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Rhythm Control vs. Rate Control in Atrial Fibrillation - by Philip Aagaard

posted Jun 15, 2015, 2:25 PM by Kevin Hauck

Rhythm Control is not dead. Rate vs. Rhythm Control Revisited

 

Background

Atrial fibrillation (AF) is the most common clinical arrhythmia and its incidence is predicted to increase due to the ageing population.[1] AF has several important clinical consequences, including an increased risk of stroke, heart failure and mortality, as well as a negative impact on quality of life.

Important risk factors for developing AF include hypertension, diabetes, and age.[2] In fact, age is the most important risk factor and the prevalence of AF increases from 0.7 % to 17.8% between the 6th and 9th decade of life.[3]

The most common triggers in new onset AF are pulmonary vein (PV) ectopy.[4] However, once an individual has developed AF, important structural and electrical remodeling occur in the atria that create a milieu which facilitates further progression and maintenance of AF, a concept known as “AF begets AF”.[5] This concept may help explain why AF commonly starts out as self-terminating episodes, i.e. paroxysmal AF, which can later progress to become persistent, and ultimately become long-standing persistent. When the patient remains in AF despite repeated attempts to maintain sinus rhytm (SR), and/or when such a strategy has been deemed futile, chronic AF is diagnosed.[6]

 

Pathophysiology

Atrial fibrillation has several negative hemodynamic consequences. Heart rate (HR) elevation in AF can cause myocardial ischemia, energy depletion and calcium handling abnormalities, eventually leading to tachycardia-induced cardiomyopathy.[7-10] Furthermore, the decreased ventricular filling during short cardiac cycles in AF cannot be fully compensated for during longer cycles, leading to a decrease in total cardiac output.[11] Finally, the loss of atrial contraction and atrio-ventricular synchrony in AF further reduces cardiac output. Importantly, patients with significant co-morbidities such as heart failure (HF), who may be less able to tolerate the loss of coordinated atrial contraction and atrioventricular synchrony during AF, may derive particular benefit from restoration and maintenance of SR.[12] In addition to its effects on cardiac performance, AF also leads to atrial blood stasis, increasing the risk of cardiac thrombus formation with a subsequent increased risk of stroke.[13] However, despite these known adverse consequences of AF, weather to choose a rhythm or rate control strategy in AF remains controversial.

 

Rate control

When a rate control strategy is chosen, the optimal rate has been considered to fall in the 60-80 BPM range at rest, and in the 90-115 BPM range during moderate exertion.[14] However, findings from the RACE-II trial failed to show a difference between strict (<80 BPM at rest and <110 BPM with moderate exertion) and more lenient rate control (<110 BPM at rest and with moderate exertion).[15] Beta-blockers or non-dihydropyridine calcium channel blockers (e.g. Diltiazem and Verapamil) are the initial drugs of choice for rate control in patients with AF. When these drugs fail to sufficiently reduce HR, digoxin can be added as an adjunctive agent. In patients who fail pharmacologic rate control, atrioventricular node ablation and ventricular pacing is an option of last resort.[16]

 

Rhythm control

Rhythm controling agents are used to maintain SR. There are several available agents including amiodarone, flecainide, propenafone, dronedarone, and dofetilide. However, their use is limited by pro-arrythmic effects (increased risk of malignant ventricular arrhythmias), significant drug–drug interactions, and adverse effects. For example, long-term use of amiodarone, one of the more commonly used rhythm control agents, is associated with significant pulmonary, hepatic, and thyroid toxicity and increases the risk for symptomatic bradycardia requiring pacemaker implantation.[17, 18] Promising newer AAD are under investigation, however, this is a topic beyond the scope of this review.[19]

Rate vs. rhythm control

Whether rhythm or rate control is the best strategy in HF failure patients with AF is, as stated previously, controversial. The AFFIRM and RACE trials showed no benefit of pharmacological rhythm control over pharmacological rate control in a general AF population.[20, 21] There was no difference, regardless of strategy, with respect to the endpoints of mortality, or hospitalization for HF or stroke. However, definite conclusions should not be drawn from these trials due to substantial crossover between treatment groups. Also, only pharmacological rhythm control therapies were evaluated and the negative results may partly reflect the poor efficacy of antiarrhythmic drugs to maintain SR. [20-22] In fact, an on-treatment analysis of the AFFIRM trial showed that patients that maintained SR had better outcomes. [23] While this may represent selection bias, it is also possible that the benefits of maintaining SR are offset by the adverse effects of the drugs. Therefore, a therapy that restores SR without the adverse effects of AADs could be superior to rate control.  AF ablation may offer such an opportunity.

 

Ablation strategies

The observation that ectopic beats originating near the pulmonary veins are responsible for the majority of paroxysmal AF episodes sparked interest in ablation as a curative therapy for AF.[24] Today, AF ablation by pulmonary vein isolation successfully restores SR in 60 to 80% of AF patients. A landmark study in 2004 showed that AF ablation resulted in significant improvements of left ventricular function, exercise tolerance, symptoms and quality of life.[12] This improvement occurred independent of the level of pre-procedural rate control, suggesting that factors other than rate (e.g. loss of atrial contraction, atrioventricular dyssynchrony, etc) also drives the deterioration of cardiac function in AF patients. Large clinical trials, including the CABANA trial, powered to also detect differences in mortality between AF ablation and rate control are currently ongoing, with Montefiore as one of the participating centers.  

References:

1.         Chugh SS, Havmoeller R, Narayanan K, et al. Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 Study. Circulation. 2014;129:837-47.

2.         Kirchhof P, Lip GY, Van Gelder IC, et al. Comprehensive risk reduction in patients with atrial fibrillation: emerging diagnostic and therapeutic options--a report from the 3rd Atrial Fibrillation Competence NETwork/European Heart Rhythm Association consensus conference. Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology. 2012;14:8-27.

3.         Heeringa J, van der Kuip DA, Hofman A, et al. Prevalence, incidence and lifetime risk of atrial fibrillation: the Rotterdam study. European heart journal. 2006;27:949-53.

4.         Kalifa J, Jalife J, Zaitsev AV, et al. Intra-atrial pressure increases rate and organization of waves emanating from the superior pulmonary veins during atrial fibrillation. Circulation. 2003;108:668-71.

5.         Wijffels MC, Kirchhof CJ, Dorland R, et al. Atrial fibrillation begets atrial fibrillation. A study in awake chronically instrumented goats. Circulation. 1995;92:1954-68.

6.         January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation. 2014;130:2071-104.

7.         Shinbane JS, Wood MA, Jensen DN, et al. Tachycardia-induced cardiomyopathy: a review of animal models and clinical studies. Journal of the American College of Cardiology. 1997;29:709-15.

8.         Van Gelder IC, Crijns HJ, Blanksma PK, et al. Time course of hemodynamic changes and improvement of exercise tolerance after cardioversion of chronic atrial fibrillation unassociated with cardiac valve disease. The American journal of cardiology. 1993;72:560-6.

9.         Wilson JR, Douglas P, Hickey WF, et al. Experimental congestive heart failure produced by rapid ventricular pacing in the dog: cardiac effects. Circulation. 1987;75:857-67.

10.       Zipes DP. Atrial fibrillation. A tachycardia-induced atrial cardiomyopathy. Circulation. 1997;95:562-4.

11.       Gosselink AT, Blanksma PK, Crijns HJ, et al. Left ventricular beat-to-beat performance in atrial fibrillation: contribution of Frank-Starling mechanism after short rather than long RR intervals. Journal of the American College of Cardiology. 1995;26:1516-21.

12.       Hsu LF, Jais P, Sanders P, et al. Catheter ablation for atrial fibrillation in congestive heart failure. The New England journal of medicine. 2004;351:2373-83.

13.       Shively BK, Gelgand EA,Crawford MH. Regional left atrial stasis during atrial fibrillation and flutter: determinants and relation to stroke. Journal of the American College of Cardiology. 1996;27:1722-9.

14.       Fuster V, Ryden LE, Cannom DS, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation. 2006;114:e257-354.

15.       Van Gelder IC, Groenveld HF, Crijns HJ, et al. Lenient versus strict rate control in patients with atrial fibrillation. The New England journal of medicine. 2010;362:1363-73.

16.       Doshi RN, Daoud EG, Fellows C, et al. Left ventricular-based cardiac stimulation post AV nodal ablation evaluation (the PAVE study). Journal of cardiovascular electrophysiology. 2005;16:1160-5.

17.       Singla S, Karam P, Deshmukh AJ, et al. Review of contemporary antiarrhythmic drug therapy for maintenance of sinus rhythm in atrial fibrillation. Journal of cardiovascular pharmacology and therapeutics. 2012;17:12-20.

18.       Weinfeld MS, Drazner MH, Stevenson WG, et al. Early outcome of initiating amiodarone for atrial fibrillation in advanced heart failure. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. 2000;19:638-43.

19.       Trulock KM, Narayan SM,Piccini JP. Rhythm Control in Heart Failure Patients With Atrial Fibrillation: Contemporary Challenges Including the Role of Ablation. Journal of the American College of Cardiology. 2014;64:710-21.

20.       Wyse DG, Waldo AL, DiMarco JP, et al. A comparison of rate control and rhythm control in patients with atrial fibrillation. The New England journal of medicine. 2002;347:1825-33.

21.       Van Gelder IC, Hagens VE, Bosker HA, et al. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. The New England journal of medicine. 2002;347:1834-40.

22.       Roy D, Talajic M, Nattel S, et al. Rhythm control versus rate control for atrial fibrillation and heart failure. The New England journal of medicine. 2008;358:2667-77.

23.       Corley SD, Epstein AE, DiMarco JP, et al. Relationships between sinus rhythm, treatment, and survival in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) Study. Circulation. 2004;109:1509-13.

24.       Haissaguerre M, Shah DC, Jais P, et al. Electrophysiological breakthroughs from the left atrium to the pulmonary veins. Circulation. 2000;102:2463-5.


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