Giuseppe Augello

Pulmonary Vein Denervation Enhances Long-Term Benefit After Circumferential Ablation for Paroxysmal Atrial Fibrillation

Background—There are no data to evaluate the relationship between autonomic nerve function modification and recurrent atrial fibrillation (AF) after circumferential pulmonary vein ablation (CPVA). This study assesses the incremental benefit of vagal denervation by radiofrequency in preventing recurrent AF in a large series of patients undergoing CPVA for paroxysmal AF. Methods and Results—Data were collected on 297 patients undergoing CPVA for paroxysmal AF. Abolition of all evoked vagal reflexes around all pulmonary vein ostia was defined as complete vagal denervation (CVD) and was obtained in 34.3% of patients. Follow-up ended at 12 months. Heart rate variability attenuation, consistent with vagal withdrawal, was detectable for up to 3 months after CPVA, particularly in patients with reflexes and CVD, who were less likely to have recurrent AF than those without reflexes (P =0.0002, log-rank test). Only the percentage area of left atrial isolation and CVD were predictors of AF recurrence after CPVA (P <0.001 and P =0.025, respectively). Conclusions—This study suggests that adjunctive CVD during CPVA significantly reduces recurrence of AF at 12 months.

Comparison of antiarrhythmic drug therapy and radiofrequency catheter ablation in patients with paroxysmal atrial fibrillation: A randomized controlled trial

CONTEXT Antiarrhythmic drugs are commonly used for prevention of recurrent atrial fibrillation (AF) despite inconsistent efficacy and frequent adverse effects. Catheter ablation has been proposed as an alternative treatment for paroxysmal AF. OBJECTIVE To determine the efficacy of catheter ablation compared with antiarrhythmic drug therapy (ADT) in treating symptomatic paroxysmal AF. DESIGN, SETTING, AND PARTICIPANTS A prospective, multicenter, randomized (2:1), unblinded, Bayesian-designed study conducted at 19 hospitals of 167 patients who did not respond to at least 1 antiarrhythmic drug and who experienced at least 3 AF episodes within 6 months before randomization. Enrollment occurred between October 25, 2004, and October 11, 2007, with the last follow-up on January 19, 2009. INTERVENTION Catheter ablation (n = 106) or ADT (n = 61), with assessment for effectiveness in a comparable 9-month follow-up period. MAIN OUTCOME MEASURES Time to protocol-defined treatment failure. The proportion of patients who experienced major treatment-related adverse events within 30 days of catheter ablation or ADT was also reported. RESULTS At the end of the 9-month effectiveness evaluation period, 66% of patients in the catheter ablation group remained free from protocol-defined treatment failure compared with 16% of patients treated with ADT. The hazard ratio of catheter ablation to ADT was 0.30 (95% confidence interval, 0.19-0.47; P < .001). Major 30-day treatment-related adverse events occurred in 5 of 57 patients (8.8%) treated with ADT and 5 of 103 patients (4.9%) treated with catheter ablation. Mean quality of life scores improved significantly in patients treated by catheter ablation compared with ADT at 3 months; improvement was maintained during the course of the study. CONCLUSION Among patients with paroxysmal AF who had not responded to at least 1 antiarrhythmic drug, the use of catheter ablation compared with ADT resulted in a longer time to treatment failure during the 9-month follow-up period. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00116428.

Prevention of Iatrogenic Atrial Tachycardia After Ablation of Atrial Fibrillation A Prospective Randomized Study Comparing Circumferential Pulmonary Vein Ablation With a Modified Approach

Background—Circumferential pulmonary vein ablation (CPVA) is effective in curing atrial fibrillation (AF), but new-onset left atrial tachycardia (AT) is a potential complication. We evaluated whether a modified CPVA approach including additional ablation lines on posterior wall and the mitral isthmus would reduce the incidence of AT after PV ablation. Methods and Results—A total of 560 patients (291 men, 52%; age, 56.5±7.3 years) entered the study; 280 were randomized to CPVA alone (group 1) and 280 to modified CPVA (group 2). The primary end point was freedom from AT after the procedure. In group 1, 28 patients (10%) experienced new-onset AT, and 41 (14.3%) experienced recurrent AF. In group 2, 11 patients (3.9%) experienced AT, and 36 (12.9%) had recurrent AF. Group 1 was more likely to experience AT than group 2 (P=0.005). Freedom from AF after ablation was similar in both groups (P=0.57). Among those in group 1, gap-related macroreentrant AT was documented in 23 of the 28 patients (82%), and focal AT was found in 5 (18%). In group 2, gap-related macroreentrant AT was found in 8 of the 11 patients (73%), and focal AT was seen in 3 (27%). Two patients in group 1 and 1 patient in group 2 had both AT and AF. The strongest predictor of AT was the presence of gaps (P<0.001). Conclusions—Modified CPVA is as effective as CPVA in preventing AF but is associated with a lower risk of developing incessant AT.

Morbidity, mortality, and quality of life after circumferential pulmonary vein ablation for atrial fibrillation ☆

Objectives This study was designed to investigate the potential of circumferential pulmonary vein (PV) ablation for atrial fibrillation (AF) to maintain sinus rhythm (SR) over time, thus reducing mortality and morbidity while enhancing quality of life (QoL). Background Circumferential PV ablation is safe and effective, but the long-term outcomes and its impact on QoL have not been assessed or compared with those for medical therapy. Methods We examined the clinical course of 1,171 consecutive patients with symptomatic AF who were referred to us between January 1998 and March 2001. The 589 ablated patients were compared with the 582 who received antiarrhythmic medications for SR control. The QoL of 109 ablated and 102 medically treated patients was measured with the SF-36 survey. Results Median follow-up was 900 days (range 161 to 1,508 days). Kaplan-Meier analysis showed observed survival for ablated patients was longer than among patients treated medically (p < 0.001), and not different from that expected for healthy persons of the same gender and calendar year of birth (p = 0.55). Cox proportional-hazards model revealed in the ablation group hazard ratios of 0.46 (95% confidence interval [CI], 0.31 to 0.68; p < 0.001) for all-cause mortality, of 0.45 (95% CI, 0.31 to 0.64; p < 0.001) for morbidities mainly due to heart failure and ischemic cerebrovascular events, and of 0.30 (95% CI, 0.24 to 0.37; p < 0.001) for AF recurrence. Ablated patients’ QoL, different from patients treated medically, reached normative levels at six months and remained unchanged at one year. Conclusions Pulmonary vein ablation improves mortality, morbidity, and QoL as compared with medical therapy. Our findings pave the way for randomized trials to prospect a wider application of ablation therapy for AF.

First human chronic experience with cardiac contractility modulation by nonexcitatory electrical currents for treating systolic heart failure: Mid-term safety and efficacy results from a multicenter study

Introduction: Conventional electrical therapies for heart failure (HF) encompass defibrillation and ventricular resynchronization for patients at high risk for lethal arrhythmias and/or with inhomogeneous ventricular contraction. Cardiac contractility modulation (CCM) by means of nonexcitatory electrical currents delivered during the action potential plateau has been shown to acutely enhance systolic function in humans with HF. The aim of this multicenter study was to assess the chronic safety and preliminary efficacy of an implantable device delivering this novel form of electrical therapy.

Cardiac Contractility Modulation by Electric Currents Applied During the Refractory Period in Patients With Heart Failure Secondary to Ischemic or Idiopathic Dilated Cardiomyopathy

We assessed the feasibility of cardiac contractility modulation (CCM) by electric currents applied during the refractory period in patients with heart failure (HF). Extracellular electric currents modulating action potential and calcium transients have been shown to potentiate myocardial contractility in vitro and in animal models of chronic HF. CCM signals were biphasic square-wave pulses with adjustable amplitude, duration, and time delay from sensing of local electric activity. Signals were applied to the left ventricle through an epicardial vein (in 12 patients) or to the right ventricular (RV) aspect of the septum endocardially (in 6 patients). Simultaneous left ventricular (LV) and aortic pressure measurements were performed using a Millar catheter (Millar Instruments, Houston, Texas). Hemodynamics during RV temporary dual-chamber pacing was regarded as the control condition. Both LV and RV CCM stimulation increased dP/dt(max) to a similar degree (9.1 +/- 4.5% and 7.1 +/- 0.8%, respectively; p <0.01 vs controls), with associated aortic pulse pressure changes of 10.3 +/- 7.2% and 10.8 +/- 1.1% (p <0.01 vs controls). Regional systolic wall motion assessed quantitatively by color kinesis echocardiography was markedly enhanced near the CCM electrode, and the area of increased contractility involved 4.6 +/- 1.2 segments per patient. In 6 patients with HF with left bundle branch block, CCM signals delivered during biventricular pacing (BVP) produced an additional 16.1 +/- 3.7% increase in dP/dt(max) and a 17.0 +/- 7.5% increase in pulse pressure compared with BVP alone (p <0.01). CCM stimulation in patients with HF enhanced regional and global measures of LV systolic function, regardless of the varied delivery chamber or whether modulation was performed during RV pacing or BVP.

Radiofrequency catheter ablation and antiarrhythmic drug therapy: A prospective, randomized, 4-year follow-up trial: The APAF study

Background— Information on comparative outcome between radiofrequency catheter ablation (RFA) and antiarrhythmic drugs (AADs) >1 year after randomization is important for clinical decision-making. Methods and Results— A total of 198 patients (age, 56±10 years) with paroxysmal atrial fibrillation were randomly assigned to RFA (99 patients) or to AADs (99 patients). We evaluated efficacy of RFA or AADs in a comparable 48-month follow-up period according to intention-to-treat analysis. Cardiac rhythm was assessed with daily transtelephonic transmissions. Quality of life was also analyzed. At 4 years, among the 99 patients first assigned to RFA, the procedure was repeated because of recurrent atrial fibrillation/atrial tachycardia in 27 patients (27.3%). Among the 99 patients randomly assigned to AADs, 87 (87.9%) crossed over to undergo RFA and 4 years after random assignment only 12 (12.1%) were in sinus rhythm with AAD alone without ablation. Despite the high level of crossovers, at 4 years the intention-to-treat analysis showed that 72.7% of patients in the ablation arm and 56.5% of those initially randomly assigned to AADs were free of recurrent atrial fibrillation/atrial tachycardia ( P =0.017). During the follow-up, 19.2% of AAD patients progressed to persistent atrial fibrillation before switching to RFA. RFA significantly improved quality of life ( P <0.001), whereas before crossing over to RFA, patients receiving AADs showed poorer quality of life. Except for new left atrial tachycardia, there were no serious complications caused by RFA. Conclusions— With follow-up extended to 4 years after randomly assigned, ablation remains superior to antiarrhythmic drug in these patients with paroxysmal atrial fibrillation. Clinical Trial Registration— URL: . Unique identifier: [NCT00340314][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00340314&atom=%2Fcircae%2F4%2F6%2F808.atomBackground— Information on comparative outcome between radiofrequency catheter ablation (RFA) and antiarrhythmic drugs (AADs) >1 year after randomization is important for clinical decision-making. Methods and Results— A total of 198 patients (age, 56±10 years) with paroxysmal atrial fibrillation were randomly assigned to RFA (99 patients) or to AADs (99 patients). We evaluated efficacy of RFA or AADs in a comparable 48-month follow-up period according to intention-to-treat analysis. Cardiac rhythm was assessed with daily transtelephonic transmissions. Quality of life was also analyzed. At 4 years, among the 99 patients first assigned to RFA, the procedure was repeated because of recurrent atrial fibrillation/atrial tachycardia in 27 patients (27.3%). Among the 99 patients randomly assigned to AADs, 87 (87.9%) crossed over to undergo RFA and 4 years after random assignment only 12 (12.1%) were in sinus rhythm with AAD alone without ablation. Despite the high level of crossovers, at 4 years the intention-to-treat analysis showed that 72.7% of patients in the ablation arm and 56.5% of those initially randomly assigned to AADs were free of recurrent atrial fibrillation/atrial tachycardia (P=0.017). During the follow-up, 19.2% of AAD patients progressed to persistent atrial fibrillation before switching to RFA. RFA significantly improved quality of life (P<0.001), whereas before crossing over to RFA, patients receiving AADs showed poorer quality of life. Except for new left atrial tachycardia, there were no serious complications caused by RFA. Conclusions— With follow-up extended to 4 years after randomly assigned, ablation remains superior to antiarrhythmic drug in these patients with paroxysmal atrial fibrillation. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00340314.

Electroanatomic Remodeling of the Left Atrium in Patients Undergoing Repeat Pulmonary Vein Ablation: Mechanistic Insights and Implications for Ablation

Introduction: There is limited information describing late changes in the electroanatomic characteristics of the left atrium (LA) associated with recurrence after an anatomical circumferential pulmonary vein ablation (CPVA) for atrial fibrillation (AF).

Combining electrical therapies for advanced heart failure: the Milan experience with biventricular pacing–defibrillation backup combination for primary prevention of sudden cardiac death

Biventricular pacing (BVP) improves hemodynamics and symptoms in patients with heart failure with bundle branch block. Patients with a left ventricular ejection fraction <0.35 and ventricular tachyarrhythmias are at risk of sudden cardiac death, and they benefit most from implantable cardioverter defibrillators (ICDs). No study has evaluated the efficacy of the BVP-ICD combination in patients with heart failure with no history of syncope or sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). Our prospective, observational study was performed on 135 consecutive patients with heart failure (aged, 64 +/- 11 years; 76% male; New York Heart Association functional class, 3.1 +/- 0.8; ejection fraction 0.28 +/- 0.06; ischemic heart failure, 43%; QRS interval duration, 153 +/- 11 msec) treated at our cardiac pacing unit between January 1999 and April 2001. In the first year (control phase), BVP alone was implanted. After that, BVP with ICD backup was used (prophylactic phase). Follow-up data were obtained by outpatient visits with electrocardiographic and echocardiographic examinations done at 3-month intervals. For patients who died, we examined hospital records, death certificates, and autopsy reports. Follow-up time averaged 840 days. The first 47 patients received BVP alone. During follow-up study, 19% of these patients died suddenly, and 11% died of worsening heart failure. None of the patients who died suddenly had hemodynamic deterioration or BVP malfunction before the event. The BVP-ICD group comprised 88 patients (18% with VT/VF inducibility on electrophysiologic testing). During follow-up study, 32% of these patients (18% with positive electrophysiologic testing) had VT/VF episodes successfully treated by ICD; 5% received inappropriate discharges on atrial fibrillation; and 6% died of heart failure with 1 sudden cardiac death. Cox proportional hazards model in the BVP-ICD group compared with BVP alone revealed hazard ratios for all-cause mortality and sudden cardiac death of 0.76 (95% confidence interval [CI], 0.58 to 0.96; p = 0.01) and 0.08 (95% CI, 0.05 to 0.42; p <0.01), respectively, adjusting for baseline characteristics and follow-up duration. Mortality in patients with heart failure remains high after BVP implantation, mainly because of sudden cardiac death. Although there are limitations with an observational study, our experience suggests that ICD backup grants increased security in BVP patients without conventional class I ICD indications.

Pulmonary vein isolation after circumferential pulmonary vein ablation: Comparison between Lasso and three-dimensional electroanatomical assessment of complete electrical disconnection

BACKGROUND Pulmonary vein isolation (PVI) is one of the common endpoints of all atrial fibrillation (AF) ablation procedures and is most often validated using a preshaped circular catheter. However, three-dimensional (3D) electroanatomical systems used for anatomy reconstruction and to guide coalescent delivery of ablation lesions avoid the use of multiple transeptal punctures and multiple catheters in the left atrium. OBJECTIVE To assess correspondence in PVI validation between a 3D electroanatomical system and a Lasso catheter. METHODS Twenty-five patients affected by nonpermanent AF were enrolled after giving informed consent. After ablation of all four pulmonary vein (PV) ostia, encircled areas were extensively mapped (15 +/- 5 points acquired for each PV ostium) to assess the absence of any electrical activity conducted from the left atrium to the PV. At the end of the procedure, the physician performing the ablation procedure judged the complete versus incomplete PVI according to Carto/ablation catheter mapping during coronary sinus pacing. Thereafter, a second operator blinded to the result of the ablation procedure positioned a preshaped Lasso catheter in each PV ostium and annotated complete/incomplete PVI during pacing from the coronary sinus. RESULTS PVI as assessed with CARTO was 100% concordant with Lasso evaluation of PVI. Fluoroscopic times were 2.5 +/- 0.9 minutes to complete circumferential PV ablation and 5.5 +/- 1.9 minutes to properly position the Lasso catheter. No acute complications were reported in this series of patients. CONCLUSIONS PVI assessment using a 3D electroanatomical system is as accurate as Lasso evaluation, with excellent concordance.