Ablation for persistent atrial fibrillation in patients with heart failure

Introduction Heart failure and atrial fibrillation are clinical conditions widely distributed in the population, particularly in the elderly, enhancing each other and difficult to treat. Whenever occurring in the same patient, as is often the case in clinical practice, a vicious circle is established, which significantly worsens the prognosis.1 The prevalence of atrial fibrillation increases with the increase in severity of heart failure (5% of the patients for functional class I and 50% for class IV). On the other hand, the prevalence of heart failure in patients with atrial fibrillation is approximately 42%.1 Whenever the arrhythmia complicates heart failure, the prognostic impact is a function of the degree of functional impairment: whenever atrial fibrillation develops in patients with severe heart failure, the early mortality rate does not increase significantly; whenever, instead heart failure is moderate the occurrence of atrial fibrillation, even in its paroxysmal form, becomes an independent prognostic factor for increased mortality. Persistent atrial fibrillation could also cause left ventricular dysfunction through three separate mechanisms: loss of atrial systolic contraction; irregular cardiac cycle; high ventricular rate. Notwithstanding the scientific and therapeutic progress, the combination of heart failure and persistent atrial fibrillation still presents some unanswered issues, which complicate the management of these patients, and in particular their treatment. Amiodarone is one of the few antiarrhythmic drugs available, but its chronic use is burdened by significant side effects, specifically affecting the pulmonary system, the liver, and the thyroid, as well as drug interaction often requiring early discontinuation. Pharmacologic cardiac rhythm control has not been encouraged by the clinical results of various randomized trials in patients with or without heart failure.2,3 This explains, at least in part, the complexity of combining the treatment of pAF and heart failure in clinical practice, and the still grim prognosis despite significant therapeutic progress in this area where our understanding is still not complete. The cardiac resynchronization therapy (CRT), in moderate-to-severe heart failure, could improve survival and quality of life and, at the same time, decrease hospitalization for cardiovascular problems.1 Nonetheless, it is still not clear whether the benefits of CRT could apply to patients with heart failure and pAF; in fact data from the major trials concern patients in sinus rhythm. Despite limited clinical evidence, CRT implant is considered as alternative treatment in the new guidelines, assigning a class IIa recommendation for selected patients with heart failure and atrial fibrillation.1 Unfortunately, not all heart-failure patients with atrial fibrillation are ‘responders’ to CRT as patients in sinus rhythm. The discrepancy is because of the persistent irregular rhythm of patients with atrial fibrillation, specifically whenever the ventricular rate is high, interfering almost constantly with biventricular capture, so that not all beats are in biventricular pacing mode. To surmount this problem, in patients with frequent and prolonged episodes of atrial fibrillation, atrioventricular node ablation has been introduced, with the intent of inducing up to 100% biventricular pacing, thus avoiding the negative effect of the spontaneous fibrillation rhythm.1 Atrioventricular node ablation and cardiac resynchronization therapy in patients with heart failure and atrial fibrillation According to a recent survey of 140 European Centers, 23% of the patients undergoing CRT have heart failure and chronic/persistent atrial fibrillation.4 Analyzing the data on 768 patients with CRT- atrial fibrillation – 339 treated with atrioventricular node ablation and 429 with pharmacologic treatment to control ventricular rate it was found that atrioventricular node ablation provided decreased all-causes and cardiovascular mortality, as well as improved NYHA (New York Heart Association) class, without improvement of the left ventricular ejection fraction (LVEF).4 Furthermore, in patients with atrial fibrillation, adding atrioventricular node ablation to CRT could improve the long-term functional capacity, and LVEF by favoring left ventricular reverse remodeling. The European Society of Cardiology guidelines recommend CRT for patients with atrial fibrillation and LVEF less than 35%, ventricular dyssynchrony and QRS greater than 130 ms, or for patients in whom it is possible to re-establish sinus rhythm. In both situations, atrioventricular node ablation should be considered alongside CRT to ensure complete ventricular capture.1 Transcatheter ablation of atrial fibrillation in patients with heart failure During the last decade, transcatheter ablation of atrial fibrillation represented a valid alternative to pharmacologic treatment in symptomatic patients with refractory atrial fibrillation.1,5–11 The numerous trials published addressed patients with paroxysmal atrial fibrillation and preserved LVEF.5–9 The results confirm transcatheter ablation as very effective, in this patient population, in reducing the recurrence of the arrhythmia.1,5–13 Unfortunately, many patients with chronic heart failure are affected with persistent atrial fibrillation, often refractory to pharmacologic and/or electrical cardioversion.1 The many studies available in the literature for patients with persistent atrial fibrillation substantiate that the success of the procedure (pulmonary veins isolation with or without substrate extension) is highly variable, and indubitably inferior to the results reported for patients with paroxysmal atrial fibrillation.1 The wide variability of the results could stem from numerous factors, among which are the different ablation techniques, the duration of the arrhythmia, the presence of structural heart disease, age, sex, and the operator experience. The recent PABA CHF (Pulmonary Vein Antrum Isolation vs. AV Node Ablation With Biventricular Pacing for Treatment of Atrial Fibrillation in Patients With Congestive Heart Failure) trial demonstrated that in patients with heart failure and paroxysmal or persistent atrial fibrillation, pulmonary veins isolation was better than atrioventricular node ablation and CRT.12 Pulmonary veins ablation improved cardiac function, exercise capacity, and quality of life, but for these benefits, more than one procedure was usually required.12 The multicentric randomized AATAC (Ablation vs. Amiodarone for Treatment of Atrial Fibrillation in Patients With Congestive Heart Failure) study proved that in patients with heart failure and persistent atrial fibrillation, transcatheter ablation (pulmonary vein antrum and posterior wall isolation) was superior to amiodarone therapy with an improvement in freedom from atrial fibrillation at 2 years. Other benefits included improvement in quality of life and exercise capacity as well as decreased hospitalization and overall mortality.13 The rate of success in this study, though, varied amongst the centers, ranging from 29 to 61%. The 2-year mortality dropped to 8% in the ablation group vs. 18% in the amiodarone group.13 These data confirmed the results published in 2006 on New England Journal of Medicine by our group, demonstrating for the first time that our technique (CPVA) not limited to pulmonary vein isolation was superior to amiodarone in patients with chronic atrial fibrillation.10 The demonstration that the ablation technique was able to re-establish stable sinus rhythm in patients with chronic atrial fibrillation should not be underestimated, considering the significant socioeconomic advantages deriving from a sharp reduction of hospitalization and mortality, particularly in patients with heart failure. In fact, re-establishing stable sinus rhythm improves left ventricular function, exercise tolerance, symptoms, and quality of life in an increasing aging population. In the current clinical practice, the challenge for the cardiologist and electrophysiologist remains the increasing number of patients, also elderly, presenting with heart failure and persistent atrial fibrillation, already treated with pulmonary vein isolation, suffering with one or more recurrences and repeated attempts at cardioversion. In this situation, it is plausible to question whether the mechanisms leading to the persistent arrhythmia are more complex or reside outside the pulmonary veins. During the last 3 years, to support the ablation procedure of patients with paroxysmal or persistent atrial fibrillation, we realized dedicated software, which allows, with tridimensional electroanatomic mapping, the identification of one or more areas, defined as ‘rotors’, which individually and simultaneously, like a small gyrator, unload regular sequential electrical impulses at very high velocity, able to sustain and perpetrate the arrhythmia in time. In patients with paroxysmal atrial fibrillation, the rotors are usually localized, in a highly variable number, around the pulmonary veins. In patients with persistent atrial fibrillation and heart failure, on the other hand, the ‘rotors’ could localize everywhere, even in the right atrium, and once localized with echography, they are sequentially ablated starting from the faster and more regular (Fig. 1). During radiofrequency release, a lengthening of the cycle before return to sinus rhythm is often noted. The procedural time, including mapping and ablation, are not long, but often exceed 60 min regardless of the type of atrial fibrillation. Whenever the presence of the ‘rotors’ is the mechanism for persistent atrial fibrillation, regardless of its clinical presentation, their identification and elimination are the true target of every ablation technique. In our experience, based on 500 patients with chronic persistent atrial fibrillation, the number of ‘rotors’ varies considerably both in number and in location, and their complete elimination is associated with return to sinus rhythm in almost all patients, 80% of whom maintain it at 12 months after a single uncomplicated procedure.Fig. 1: Example of ‘rotors’ electroanatomic mapping in a patient with persistent atrial fibrillation and heart failure, in posteroanterior projection (left side) and anteroposterior (right side). The mapping is constructed during atrial fibrillation and assigns a color coding, through the use of dedicated software, to each repetitive atrial electrical activity, regular and stable according to the length of the cycle (AA). In this case, the regular/stable faster activities (‘rotors’) are represented in red (cycle 130 ms), the less rapid in yellow/light green (cycle 180 ms), or blue (cycle 210 ms). Areas with fragmented activity are represented by dark brown color and the scars in gray. The left side map, in posteroanterior (PA) projection, shows a very fast and regular activity inside the left superior pulmonary vein, and less rapid and regular areas are shown around and inside the right pulmonary vein. In the anteroposterior (AP) mapping on the right side are shown broad slower but regular areas mainly in the left atrial appendage. These areas are often documented in patients with paroxysmal or persistent atrial fibrillation. They could vary in number from patient to patient, and are capable to maintain the arrhythmia (‘rotors’), and are the specific targets for an effective procedure.The limited and variable success rates reported by other authors12,13 are attributed to different ablation techniques not focused on ‘rotors’ identification, whose elimination assures the final success. In patients with persistent atrial fibrillation and heart failure, electric isolation of the pulmonary veins is not enough for restoration of sinus rhythm whenever other triggers are present outside the pulmonary veins. The AATAC Trial reported a variability of the success rate after the ablation of various substrates (pulmonary veins, antral and posterior regions, complex and fractionated activity) in terms of recurrence amongst the various centers participating in the study ranging between 29 and 61%.13 In our experience, this wide variability, regardless of a common ablation strategy, could depend not necessarily on the ability of the single operator or center, but rather from the insufficient number of ‘rotors’ eliminated. The ablation procedure in patients with atrial fibrillation and heart failure received a class IIb recommendation in selected patients in the guidelines, but our experience would suggest that the indication and the potential for transcatheter ablation are undervalued considering the alternative procedure of trigger elimination. Conclusion Identification and elimination of the triggers (‘rotors’) with the ablation technique, as recently reported by our laboratory, could be considered an effective strategy, particularly for patients with heart failure and persistent atrial fibrillation. It is expected that this ablation technique will be implemented by a growing number of centers and, with the accumulated experience, could become the treatment of choice in patients with atrial fibrillation, regardless of the duration of the arrhythmia or the presence of comorbidities. Acknowledgements Conflicts of interest There are no conflicts of interest.