Raffaele Fanelli

Pulmonary-Vein Isolation for Atrial Fibrillation in Patients with Heart Failure

BACKGROUND Pulmonary-vein isolation is increasingly being used to treat atrial fibrillation in patients with heart failure. METHODS In this prospective, multicenter clinical trial, we randomly assigned patients with symptomatic, drug-resistant atrial fibrillation, an ejection fraction of 40% or less, and New York Heart Association class II or III heart failure to undergo either pulmonary-vein isolation or atrioventricular-node ablation with biventricular pacing. All patients completed the Minnesota Living with Heart Failure questionnaire (scores range from 0 to 105, with a higher score indicating a worse quality of life) and underwent echocardiography and a 6-minute walk test (the composite primary end point). Over a 6-month period, patients were monitored for both symptomatic and asymptomatic episodes of atrial fibrillation. RESULTS In all, 41 patients underwent pulmonary-vein isolation, and 40 underwent atrioventricular-node ablation with biventricular pacing; none were lost to follow-up at 6 months. The composite primary end point favored the group that underwent pulmonary-vein isolation, with an improved questionnaire score at 6 months (60, vs. 82 in the group that underwent atrioventricular-node ablation with biventricular pacing; P<0.001), a longer 6-minute-walk distance (340 m vs. 297 m, P<0.001), and a higher ejection fraction (35% vs. 28%, P<0.001). In the group that underwent pulmonary-vein isolation, 88% of patients receiving antiarrhythmic drugs and 71% of those not receiving such drugs were free of atrial fibrillation at 6 months. In the group that underwent pulmonary-vein isolation, pulmonary-vein stenosis developed in two patients, pericardial effusion in one, and pulmonary edema in another; in the group that underwent atrioventricular-node ablation with biventricular pacing, lead dislodgment was found in one patient and pneumothorax in another. CONCLUSIONS Pulmonary-vein isolation was superior to atrioventricular-node ablation with biventricular pacing in patients with heart failure who had drug-refractory atrial fibrillation. (ClinicalTrials.gov number, NCT00599976.)

Circulating Levels of Cytokines and Their Endogenous Modulators in Patients With Mild to Severe Congestive Heart Failure Due to Coronary Artery Disease or Hypertension

OBJECTIVES This study sought to determine the circulating levels of cytokines and their respective endogenous modulators in patients with congestive heart failure of variable severity. BACKGROUND Activation of immune elements localized in the heart or periphery, or both, may promote release of cytokines in patients with congestive heart failure. Although an increased circulating level of tumor necrosis factor-alpha (TNF-alpha) and its soluble receptor type II (sTNF-RII) is well documented, less is known about other cytokines (i.e., interleukin-1-beta [IL-1-beta], interleukin-6 [IL-6] and interleukin-2 [IL-2] and their soluble receptor/receptor antagonists). METHODS Circulating levels of TNF-alpha and sTNF-RII, IL-1-beta, IL-1 receptor antagonist (IL-1-Ra), IL-6, IL-6 soluble receptor (IL-6-sR), IL-2 and IL-2 soluble receptor-alpha were measured using enzyme-linked immunosorbent assay kits (Quantikine, R&D Systems) in 80 patients with congestive heart failure due to coronary artery disease or hypertension. The severity of their symptoms, which ranged from New York Heart Association functional class I to IV, was confirmed by measurement of peak oxygen consumption. RESULTS The percentage of patients with elevated levels of cytokines and their corresponding soluble receptor/receptor antagonists significantly increased with functional class. For TNF-alpha and IL-1-beta, the percentage of patients with elevated levels of soluble receptor/receptor antagonists was higher than that of patients with elevated levels of the cytokine itself. For IL-6, the percentage of patients with elevated levels of IL-6-sR tended to be lower than that of patients with elevated levels of IL-6. All but two patients had undetectable levels of IL-2, and all but seven had levels of IL-2-sR within a normal range. CONCLUSIONS In patients with congestive heart failure, circulating levels of cytokines increased with the severity of symptoms. In these patients, circulating levels of sTNF-RII and IL-1-Ra are more sensitive markers of immune activation than are circulating levels of TNF-alpha and IL-1-beta, respectively. Levels of IL-2 and IL-2-sR are not elevated when congestive heart failure is due to coronary artery disease or hypertension.

Circular Mapping and Ablation of the Pulmonary Vein for Treatment of Atrial Fibrillation Impact of Different Catheter Technologies

OBJECTIVES We conducted this study to compare the efficacy and safety of different catheter ablation technologies and of distal versus ostial pulmonary veins (PV) isolation using the circular mapping technique. BACKGROUND Electrical isolation of the PVs in patients with atrial fibrillation (AF) remains a technical challenge. METHODS Two hundred eleven patients (163 men; mean age 53 +/- 11 years) with symptomatic AF were included in this study. In the first 21 patients (group 1), distal isolation (> or = 5 mm from the ostium) was achieved targeting veins triggering AF. In the remaining 190 patients (group 2), ostial isolation of all PVs was performed using 4-mm tip (47 patients), 8-mm tip (21 patients), or cooled-tip (122 patients) ablation catheters. RESULTS Distal isolation was able to eliminate premature atrial contractions (PACs) and AF in six of 21 patients (29%) and 10 of 34 PVs. After a mean follow-up time of 6 +/- 4 months, no patients treated with the 8-mm tip catheter experienced recurrence of AF, whereas 21% (10 of 47 patients) and 15% (18 of 122 patients) of the patients ablated with the 4-mm tip and the cooled-tip ablation catheters experienced recurrence of AF after a mean follow-up of 10 +/- 3 and 4 +/- 2 months, respectively. Significant complications including stroke, tamponade, and severe stenosis occurred in 3.5% (8/211) of patients. CONCLUSIONS Catheter technologies designed to achieve better lesion size appeared to have a positive impact on procedure time, fluoroscopy time, number of lesions, and overall efficacy. Although distal isolation can be achieved with fewer lesions, ostial isolation is required in the majority of patients to eliminate arrhythmogenic PACs and AF.

Pulmonary Vein Stenosis After Radiofrequency Ablation of Atrial Fibrillation Functional Characterization, Evolution, and Influence of the Ablation Strategy

Background—Pulmonary vein (PV) stenosis is a complication of ablation for atrial fibrillation. The impact of different ablation strategies on the incidence of PV stenosis and its functional characterization has not been described. Methods and Results—PV isolation was performed in 608 patients. An electroanatomic approach was used in 71 and circular mapping in 537 (distal isolation, 25; ostial isolation based on PV angiography, 102; guided by intracardiac echocardiography, 140; with energy delivery based on visualization of microbubbles, 270). Severe (≥70%) narrowing was detected in 21 patients (3.4%), and moderate (50% to 69%) and mild (<50%) narrowing occurred in 27 (4.4%) and 47 (7.7%), respectively. Severe stenosis occurred in 15.5%, 20%, 2.9%, 1.4%, and 0%, respectively. Development of symptoms was correlated with involvement of >1 PV with severe narrowing (P =0.01), whereas all patients with mild and moderate narrowing were asymptomatic. In the latter group, lung perfusion (V/Q) scans were normal in all but 4 patients. All patients with severe stenosis had abnormal perfusion scans. Conclusions—V/Q scans are useful to assess the functional significance of PV stenosis. Mild and moderate degrees of PV narrowing are not associated with development of symptoms and seem to have no or minimal detrimental effect on pulmonary flow. The incidence of severe PV stenosis seems to be declining with better imaging techniques to ensure ostial isolation and to guide power titration. Mild narrowing 3 months after ablation does not preclude future development of severe stenosis and should be assessed with repeat imaging studies.

Response of Atrial Fibrillation to Pulmonary Vein Antrum Isolation Is Directly Related to Resumption and Delay of Pulmonary Vein Conduction

Background—The role of pulmonary vein (PV) isolation in ablative treatment of atrial fibrillation (AF) has been debated in conflicting reports. We sought to compare PV conduction in patients who had no AF recurrence (group I), patients who could maintain sinus rhythm on antiarrhythmic medication (group II), and patients who had recurrent AF despite antiarrhythmic medication (group III) after PV antrum isolation (PVAI). Methods and Results—PV conduction was examined in consecutive patients undergoing second PVAI for AF recurrence. We also recruited some patients cured of AF to undergo a repeat, limited electrophysiological study at >3 months after PVAI. All patients underwent PVAI with an intracardiac echocardiography (ICE)–guided approach with complete isolation of all 4 PV antra (PVA). The number of PVs with recurrent conduction and the shortest atrial to PV (A-PV) conduction delay was measured with the use of consistent Lasso positions defined by ICE. Late AF recurrence was defined as AF >2 months after PVAI with the patient off medications. Patients in groups I (n=26), II (n=37), and III (n=44) did not differ at baseline (38% permanent AF; ejection fraction 53±6%). Recurrence of PV–left atrial (LA) conduction was seen in 1.7±0.8 and 2.2±0.8 PVAs for groups II and III but only in 0.2±0.4 for group I (P=0.02). In patients with recurrent PV-LA conduction, the A-PV delay increased from the first to second procedure by 69±47% for group III, 267±110% for group II, and 473±71% for group I (P<0.001). When pacing was at a faster rate, A-PV block developed in all 5 of the group I patients with recurrent PV-LA conduction. Conclusions—The majority of patients with drug-free cure show no PV-LA conduction recurrence. Substantial A-PV delay is seen in patients able to maintain sinus rhythm on antiarrhythmic medication or cured of AF compared with patients who fail PVAI.

Ablation for longstanding permanent atrial fibrillation: Results from a randomized study comparing three different strategies

BACKGROUND This prospective multicenter randomized study aimed to compare the efficacy of 3 common ablation methods used for longstanding permanent atrial fibrillation (AF). METHODS A total of 144 patients with longstanding permanent AF (median duration 28 months) were randomly assigned to circumferential pulmonary vein ablation (CPVA, group 1, n = 47), to pulmonary vein antrum isolation (PVAI, group 2, n = 48) or to a hybrid strategy combining ablation of complex fractionated or rapid atrial electrograms (CFAE) in both atria followed by a pulmonary vein antrum isolation (CFAE + PVAI, group 3, n = 49). RESULTS Scarring in the left atrium and structural heart disease/hypertension were present in most patients (65%). After a mean follow-up of 16 months, 11% of patients in group 1, 40% of patients in group 2 and 61% of patients in group 3 were in sinus rhythm after one procedure and with no antiarrhythmic drugs (P < .001). Sinus rhythm maintenance would increase respectively to 28% (group 1), 83% (group 2), and 94% (group 3) after 2 procedures and with antiarrhythmic drugs (AADs, P < .001). The AF terminated during ablation, either by conversion to sinus rhythm or organization into an atrial tachyarrhythmia, in 13% of patients (group 1), 44% (group 2), and 74% (group 3) respectively. CFAE alone, performed as the first step of the ablation in group 3, organized AF in only 1 patient. CONCLUSION In this study, the hybrid AF ablation strategy including antrum isolation and CFAE ablation had the highest likelihood of maintaining sinus rhythm in patients with longstanding permanent AF. Electrical isolation of the PVs, although inadequate if performed alone, is relevant to achieve long-term sinus rhythm maintenance after ablation. Bi-atrial CFAE ablation had a minimal impact on AF termination during ablation.

First Human Experience With Pulmonary Vein Isolation Using a Through-the-Balloon Circumferential Ultrasound Ablation System for Recurrent Atrial Fibrillation

BackgroundStandard mapping and ablation of focal sources of atrial fibrillation are associated with very long procedure times and low efficacy. An anatomic approach to complete pulmonary vein isolation could overcome these limitations. Methods and ResultsFifteen patients with atrial fibrillation refractory to medication underwent circumferential isolation of the pulmonary veins by using a novel catheter, with an ultrasound transducer (8-MHz) mounted near the tip, in a saline-filled balloon. Twelve atrial foci and/or atrial fibrillation triggers were identified in 9 patients (pulmonary vein locations: left upper, 3; right upper, 6; right middle, 1; right lower, 1; and left inferior, 1). In 5 patients, lesions were placed in the absence of any mapped triggers. Irrespective of trigger mapping, circumferential isolation of both upper pulmonary veins was attempted in all patients. The lower pulmonary veins were ablated when sinus rhythm activation mapping revealed evidence of a sleeve of atrial muscle in the vein. The median number of lesions per patient required to isolate 1 pulmonary vein was 4 (range, 1 to 29). After ablation, no evidence of narrowing was seen with repeat venography or follow-up computed tomography scan. After a mean follow-up of 35±6 weeks, 5 patients had recurrence of atrial fibrillation. Three responded to drugs that were previously ineffective, and 2 remained in atrial fibrillation. ConclusionsThis novel ultrasound ablation system can successfully isolate multiple pulmonary veins. At early follow-up, this approach seems to be effective in preventing recurrent atrial fibrillation in a significant number of patients.

Randomized Study Comparing Combined Pulmonary Vein–Left Atrial Junction Disconnection and Cavotricuspid Isthmus Ablation Versus Pulmonary Vein–Left Atrial Junction Disconnection Alone in Patients Presenting With Typical Atrial Flutter and Atrial Fibrillation

Background—Atrial flutter (AFL) and atrial fibrillation (AF) frequently coexist in the same patient. Recently it has been demonstrated that the triggers for both AF and AFL may originate in the pulmonary veins (PVs). We hypothesized that in patients with both AF and typical AFL, pulmonary vein–left atrial junction (PV-LAJ) disconnection may eliminate both arrhythmias. Methods and Results—Consecutive patients with documented symptomatic AF and typical AFL were randomly assigned to have PV-LAJ disconnection combined with cavotricuspid isthmus (CTI) ablation (group 1, n=49) or PV-LAJ disconnection alone (group 2, n=59). Within the first 8 weeks after ablation, 32 of the group 2 patients had typical AFL documented, whereas none was seen in group 1. Twenty of these 32 converted to sinus rhythm after initiating antiarrhythmic drugs (AADs). Twelve were cardioverted, and AADs were started. After 8 weeks, all AADS were stopped, and only 3 patients continued to have recurrent sustained typical AFL that was eliminated by CTI ablation. Beyond 8 weeks of follow-up, 7 patients in group 1 and 6 patients in group 2 (14% and 11%, respectively) continued to have AF. Ten of these 13 patients underwent a repeat PV-LAJ disconnection procedure and were cured. The remaining 3 remained in normal sinus rhythm while taking AADs. Conclusions—In patients with both AFL and AF, PV-LAJ disconnection alone may be sufficient to control both arrhythmias. CTI block reduced early postablation recurrence of arrhythmias, which in the majority of patients reflects a short-term clinical problem.

Atrial Fibrillation Ablation Strategies for Paroxysmal Patients: randomized comparison between different techniques.

Background— Whether different ablation strategies affect paroxysmal atrial fibrillation (AF) long-term freedom from AF/atrial tachyarrhythmia is unclear. We sought to compare the effect of 3 different ablation approaches on the long-term success in patients with paroxysmal AF. Methods and Results— One hundred three consecutive patients with paroxysmal AF scheduled for ablation and presenting in the electrophysiology laboratory in AF were selected for this study. Patients were randomized to pulmonary vein antrum isolation (PVAI; n=35) versus biatrial ablation of the complex fractionated atrial electrograms (CFAEs; n=34) versus PVAI followed by CFAEs (n=34). Patients were given event recorders and followed up at 3, 6, 9, 12, and 15 months postablation. There was no statistical significant difference between the groups in term of sex, age, AF duration, left atrial size, and ejection fraction. At 1 year follow-up, freedom from AF/atrial tachyarrhythmia was documented in 89% of patients in the PVAI group, 91% in the PVAI plus CFAEs group, and 23% in the CFAEs group ( P <0.001) after a single procedure and with antiarrhythmic drugs. Conclusion— No difference in terms of success rate was seen between PVAI alone and PVAI associated with defragmentation. CFAEs ablation alone had the smallest impact on AF recurrences at 1-year follow-up. These results suggest that antral isolation is sufficient to treat most patients with paroxysmal AF. Received March 19, 2008; accepted February 11, 2009. # CLINICAL PERSPECTIVE {#article-title-2}Background—Whether different ablation strategies affect paroxysmal atrial fibrillation (AF) long-term freedom from AF/atrial tachyarrhythmia is unclear. We sought to compare the effect of 3 different ablation approaches on the long-term success in patients with paroxysmal AF. Methods and Results—One hundred three consecutive patients with paroxysmal AF scheduled for ablation and presenting in the electrophysiology laboratory in AF were selected for this study. Patients were randomized to pulmonary vein antrum isolation (PVAI; n=35) versus biatrial ablation of the complex fractionated atrial electrograms (CFAEs; n=34) versus PVAI followed by CFAEs (n=34). Patients were given event recorders and followed up at 3, 6, 9, 12, and 15 months postablation. There was no statistical significant difference between the groups in term of sex, age, AF duration, left atrial size, and ejection fraction. At 1 year follow-up, freedom from AF/atrial tachyarrhythmia was documented in 89% of patients in the PVAI group, 91% in the PVAI plus CFAEs group, and 23% in the CFAEs group (P<0.001) after a single procedure and with antiarrhythmic drugs. Conclusion—No difference in terms of success rate was seen between PVAI alone and PVAI associated with defragmentation. CFAEs ablation alone had the smallest impact on AF recurrences at 1-year follow-up. These results suggest that antral isolation is sufficient to treat most patients with paroxysmal AF.

AV node ablation and pacemaker implantation after withdrawal of effective rate-control medications for chronic atrial fibrillation: effect on quality of life and exercise performance.

We assess whether AV node ablation and pacemaker implantation after discontinuation of effective rate‐control medical therapy for chronic atrial fibrillation had a positive impact on quality of life and exercise performance. To assess the possibility of a placebo effect following pacemaker implantation, the study included three groups of patients. Group 1 underwent an echocardiogram, treadmill exercise, and quality of life measurement 1 month prior to and 6 months following AV node ablation and pacemaker implantation associated with discontinuation of rate‐control medications. Group 2 underwent AV node ablation and pacemaker implantation without discontinuation of antiarrhythmic rate‐control drugs. Group 3 underwent pacemaker implantation without performing AV node ablation and continuing rate‐control medical therapy. At the 1‐ and 6‐month evaluation, the patients in group 1 showed a significant improvement of left ventricular ejection fraction, quality of life, and activity scores. The exercise duration and the maximal VO2 consumption, however, did not change significantly. A slight improvement of the quality of life and physical activity scores was observed in the group undergoing AV node ablation without withdrawal of medications. However, no significant changes were observed in the group receiving only the pacemaker without modification of medical therapy and with intact AV node conduction. In conclusion, in patients with chronic atrial fibrillation, discontinuation of effective rate‐control medical therapy followed by AV node ablation and permanent pacing appeared to improve quality of life and activity scores despite no change in exercise duration. The improvement observed does not seem to reflect a placebo effect.