Noushin Sultana, MD
Rate or Rhythm Control?
Image courtesy of google images: emdose.org
63yo obese F pmh atrial fibrillation ((Afibb) on Coumadin), chronic obstructive pulmonary disease (COPD), obstructive sleep apnea (on home CPAP), hypertension, diabetes mellitus, presenting with worsening fatigue and generalized weakness and shortness of breath. The symptoms initially started with fatigue for 2 weeks and then progressed to dyspnea. The patient says she feels weak just walking around the house. She initially thought it was her COPD and gave herself nebulizer treatments, which did not help. She also complains of palpitations recently but denies chest pain.
VS: 165/80 P130 RR22 sat 99% on RA
CV: tachycardia and irregularly irregular pulse.
Resp: the lungs were clear bilaterally and patient was speaking in full sentences
ED course: EKG showed A fibb with rapid ventricular rate and no ischemic changes. She was given PO metoprolol and pushes of diltiazem to which she transiently responded. She was then placed on diltiazem drip and transferred to CCU. In the CCU her Afibb proved difficult to control even while on a diltiazem drip. To better control her rate she was loaded with digoxin. The digoxin improved her tachycardia but she remained in A fib and still was having symptoms. Th decision was made to start pharmacologic cardioversion with amiodarone which returned her to sinus rhythm.
Atrial fibrillation is one of the most common arrhythmias in the US. When patients present to the ED with Afibb, our goal is rate control. There has always been a debate about why not rhythm control. In theory, the restoration of sinus rhythm may prevent worsening disease and other complications secondary to the disease. Additionally, Afibb has a high rate of recurrence without anti-arrhythmic intervention. Rhythm control can be considered when patients are symptomatic even when rate controlled.
The current available drugs for rhythm control in Afibb are the class IA (quinidine, disopyramide), class IC (flecainide, propafenone), class III (amiodarone, dofelitide, sotalol). These rhythm control drugs have many harmful, pro-arrhythmic side effects including torsades, which class IA and III are known to cause. For example, propafenone and flecainide are contraindicated in ischemic heart disease and class IC drugs can cause Afibb to turn into atrial flutter with slow ventricular rate and wide QRS which can lead to cardiovascular collapse. Therefore, the use of these drugs involves careful decision making to identify appropriate candidates.
Many meta-analyses have been done on rate control vs rhythm control, the most prominent of which is the AFFIRM trial. This was a large, randomized, multi-center trial which first compared patients with pharmacologic rate vs rhythm control with anti-arrhythmic drugs and if these drugs were exhausted then electrical cardioversion was used. A limitation of this trial was that the numbers might have been diluted so that there were many patients in sinus rhythm during randomization to the control group and many who could not maintain sinus rhythm in the rhythm control group. Despite any limitations this trial showed no significant mortality benefit to maintaining sinus rhythm.
The RACE trial was similar to AFFIRM but only included patients with persistent Afibb and they had to have prior cardioversion. Thus, none of these patients were in sinus rhythm and they were randomized to either rate control only or repeat electrical cardioversion in addition to anti-arrythmic drugs. The end points they studied (cardiovascular death, heart failure, thromboembolism, bleeding, pacemaker insertion) did not differ between these two groups. Other meta-analyses included randomized controlled trials comparing rate and rhythm control. Two meta-analyses (Caldeira 2012, Cordina and Mead 2005) showed no difference in all cause mortality but did show an increase in hospitalizations in rhythm controlled patients.
There are guidelines that exist to determine whether rate or rhythm control is appropriate for a patient. In addition to other factors such as the type of atrial fibrillation (persistent, paroxysmal, permanent) and other comorbidities, the 2010 Canadian Cardiovascular Society offered that the following patients should be considered for rhythm control: newly detected Afibb, age younger than 65, and no previous anti-arrhythmic drug failure. The guidelines also offer an algorithm for what drugs to consider depending on left ventricular function: drugs for normal left ventricular function include dronedarone, flecainade, propafenone, sotalol and drugs from abnormal left ventricular function include amiodarone for severely decreased ejection fraction (<35%) and amiodarone, donedarone, and propafenone for an ejection fraction <35%.
One systematic review looking at effectiveness of anti-arrhythmic drugs to maintain sinus rhythm showed that all class IA, IC, and II (aside from drodenarone) drugs were effective, reducing recurrence by 30-50%. Of these drugs only class IA drugs seemed to significantly increase mortality. Compared to other drugs, amiodarone showed less mortality than the class I drugs but had no mortality benefit over placebo. Amiodarone also showed less adverse and pro-arrhythmic events compared to the class I drugs.
In conclusion, many studies show no mortality benefit to rhythm control and some even show increasing mortality with some anti-arrhythmics. This being said, patient’s with difficult to control Afibb may benefit from rhythm control tactics as a second line strategy. Of the anti-arrhythmic drugs, amiodarone seems to be the most safe and quinidine the least, relatively. The patient in the mentioned case had a good outcome with amiodarone and was discharged with both diltiazem and amiodarone. However, every case is different and consideration should be given to side effect profile of these drugs especially in combination with other drugs the patient is taking. The consensus seems to be that rhythm control is no better than rate control in terms of mortality but rhythm control often is successful in maintaining sinus rhythm and possibly controlling symptoms. If this is the case why not move toward initiating carefully chosen rhythm control as well if symptoms and quality of life improves without worsening mortality?
1. A Comparison of Rate Control and Rhythm Control in Patients with Atrial Fibrillation, New England Journal of Medicine 2002 347: 1825-1833
2. Zimetbaum, P. Anti-arrhythmic Drug Therapy in Atrial Fibrillation. Circulation. 2012. 125:381-389
3. Bunch, J. Rhythm Control Strategies and the Role of Anti-arrhythmic Drugs in the Management of Atrial Fibrillation. JGIM. 2010
4. Rate vs Rhythm Control in Atrial Fibrillation. Canadian Family Physician. Feb 2010 vol 59.
5. Anti-arrhythmic Drugs for Maintaining Sinus Rhythm After Cardioversion of Atrial Fibrillation: A Systematic Review of Randomized Controlled Trials. Arch Intern Med. 2006;166(7):719-728.
6. Ten Pearls for the Use of Anti-arrhythmics in Atrial Fibrillation. http://afibprofessional.cardiosource.org/Hot-Topics/2012/08/Ten-Pearls-for-the-Use-of-Antiarrhythmic-Drugs-for-Atrial-Fibrillation.aspx
7. Newer anti-arrhythmic agents for maintaining sinus rhythm in atrial fibrillation: simplicity or complexity? European Heart Journal. Volume 9.