CHAPTER 3

The 2 alternative rhythm-management strategies for atrial fibrillation [or atrial flutter (AF/AFL)] are heart rate control and maintenance of sinus rhythm. The focus of this chapter is the comparison of the 2 strategies without discussing individual therapies, which are covered in Chapters 4–7 and 9. The discussion in this chapter is in the context of long-term care of recurrent AF/AFL. Emergency or acute care, where the therapeutic imperatives are different and there is a paucity of quality data,¹ is not covered here. Newly discovered, first episodes of AF/AFL patients are not included in the studies discussed below, and they may also have somewhat different therapeutic imperatives.

Each strategy is a recognized and a useful treatment option for rhythm management with its own limitations. Recurrent AF/AFL in most instances is a chronic problem and often progressive. Reassessment of treatment will frequently be needed over a lifetime. It is not uncommon for patients to move back and forth between the 2 rhythm-management strategies. The challenge is to choose the right strategy at a particular moment in time and recognize when it needs to be changed. The complexity and ever-changing character of overall management of AF/AFL means that care often falls to a team of healthcare professionals rather than a single individual (Chapter 13). In the shared-care model (Section 2: Multidisciplinary Team Approach to the Care of the AF Patient), it needs to be clear to the team who is the individual responsible for decisions about rhythm management.

RATE CONTROL—WHAT IS IT?

The electrocardiographic objective of the strategy of rate control is to keep the heart rate within certain limits while allowing AF/AFL to continue and/or recur. The physiologic basis for this approach has been reviewed elsewhere.2 The desired electrocardiographic outcome is prespecified range of heart rates. There is no clear consensus on whether the target heart rate range has only an upper limit or both upper and lower limits. There is also no clear consensus on how the electrocardiographic outcome should be measured—simple resting heart rate, 24-hour ambulatory ECG monitoring, or even more detailed assessment. The goal for the upper limit for heart rate has been more thoroughly explored, and complex assessment has no apparent advantage.³ There are guidelines for the upper rate that are not entirely congruent.⁴ On balance, the minimum standard is probably a resting heart rate of <100 bpm.⁵ A specific heart rate goal is really only applicable for persistent/permanent AF/AFL. There is no evidence for (or against) a specific heart rate goal for paroxysmal AF/AFL. In paroxysmal AF/AFL, the heart rate goal is highly individualized and empiric. Except when a pacemaker is involved in the therapy, there is no attempt in the heart rate-control strategy to restore regularity to the heart rate.²

The therapeutic choices for the rate-control strategy include: pharmacologic, nonpharmacologic (commonly atrioventricular junction ablation and a pacemaker, although pacing alone with specialized heart-rate algorithms, and atrioventricular junction modification without pacing have been tried), and hybrid (usually pharmacologic therapy plus a pacemaker) therapies. Although not as thoroughly investigated as intermittent pharmacologic rhythm control,⁶ intermittent pharmacologic rate control (pill-in-the-pocket) can be a useful gambit in selected patients when paroxysmal AF/AFL event rates are infrequent and last at least a few hours.

RHYTHM CONTROL—WHAT IS IT?

The electrocardiographic objective of the strategy of rhythm control is to restore and maintain sinus rhythm (or in some cases, an atrial paced rhythm) when AF/AFL is persistent, or to prevent episodes or at least decrease their frequency and/or shorten their duration when AF/AFL is paroxysmal. The hemodynamic advantages that are added to rate control by the rhythm-control strategy are restoration of atrioventricular synchrony and regularization of the heart rate. There is no consensus about how one determines whether or not the electrocardiographic objective of rhythm control has been met. When symptoms are thought to be reliably related to episodes of AF/AFL, symptoms may be the measure of success. However, many patients do not have symptoms. Even those with symptoms will also have asymptomatic episodes or attribute symptoms of extrasystoles to AF/AFL.⁷ Thus, suppression of symptoms is not a reliable assessment of the electrocardiographic outcome, although it is a perfectly reasonable clinical goal. A 24-hour ambulatory ECG monitor is probably only useful for electrocardiographic outcome when AF/AFL is likely to be present within a given 24-hour period. In research studies, and when it is clinically important, longer durations of Holter monitoring, wearable loop recorders, or even implantable loop recorders are increasingly used to assess electrocardiographic suppression of AF/AFL, which is then colloquially referred to as the semiquantitative concept of AF/AFL “burden.” Complete electrocardiographic suppression of AF/AFL over long periods of time, regardless of mode of therapy for rhythm control, is an infrequent event8 and probably an unachievable goal in most instances.

There are many therapies to achieve the electrocardiographic objectives of rhythm control. The available approaches include pharmacologic, nonpharmacologic (including catheter ablation, pacemakers with special antitachycardia software, surgery; and, for a short time, there was interest in implantable devices that would automatically electrically cardiovert), and hybrid therapies that include both pharmacologic and nonpharmacologic components. For persistent AF/AFL, transthoracic electrical cardioversion can be part of the therapy and will be discussed in Chapter 4. Intermittent pharmacologic rhythm control (pill-in-the-pocket) can be used to achieve a pharmacologic cardioversion when episodes of AF are infrequent but last at least a few hours.⁶

COMPARISON OF THE IMPACT OF RATE- AND RHYTHM-CONTROL STRATEGIES ON OUTCOMES OTHER THAN ELECTROCARDIOGRAPHIC OBJECTIVES

So far, we have merely described the electrocardiographic objectives of these 2 rhythm-management strategies. More importantly for the patient and the clinician is their impact on clinical and societal outcomes. Thoughtful consideration of the relative impact of the 2 treatment strategies and informed patient preference, including thoughtful evaluation of competing risk, is the basis for making informed decisions about which approach to use.⁴ Informed patient preference implies importance to patient education, as will be discussed in the context of multidisciplinary care in Chapter 13.

In the remainder of this chapter, the available data comparing the following outcomes: death, stroke/systemic embolus, worsening congestive heart failure, relief of symptoms/quality of life, and cost will be briefly considered. The data compares the 2 strategies to each other when used as first therapy at a particular point in time. Such a comparison primarily determines whether or not on average there is incremental value over rate control by attempting to restore and maintain sinus rhythm.

The following discussion will focus on pharmacologic rate and rhythm control. Pharmacologic therapy is still the mode of therapy for the vast majority of AF/AFL patients, and the evidence base is more robust, although incomplete. A brief perspective on catheter ablation with respect to choice of strategy will be included at the end of this chapter, but catheter ablation is primarily covered in Chapters 6 and 7. Other nonpharmacologic therapies and hybrid therapies will not be discussed here, as the evidence base with respect to these clinical outcomes is modest at best and nonexistent at worst. They are discussed in Chapters 6 and 7.

Death

The existence of a causative association between AF/AFL and death remains controversial. Rhythm management for AF/AFL can only be expected to impact death caused by AF/AFL or death owing to adverse effects of rhythm-management therapy. Perhaps the best epidemiological evidence about the relationship between death and AF/AFL comes from the Framingham Heart Study,⁹ which is often misquoted, usually by citing unadjusted hazard ratios. After adjustment for other available covariates associated with death and removal of those who died within 30 days of incident AF/AFL, the hazard ratios for death were rather modest and statistically insignificant for men: men = 1.1 (0.9–1.4); women = 1.5 (1.2–1.8).

The question to be considered here is whether or not one rhythm-management strategy has an advantage with respect to impact on death. That question can only be answered in well-designed randomized clinical trials that include a suitable number of patients with comorbidities that enhance the risk of death that might actually be directly or indirectly caused by AF/AFL. Such information is really only available in the case of pharmacologic rate- and rhythm-control strategies. The results of the 3 largest and most relevant trials with a total of approximately 6000 patients enrolled are summarized in Table 3.1.^10–12 The 3 trials^10–12 are not directly comparable, as they differ in size and length of follow-up; Rate Control Versus Electrical Cardioversion for Persistent Atrial Fibrillation (RACE) only enrolled persistent AF/AFL, and Atrial Fibrillation and Congestive Heart Failure (AF-CHF) only enrolled patients with AF/AFL and heart failure with reduced left ventricular systolic function. Nevertheless, as can be seen from Table 3.1, there is no clear advantage of one rhythm strategy over the other with respect to death in this broad spectrum of AF/AFL patients.

*Unpublished

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