Assessing and Defining Symptomatology

Patients with persistent AF often complain of nonspecific symptoms such as fatigue or exercise intolerance, making it difficult to ascertain whether a concomitant problem such as obesity, sleep apnea, or clinical heart failure is the major instigator. In addition, patients are often unaware when AF started and may feel minimal palpitations, which may give the false impression that AF is asymptomatic. In that sense, symptomatology attributable to AF may be in the eye of the beholder. In this circumstance one should consider direct current cardioversion (DCCV) with or without an antiarrhythmic medication for the purpose of determining improvement in symptomatology when in sinus rhythm. The patient is encouraged to keep a literal or mental symptom diary for the days and weeks preceding and following cardioversion. Most patients with persistent AF will experience some improvement of symptoms after cardioversion. If a patient with persistent AF experiences no symptomatic improvement with a trial of sinus rhythm, rhythm control is less appealing, given that multiple ablations and/or continuation of antiarrhythmic drugs may be needed to achieve long-term success. More than 10% of patients will fail to have even momentary restoration of sinus rhythm, even at 360 J, in which case placement of two sets of defibrillator pads (one in anteroposterior configuration and one in anterolateral configuration) connected to two separate external defibrillators can be synchronized and fired simultaneously (by a single operator) with near universal success. We recommend very firm pressure on the two anterior patches (this can best be done from on top of the stretcher or with the bed very low) with dry towels and rubber gloves to ensure no current is leaked through the operator applying pressure. In addition, pretreatment with ibutilide can also be used to aid cardioversion. Of note, amiodarone may raise the defibrillation threshold.

Presenting Rhythm

Among patients with a clinical diagnosis of persistent AF, those who present to the electrophysiology (EP) lab in sinus rhythm, or who have early conversion to sinus rhythm during the procedure (before the completion of the planned ablation), have a significantly greater likelihood of long-term success. This is probably because, at least in part, of the presence of sinus rhythm being a marker of a phenotype, which is likely to have improved outcomes. Arriving to the lab in sinus rhythm, all other things being equal, is statistically more likely in patients with a lower AF burden. Conversion early during the procedure could be a marker of a patient with a more paroxysmal, self-terminating phenotype, which may have terminated even in the absence of ablation. By the same reasoning a patient with persistent AF, who presents to clinic in sinus rhythm, may be expected to have better outcomes with ablation than one who does not.

Atrial Fibrillation Burden and Chronicity

As discussed earlier, patients with persistent AF are more likely to experience recurrence than those with paroxysmal AF (see Table 19.1 ). Among patients with persistent AF, those classified as persistent AF for more than 1 year seem to be approximately twice as likely to have recurrence as compared to those diagnosed with persistent AF for less than 1 year. Additionally, those with long-standing persistent AF (>1 year of continuous AF) have worsened outcomes as compared with those who have been in AF less than twelve months.

Disease Processes Exacerbated by Atrial Fibrillation

When determining how aggressively to treat AF, it is reasonable to consider comorbidities. In patients with heart failure and AF, AF ablation has been associated with an improvement in left ventricular ejection fraction (LVEF) of 8.5%, as well as an improvement in 6-minute walk and quality of life when compared with rate control. Additionally, AF ablation compared favorably to atrioventricular (AV) node ablation with biventricular pacing in heart failure patients with significantly greater quality of life, 6-minute walk, and left ventricular (LV) ejection fraction in the AF ablation group. Most notably, recent evidence from the randomized controlled Catheter Ablation for Atrial Fibrillation with Heart Failure (CASTLE-AF) trial showed a significant reduction in the primary composite end point of death or hospitalization for worsening heart failure (hazard ratio [HR] 0.62; P =.007) among patients with LVEF 35% or less randomized to ablation as opposed to medical therapy (rate or rhythm control) for AF. The study also showed significant reductions in the individual end points of all-cause mortality (HR 0.53; P =.010), cardiac mortality (HR 0.49; P =.009), and hospitalization for worsened heart failure (HR 0.56; P =.004) in the ablation group. Similar to prior studies, LVEF and 6-minute walk also showed significant improvements in the ablation group. Interestingly, these effects were seen in the setting of a 50% recurrence rate in the ablation group, but a reduction in AF burden (rather than complete elimination) to around 25% as opposed to 60% for those receiving medical therapy alone.

In addition, patients with tachy-brady syndrome plagued by symptomatic sinus bradycardia or long postconversion pauses in the setting of needed rate or rhythm control medications for AF, may benefit from an early ablative approach to avoid or postpone the need for placement of a permanent pacemaker.

Lastly, observational data suggests that AF ablation is associated with a reduced incidence of stroke or TIA as compared to propensity-matched patients with AF who do not undergo ablation. This effect seems to be greater in patients without recurrence of arrhythmia after ablation. However, despite propensity matching, it is possible that the decision to perform ablation and also ablation success may be a marker of a healthier patient population, who would be less likely to suffer a stroke regardless of ablation. Therefore a randomized trial will be needed to determine the true effect, if any, that AF ablation has on long-term stroke risk. Notably, recent guidelines state that “a patient’s desire to eliminate the need for long-term anticoagulation by itself should not be considered an appropriate selection criterion for AF ablation.”

Antiarrhythmic Drug Options

In many patients with persistent AF, antiarrhythmic drug options are limited. Patients with persistent AF and structural heart disease should not be prescribed class 1c antiarrhythmic medications. In this group sotalol, dofetilide, dronedarone, and amiodarone are options. For those with heart failure dronedarone, and to some extent sotalol, are also contraindicated. In addition, patients with poor or fluctuating renal function or serum potassium levels are at elevated risk of Torsades de Pointes with the class III antiarrhythmic drugs sotalol and dofetilide. For those who do qualify for a class III drug, several days of hospitalization for drug loading is recommended. Finally, any patients with advanced lung disease or those with an expected lifespan of a decade or more are not ideal candidates for amiodarone, given the risk of long-term, potentially fatal, toxicities. After all of these considerations are taken into account, there is a significant cohort of persistent AF patients with few or no good antiarrhythmic drug options. Despite this, operators should be aware that patients with persistent AF, and especially those with long-standing persistent AF, may require continuation or initiation of antiarrhythmic drug therapy after ablation to maintain sinus rhythm.

Potential Contraindications to Ablation

Ablation of AF is contraindicated or certainly riskier in certain populations. Given the elevated incidence of periprocedural stroke in the absence of anticoagulation, intraprocedural heparin, and oral anticoagulation is recommended for at least 2 months after ablation in all patients, regardless of baseline stroke risk. The 2014 ACC/AHA/HRS guidelines state that “AF catheter ablation should not be performed in patients who cannot be treated with anticoagulant therapy during and following the procedure.” In patients with heparin-induced thrombocytopenia or other specific contraindication to heparin, bivalirudin can be used for the acute procedure.

In addition, those with an exceptionally high risk for general anesthesia, such as those with advanced lung disease and concomitant morbid obesity, should warrant special consideration and attention prior to referral for ablation. Most patients with inferior vena cava (IVC) filters can safely undergo AF ablation. Fluoroscopy, and occasionally contrast venography, should be used to ensure safe passage of wires and sheaths. Occasionally chronic thrombus may prevent access through a filter.

Patients with congenital heart disease are at significantly elevated risk of AF, and the risk increases as one ages. Simple congenital heart disease, in which the atrial septum has been repaired, requires extra care to perform transseptal puncture. This has been performed in high-volume centers using intracardiac echocardiography, with a high degree of success and few complications. AF ablation in complex congenital heart disease, which may include surgical baffles and severely distorted anatomy, should be referred to an operator experienced with these patients.

Patients with Atrial Fibrillation Undergoing Cardiac Surgery

In patients with symptomatic AF who are undergoing cardiac surgery (specifically mitral valve surgery, aortic valve surgery, or coronary artery bypass grafting), concomitant surgical ablation of AF is recommended. In addition, in patients with AF undergoing cardiac surgery, it is reasonable to perform left atrial appendage excision or exclusion, whether or not surgical ablation of AF is performed. While the original Cox-Maze procedure consisted of a cut-and-sew lesion set, the Cox-Maze IV procedure switched to limited atriotomy (often in the setting of mitral valve surgery), with both radiofrequency and cryoablation performed from both endocardial and epicardial locations, making the procedure shorter and less technically challenging. Because aortic valve and coronary artery bypass surgeries do not necessitate an atriotomy, approaches have been developed that are performed exclusively from an epicardial approach, although these approaches cannot reliably create a contiguous line of ablation down to the mitral valve annulus. In patients with persistent and long-standing persistent AF, extensive surgical lesion sets seem to have very good efficacy; however, paroxysmal AF patients may not have an added benefit with extensive linear ablation.

Pulmonary Vein Isolation

PVI remains the cornerstone of all widely accepted strategies for ablation of AF and is recommended as a class I indication during all AF ablation procedures ( Fig. 19.1 ). Between 2011 and 2016 several studies have shown success rates of 47% to 82% for around 1-year arrhythmia-free survival (pooled mean 67%) in relatively healthy populations of patients with persistent AF undergoing PVI-only ablation, with either radiofrequency or cryoballoon. Notably, many of these studies excluded long-standing persistent AF. In addition, the mean left atrial (LA) size (4.5 cm) may be smaller and LVEF (57%) may be greater than what could be expected in a real-world long-standing persistent cohort. In fact, among a group of patients with more advanced persistent AF with LA size 5.1 cm and LVEF 50%, the Hopkins group showed a single-procedure success rate of 36% at about 11 months follow-up. Those with long-standing persistent AF had 20% success.

A multispline catheter (labeled LA 1-20) (Pentaray, Biosense-Webster, Diamond Bar, CA) is in the left upper pulmonary vein shortly after pulmonary vein isolation has been achieved in a patient with persistent atrial fibrillation. A decapolar catheter is in the coronary sinus (labeled CS) , and an ablation catheter (labeled ABL) is at the pulmonary vein antrum. Despite isolation of the vein, a brief, fast run of pulmonary vein tachycardia is seen. This underscores the importance of durable pulmonary vein isolation.

Some evidence suggests that performing wide-area circumferential ablation around the PVs (rather than ostial ablation) may be more efficacious. In a trial by Nilsson et al., this effect appeared to be magnified in persistent AF patients, who had an 85% recurrence rate with ostial ablation, and 48% recurrence with extraostial ablation, with allowance for one reablation. The largest anatomic difference in PVI lines between an ostial approach and wide-area approach is the wider placement of the posterior lines, which isolates a much larger portion of the posterior wall. Our method of ablating posterior to the PVs is described later.

Posterior Wall Isolation/Ablation

During embryologic development, a single embryonic PV arises from the posterior wall and then branches into the four main PVs and their distal branches ( Fig. 19.2 ). As a result, the smooth tissue of the PVs extends into the LA tissue and incorporates the posterior LA wall as well as some of the LA roof and interatrial septum. Ablation of the posterior wall has been considered an additional potential target in AF ablation, and there is compelling evidence that ablation and isolation of the left atrial posterior wall may reduce recurrence of persistent AF.

The primordial pulmonary vein interfaces with the primordial left atrium. At 5 weeks gestation (A), a single branching primordial pulmonary vein empties into the primordial left atrium. The antrum of the vein expands and begins to form part of the left atrial wall, while the branch point becomes nearer the left atrial cavity. (B), By 6 weeks (C), the right and left veins are arising from two separate ostia, and a larger portion of the left atrial posterior wall is made up of what was initially pulmonary vein tissue. At 8 weeks (D), four separate pulmonary vein ostia are seen. Eventually, most of the left atrium is formed by absorption of the primordial pulmonary vein and its branches.

From Moore KL, Torchia MG (Eds.) Cardiovascular System in the Developing Human. 10 ^th ed. Philadelphia, PA, USA: Elsevier. 2016.

After transitioning from the cut-and-sew Cox-Maze III to the primarily radiofrequency and cryoablation Cox-Maze IV, the initial lesion set at Washington University in St. Louis included an ablation line connecting the right and left lower pulmonary veins. Later, a roofline connecting the two upper veins was added to complete a posterior box. Among the first 100 patients, recurrence of antiarrhythmic medication was 53%, with only an inferior connecting line placement versus 15% in those with a posterior box. A larger follow-up study from the same group revealed an odds ratio of 0.382 for atrial fibrillation/atrial tachycardia (AF/AT) recurrence with completion of a posterior box when adjusted for other factors. A study performed on 17 patients greater than 4 years after a surgical epicardial ablation of the posterior wall and PVs using high-intensity focused ultrasound revealed that among patients with AF recurrence, 100% (11/11) had posterior wall reconnection. Only 33% (2/6) of patients without AF recurrence had posterior wall reconnection. A similar finding was seen in a study of patients with persistent AF by Bai et al., which showed a hazard ratio of 2.22 for AF recurrence with PVI alone (first 20 consecutive patients) versus PVI with extensive posterior wall, coronary sinus (CS), and septal ablation (next 32 consecutive patients). Additional observational data for posterior wall ablation comes from a post hoc analysis of the AATAC trial of catheter ablation versus amiodarone. In this study of patients with heart failure and persistent AF, those who underwent complete posterior wall isolation (diffuse ablation of all signals, rather than placement of lines) had 79% arrhythmia-free survival versus 36% who had PVI only. Conclusions are limited by small numbers, the fact that this was not a randomized component of the trial, and the fact that the ablation strategy was likely a direct reflection of the operator performing the procedure.

Based on these observations, it seems plausible that durable posterior wall ablation/isolation may benefit patients with persistent AF, but randomized data is lacking. Furthermore, the preferred method of ablating the posterior wall remains unknown. Kumar et al. showed that a standard posterior box by endocardial catheter ablation (roofline connecting the left upper to right upper PV, as well as inferior line connecting the left lower to right lower PV) only succeeds in isolating the posterior wall 23% of the time acutely. Of the patients in whom posterior wall isolation was successful but who had reablation for recurrence, 0 of 5 still had isolation of the posterior wall. Therefore a standard posterior box via catheter ablation does not seem to be a reliable method using current technologies. In the LIBERATION study, where posterior wall ablation was diffuse, obligate repeat mapping was performed 3 months after the first procedure. This showed that 63% of patients who had PVI and posterior wall ablation had durable isolation of both the PVs and the posterior wall. The difference in successful posterior wall isolation between these studies would seem to be the method of ablation–linear ablation with a roof and inferior line seems to be less successful in achieving acute and long-term posterior wall isolation.

We take these data to suggest that posterior wall ablation/isolation is likely to be beneficial in patients with persistent and long-standing persistent AF if it can be achieved, and that mapping and ablating all signals on the posterior wall seems to be the preferred approach. A contingent of electrophysiologists has long advocated posterior wall ablation by moving a multipolar Lasso catheter all around the posterior wall and ablating all visible signals until electrical silence is achieved. However, many operators are understandably hesitant to ablate indiscriminately across the posterior wall of the left atrium due to the risk of atrioesophageal fistula.

The posterior LA is a smooth, thin-walled structure that nearly always directly overlies the esophagus. An ideal ablation strategy would be one that creates transmural lesions across the LA wall but does not heat the adjacent esophageal tissue. Most operators currently use low-power settings (∼20 W) on the posterior wall with irrigated catheters. However, there are proponents of relatively high-power settings with shorter lesion duration. We employ a low-flow (2 mL per minute) 25–30 W, 6 to 10 seconds per lesion protocol for posterior wall ablation to attain rapidly effective endocardial ablation without causing deep tissue heating. The optimal combination of power, duration, and irrigation rate will need to be explored through further study.

Our Method of Pulmonary Vein Isolation with Posterior Wall Ablation

We perform complete isolation/ablation of the posterior wall using low-flow settings in most patients with persistent and long-standing persistent AF. After substrate and anatomic mapping is performed using a multispline catheter (Pentaray, Biosense-Webster, Diamond Bar, CA), we perform pulmonary vein antral isolation using a deflectable sheath (Agilis, St. Jude Medical, St. Paul, MN) and a contact force sensing ablation catheter (SmartTouch, Biosense-Webster, Diamond Bar, CA) with typical irrigated settings at 30 to 35 W except for posterior to the pulmonary veins, where we set the irrigation at 2 mL per minute continuous (same as during mapping with the catheter) with output at 25–30 W. We aim for contact force of at least 10g throughout the LA. During low-flow posterior LA lesions, we limit lesion duration to no more than 10 seconds, but as low as 6 seconds directly over the esophagus. With this we aim for impedance decrease of 10 Ω and electrogram diminution, which can usually be achieved with slightly greater contact force of 15 to 20 g if necessary.

After PVI is accomplished, we then target all local signals within the posterior box area ( Fig. 19.3 ) with 6 to 10 second low-flow lesions (setting maximal lesion duration at 10 seconds is adequate in most patients). We typically see rapid electrogram diminution at ablation sites. After all local signals seem to be ablated within this region, testing for pace-capture at 10 mA or higher can help to ensure adequate lesion delivery has been achieved. This method will require varying amounts of ablation. Overall the number of lesions required to obtain posterior wall isolation is not excessive and is often no more time intensive than placement of a successful roofline, which is effectively created by this strategy anyway. We do not create initial roof and inferior lines because the goal is to ablate all posterior wall tissue. We never ablate with a transesophageal echocardiography probe in place due to mechanical stenting of the anterior esophageal tissue into the posterior LA, and we adjust the position of an insulated esophageal temperature probe to approximately match the position of the ablation catheter so that reablation in an area of esophageal heating would only occur after return to baseline esophageal temperature.

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