ventricular Pacing: Meta-Analysis of Randomized Trials, Using Individual Patient Data.Circulation. 2006; 114: 11-17Crossref PubMed Scopus (123) Google Scholar, 29Andersen H.R. Nielsen J.C. Thomsen P.E.B. et al.Long-term follow-up of patients from a randomised trial of atrial versus ventricular pacing for sick-sinus syndrome.The Lancet. 1997; 350: 1210-1216Abstract Full Text Full Text PDF PubMed Google Scholar In the Mode Selection Trial, which enrolled 2010 patients with sick sinus syndrome, the risk of AF increased linearly with the increasing percentage of RV pacing.30Sweeney M.O. Adverse Effect of Ventricular Pacing on Heart Failure and Atrial Fibrillation Among Patients With Normal Baseline QRS Duration in a Clinical Trial of Pacemaker Therapy for Sinus Node Dysfunction.Circulation. 2003; 107: 2932-2937Crossref PubMed Scopus (823) Google Scholar At the same time, deleterious effects of RV pacing in patients with LV dysfunction (left ventricular ejection fraction [LVEF] ≤40%) implanted with dual-chamber ICD systems were observed in the Dual Chamber and VVI Implantable Defibrillator (DAVID) trial, which included 506 ICD patients without indications for bradycardia pacing. Patients within the DDDR-70 group (with paced and sensed atrioventricular delays of 170 and 150 ms, respectively, in most of the DDDR group patients) showed a trend toward higher mortality and an increased incidence of HF compared with the patients programmed to ventricular backup pacing—the VVI-40 group. Within the DDDR-70 group, there were more cardiac events when the percentage of ventricular pacing exceeded 40% (P = .09) compared with patients with <40% of RV pacing, although almost all the patients had >95% RV stimulation (DDDR-70) or <5% RV stimulation (VVI-40).31The DTIDual-Chamber Pacing or Ventricular Backup Pacing in Patients With an Implantable Defibrillator.JAMA. 2002; 288: 3115Crossref PubMed Scopus (1214) Google Scholar, 32Sharma A.D. Rizo-Patron C. Hallstrom A.P. et al.Percent right ventricular pacing predicts outcomes in the DAVID trial.Heart Rhythm. 2005; 2: 830-834Abstract Full Text Full Text PDF PubMed Scopus (165) Google Scholar However, a more detailed post hoc analysis of the Inhibition of Unnecessary RV Pacing With Atrial-Ventricular Search Hysteresis in ICDs (INTRINSIC RV) trial revealed that the most favorable clinical results were not in the VVI groups with the least percentage of RV pacing but in the subgroup that had DDD pacing with longer atrioventricular delays and 11%–19% of ventricular pacing. This parameter selection probably helped patients to avoid exceedingly low heart rates while preserving intrinsic atrioventricular conduction most of the time.31The DTIDual-Chamber Pacing or Ventricular Backup Pacing in Patients With an Implantable Defibrillator.JAMA. 2002; 288: 3115Crossref PubMed Scopus (1214) Google Scholar, 33Olshansky B. Day J.D. Moore S. et al.Is dual-chamber programming inferior to single-chamber programming in an implantable cardioverter-defibrillator? Results of the INTRINSIC RV (Inhibition of Unnecessary RV Pacing With AVSH in ICDs) study.Circulation. Jan 2 2007; 115: 9-16Crossref PubMed Scopus (114) Google Scholar In the Second Multicenter Automated Defibrillator Implantation Trial (MADIT II), a higher risk of HF was observed in patients who had a greater than 50% burden of RV pacing.34Steinberg J.S. Fischer A.V.I. Wang P. et al.The Clinical Implications of Cumulative Right Ventricular Pacing in the Multicenter Automatic Defibrillator Trial II.J Cardiovasc Electrophysiol. 2005; 16: 359-365Crossref PubMed Scopus (220) Google Scholar In another large observational study of 456 ICD patients without HF at baseline, a high RV pacing burden (RV pacing more than 50% of the time) was associated with an increased risk of HF events and appropriate ICD shocks.35Smit M.D. Van Dessel PFHM Nieuwland W. et al.Right ventricular pacing and the risk of heart failure in implantable cardioverter-defibrillator patients.Heart Rhythm. 2006; 3: 1397-1403Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar Optimally, RV stimulation should be avoided, but the precise tradeoff between the percentage of ventricular pacing and atrioventricular timing is unclear in non-CRT patients. The importance of reducing or avoiding RV pacing in ICD patients with LV dysfunction was illustrated in the DAVID trial.31The DTIDual-Chamber Pacing or Ventricular Backup Pacing in Patients With an Implantable Defibrillator.JAMA. 2002; 288: 3115Crossref PubMed Scopus (1214) Google Scholar The feasibility of algorithms designed to decrease the burden of unnecessary ventricular pacing has been demonstrated in patients with dual-chamber pacemakers.36Gillis A.M. Purerfellner H. Israel C.W. et al.Reducing Unnecessary Right Ventricular Pacing with the Managed Ventricular Pacing Mode in Patients with Sinus Node Disease and AV Block.Pacing Clin Electrophysiol. 2006; 29: 697-705Crossref PubMed Scopus (104) Google Scholar, 37Kolb C. Schmidt R. Dietl J.U. et al.Reduction of Right Ventricular Paci