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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



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]



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.  


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