Atrial fibrillation: Management

Pharmacologic therapy

Oral or intravenous (IV) atrioventricular nodal (AVN) blockers are utilized for rate control, depending on the severity of symptoms and the degree of hemodynamic compromise caused by the tachycardia. The choice of rate-controlling drugs, alone or in combination, depends on symptoms, comorbidities, and potential side effects.

Beta-blockers or nondihydropyridine calcium channel blockers (verapamil and diltiazem) are the drugs of choice for rate control, and they appear to have equivalent efficacy. Care should be used in administering those medications in patients with acutely decompensated heart failure.

Beta-blockers are preferred in patients with cardiomyopathy, ischemic heart disease, and following surgical procedures. Based on older studies of beta-blocker therapy in patients with asthma that demonstrated acute drops in expiratory volumes and concerns for acute bronchoconstriction due to beta-receptor antagonism, verapamil and diltiazem have been preferred to beta-blockers for rate control of AF in patients with obstructive lung disease. However, it is worth noting that there is a growing body of evidence demonstrating that rate control of AF with either selective and nonselective beta-blockers is associated with lower mortality than with calcium channel blockers or digoxin, and without an adverse effect on pulmonary function.

Digoxin is less effective and requires a longer time to achieve rate control but may be considered if beta-blockers and calcium channel blockers have failed or have intolerable side effects. While digoxin reduces the resting heart rate, it is seldom effective in ambulatory patients because its effects are mediated by enhancement of vagal tone, which is offset during exertion. Thus, digoxin has traditionally been used as a second-line agent, usually in sedentary patients or those with heart failure or hypotension. Importantly, recent systematic reviews and meta-analyses found that digoxin use was independently associated with a greater risk for mortality in patients with AF, regardless of concomitant heart failure. Some studies have suggested that AF nullifies the effect of digoxin in reducing hospitalizations for heart failure patients. Hence, the long-term use of digoxin is discouraged.

Amiodarone can be considered for rate control when other AVN blockers are unsuccessful or not tolerated. IV amiodarone is useful for acute control of the ventricular rate and can be of particular value in acutely ill patients or those with acutely decompensated heart failure or severe hemodynamic compromise. Because of the probability of termination of AF by amiodarone, though very small, pericardioversion anticoagulation strategies should be considered, depending on the individual patient’s risk/benefit profile. Oral amiodarone can be useful for ventricular rate control when other measures are unsuccessful or contraindicated; however, long-term potential toxicity should be carefully considered.

In patients with AF and ventricular preexcitation causing rapid ventricular response, prompt direct-current cardioversion is recommended, especially when hemodynamic compromise is present. IV procainamide or ibutilide to restore NSR or slow the ventricular rate can be considered in hemodynamically stable patients. Importantly, drugs that preferentially slow AVN conduction without prolonging bypass tract refractoriness (such as verapamil, diltiazem, adenosine, oral or IV digoxin, and IV amiodarone) can accelerate the ventricular rate and potentially precipitate hemodynamic collapse and ventricular fibrillation (VF) in high-risk patients. Unlike the IV route of administration, chronic oral amiodarone therapy can slow or block bypass tract conduction. Limited data exist regarding the use of beta-blockers; nonetheless, these drugs theoretically pose a similar potential risk, and they should be used with caution.

Assessing adequacy of rate control

Adequacy of rate control should be assessed at rest and during activity. However, parameters for optimal rate control in AF remain controversial. It appears reasonable to target a resting heart rate of 60 to 80 beats/min and 90 to 115 beats/min during moderate exercise. Ambulatory monitoring can help assess adequacy of rate control; goals of therapy include a 24-hour average heart rate lower than 100 beats/min and no heart rate higher than 100% of the maximum age-adjusted predicted exercise heart rate. Also, a maximum heart rate of 110 beats/min during a 6-minute walk test is a commonly used target.

Nonetheless, a more lenient rate control (resting heart rate less than 110 beats/min) has been found to be noninferior to strict rate control (heart rate less than 80 beats/min at rest and less than 110 beats/min during moderate exercise). Such an approach can be more convenient in clinical practice and can be considered especially in asymptomatic patients with permanent AF and no significant structural heart disease, but periodic monitoring of left ventricular (LV) function is mandatory to evaluate for the potential risk of tachycardia-mediated cardiomyopathy. The 2020 European Society of Cardiology AF guidelines recommended lenient rate control as an acceptable initial approach regardless, with stricter control reserved for patients with tachycardia-induced cardiomyopathy, when patients remain symptomatic, or when there is biventricular pacing in order to achieve higher biventricular pacing percentage.

In some patients with sinus node dysfunction (SND) or tachycardia-bradycardia syndrome, pacemaker implantation can be required to protect from severe bradycardia while allowing the use of AVN blockers for adequate control of fast ventricular rates during AF or the use of antiarrhythmic drug therapy for maintenance of NSR (see Fig. 9.6 ). In one report, nearly 20% of patients with AF required pacemaker placement for symptomatic bradycardia, most within 5 years of their AF diagnosis, which was especially common in those with a history of heart failure. In patients with SND, atrial or dual-chamber pacing significantly decreases the incidence of subsequent AF compared with ventricular pacing.

Atrioventricular junction ablation

Ablation of the AV junction combined with permanent pacemaker implantation (the “ablate and pace” approach), provides robust control of ventricular rate as well as regularization of the R-R interval. However, because it is permanent and mandates lifelong pacing, AV junction ablation usually is considered as a last resort approach in AF patients when rhythm control strategies fail and pharmacological rate control therapy is poorly tolerated or unsuccessful. AV junction ablation is especially useful when excessive ventricular rates induce a tachycardia-mediated decline in LV systolic function, despite appropriate medical therapy.

Furthermore, among patients with LV systolic dysfunction and AF, AV junction ablation has emerged as an important adjunctive therapy for cardiac resynchronization recipients. It has been estimated that 20% to 25% of those eligible for cardiac resynchronization have AF, and the cumulative incidence of new-onset AF/ATs ranges between 20% and 40%, according to device interrogations. In patients with permanent AF or frequent persistent or paroxysmal arrhythmia episodes despite attempts to maintain NSR, intrinsic ventricular rate during AF (even though within the normal rate range) can override the biventricular pacing rate and reduce the percentage of effectively biventricular paced QRS complexes, thus precluding optimal ventricular resynchronization. Ablation of the AV junction in this setting has been associated with a reduction in all-cause mortality, a reduction in cardiovascular mortality, and an improvement in LV ejection fraction (LVEF) compared with those patients who were managed medically. It is important to note that the percentage of biventricular pacing determined by device counters often is artificially high because of invalid counting of fusion (hybrid between paced and intrinsic QRS morphologies) and pseudo–fusion complexes (pacing artifacts delivered but intrinsic QRS morphology not altered). In these patients, exercise ECG testing can help detect loss of effective ventricular synchronization and determine the percentage of pure biventricular pacing. AV junction ablation can also be required in ICD patients experiencing inappropriate therapies triggered by fast ventricular rates during AF.

Reversion to sinus rhythm

When rhythm control strategy is chosen, both electrical and pharmacological cardioversion methods are appropriate options. The timing of attempted cardioversion is influenced by the duration of AF, severity of patient’s symptoms, adequacy of rate control, and risk of thromboembolism. Prompt cardioversion is recommended for patients with rapid ventricular rates and hemodynamic compromise attributed to AF (hypotension, acute heart failure, myocardial ischemia) or ventricular preexcitation, when rate-control drug therapy is unsuccessful or not tolerated. Cardioversion is also considered to restore NSR in stable but symptomatic patients with persistent AF, especially when ventricular rate control remains suboptimal.

Maintenance of sinus rhythm

Although electrical cardioversion restores NSR in up to 90% of patients, the rate of AF recurrence without chronic antiarrhythmic therapy is 57% to 63% within 4 weeks and 70% to 80% within 1 year. Arrhythmia recurrence is less likely in patients with AF for less than 1 year, no enlargement of the LA (less than 4.0 cm), and a reversible cause of AF (such as hyperthyroidism, pericarditis, pulmonary embolism, or cardiac surgery). It has been thought that the drugs most likely to maintain NSR suppress triggering ectopic beats and arrhythmias and affect atrial electrophysiological (EP) properties to diminish the likelihood of AF. There is, therefore, a strong rationale for antiarrhythmic drug therapy in patients who have a moderate to high risk of recurrence, provided that the therapy is effective and that toxic and proarrhythmic effects are low. Prophylactic drug treatment is seldom indicated in patients with a first-detected episode of AF and can also be avoided in patients with infrequent and well-tolerated paroxysmal AF.

Amiodarone has been directly compared to dronedarone, sotalol, and propafenone and found to be substantially more effective, with a 1-year rate of maintaining NSR of 65%. Dofetilide offers 50% to 65% efficacy in maintaining NSR at 1 year. Other antiarrhythmic agents have only modest efficacy (30%–50% at 1 year). Drug selection is largely driven by the safety profile, the presence and extent of concomitant cardiovascular disease, hepatic and renal dysfunction, and drug-drug interactions. A safer, although possibly less efficacious, drug is usually recommended before resorting to more effective but less safe therapies ( Fig. 18.1 ; Table 18.1 ).

In patients with AF with and minimal or no heart disease, flecainide, propafenone, sotalol, and dronedarone are preferred; amiodarone should be chosen later in the sequence of drug therapy because of its potential toxicity. In patients with adrenergically mediated AF, beta-blockers represent first-line treatment, followed by sotalol. The anticholinergic activity of long-acting disopyramide makes it a relatively attractive choice for patients with vagally mediated AF. In contrast, propafenone is not recommended in vagally mediated AF because its (weak) intrinsic beta-blocking activity may aggravate this type of paroxysmal AF.

In patients with substantial LV hypertrophy (LV wall thickness >1.4 cm), it is recommended to avoid sotalol, flecainide, and propafenone because of concern of increased proarrhythmic risk. Dronedarone, although not specifically tested in this population, is likely to be safe. Amiodarone is usually considered in these patients when symptomatic AF recurrences continue to affect the quality of life.

In patients with coronary artery disease, sotalol, dofetilide, or dronedarone are recommended as first-line therapy, while flecainide and propafenone are contraindicated. Amiodarone is considered the drug of last resort in this population because of its potential toxicity.

Dofetilide and amiodarone are the only agents available for patients with AF with concomitant heart failure; other antiarrhythmic agents can be associated with substantial toxicity and proarrhythmia.

Quinidine is associated with increased mortality, likely the result of ventricular proarrhythmia secondary to QT interval prolongation. Hence, this drug has largely been abandoned for AF therapy.

Given the suboptimal efficacy of antiarrhythmic drug therapy, expectations and treatment goals have to be pragmatic. Reduction of the burden of AF and its impact on quality of life can be a reasonable outcome. Occasional AF recurrences may not require a change in antiarrhythmic drug therapy. When treatment with a single drug fails, combinations of antiarrhythmic drugs can be tried. Useful combinations include sotalol or amiodarone in addition to a class IC agent. However, when drug therapy is deemed unsuccessful and a rhythm control strategy is abandoned, antiarrhythmic drug should not be continued.

Pharmacologic rhythm control versus rate control

Two major randomized clinical trials—AFFIRM (Atrial Fibrillation Follow-Up Investigation of Rhythm Management) and RACE (RAte Control versus Electrical Cardioversion for Persistent Atrial Fibrillation)—compared pharmacologic rhythm control and rate control in a select population at moderate stroke risk and found an almost significant trend toward a lower incidence of the primary endpoint with rate control strategy, with no difference in the functional status or quality of life. Hence, those trials provided evidence that both rhythm control and rate control are reasonable approaches. The AF-Congestive Heart Failure (AF-CHF) study demonstrated similar results among patients with AF with concomitant LV dysfunction and heart failure. The results of those randomized controlled comparisons of rhythm and rate control therapies were confirmed by more recent observation studies, registries, and meta-analyses.

However, it would be incorrect to extrapolate that NSR offers no benefit over AF and that effective treatments to maintain NSR need not be pursued. First, these trials were not comparisons of NSR and AF; they compared a rate control strategy to a rhythm control strategy that attempted to maintain NSR but fell short, and crossover between treatment arms occurred at a high rate. The failure of AFFIRM and RACE trials in showing any difference between rate and rhythm control is not so much a positive statement for rate control but rather a testimony to the ineffectiveness of side effects of antiarrhythmic drug therapy in maintaining NSR over the long term. When the data from these trials were analyzed according to the patient’s actual rhythm (as opposed to his or her treatment strategy), the benefit of NSR over AF became apparent: the presence of NSR was found to be one of the most powerful independent predictors of survival, along with the use of warfarin, even after adjustment for all other relevant clinical variables. Patients in NSR are almost half as likely to die compared with those with AF. This benefit, however, is offset by the use of antiarrhythmic drug therapy, which increases the risk of death.

Therefore, achieving and maintaining NSR remain viable and important treatment goals. However, because currently available antiarrhythmic agents commonly fail to suppress AF completely and have safety profiles that are less than ideal, it is reasonable to reserve it to the populations of patients likely to derive the greatest benefit from rhythm control. Therefore, when antiarrhythmic drug therapy is the only option available for rhythm control, the selection of rhythm control or rate control strategies should be individualized and take into consideration the nature, intensity, and frequency of symptoms, patient preferences, comorbid conditions, and the risk of recurrent AF. According to analyses of available data, rhythm control can be an appropriate approach in young AF patients and those with newly diagnosed AF, significant symptoms, poorly controlled ventricular response, or tachycardia-mediated cardiomyopathy. On the other hand, asymptomatic or mildly symptomatic elderly patients, especially those with severe comorbidities or very limited functional capacity can be better suited for rate control therapy. As discussed later in this chapter, catheter ablation has become broadly available and, when successful, minimizes exposure to antiarrhythmic drugs and favorably affects clinical outcomes. Therefore, ablation should be considered early in the course of AF, a strategy that can potentially favorably impact disease progression and AF-related outcomes.

It is important to note that current guidelines do not routinely recommend a rhythm control strategy for reducing the risk of mortality, stroke, or heart failure; rather, the primary indication for rhythm control therapy is for the reduction of symptoms and improvement in quality of life.

Catheter ablation as first-line therapy

Recent studies have demonstrated superior efficacy of catheter ablation as a first-line therapy as compared to pharmacological therapy, though most patients enrolled in those studies were generally healthy with predominantly paroxysmal AF. It remains to be investigated whether the results of these studies can be extrapolated to patients with more persistent AF.

In a recent meta-analysis of 6 randomized clinical trials, including 1212 patients, which compared catheter ablation as a first-line therapy versus antiarrhythmic drug therapy in patients with symptomatic paroxysmal AF, catheter ablation resulted in a significantly lower rate of any recurrent atrial tachyarrhythmias when used in antiarrhythmic naïve patients. This effect was observed regardless of follow-up duration (short versus long term), and type of catheter ablation (RF versus cryoablation). Despite the invasive nature of an AF ablation procedure, the risk of serious treatment-related adverse events was comparable between initial catheter ablation and initial antiarrhythmic drug therapy.

According to the 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement, it is reasonable to consider catheter ablation as a first-line rhythm-control treatment (before therapeutic trials of class I or III antiarrhythmic drug therapy) for AF in select patients with symptomatic paroxysmal or persistent AF who prefer interventional therapy ( Fig. 18.2 ). This approach can be of particular value when poor tolerance to antiarrhythmic drugs is anticipated, such as in patients with tachycardia-bradycardia syndrome in whom pharmacological rhythm control strategies would necessitate pacemaker implantation. Similarly, catheter ablation often is recommended as an initial approach in high-level competitive athletes with paroxysmal or persistent AF in whom pharmacologic therapy can negatively affect athletic performance. The efficacy of this approach in unselected patient populations, however, still awaits confirmation by randomized studies, and the risk-benefit ratio of this approach in the individual patient should be carefully considered.

Catheter ablation of atrial fibrillation in heart failure patients

Randomized trials in patients with AF and heart failure have shown that rhythm control strategy with catheter ablation can improve quality of life and functional capacity. Some, but not all, studies also found significant improvement in LVEF in patients undergoing catheter ablation compared to rate control in patients with persistent AF. Additionally, there is increasing, but limited, data showing improvement of hard endpoints such as all-cause mortality and heart failure hospitalization with rhythm control, especially with early rhythm control and with catheter ablation. Taking into consideration those recent studies, first-line catheter ablation of AF in patients with heart failure with reduced or preserved LVEF is a class IIA recommendation in the recently published European Society of Cardiology guidelines. In the 2019 AHA/ACC/HRS AF guideline update, catheter ablation for AF in heart failure with reduced LVEF was given a class IIB indication. However, heart failure populations with AF are highly heterogeneous, and patients with advanced heart failure do not appear to benefit from AF ablation, even if NSR maintenance is achieved. Therefore, catheter ablation should still be used selectively, taking into consideration the patient’s comorbidities and risk of complications.

Catheter ablation for asymptomatic atrial fibrillation

Given the inconsistent findings regarding the impact of catheter ablation on mortality and morbidity, the procedure should currently only be offered to patients on the basis of reducing AF-related symptoms and improving quality of life.

It is important to note that symptoms of persistent AF can be quite subtle and nonspecific (e.g., lack of energy, effort intolerance) and may not be recognized by the patients or can be attributed to other comorbidities (such as sleep apnea or heart failure). Before labeling AF patients as “asymptomatic,” it is important to obtain a careful history to elicit symptoms. Also, it is appropriate to attempt restoration of NSR (with electrical or pharmacological cardioversion, with or without long-term antiarrhythmic drug therapy) and then assess the patients’ symptom status while in NSR as compared to AF.

According to the 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement, catheter ablation of AF may still be considered (class IIb) in select patients with truly asymptomatic paroxysmal or persistent AF (those who did not experience any improvement during a “trial of NSR”) when performed by an experienced operator and following a detailed discussion of the risks and benefits. The patient should be informed that AF, whether symptomatic or asymptomatic, is associated with an increased risk of stroke, heart failure, dementia, and mortality, and while it is possible that maintenance of NSR with AF ablation can potentially reduce these risks, these potential benefits remain unproven. Deferring ablation while awaiting the results of clinical trials can potentially allow the progression of AF to a stage when the efficacy of AF ablation is significantly reduced. Importantly, while this approach can be acceptable in select asymptomatic patients, it is not recommended for patients with long-standing persistent AF and those whose clinical profile would likely be associated with low procedural efficacy and safety.

Cox-maze procedure

The classic Cox-maze procedure involves creating a series of incisions in the left and right atria designed to direct the propagation of the sinus impulse through both atria while interrupting the multiple macroreentrant circuits thought to be responsible for AF. This procedure is the most effective means of curing AF, eliminating the arrhythmia in 75% to 95% for up to 15 years after surgery. Improvements and simplifications of the surgical technique culminated in the Cox-maze III procedure, which became the gold standard for the surgical treatment of AF. Nonetheless, because of its complexity, technical difficulty, requirement of cardiopulmonary bypass, and risk of mortality and other complications, the maze procedure did not gain widespread acceptance.

To simplify the procedure, the standard cut-and-sew surgical technique has been replaced with the modified Cox-maze IV procedure, whereby linear epicardial ablation is performed using unipolar or bipolar RF ablation, cryoablation, laser, high-frequency ultrasound, or microwave energy. LAA closure is typically performed in conjunction with the Cox-maze procedure to decrease the incidence of short-term and long-term strokes in patients who may fail the surgical AF ablation.

Although the modified Cox-maze IV simplifies the procedure, it is rarely performed as a stand-alone procedure. Nonetheless, there is strong evidence that shows that the surgical ablation of AF can be performed safely and effectively in conjunction with an isolated valve surgery, isolated coronary bypass graft surgery, or combination of coronary bypass grafting and valve surgery. Therefore, surgical ablation of AF is recommended in patients undergoing concomitant open heart surgery (whether ablation is performed after failure of antiarrhythmic drug therapy or as first-line therapy and regardless of the duration of the arrhythmia). Such an approach is also reasonable in patients undergoing closed cardiac surgery (e.g., coronary bypass surgery) ( Fig. 18.3 ). Importantly, meticulous attention by the surgeon is required to ensure that every lesion is uniformly transmural and placed in the recommended atrial locations to improve procedural outcome.

Minimally invasive maze

Current surgical instrumentation now enables minimally invasive approaches to be performed epicardially on the beating heart through mini-thoracotomies with video assistance, and without the use of the extracorporeal circulation. Cryoenergy and bipolar RF are the predominant energy source used, and bilateral PV isolation (PVI) is the most common lesion set, with some approaches adding ganglionic plexus ablation, as well as exclusion of the LAA. However, despite elimination of the need for median sternotomy and cardiopulmonary bypass, these procedures are still relatively invasive. To minimize the invasiveness of the procedure further, a totally thoracoscopic approach has been developed. Although multiple series described high success rates for paroxysmal AF (89% at 12 months of follow-up), success has been limited in patients with persistent and longstanding persistent AF (25%–87%). In one report, the overall complication rate was 10%, with a perioperative mortality rate of 1.8%.

More extensive ablation lines, in addition to PV antral isolation and ganglionic plexus ablation, as well as documentation of complete PVI by demonstration of EP entrance or exit block, conduction block across ablation lines, and the detection and confirmation of ablation of the parasympathetic component of the ganglionic plexuses, are being evaluated to improve outcome.

Although surgical ablation was found in one report to have superior efficacy to catheter ablation, the complication rate after surgical ablation was higher. Hence, the decision to recommend surgical AF ablation before considering catheter ablation for patients with symptomatic AF refractory to drug therapy and no other indication for cardiac surgery remains controversial, and it should be based on institutional experience with both techniques, the relative outcomes and risks of each in the individual patient, as well as patient preference ( Fig. 18.3 ). Given the degree of patient discomfort, longer hospitalizations and recovery times, and the risk of bleeding following surgery, most patients prefer catheter to surgical ablation.

Hybrid thoracoscopic procedure

To improve procedure efficacy, hybrid surgical and catheter-based approaches to AF ablation have been developed, in which thoracoscopic epicardial surgical ablation is complemented by percutaneous endocardial mapping and ablation. The surgical epicardial approach enables deploying extensive ablation lesion set while minimizing the risk of injury to the phrenic nerve, PV orifices, and esophagus. Additionally, the ganglionic plexuses and ligament of Marshall can be ablated under direct visualization, and the LAA can be excluded.

Following the epicardial procedure, percutaneous endocardial mapping is performed to verify PVI and complete conduction block across the ablation lines. Gaps in the epicardial often require endocardial ablation to sites not accessible through the epicardial approach (such as the mitral isthmus lesion or at areas where increased epicardial fat hinders transmurality of epicardial lesions). Also, the endocardial approach is used for ablation of additional arrhythmias (e.g., typical AFL) that cannot be targeted via the epicardial approach. A recent systematic review and meta-analysis comparing hybrid procedures with catheter ablation for long-standing persistent AF showed a clear superiority for the hybrid procedures.

Currently, stand-alone and hybrid surgical AF ablation can be considered for patients with symptomatic, drug-refractory persistent, or long-standing persistent AF who have failed one or more attempts at catheter ablation, those who prefer a surgical approach, or those who are not candidates for catheter ablation (e.g., patients not candidates for long-term anticoagulation and those with an LA thrombus).

Hybrid convergent procedure

The hybrid convergent procedure is a minimally invasive closed-chest procedure performed epicardially on the beating heart through a subxiphoid approach followed by endocardial catheter ablation. Unlike the hybrid thoracoscopic procedure, the convergent approach is not a complex surgical procedure but a compliment to catheter ablation.

The convergent procedure utilizes a vacuum-assisted, closed-irrigation, unipolar linear RF ablation catheter device positioned inside a pericardial cannula under endoscopic visualization. Epicardial ablation is focused on the LA posterior wall, where overlapping lesions are performed to create a homogeneous region of electrical silence and debulk as much of the LA posterior wall as can be accessed (principally limited by the oblique sinus). Posterior segments of the PV antra also can be reached and ablated in most cases. The RF energy is directed toward the heart and away from the esophagus, minimizing the risk of esophageal injury.

Endocardial catheter ablation is then performed either at the same sitting or at a later date (after days to weeks). The endocardial component supplements the epicardial lesions around the pericardial reflections and any incompletely ablated LA posterior wall regions and also complete electrical isolation of the PVs by ablating the anterior aspects of the PV antra.

Previous observational studies and a recent prospective, randomized trial demonstrated superiority of the hybrid convergent approach versus an endocardial-only approach in treating nonparoxysmal AF. Single- and multicenter studies have reported freedom from AF or any atrial tachyarrhythmia to be 66% to 95% at 1 year after the hybrid convergent procedure, with 52% to 81% arrhythmia-free without antiarrhythmic drugs.

Atrial antitachycardia pacing

Several pacing algorithms have been developed to inhibit the initiation of AF episodes. These include continuous atrial pacing just faster than the intrinsic sinus rate, overdrive atrial pacing after a premature atrial complex (PAC), algorithms for preventing pauses after PACs, and overdrive atrial pacing after the termination of an episode of AF to suppress an early arrhythmia recurrence. A multitude of studies tested the efficacy of those algorithms and showed no consistent reduction in AF burden or improvement in AF symptoms. Similarly, dual-site atrial pacing and atrial septal pacing site did not show benefits.

Modern pacemakers are equipped with a variety of atrial antitachycardia pacing (ATP) algorithms designed to terminate atrial tachyarrhythmias. ATP is delivered at an atrial cycle length (CL) shorter than the detected arrhythmia with the administration of a number of pulses of fixed duration (burst pacing), or sequences at progressively shorter intervals (ramp pacing) to abort episodes of AFL or atrial tachycardia (AT). Prior generations of ATP algorithms demonstrated a modest efficacy (30%–60%) in terminating slow regular ATs, less effective with rapid ATs, and ineffective at treating established AF. Further, the clinical impact of these algorithms on the burden of the arrhythmia is small. It is important to note that, besides the need for organized atrial tachyarrhythmias, the efficacy of ATP is crucially reliant on early detection of AT and correct rhythm classification by the device.

More recently, a new-generation atrial ATP (“reactive ATP”) was developed to target atrial tachyarrhythmias at onset (when the atrial CL is relatively long) and after any change in rate or regularity when the episode may be most amenable to termination by pacing. Transitions toward more regular or slower rhythms are not infrequent (reportedly occurring in 64% of atrial tachyarrhythmia episodes), even after hours following the onset of the arrhythmia. Unlike standard ATP algorithms, reactive ATP continues to monitor atrial rhythm and watches for any change in rate or regularity, and then opportunistically applies ATP when the episode is most amenable to termination by pacing ( eFig. 18.1 ). In a recent study, reactive ATP reduced the risk of progression of AF to permanent or persistent AF.

Currently, pacemaker implantation is not indicated for the sole purpose of prevention or treatment of AF in patients without other indications for pacemaker implantation. Nonetheless, ATP offers a therapeutic option for rhythm control in patients with permanent dual-chamber pacemakers or defibrillators that have this feature.

Atrial defibrillators

Atrial defibrillators can terminate AF with high acute success rates, but the need for repeated shocks and the resulting patient discomfort often render this option intolerable. Therefore, implanted defibrillators are no longer recommended for rhythm control in AF patients.

Autonomic neuromodulation

Given the important role of the cardiac autonomic nervous system in the pathophysiology of AF, several novel neuromodulation therapies have been attempted to manage patients with AF, including ganglionated plexus ablation, renal sympathetic denervation, and low-level vagus nerve stimulation. Other experimental autonomic neuromodulation techniques include baroreceptor stimulation, stellate ganglion block, spinal cord stimulation, and epicardial injections for temporary neurotoxicity.

Several small prospective randomized and nonrandomized studies demonstrated significant reductions in AF recurrence when renal sympathetic denervation was added to PVI in patients with resistant hypertension and AF. Most recently, the ERADICATE-AF (Evaluate Renal Artery Denervation in Addition to Eliminate Atrial Fibrillation) trial randomized patients with paroxysmal AF to either cryoablation PVI or cryoablation plus renal denervation and found a greater freedom from AF 1-year follow-up among patients who received adjunctive renal denervation. In a recent pooled analysis including all prior studies, patients with symptomatic paroxysmal or persistent AF with a history of hypertension, adjunctive renal denervation in addition to AF catheter ablation resulted in a significantly increased likelihood of freedom from AF compared with AF ablation alone (with a mean reduction of 32% on long-term follow-up). The benefit observed with adjunctive renal denervation appears to be independent of blood pressure control and is probably mediated by modulating the systemic sympathetic nervous system and, as a result, preventing atrial electrophysiological and structural remodeling that promotes arrhythmogenesis. Renal denervation is thought to attenuate afferent sympathetic input from the aortico-renal ganglion to the central nervous system, and also attenuate efferent signaling from the aortico-renal ganglion to the renal parenchyma, reducing renin–angiotensin–aldosterone system activation.

Vagal nerve stimulation shortens atrial action potential duration and refractoriness in the PV and is a reliable technique used for the experimental induction of AF. Low-level cervical vagal nerve stimulation (via a temporary bipolar pacing wire was sutured to vagal nerve preganglionic fibers near the superior vena cava [SVC]) has been evaluated in small studies of patients undergoing cardiac surgery and was found to reduce the occurrence of AF and attenuate the inflammatory response post-cardiac surgery. Vagal stimulation has also been achieved transcutaneously by targeting the auricular branch of the vagus nerve (which has communication with the skin of the tragus), and in a recent pilot study, the use of noninvasive low-level transcutaneous electrical stimulation of the greater auricular nerve was found to reduce the risk of postoperative AF. Greater auricular nerve stimulation has the advantage of being noninvasive, in contrast to vagal nerve stimulation which is delivered via a pair of epicardial temporary pacing wires that may increase operative time and risk and must be removed at the end of the therapy.

Other novel autonomic modulation strategies have been studied to reduce postoperative AF. In a pilot study of patients with history of paroxysmal AF undergoing coronary artery bypass grafting, injection of botulinum toxin (which inhibits acetylcholine release and reduces atrial cholinergic neurotransmission) into the epicardial fat pads was found to reduce the recurrence rate of atrial tachyarrhythmias at 12, 24, and 36 months.

At this time, these emerging neuromodulation methods remain investigational and require further clinical evaluation to determine their role in managing AF. Further, basic science studies are necessary to investigate the exact autonomic and antiarrhythmic mechanisms of these modalities.

Hypertension

Hypertension is a key cardiovascular risk factor known to be strongly associated with AF and stroke. Although treatment of hypertension has not been consistently shown to decrease AF risk, some studies found that treatment of hypertension, targeting a systolic blood pressure of less than 130 mm Hg, was associated with up to 40% reduction of the risk of incident AF. Data also support BP control as a strategy to lower stroke risk in patients with AF. Optimizing management of hypertension is an important component of reducing cardiovascular complications and thromboembolic risk.

Diabetes

Diabetes is an independent risk factor for the development of AF and thromboembolic complications. Observational studies demonstrated that glycemic control is associated with reduced risk of AF development and recurrence. Therefore, optimization of diabetes management may be an important strategy to reduce AF burden.

Sleep disordered breathing

An independent association exists between AF and obstructive sleep apnea. Therefore, AF patients should be actively screened for undiagnosed obstructive sleep apnea and evaluated when clinically suspected. Treatment of sleep apnea, when diagnosed, is an important component of AF management. Continuous positive airway pressure (CPAP) therapy is associated with more than 40% relative risk reduction in AF recurrence in patients with obstructive sleep apnea, regardless of the AF treatment strategy (pharmacological or invasive).

Obesity

Obesity is an independent risk factor for AF. Several studies have demonstrated that significant and sustained weight loss, particularly as part of a comprehensive risk factor management program, can reduce the burden of AF, slow or even reverse the natural progression of AF, and improve the outcome of catheter-based and pharmacological rhythm-control strategies. In a recent study, AF burden reduction could be achieved with initial targets of at least a 10% reduction in weight and a BMI <27 kg/m ² in conjunction with the management of concurrent risk factors. Additionally, observational studies demonstrated that bariatric surgery in morbidly obese patients (BMI ≥40 kg/ m ² ) was associated with reduced risk of new AF, reduced burden of AF, and reduced risk of AF recurrence after ablation. Further mechanistic and clinical studies are needed to define populations at risk and how best to target obesity in AF.

Physical activity

Regular, moderate aerobic exercise is beneficial for preventing and treating AF and can also improve AF-related symptoms and quality of life. The benefits gained from cardiorespiratory fitness are additive to the effect of weight loss. Increased cardiorespiratory fitness is associated with beneficial effects on blood pressure, diabetic control, lipid profile, and inflammation, all of which can potentially contribute to reduced AF burden.

One study found a significant dose-response relationship between baseline cardiorespiratory fitness with a 9% reduction in the risk of AF recurrence for every metabolic equivalent (MET) increase in baseline cardiorespiratory fitness. Improvements in exercise capacity as small as two or more METs in overweight individuals on top of weight loss were associated with a twofold greater freedom from AF. Additionally, reduction in the risk of AF by approximately 10% is observed at a weekly physical activity dose exceeding 1000 MET-minutes, or approximately 3.5 hours of moderate walking per week. Although no exact dose–response relationship has been established between physical activity and reduction of incident AF, encouraging moderate-intensity exercise of >150–200 minutes per week is likely an appropriate recommendation for AF patients.

Caffeine

Caffeine, a methylxanthine compound that is chemically similar to theophylline, increases neurohormonal and sympathetic stimulation. Therefore, caffeine has been addressed as a potential trigger for AF. In fact, of patients with AF, 25%–28% report caffeine as a trigger of AF episodes. However, studies failed to demonstrate a significant relationship between habitual or heavy caffeine consumption and incident AF. In contrast, some studies suggest a possible protective role; a meta-analysis identified a weak association between caffeine exposure and reduced AF risk; with habitual caffeine intake, there was a 6% relative risk reduction in AF incidence for every 300-mg/day increment in caffeine use. Prospective studies on the role of caffeine reduction in patients with AF are lacking. At this time, lowering or limiting caffeine intake has not been demonstrated to confer a beneficial effect in reducing AF incidence or burden and, therefore, caffeine restriction is not a ubiquitously used management strategy in AF risk factor modification. The exception may be a patient who can definitely document caffeine-triggered episodes of AF.

Alcohol

Habitual and binge alcohol drinking increases the risk of new-onset AF as well as the risk of arrhythmia progression in patients with AF. A recent study reported that abstinence from alcohol intake in patients with AF drinking ≥10 drinks/week was associated with improved AF rhythm control. Therefore, reducing alcohol consumption can potentially be an effective strategy for primary and secondary AF prevention, and AF patients with moderate or high levels of alcohol habitual consumption should be counseled to reduce their intake. In this context, however, a safe level of daily alcohol consumption in AF patients has not been established.

Smoking

Data suggest a dose-dependent relationship between smoking and AF risk; however, the influence of smoking cessation on the incidence or progression of AF has not been fully investigated. Nonetheless, smoking cessation support and counseling are recommended as part of general lifestyle and risk factor modification for AF prevention.

Primary prevention

Multiple strategies for preventing postoperative AF have been studied. Prophylaxis of AF using perioperative beta-blockers, amiodarone, and sotalol has shown promising results. However, no strategy completely eliminates the occurrence of postoperative AF.

Rate versus rhythm control

Beta-blockers are the drugs of choice for rate control in patients with postoperative AF. The indications for cardioversion of AF and recommendations for rhythm- versus rate-control strategies are similar to those discussed for nonsurgical patients. When antiarrhythmic drug therapy is required for rhythm control, amiodarone is the drug of choice. Sotalol can be considered if amiodarone is contraindicated. Class IC agents, such as flecainide and propafenone, generally are avoided in these patients given the presence of structural heart disease.

Prevention of systemic embolization

Guidelines for stroke prevention in nonsurgical AF patients apply to those with postoperative AF. Most of these patients have multiple stroke risk factors but also an increased risk of bleeding in the postoperative phase. Therefore, the decision to initiate anticoagulation therapy should be guided by the individual patient’s bleeding risk and CHA ₂ DS ₂ -VASc score. Data are lacking regarding the threshold burden or duration of postoperative AF at which anticoagulation is favored, but AF lasting for longer than 48 hours should prompt strong consideration of anticoagulation therapy. The optimal duration for which anticoagulation must be continued after cessation of postoperative AF is uncertain.

Follow-up of patients with postoperative atrial fibrillation

Follow-up is recommended at 6 to 12 weeks after surgery to evaluate the presence of persistent or paroxysmal AF and reassess management strategy. Ambulatory cardiac monitoring should be considered to screen for asymptomatic paroxysmal arrhythmias. The optimal frequency and intensity of cardiac rhythm monitoring beyond the 3-month period are not known. If AF is documented, long-term anticoagulation should be considered based on the CHA ₂ DS ₂ -VASc score, and the need for rate versus rhythm control should be reassessed. If there is no evidence of symptomatic or asymptomatic AF beyond the immediate postoperative period, discontinuation of antiarrhythmic drug therapy, if initiated after cardiac surgery, may be considered. However, it is important to note that a recent study in patients with transient post-operative AF who received implantable loop recorders for continuous monitoring found high AF recurrence rates (in 57% of patients within the first month postoperatively and in 71% within a mean follow-up period of 1.7 years).

Evolution of catheter ablation approaches for atrial fibrillation

Periprocedural management

Transesophageal echocardiography

TEE is performed in most patients undergoing AF ablation to screen for LA thrombus. Although it is optional in patients with paroxysmal AF and no structural heart disease, preablation TEE is often performed in patients who are in AF at the time of the procedure, regardless of the anticoagulation status prior to ablation. The presence of intracardiac thrombus should prompt cancellation of the procedure and mandate 4 to 8 more weeks of anticoagulation, followed by another TEE.

Some reports suggested that a TEE may not be necessary in patients receiving uninterrupted oral anticoagulation therapy for 4 weeks preceding the ablation and through the day of the procedure. However, other studies reported a substantial prevalence of LAA clots among patients with full anticoagulation and in those with paroxysmal AF (up to 6.4% in those with high CHA ₂ DS ₂ -VASc score), and suggested that TEE should be performed in all patients prior to ablation. Therefore, until more data are available, the risk of a thromboembolic event must be weighed against relatively low risk of moderate sedation and TEE, by taking into consideration the type of AF (paroxysmal versus persistent), anticoagulation status, CHA ₂ DS ₂ -VASc score, LA diameter, and LV function. At this time, it may be reasonable to perform TEE in all patients, with the possible exception of those with paroxysmal AF and a CHA ₂ DS ₂ -VASc score of 0.

The technique of 64-slice computed tomography (CT) scanning has been used to screen for atrial thrombi with reportedly high diagnostic accuracy, but TEE remains the gold standard and the preferred imaging modality. Additionally, the use of intraprocedural intracardiac echocardiography (ICE) may be considered for screening of LAA thrombi (imaging from the pulmonary artery is preferred, Fig. 18.5 ) in patients who cannot undergo TEE; however, the data are currently insufficient to recommend widespread use of ICE imaging as an alternative to TEE ( eFig. 18.2 ).

Technical aspects common to different methods of ablation