Atrial Fibrillation and Heart Failure

HomeCirculationVol. 119, No. 18Atrial Fibrillation and Heart Failure Free AccessReview ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessReview ArticlePDF/EPUBAtrial Fibrillation and Heart FailureTreatment Considerations for a Dual Epidemic Elad Anter, MD, Mariell Jessup, MD and David J. Callans, MD Elad AnterElad Anter From the Cardiovascular Division, Department of Medicine, University of Pennsylvania, Philadelphia. Search for more papers by this author , Mariell JessupMariell Jessup From the Cardiovascular Division, Department of Medicine, University of Pennsylvania, Philadelphia. Search for more papers by this author and David J. CallansDavid J. Callans From the Cardiovascular Division, Department of Medicine, University of Pennsylvania, Philadelphia. Search for more papers by this author Originally published12 May 2009https://doi.org/10.1161/CIRCULATIONAHA.108.821306Circulation. 2009;119:2516–2525Atrial fibrillation (AF) and heart failure have emerged as new cardiovascular epidemics over the last decade.1 Heart failure affects ≈5 million patients in the United States, and >550 000 patients are diagnosed with new heart failure each year.2 Although the incidence of heart failure remained stable over the past 50 years, the prevalence of heart failure in the United States has steadily increased. Heart failure is the primary reason for 12 to 15 million office visits and 6.5 million hospital days yearly.3 From 1990 to 1999, the annual number of hospitalizations increased from ≈800 000 to >1 million for heart failure as a primary diagnosis and from 2.4 to 3.6 million for heart failure as a primary or secondary diagnosis.4 The steadily increasing number of patients with heart failure is due partially to better treatment and “salvage” of patients with acute myocardial infarctions earlier in life.2 As a consequence, heart failure carries a significant economic burden on our society because it is the most common discharge diagnosis and because more Medicare dollars are spent for the diagnosis and treatment of heart failure than for any other diagnosis.5 In 2007, the American Heart Association estimated that $33 billion was spent on heart failure alone.6AF is the most common arrhythmia in clinical practice, accounting for approximately one third of admissions resulting from cardiac rhythm disturbances. An estimated 2.3 million people in North America have AF. During the last 20 years, hospital admissions for AF have increased by 66% for a number of reasons, including the aging of the population, the rising prevalence of chronic heart disease, and more frequent diagnosis as a result of increased monitoring.7 The recent Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) study projected that the prevalence of AF will increase 2.5-fold by the year 2050, affecting nearly 5.6 million Americans, an estimate based on the growing proportion of elderly individuals in the United States.8 The predicted future prevalence of AF was even greater in a community-based study by Miyasaka and colleagues.9 They observed that the age-adjusted incidence of AF increased by 12.6% over the period from 1980 to 2000. Assuming the rate of increase in incidence remains unabated and assuming that these incidence rates can be applied to the entire US population, the projected number of persons with AF in the United States could reach 15.9 million by 2050.The Association Between AF and Heart FailureThe association between AF and heart failure was appreciated almost a century ago10; Paul Dudley White noted, “Since auricular fibrillation so often complicates very serious heart disease, its occurrence may precipitate heart failure or even death, unless successful therapy is quickly instituted.”11 The reported prevalence of AF in modern heart failure series ranges from 13% to 27%.12–16 In the Framingham Heart Study, 1470 participants developed either new AF or heart failure between the years 1948 and 1995. Among these participants, a total of 383 individuals (26%) developed both AF and heart failure.17 Moreover, the prevalence of AF in patients with heart failure increased in parallel with the severity of the disease, ranging from 5% in patients with mild to 10% to 26% among patients with moderate up to 50% in patients with severe heart failure.18Although the causative relationship between the 2 conditions has not been fully determined, their coexistence can be explained to some degree by the presence of common risk factors such as age, hypertension, diabetes, and obesity, as well as valvular, ischemic, and nonischemic structural heart disease. These factors are associated with myocardial cellular and extracellular alterations, electrophysiological and neurohormonal changes that combine to create an environment that predisposes the heart to both myocardial failure and AF.19AF and Heart Failure: A Cause or a Consequence?The pathophysiological relationship between AF and heart failure has been only partially elucidated and has therefore remained a subject of vibrant research. AF may facilitate the development or progression of heart failure in several ways (Figure 1). The increase in resting heart rate and the exaggerated heart rate response to exercise result in shorter diastolic filling time, leading to a reduction in cardiac output. This is further affected by the irregularity of the ventricular response: The reduction in left ventricular (LV) filling during short cycles is not completely compensated for by increased filling during longer cycles. The loss of effective atrial contractile function also contributes, even more importantly in patients with diastolic dysfunction. In a prospective study of 344 patients with heart failure and sinus rhythm, the onset of AF was associated with highly significant worsening of the New York Heart Association (NYHA) functional class, peak oxygen consumption, and cardiac index, along with increased mitral and tricuspid regurgitation.20 Restoration of sinus rhythm improves cardiac output, exercise capacity, and maximal oxygen consumption.21Download figureDownload PowerPointFigure 1. AF and heart failure (HF): a vicious pathophysiological cycle. LA indicates left atrial; MR, mitral regurgitation; and TR, tricuspid regurgitation.AF is the most common cause of tachycardia-induced cardiomyopathy (Figure 2). The first case of tachycardia-induced cardiomyopathy was reported in 1913 in a young man with AF and a rapid ventricular rate who developed unexplained LV dilatation and heart failure.22 In 1937, a similar case was reported in which heart failure was reversed after restoration of sinus rhythm.23 Whipple et al24 provided the first experimental model for this condition, demonstrating that rapid and protracted atrial pacing led to low-output heart failure. Subsequent investigations have confirmed that persistent tachycardias can cause heart failure and that elimination of these arrhythmias reverses the hemodynamic and clinical manifestations associated with this syndrome.25–29 The mechanisms responsible for tachycardia-induced cardiomyopathy have not been fully elucidated; however, experiments in animal models suggest that myocardial ischemia, myocardial energy depletion, and abnormalities in calcium regulation all may contribute.30 The incidence of tachycardia-induced cardiomyopathy is unknown; most reports have been small, retrospective series or case studies involving mostly patients with AF. Nevertheless, some component of tachycardia-induced myopathy is seen in 25% to 50% of those with LV dysfunction and AF.31–33 The detrimental effects of AF on heart failure also may derive from the antiarrhythmic therapy itself. Some antiarrhythmic drugs have negative inotropic effects, whereas others are associated with an increased proarrhythmic risk, especially in patients with structural heart disease.34Download figureDownload PowerPointFigure 2. Ventricular reverse remodeling in an 18-year-old patient with unrecognized atrial tachycardia-induced cardiomyopathy. After atrial tachycardia ablation, a significant reduction in LV dimension was noted, corroborated by a gradual increase in LVEF from 12% to 45%. EDD indicates end-diastolic dimension; ESD, end-systolic dimension. Modified from Ilkanoff et al. Changes in ventricular dimensions and function during recovery of atrial tachycardia-induced cardiomyopathy treated with catheter ablation. J Cardiovasc Electrophysiol. 2007;18:1104–1106, with permission of the publisher. Copyright © 2007 Wiley-Blackwell.Similarly, heart failure can increase the risk for the development of AF in several ways, including elevation of cardiac filling pressures, dysregulation of intracellular calcium, and autonomic and neuroendocrine dysfunction (Figure 1). Atrial stretch results in activation of stretch-activated ionic currents, leading to increased dispersion of refractoriness and alterations in anisotropic and conduction properties, facilitating AF.35 Inhibition of these stretch-activated currents by gadolinium can reduce the susceptibility to AF in response to atrial pressure overload.36 Heart failure has been associated with increased interstitial fibrosis.37 This increase in fibrosis can lead to abnormal conduction through the atria, creating a substrate for AF in animal models.37–39 Dysregulation of intracellular calcium, an important feature in the pathophysiology of heart failure, also has been found to be associated with AF. The key regulators of intracellular calcium metabolism, the ryanodine receptor and the sarcoplasmic reticulum Ca2+-ATPase, are downregulated in AF.40,41 In addition, heart failure is characterized by neurohormonal activation, with elevated concentrations of catecholamine and angiotensin II; the degree of neurohormonal activation correlates with the severity of heart failure and has become a target of pharmacological inhibition. Interestingly, neurohormonal activation also promotes structural remodeling and atrial fibrosis, thus altering atrial conduction properties and promoting AF.37,42AF: Independent Risk Factor or a Marker of Advanced Disease?The prognostic significance of AF in patients with heart failure remains controversial because no consensus exists that AF is an independent risk factor of adverse outcome (the Table).13,43–45b In the Framingham Heart Study, AF was associated with twice the cardiovascular mortality compared with sinus rhythm. However, the independent contribution of AF to mortality was not assessed.46 In the Vasodilator Heart Failure Trial (V-HeFT), the presence of AF was not associated with a worse outcome in 1427 patients with mild to moderate heart failure.13 Two other relatively small studies also revealed no independent prognostic significance of AF in patients with heart failure.14,47 The results of these studies contrast with other, more recent, large heart failure trails. In a retrospective analysis of the Studies of Left Ventricular Dysfunction (SOLVD) trial, which enrolled 6500 patients with LV ejection fraction (LVEF) <35%, baseline AF was an independent predictor for all-cause mortality, progressive pump failure, and the combined end point of death or hospitalization for heart failure.48 In the SOLVD registry data, the odds ratio for total mortality among heart failure patients with AF compared with patients in sinus rhythm was 1.81 (P<0.0001).49 In the Valsartan in Acute Myocardial Infarction (VALIANT) trial of 14 703 patients with acute myocardial infarction complicated by heart failure, AF also was associated with greater long-term morbidity and mortality.50 In a retrospective analysis of the Carvedilol or Metoprolol European Trial (COMET), which included 3029 patients with LVEF <35%, baseline AF significantly increased the risk for death and heart failure hospitalization. However, after adjustment for other predictors of prognosis, AF was no longer an independent risk factor for mortality.51 Middlekauf et al12 found that patients with advanced heart failure and AF had significantly reduced 1-year survival compared with sinus rhythm patients. Moreover, AF seemed to be a stronger predictor of negative outcome in the subset of patients with mild to moderate heart failure compared with patients with severe heart failure, in whom the contribution of AF to further impairment in survival was limited. Similarly, Corell et al52 found that the presence of AF in outpatients with heart failure also was associated with increased morbidity and mortality and that AF was a stronger predictor of adverse outcome in patients with better cardiac function (LVEF >35%). In the Trandolapril Cardiac Evaluation (TRACE) study, Pedersen et al53 found that long-term mortality was increased in all subgroups of patients with AF except those with the most advanced disease (LVEF <25%). From these trials, it appears that AF serves as a negative prognostic marker in patients with systolic heart failure, and the independent effect of AF on mortality is inversely related to the severity of heart failure. Table. Prognostic Significance of AF in Patients With Heart FailureAuthor/SubstudyYearNYHA ClassPatients, nAF, %Follow-Up, yPatients in SR, nPatients With AF, nPPredictorSR indicates sinus rhythm; DIG, Digitalis Investigation Group; PRIME II, Prospective Randomized study of Ibopamine on Mortality and Efficacy.*After adjustment for important prognostic variables.Middlekauff et al121991III–IV395191.529480.0013YesCarson et al13 V-HeFT I1993II–III632152.564540.86No V-HeFT IIII–III795132.052460.68Dries et al48/SOLVD1998I–IV651762.82334<0.001YesMahoney et al141999III–IV234271.116230.21NoMiddlekauf et al12 1985–19891998III–IV359202.045610.002Yes 1990–1993III–IV391242.025340.09NoMathew/DIG45a2000I–IV7788113.032430.0001YesCrijns/PRIME II45b2000III–IV409843.44760NS*NoKøber/VALIANT2006I–IV14703153.02037<0.0001YesSwedberg et al51/COMET2005II–IV3029205.03742NSNo*Although multicenter studies in patients with heart failure have provided valuable data on the importance of AF in this setting, it is critical to realize that AF was not the focus of these studies and that the data quality with respect to the presence of AF has not been adjudicated. In most of these trials, monitoring for the onset of AF or recurrence, in the absence of hospitalization, consists of ECGs at the study onset and scheduled visits. This approach lacks the power to detail the variety of ways AF affects patients.Even taking this limitation into account, it is interesting that many studies have found that new-onset AF carries a particularly grave prognosis in patients with heart failure. Ahmed and Perry54 found that among 944 elderly patients hospitalized with heart failure, the onset of new AF carried a significantly higher risk for death compared with patients with no AF or those with chronic AF (hazard ratio, 1.41; 95% confidence interval, 1.08 to 1.83). Over 80% of patients hospitalized with heart failure and found to have new-onset AF died within 4 years of discharge compared with only 61% to 66% in those without AF or with persistent AF. In a 21-year community-based cohort study of patients with newly diagnosed AF, the mortality risk was substantially higher within the first 4 months, with an hazard ratio of 9.62 (95% confidence interval, 8.93 to 10.32) compared with the hazard ratio of 1.66 (95% confidence interval, 1.59 to 1.73) thereafter (Figure 3).55 In an analysis of COMET, new-onset AF, but not baseline AF, remained an independent predictor of all-cause mortality.51 Development of new AF was associated with increased mortality in the Framingham Heart Study as well.17 Pozzoli et al20 prospectively studied patients with mild heart failure in sinus rhythm and found that the onset of AF was associated with a clinical and hemodynamic deterioration, predisposition to systemic thromboembolism, and overall poorer prognosis. The association between new-onset AF and heart failure progression is not evidence for a causative relationship and may simply be a marker for disease progression. Nonetheless, few plausible mechanisms may explain how new development of AF can lead to clinical and hemodynamic deterioration. First, the adequacy of rate control achieved either naturally over time or by medications is usually better than ventricular rates accompanying a new presentation of AF. Second, the potential to develop adverse effects to antiarrhythmic medications is highest during the initiation phase. Third, initiation of warfarin therapy, especially in elderly patients, carries considerable risk for both underanticoagulation and overanticoagulation despite adherence to well-established warfarin initiation protocols.56 Fourth, development of new AF in a failing heart may pose a significant metabolic demand on the myocardial tissue until compensatory metabolic pathways are upregulated. Download figureDownload PowerPointFigure 3. Survival of patients with AF compared with age- and gender-matched control subjects in a 21-year community-based study. Survival for the entire study population of patients diagnosed with first AF (left) and for the subgroup of survivors who lived beyond the first 4 months after the initial diagnosis (Dx) (right) compared with the age- and gender-matched general Minnesota population. Adapted from Miyasaka et al. Mortality trends in patients diagnosed with first atrial fibrillation: a 21-year community-based study. J Am Coll Cardiol. 2007;49:986–992, copyright © 2007, with permission from the American College of Cardiology.Therapeutic ConsiderationsRate or Rhythm ControlAF with rapid ventricular response can lead to systolic heart failure, whereas restoration of sinus rhythm or appropriate rate control can reverse this process.57 Controversy still exists as to whether patients with heart failure respond better to rhythm restoration or ventricular rate control, commonly referred to as the issue of rhythm or rate control. The AF Follow-Up Investigation of Rhythm Management (AFFIRM) and the Rate Control Versus Electrical Cardioversion for Persistent AF (RACE) found that a rhythm control strategy provided no benefit and actually showed a trend toward harm in the general population of patients compared with rate control.58,59 Subsequent analyses have demonstrated a powerful benefit (hazard ratio, 0.5) of actually maintaining sinus rhythm as opposed to assignment to the rhythm control strategy, which seemed to be completely offset by the hazard of antiarrhythmic drug therapy (hazard ratio, 1.49).60 This response might be confounding because patients who were able to maintain sinus rhythm in AFFIRM may just be healthier than those who did not. Three other prospective randomized trials have compared rate and rhythm control. These studies include the How to Treat Chronic Atrial Fibrillation (HOT CAFE),61 Strategies of Treatment of Atrial Fibrillation (STAF),62 and Pharmacological Intervention in Atrial Fibrillation (PIAF)63 clinical trials. Each had similar results, showing equivalent outcomes in both arms. However, only 23% to 64% of patients assigned to rhythm control remained in sinus rhythm.Nevertheless, extrapolation from these studies to patients with heart failure should be done with caution. These studies included older patients or young patients with increased risk for stroke who were sufficiently tolerant of AF to be randomized. LV function was normal in 76% of AFFIRM patients, and only 9% had an NYHA functional class of II or greater. A separate large study of >1000 patients with heart failure and AF similarly demonstrated no benefit on overall mortality of rhythm compared with rate control.64 The recently published Atrial Fibrillation and Congestive Heart Failure (AF-CHF) trial was the first prospective randomized study to examine the effect of rate versus rhythm control in a heart failure population.65 A total of 1376 patients with AF and systolic heart failure (mean LVEF, 27%) were randomized to rhythm control (typically with amiodarone) versus rate control. After a mean follow-up of 3 years, the investigators found that rhythm control did not improve mortality, hospitalization resulting from heart failure exacerbation, or stroke compared with rate control. This study therefore extends the findings of the AFFIRM trial to patients with heart failure, in whom the theoretical benefit of rhythm control would seem to be higher. Clinicians should be cautious in their acceptance of the AF-CHF trial as the final and definitive study about the role of rate or rhythm control in patients with heart failure. First, patients assigned to rate control were considered to be stable if they achieved adequate rate control both at rest and at low-level exercise, which may not necessarily be the case in “real-life” patients. Second, the benefit of sinus rhythm could have been counterbalanced by the harm of antiarrhythmic medications in a fashion similar to the AFFIRM study. Third, although the prevalence of sinus rhythm in the group assigned to rhythm control was as high as 80%, the actual percentage of patients free of AF after randomization may have been lower, reflecting a more traditional success rate of amiodarone in the range of 60% to 65%.66In addition, heart failure is caused by heterogeneous pathophysiological processes; hence, the hemodynamic effects of AF may be different in various forms of heart failure. It is plausible that the reduction in diastolic filling time (caused by elevation in heart rate) and the atrial contribution to LV filling is greater in patients with restrictive physiology such as patients with diastolic dysfunction. In theory, these patients may have a greater benefit from rhythm control. AF-CHF, however, studied only patients with systolic heart failure. Moreover, we currently know little about the characteristics of incident versus prevalent AF in AF-CHF, and it is possible that, similar to AFFIRM, only patients with relatively stable symptoms referable to AF were submitted to randomization.Ventricular Rate ControlOptimal ventricular rate in patients with AF is 60 to 80 bpm at rest and 90 to 115 bpm during moderate exertion.67 Therefore, adequate rate control cannot be determined by resting ECGs alone and should be assessed with 24-hour Holter monitors or by the evaluation of the chronotropic response during exercise. β-Blockers should be the first choice for rate control in patients with chronic heart failure and AF. β-Blockers may both control the ventricular response to AF and improve survival in patients with heart failure. A retrospective analysis of the US Carvedilol Heart Failure Trial demonstrated that carvedilol therapy improved outcome in patients with concomitant AF and heart failure.68 A retrospective analysis of COMET demonstrated a survival benefit for carvedilol in patients with AF, similar to the larger trial.51 In acute AF with rapid ventricular response, the use of digoxin, which has a relatively slow onset of action, is likely to be ineffective. Moreover, digoxin slows ventricular response to AF through enhancement of vagal tone and therefore is less effective in states of increased sympathetic tone such as exercise or worsening heart failure. However, digoxin improves symptoms and reduces hospitalizations in patients with heart failure and exerts a synergistic effect with β-blockers.69–71 A retrospective analysis of the US Carvedilol Heart Failure Trials program demonstrated improved survival with carvedilol in patients also treated with digoxin.68 Therefore, digoxin may be useful as an adjunct therapy to β-blockers in patients with AF and heart failure. Nondihydropyridine calcium channel blockers (including verapamil and diltiazem) also are effective rate-controlling agents. However, because of their negative inotropic effect, they may not be tolerated at doses required for optimal ventricular rate control, especially in patients with low LVEF.Rhythm Restoration or ControlAlthough a variety of antiarrhythmic agents are available for the treatment of AF in patients with structurally normal hearts, patients with heart failure are particularly susceptible to side effects of some commonly used antiarrhythmic agents. The Cardiac Arrhythmia Suppression Trial (CAST) was a randomized, placebo-controlled study that examined the effect of class IC antiarrhythmic drugs on patients with ventricular ectopy after myocardial infarction. This study showed that therapy with either flecainide or encainide was associated with increased mortality.72,73 The applicability of the CAST results to other populations (eg, those with chronic heart failure and no active ischemia) or other class IC antiarrhythmic drugs such as propafenone is uncertain. However, currently, it is prudent to consider any class IC antiarrhythmic to have a significant risk in patients with structural heart disease.The cornerstone of antiarrhythmic therapy in patients with heart failure is amiodarone, sotalol, and dofetilide. Amiodarone is among the most effective antiarrhythmic agents for the suppression of AF. Amiodarone is a class III agent (potassium channel blocker) with some overlap functional activity of class I agents such as β-blockers and calcium channel blockers. Amiodarone appears to be safe and effective in patients with heart failure.74 Despite its effectiveness, the use of amiodarone in patients with heart failure is associated with increased risk for symptomatic bradycardia requiring implantation of permanent pacemaker.75Dofetilide, a newer class III antiarrhythmic agent, also is commonly used to suppress AF. In the Danish Investigations of Arrhythmia and Mortality on Dofetilide (DIAMOND) congestive heart failure substudy, dofetilide was significantly more effective than placebo in restoring and maintaining sinus rhythm in patients with AF and heart failure.76 In addition, dofetilide therapy was associated with reduced hospitalizations for heart failure. Therapy with dofetilide is usually initiated in the hospital with close monitoring of the QT interval and dosage adjustments in patients with impaired renal function. Nevertheless, even with careful monitoring, therapy with dofetilide has been associated with increased risk for torsades de pointes, particularly in elderly patients with heart failure.Other, nonantiarrhythmic drug therapy has demonstrated effectiveness in reducing the incidence and recurrent rates of AF in the general population and in patients with heart failure. Inhibition of the renin-angiotensin-aldosterone system attenuates atrial electric remodeling and fibrosis, processes that are associated with an increased risk for development of AF.77–80 Clinical studies have demonstrated that renin-angiotensin-aldosterone system blockade with angiotensin receptor-1 blockers can reduce the incidence and recurrence rates of AF in patients with heart failure.81,82 In the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) study, treatment with candesartan reduced the incidence of AF in a large, broadly based population with heart failure.Therapy with β-blockers also was associated with reduced risk for AF. In a meta-analysis of 7 randomized, placebo-controlled trials including 11 952 patients with heart failure already taking angiotensin-converting enzyme inhibitors, β-blockers significantly reduced the incidence of new AF from 39 to 28 per 1000 patient-years (relative risk reduction, 27%).83Recent studies suggest that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statin) therapy may reduce the incidence and recurrence of AF in patients with heart failure.84,85 A recent meta-analysis of randomized trials with statins showed that their use was associated with a significant decreased risk of AF compared with control subjects (odds ratio, 0.39; 95% confidence interval, 0.18 to 0.85, p = 0.02). Moreover, the benefit of statin therapy seemed more marked in secondary prevention of AF (odds ratio, 0.33) than for new-onset or postoperative AF (odds ratio, 0.60).86Ablation and Pacemaker TherapyIn patients with symptomatic AF and rapid ventricular response refractory to pharmacological therapy, radiofrequency atrioventricular (AV) nodal ablation with subsequent pacemaker placement can improve cardiac performance. Manolis et al87 showed that in 46 patients with atrial tachyarrhythmias and rapid ventricular response refractory to medical therapy who underwent AV nodal ablation with placement of a permanent pacemaker, the LVEF improved from a mean of 42±16% to a mean of 50±14% after a 2-year follow-up. In the subgroup of patients with heart failure, the degree of improvement was even greater (32±9% to 48±8%). Moreover, the NYHA functional class improved from 2.7±0.6 to 1.4±0.8 (P<0.001).However, long-term outcomes of the “ablate and pace” strategy have been less favorable. In a study of 71 elderly patients with pharmacologically refractory AF assigned to either AV nodal ablation with pacing or AF ablation, AV nodal ablation with pacing was associated with a higher incidence of new heart failure compared with ablation of the AF after 5 years of follow-up (53% versus 24%). AV node ablation with pacing resulted in a significantly lower LVEF (44±8% versus 51±10%) and a higher NYHA functional class (1.7±0.9 versus 1.4±0.7) compared with the group assigned to AF ablation.88A large body of evidence has emerged recently that underscores the harmful effects of long-term right ventricular pacing. LV dyssynchrony imposed by right ventricular pacing can lead to LV remodeling with dilatation and decreases in LVEF.89 Mechanical ventricular dyssynchrony is an established contributor to heart failure, and cardiac resynchronization therapy (CRT) has emerged as an effective device-based therapy to improve symptoms and mortality in patients.90 This therapy also has proved to be ef