D e v i c e T h e r a p y fo r A c u t e S y s t o l i c H e a r t Fa i l u re a n d Atrial Fibrillation Steven K. Carlson, MD, Rahul N. Doshi, MD* KEYWORDS Cardiac resynchronization therapy Atrial fibrillation Atrioventricular node ablation Pacemaker Internal cardiac defibrillator
KEY POINTS Placement of an internal cardiac defibrillator (ICD) requires a waiting period of 40 days after myocardial infarction or 3 months on optimal medical treatment after the diagnosis of congestive heart failure. In patients with newly diagnosed cardiomyopathy who require nonelective permanent pacing and also meet the primary prevention criteria for implantation of an ICD, the device should include ICD capability only if left ventricular ejection fraction (LVEF) is not expected to resolve. Tachycardia-mediated cardiomyopathy should be suspected in patients with longstanding, uncontrolled tachyarrhythmias. Cardiac resynchronization therapy (CRT) must be operating at or near 100% of the time to be effective. In patients with atrial fibrillation, this often necessitates atrioventricular (AV) node ablation. CRT over standard pacing is recommended in patients with atrial fibrillation and LVEF less than 35% undergoing AV node ablation, regardless of QRS width.
The authors have nothing to disclose. Department of Internal Medicine, Division of Cardiovascular Medicine, Keck School of Medicine of University of Southern California, 1510 San Pablo Street, Suite 322, Los Angeles, CA 90033, USA * Corresponding author. E-mail address: [email protected]
Card Electrophysiol Clin 7 (2015) 469–477 http://dx.doi.org/10.1016/j.ccep.2015.05.016 1877-9182/15/$ – see front matter Ó 2015 Elsevier Inc. All rights reserved.
A 56-year-old man presents with a first diagnosis of acute severe systolic heart failure and atrial fibrillation and rapid ventricular rates. The echocardiogram shows a global cardiomyopathy and a left ventricular ejection fraction of 15% to 20%. During the hospitalization, the patient has episodes of nonsustained ventricular tachycardia without severe symptoms. Rate control with medical therapy has been unsuccessful and does not seem feasible. Because of the poor heart rate control, management of his heart failure cannot be optimized. After intravenous and then oral amiodarone loading, attempts to restore sinus rhythm during the hospitalization with electrical cardioversion have resulted in sinus rhythm for only 1 to 2 minutes then resumption of atrial fibrillation. The patient has not had syncope or near syncope. The plan is atrioventricular junction ablation. What device do you implant: VVI internal cardiac defibrillator (ICD), VVI pacemaker, cardiac resynchronization therapy (CRT) ICD, or CRT pacemaker?
Carlson & Doshi INTRODUCTION The presented case essentially poses 2 important questions that are reviewed in detail within this article. The first is in regard to placement of an internal cardiac defibrillator (ICD) versus pacemaker in a patient with newly diagnosed cardiomyopathy who requires pacing. The second question, which has been the topic of many studies in the last decade, is in regard to the optimal pacing method for patients with atrial fibrillation (AF) undergoing atrioventricular (AV) nodal ablation. Over the course of this article, the reader should be convinced that the best approach to this patient is placement of a cardiac resynchronization therapy pacemaker (CRT-P).
PACEMAKER VERSUS INTERNAL CARDIAC DEFIBRILLATOR The patient in this case history clearly requires a pacemaker given AV nodal ablation. The question is whether the patient, given his impaired cardiac function, will additionally benefit from an ICD in preventing future sudden cardiac death (SCD) caused by lethal ventricular arrhythmia. Although this seems a simple question, there are several issues in this case that make the decision difficult. In order to fully understand the answer it is important to review the indications for ICD therapy in patients with cardiomyopathy. This issue was examined thoroughly by several landmark trials. The Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II and the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) were 2 large prospective randomized trials looking at the benefit of ICD placement in patients with left ventricular ejection fraction (LVEF) less than 30% and 35%, respectively. The MADIT-II trial enrolled only patients with ischemic cardiomyopathy (ICM) versus the SCD-HeFT trial, which examined patients with heart failure with both ICM and non-ICM. Both showed a large risk reduction in mortality compared with medical therapy alone.1,2 The Prophylactic Defibrillator Implantation in Patients with Nonischemic Dilated Cardiomyopathy (DEFINITE) study specifically looked at the role of prophylactic ICD in patients with non-ICM and nonsustained ventricular tachycardia (NSVT). This study did not show as clear a benefit as MADIT-II or SCD-HeFT. There was a decrease in arrhythmic death but only a trend toward improved survival.3 Important to note is that all patients in these studies were required to be stable and on optimal medical therapy. In addition, there was significant variability in the timing of ICD implantation in relation to diagnosis of
cardiomyopathy. In The MADIT II trial, patients were excluded if they had revascularization within 3 months or had a myocardial infarction (MI) within 30 days. In the SCD-HeFT trial, the average duration of heart failure at the time of entry into the trial was 2.5 years. In the DEFINITE study, this same measure was 2.8 years.4 The patient in this case, however, is presenting with new-onset cardiomyopathy. The question of whether or not prophylactic ICD placement would be beneficial early after diagnosis of cardiomyopathy was addressed in 3 large trials, Prophylactic Use of an Implantable Cardioverter-Defibrillator after Acute Myocardial Infrarction (DINAMIT), Immediate Risk-Stratification Improves Survival (IRIS), and Coronary Artery bypass graft (CABG)-Patch. In DINAMIT, patients who had sustained an MI within 6 to 40 days resulting in cardiomyopathy with EF less than 35% were randomized to ICD therapy versus medical therapy. Although there was a reduction in arrhythmic mortality, nonarrhythmic mortality was actually higher in the ICD group leading to, overall, no difference in mortality between the two groups.5 In IRIS, patients who had sustained an MI within 5 to 31 days were randomized to ICD therapy versus medical therapy. In contrast to DINAMIT, patients were included if they had either an LVEF of 40% or less or NSVT greater than 3 beats. Similar to DINAMIT, there was a reduction in arrhythmic mortality, however, an increase in nonarrhythmic mortality.6 In CABG-Patch, patients with an LVEF of 35 or less and abnormal signalaveraged electrocardiogram (ECG) were assigned to either medical therapy or ICD using epicardial patches at the time of CABG. Again, there was no evidence of improved survival.7 All 3 of these large studies included only patients with ICM. There is a paucity of data in the population with recently diagnosed non-ICM. Some insight can be gained from studies examining the event rate in patients receiving wearable automated external defibrillators in the waiting period before ICD implantation. In a recent study in a population that included both non-ICM and ICM, there were no shocks within the waiting period.8 This study included both patients whose LVEF improved to greater than 35% and those whose LVEF remained less than 35%. It should be noted that this was a relatively small study, including only 125 patients, 77 of which were nonischemic. In a much larger study looking only at patients after MI receiving an automated external defibrillator, they found only 1.4% of 8453 patients received appropriate shocks in the immediate post-MI period.9 It is clear that ICDs are useful in reducing mortality in patients with an established diagnosis of cardiomyopathy. Although ICDs may also reduce
Heart Failure and Atrial Fibrillation arrhythmic mortality in patients with new-onset cardiomyopathy, there has not been a clear demonstration of an overall mortality benefit. The absence of a clear mortality benefit may be secondary to the risks involved with device placement or competing risks, such as progressive heart failure or mechanical complications after MI given the low utilization of device therapy during this period. Given the results of the aforementioned studies, the American Heart Association (AHA)/American College of Cardiology (ACC) has set guidelines on the implantation of ICD in patients with cardiomyopathy. Relevant to the case, the class I indications for placement of ICD are10 ICD therapy is indicated in patients with nonischemic dilated cardiomyopathy who have an LVEF less than or equal to 35% and who are New York Heart Association (NYHA) functional class II or III. ICD therapy is indicated in patients with an LVEF less than or equal to 35% caused by prior MI who are at least 40 days after MI and are NYHA class II or III. (If LVEF is <30%, then patients with NYHA class I are also included.) Key timing issues from the guidelines include Must be more than 40 days since MI. Must be more than 3 months since revascularization. Must be more than 3 months since diagnosis of congestive heart failure and on optimal medical treatment. The last point in timing is important. This patient has an indication for a permanent pacemaker inside the waiting period for ICD implantation. Although exposing the patient to the risk of a second procedure (subsequent upgrade from a pacemaker to ICD) is not entirely benign, there are clear benefits in avoiding unnecessary ICD implantation, such as device longevity, potential source of infection, and risk of inappropriate shock. Current guidelines for ICD placement are based significantly on clinical trial outcomes. Given the lack of data regarding patients with recently diagnosed cardiomyopathy requiring pacemakers within the 3-month waiting period, there are no recommendations given regarding this patient population in the most recent guidelines. Understanding that clinicians are often asked to make decisions regarding ICD therapy in patients not included in clinical trials, the Heart Rhythm Society (HRS)/ACC/AHA recently published an Expert Consensus Statement on ICD therapy in patients
not included or well represented in clinical trials. The current consensus is11 In patients less than 9 months from the initial diagnosis of nonischemic cardiomyopathy (NICM) who require nonelective permanent pacing, who would meet primary prevention criteria for implantation of an ICD, and recovery of LVEF is uncertain or not expected, implantation of an ICD with the appropriately selected pacing abilities is recommended. Thus, the challenge in the management of this clinical scenario is predicting whether or not there will be improvement in left ventricular function once control of the ventricular rate and initiation of optimal medical therapy is achieved. The natural history of left ventricular function in patients with recent-onset, non-ICM has been examined. The Intervention in Myocarditis and Acute Cardiomyopathy (IMAC)-2 study evaluated patients with newly diagnosed idiopathic dilated cardiomyopathy or myocarditis and found that, at 6 months, 70% had an increase in LVEF of greater than 10%, whereas 39% had an increase in LVEF greater than 20%. Furthermore, 25% of patients had full recovery in ventricular function.12 In this case specifically, there are 2 concepts that must be discussed in order to better predict this patient’s chances at recovering cardiac function and future risk of SCD: the concept of tachycardia-mediated cardiomyopathy and the role of NSVT in predicting future SCD. Tachycardia-mediated cardiomyopathy is caused by persistent supraventricular or ventricular tachyarrhythmias that lead to both neurohormonal and hemodynamic alterations within the cardiovascular system.13 The subsequent result is impaired myocardial function that is reversible with normalization of the heart rate. Several studies have shown that in patients with refractory AF referred for AV node ablation, a large percentage had tachycardia-mediated cardiomyopathy with normalization of LVEF after the heart rate was controlled (Table 1). In early studies of patients who have had an MI, NSVT was shown to be a risk factor for SCD following the first 24 hours after infarction.14,15 Further studies challenged these assertions. In the GISSI-2 trial (Italian group for the study of the survival of Myocardial Infarction) and the Electrophysiologic Study Versus Electromagnetic Monitoring (ESVEM) trial, NSVT was a predictor of mortality in a univariate analysis; but when examined independently of other risk factors, such as LVEF, in a multivariate analysis, it was not found
Carlson & Doshi
Table 1 Frequency of tachycardia-induced cardiomyopathy in patients with AF or atrial flutter referred for AV node ablation or modification
Author Luchsinger & Steinberg,41 1998 Redfield et al,42 2000 Edner et al,43 1995 Rodriguez et al,44 1993
Type of Arrhythmia
Ejection Fraction (%)
Total Number of Patients
Number of Patients (%) with Tachycardia-Induced Cardiomyopathy
AF AF AF
45 50 50
63 14 12
16 (25) 11 (78) 9 (75)
From Umana E, Solares CA, Alpert MA. Tachycardia-induced cardiomyopathy. Am J Med 2003;114(1):52; with permission.
to be predictive.16,17 These studies predominately examined patients with ICM. A recent meta-analysis was performed to evaluate the prognostic effect of NSVT found on 24-hour ambulatory monitoring in both ischemic and nonischemic patients. In this analysis, 11 studies were identified, 6 of which included both types of patients and 5 that included only patients with non-ICM. The investigators found that NSVT is a statistically significant predictor for arrhythmic events (combined SCD, resuscitated ventricular fibrillation, or sustained VT) in patients with left ventricular systolic dysfunction, regardless of cause or LVEF.18 It must be noted that studies involving patients with newly diagnosed ICM (<8 weeks) were excluded from the metaanalysis, limiting the conclusions that can be made regarding SCD risk in patients with recently diagnosed cardiomyopathy. Thus, although NSVT is certainly a marker of cardiac instability, it is still unclear whether its presence should prompt early implantation of an ICD. Several studies have suggested the inclusion of NSVT in a risk score model along with other parameters, such as increased left ventricular end diastolic diameter, elevated brain natriuretic peptide, and diabetes, that may allow for better selection of patients at risk for SCD.19,20 However, this model has not been widely implemented. Based on the results of the Multicenter Unsustained Tachycardia Trial (MUSST), current guidelines recommend the implantation of an ICD in patients with ICM, LVEF less than 40%, and NSVT only if inducible, sustained VT is found during an electrophysiologic study.21 The patient in the case presented requires a full evaluation to determine the cause of his heart failure, with subsequent treatment of the underlying cause and guideline-directed heart failure therapy. There is a significant chance that his LVEF will
improve with adequate rate control; thus, he must wait for 3 months before any consideration of ICD placement.
VVI VERSUS CARDIAC RESYNCHRONIZATION THERAPY The conventional approach to pacemaker placement for patients with permanent AF has been to place a right ventricular single-chamber pacemaker set to VVI mode. This mode allows for demand pacing of the ventricle and is essentially naı¨ve to the electrical activity in the atrium, which is preferred, as tracking of chaotic atrial activity is not desired. Maximum titration of rate control agents can then be initiated. In some cases, control of the ventricular response to AF is not achievable. In these situations, ablation of the AV node will disassociate the atrium from the ventricle, allowing for controlled pacing. This ablate and pace strategy has been shown to improve a broad range of clinical outcomes for patients with medically refractory AF, including exercise duration, quality of life, and LVEF.22,23 However, in traditional dual chamber pacemaker systems, chronic right ventricular pacing may lessen this potential benefit. Iatrogenic ventricular desynchronization can lead to progressive left ventricular dysfunction and the development of heart failure. In a long-term study that followed patients for 8 years after conventional dual-chamber pacemaker placement for acquired AV block, 26% of patients developed heart failure.24 CRT involves placing a left ventricular lead via the coronary sinus to pace both ventricles simultaneously (biventricular pacing). This method of pacing has been demonstrated to reduce mortality and hospitalization as well as to improve LVEF, exercise tolerance, and quality of life in patients with heart failure with ventricular dysynchrony. Two
Heart Failure and Atrial Fibrillation major landmark trials, the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) and the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT), have proven its efficacy in patients with a decreased ejection fraction and interventricular conduction delay on the ECG, specifically left bundle branch block.25,26 Both of these studies demonstrated an overall mortality benefit from CRT with defibrillator therapy (CRT-D). The Cardiac Resynchronization–Heart Failure (CARE-HF) study demonstrated a similar result in the same population with CRT-P.27 More recently, CRT has emerged as a potential first-line therapy for patients requiring permanent or near-permanent pacing despite having an LVEF greater than 35% and narrow QRS given the concern for pacemaker-mediated cardiomyopathy. The Biventricular Versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block (Block-HF) trial showed a reduction in heart failure events with implantation of a CRT-P device compared with a traditional dual-chamber pacemaker in a population with AV block and an LVEF of less than 50% and no restriction of QRS width.28
It is clear that CRT is beneficial in patients with heart failure and either wide QRS or need for permanent pacing. The focus of the remainder of this section is to review the data supporting the specific use of CRT in patients with AF and heart failure in whom permanent pacing is required because of AV nodal ablation. In order to achieve the benefit of CRT, it must be operating at or near 100% of the time. This level can be difficult to achieve in patients with medically refractory AF because of sustained heart rates greater than the lower rate limit of the pacemaker. Several studies have shown that AV node ablation is necessary to produce the greatest benefit in patients with AF receiving CRT.29–31 In one such study, patients with AF and a standard indication for CRT therapy (EF <35%, QRS >120, NYHA II/III) were followed. Patients with less than 85% biventricular pacing after 2 months were referred for AV node ablation. Only the patients who received AV node ablation had improvement in symptoms and left ventricular function (Fig. 1).30 Whether or not patients in permanent AF receiving CRT benefit in the same manner as those in sinus rhythm has been addressed. In the recent
Fig. 1. In patients (pts) receiving CRT, this figure presents sequential changes of LVEF (A), exercise capacity (functional capacity score) (B), and changes in left ventricular end-systolic volume (C) in patients with sinus rhythm (SR) and AF with and without AV junction (AVJ) ablation. Also included is the total number of patients reaching the different follow-up visits and the number of deaths that occurred in the time interval since last follow-up (D). (From Gasparini M, Auricchio A, Regoli F, et al. 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):740; with permission.)
Carlson & Doshi MILOS (Long-term survival in patients undergoing cardiac resynchronization therapy: the importance of atrio-ventricular junction ablation in patients with permanent atrial fibrillation) study, a survival benefit was found in patients with heart failure with permanent AF receiving a CRT device. This benefit was similar to those patients in sinus rhythm, but again, only if the patients had also received and AV node ablation.31 The aforementioned studies show that in patients with heart failure and standard indications for CRT implantation, the presence of permanent AF does not reduce the overall benefit of CRT, as long as AV node ablation has been performed. There have been several trials that demonstrate the clinical benefit of biventricular pacing over right ventricular pacing in patients with heart failure with AF after AV node ablation, even in patients with an LVEF greater than 35% and narrow QRS.32–35 In the PAVE (Left Ventricular-Based Cardiac Stimulation Post AV Nodal Ablation Evaluation) study, patients receiving AV node ablation for medically refractory AF were randomized to either biventricular or right ventricular pacing. The biventricular group showed a significant improvement in the 6-minute hallway walk test and ejection fraction (Fig. 2). The investigators noted that this finding seemed to be greatest in patients with impaired systolic function or with symptomatic heart failure.32 Similarly, the APAF trial (Cardiac resynchronization therapy in patients undergoing atrioventricular junction ablation for permanent atrial fibrillation: a randomized trial) showed decreased heart failure events in the same population undergoing ablate and pace therapy with a CRT device compared with right ventricular pacing.36
Together, the aforementioned information has led to a recent update in the AHA/ACC’s guidelines regarding placement of CRT devices. The 2012 updated guidelines propose the following class IIa recommendations. CRT can be useful in patients with AF and LVEF less than or equal to 35% if (1) patients require ventricular pacing or otherwise meets the criteria and (2) AV nodal ablation or pharmacologic rate control will allow near 100% ventricular pacing CRT can be useful for patients who have an LVEF less than or equal to 35% and are undergoing new or replacement device placement with an anticipated requirement for significant (>40%) ventricular pacing. Although guidelines have reflected the benefit of CRT in patients with reduced LVEF despite narrow QRS if frequent pacing is required, further studies are needed to fully evaluate whether biventricular pacing is necessary over right ventricular pacing in patients with normal cardiac function. This need for further evaluation is partly caused by a recent meta-analysis looking at 4 studies that included patients with both normal and reduced LVEF who underwent AV node ablation for medically refractory AF and received either biventricular or right ventricular pacing. In the analysis it was found that, although there were significant improvements in structural and functional response to biventricular pacing, the survival benefit was the same between the two groups.37 It is hoped that this question will be answered by the ongoing Biventricular Pacing for Atrioventricular Block to Prevent Cardiac Desynchronization (BIOPACE)
Fig. 2. (A, B) Temporal changes in the 6-minute hallway walk test stratified by LVEF (>45% vs 45%) and NYHA class for patients randomized to biventricular (BV) versus right ventricular (RV) pacing. (A) a P<.05 compared with baseline, b P<.05 compared with RV 45% or less pacing. (B) a P<.05 compared with baseline, b P<.05 compared with NYHA II and III RV pacing. (From Doshi RN, Daoud EG, Fellows C, et al. Left ventricular-based cardiac stimulation post AV nodal ablation evaluation (the PAVE study). J Cardiovasc Electrophysiol 2005;16(11):1163–4; with permission.)
Heart Failure and Atrial Fibrillation study. This multicenter controlled randomized study will enroll 1200 patients to determine whether synchronous biventricular pacing to prevent iatrogenic ventricular desynchronization confers a clinical and survival benefit in patients with conventional indications for permanent ventricular pacing, regardless of QRS duration or LV size and function.38 Finally, it should be noted that curative therapy for drug-refractory AF may result in even more substantial improvements in symptoms and left ventricular function. The PABA-CHF (PulmonaryVein Isolation for Atrial Fibrillation in Patients with Heart Failure) trial compared curative ablation via pulmonary vein isolation, with AV node ablation and CRT device placement in patients with heart failure who had drug-refractory AF. The pulmonary vein ablation strategy was superior in several measures, including quality of life, symptoms, and LVEF.39 Prospective studies evaluating AF ablation as first-line therapy for AF in the heart failure population, such as the Catheter Ablation versus Antiarrhythmic Drug Therapy for Atrial Fibrillation (CABANA) trial, are currently in progress.40 In summary, the aforementioned patient requires a permanent pacemaker but does not meet the criteria for ICD given the new diagnosis of cardiomyopathy and need for further evaluation and treatment. In addition, it is reasonable to expect that his LV function will improve. CRT should be instituted over single-chamber right ventricular pacing given the proven benefit in regard to exercise tolerance, cardiac function, and survivability in patients with heart failure and medically refractory AF undergoing AV node ablation with subsequent permanent pacing.
REFERENCES 1. Moss AJ, Zareba W, Hall WJ, et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 2002;346(12):877–83. 2. Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 2005;352(3):225–37. 3. Kadish A, Dyer A, Daubert JP, et al. Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy. N Engl J Med 2004; 350(21):2151–8. 4. Buxton AE. Should everyone with an ejection fraction less than or equal to 30% receive an implantable cardioverter-defibrillator? Not everyone with an ejection fraction < or 5 30% should receive an implantable cardioverter-defibrillator. Circulation 2005; 111(19):2537–49 [discussion: 2537–49].
5. Hohnloser SH, Kuck KH, Dorian P, et al. Prophylactic use of an implantable cardioverter-defibrillator after acute myocardial infarction. N Engl J Med 2004; 351(24):2481–8. 6. Steinbeck G, Andresen D, Seidl K, et al. Defibrillator implantation early after myocardial infarction. N Engl J Med 2009;361(15):1427–36. 7. Bigger JT Jr. Prophylactic use of implanted cardiac defibrillators in patients at high risk for ventricular arrhythmias after coronary-artery bypass graft surgery. Coronary artery bypass graft (CABG) patch trial investigators. N Engl J Med 1997;337(22): 1569–75. 8. Mitrani RD, McArdle A, Slane M, et al. Wearable defibrillators in uninsured patients with newly diagnosed cardiomyopathy or recent revascularization in a community medical center. Am Heart J 2013; 165(3):386–92. 9. Epstein AE, Abraham WT, Bianco NR, et al. Wearable cardioverter-defibrillator use in patients perceived to be at high risk early post-myocardial infarction. J Am Coll Cardiol 2013;62(21):2000–7. 10. Epstein AE, DiMarco JP, Ellenbogen KA, et al. ACC/ AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: executive summary: a report of the American College of Cardiology/American Heart Association task force on practice guidelines (writing committee to revise the ACC/AHA/ NASPE 2002 guideline update for implantation of cardiac pacemakers and antiarrhythmia devices): developed in collaboration with the American Association for Thoracic Surgery and Society of Thoracic Surgeons. Circulation 2008;117(21):2820–40. 11. Kusumoto FM, Calkins H, Boehmer J, et al. HRS/ ACC/AHA expert consensus statement on the use of implantable cardioverter-defibrillator therapy in patients who are not included or not well represented in clinical trials. J Am Coll Cardiol 2014; 64(11):1143–77. 12. McNamara DM, Starling RC, Cooper LT, et al. Clinical and demographic predictors of outcomes in recent onset dilated cardiomyopathy: results of the IMAC (Intervention in Myocarditis and Acute Cardiomyopathy)-2 study. J Am Coll Cardiol 2011; 58(11):1112–8. 13. Umana E, Solares CA, Alpert MA. Tachycardiainduced cardiomyopathy. Am J Med 2003;114(1): 51–5. 14. Mukharji J, Rude RE, Poole WK, et al. Risk factors for sudden death after acute myocardial infarction: twoyear follow-up. Am J Cardiol 1984;54(1):31–6. 15. Bigger JT Jr, Fleiss JL, Kleiger R, et al. The relationships among ventricular arrhythmias, left ventricular dysfunction, and mortality in the 2 years after myocardial infarction. Circulation 1984;69(2):250–8. 16. Maggioni AP, Zuanetti G, Franzosi MG, et al. Prevalence and prognostic significance of ventricular
Carlson & Doshi
arrhythmias after acute myocardial infarction in the fibrinolytic era. GISSI-2 results. Circulation 1993; 87(2):312–22. Caruso AC, Marcus FI, Hahn EA, et al. Predictors of arrhythmic death and cardiac arrest in the ESVEM trial. Electrophysiologic Study Versus Electromagnetic Monitoring. Circulation 1997;96(6):1888–92. de Sousa MR, Morillo CA, Rabelo FT, et al. Non-sustained ventricular tachycardia as a predictor of sudden cardiac death in patients with left ventricular dysfunction: a meta-analysis. Eur J Heart Fail 2008;10(10):1007–14. Watanabe J, Shinozaki T, Shiba N, et al. Accumulation of risk markers predicts the incidence of sudden death in patients with chronic heart failure. Eur J Heart Fail 2006;8(3):237–42. Grimm W, Christ M, Bach J, et al. Noninvasive arrhythmia risk stratification in idiopathic dilated cardiomyopathy: results of the Marburg Cardiomyopathy Study. Circulation 2003;108(23):2883–91. Buxton AE, Lee KL, DiCarlo L, et al. Electrophysiologic testing to identify patients with coronary artery disease who are at risk for sudden death. Multicenter unsustained tachycardia trial investigators. N Engl J Med 2000;342(26):1937–45. Wood MA, Brown-Mahoney C, Kay GN, et al. Clinical outcomes after ablation and pacing therapy for atrial fibrillation: a meta-analysis. Circulation 2000; 101(10):1138–44. Tan ES, Rienstra M, Wiesfeld AC, et al. Long-term outcome of the atrioventricular node ablation and pacemaker implantation for symptomatic refractory atrial fibrillation. Europace 2008;10(4):412–8. Zhang XH, Chen H, Siu CW, et al. New-onset heart failure after permanent right ventricular apical pacing in patients with acquired high-grade atrioventricular block and normal left ventricular function. J Cardiovasc Electrophysiol 2008;19(2):136–41. Bristow MR, Saxon LA, Boehmer J, et al. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med 2004;350(21):2140–50. Moss AJ, Hall WJ, Cannom DS, et al. Cardiac-resynchronization therapy for the prevention of heart-failure events. N Engl J Med 2009;361(14): 1329–38. Cleland JG, Daubert JC, Erdmann E, et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med 2005;352(15): 1539–49. Curtis AB, Worley SJ, Adamson PB, et al. Biventricular pacing for atrioventricular block and systolic dysfunction. N Engl J Med 2013;368(17):1585–93. Dong K, Shen WK, Powell BD, et al. Atrioventricular nodal ablation predicts survival benefit in patients with atrial fibrillation receiving cardiac resynchronization therapy. Heart Rhythm 2010;7(9):1240–5.
30. Gasparini M, Auricchio A, Regoli F, et al. 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. 31. Gasparini M, Auricchio A, Metra M, et al. 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. 32. Doshi RN, Daoud EG, Fellows C, et al. Left ventricular-based cardiac stimulation post AV nodal ablation evaluation (the PAVE study). J Cardiovasc Electrophysiol 2005;16(11):1160–5. 33. Orlov MV, Gardin JM, Slawsky M, et al. 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. 34. Yu CM, Chan JY, Zhang Q, et al. Biventricular pacing in patients with bradycardia and normal ejection fraction. N Engl J Med 2009;361(22):2123–34. 35. Kay GN, Ellenbogen KA, Giudici M, et al. The Ablate and Pace trial: a prospective study of catheter ablation of the AV conduction system and permanent pacemaker implantation for treatment of atrial fibrillation. APT investigators. J Interv Card Electrophysiol 1998;2(2):121–35. 36. Brignole M, Botto G, Mont L, et al. Cardiac resynchronization therapy in patients undergoing atrioventricular junction ablation for permanent atrial fibrillation: a randomized trial. Eur Heart J 2011; 32(19):2420–9. 37. Chatterjee NA, Upadhyay GA, Ellenbogen KA, et al. Atrioventricular nodal ablation in atrial fibrillation: a meta-analysis of biventricular vs right ventricular pacing mode. Eur J Heart Fail 2012;14(6):661–7. 38. Funck RC, Blanc JJ, Mueller HH, et al. Biventricular stimulation to prevent cardiac desynchronization: rationale, design, and endpoints of the ’Biventricular Pacing for Atrioventricular Block to Prevent Cardiac Desynchronization (BioPace)’ study. Europace 2006; 8(8):629–35. 39. Khan MN, Jais P, Cummings J, et al. Pulmonary-vein isolation for atrial fibrillation in patients with heart failure. N Engl J Med 2008;359(17):1778–85. 40. Cleland JG, Coletta AP, Buga L, et al. Clinical trials update from the American College of Cardiology meeting 2010: DOSE, ASPIRE, CONNECT, STICH, STOP-AF, CABANA, RACE II, EVEREST II, ACCORD, and NAVIGATOR. Eur J Heart Fail 2010; 12(6):623–9. 41. Luchsinger JA, Steinberg JS. Resolution of cardiomyopathy after ablation of atrial flutter. J Am Coll Cardiol 1998;32:205–10.
Heart Failure and Atrial Fibrillation 42. Redfield MM, Kay GN, Jenkins LS, et al. Tachycardia-related cardiomyopathy: a common cause of ventricular dysfunction in patients with atrial fibrillation referred for atrioventricular ablation. Mayo Clin Proc 2000;75:790–5. 43. Edner M, Caidahl K, Bergfeldt L, et al. Prospective study of left ventricular function after radiofrequency
ablation of atrioventricular junction in patients with atrial fibrillation. Br Heart J 1995;74:261–7. 44. Rodriguez LM, Smeets JL, Xie B, et al. Improvement in left ventricular function by ablation of atrioventricular nodal conduction in selected patients with lone atrial fibrillation. Am J Cardiol 1993;72: 1137–41.