Journal of the American College of Cardiology Vol. 48, No. 11, 2006 2006 by the American College of Cardiology Foundation ISSN 0735-1097/06/$32.00 Published by Elsevier Inc.
A Randomized Trial of CircumferentialPulmonary Vein Ablation Versus AntiarrhythmicDrug Therapy in Paroxysmal Atrial FibrillationThe APAF Study Carlo Pappone, MD, PHD, FACC,* Giuseppe Augello, MD,* Simone Sala, MD,*Filippo Gugliotta, BENG,* Gabriele Vicedomini, MD,* Simone Gulletta, MD,* Gabriele Paglino, MD,*Patrizio Mazzone, MD,* Nicoleta Sora, MD,* Isabelle Greiss, MD,* Andreina Santagostino, MD,*Laura LiVolsi, MD,* Nicola Pappone, MD,† Andrea Radinovic, MD,* Francesco Manguso, MD, PHD,*Vincenzo Santinelli, MD*Milan and Telese Terme, Italy We compared ablation strategy with antiarrhythmic drug therapy (ADT) in patients withparoxysmal atrial fibrillation (PAF).
Atrial fibrillation (AF) ablation strategy is superior to ADT in patients with an initial historyof PAF, but its role in patients with a long history of AF as compared with ADT remains achallenge.
One hundred ninety-eight patients (age, 56 ⫾ 10 years) with PAF of 6 ⫾ 5 years' duration(mean AF episodes 3.4/month) who had failed ADT were randomized to AF ablation bycircumferential pulmonary vein ablation (CPVA) or to the maximum tolerable doses ofanother ADT, which included flecainide, sotalol, and amiodarone. Crossover to CPVA wasallowed after 3 months of ADT.
By Kaplan-Meier analysis, 86% of patients in the CPVA group and 22% of those in the ADTgroup who did not require a second ADT were free from recurrent atrial tachyarrhythmias(AT) (p ⬍ 0.001); a repeat ablation was performed in 9% of patients in the CPVA group forrecurrent AF (6%) or atrial tachycardia (3%). At 1 year, 93% and 35% of the CPVA and ADTgroups, respectively, were AT-free. Ejection fraction, hypertension, and age independentlypredicted AF recurrences in the ADT group. Circumferential pulmonary vein ablation wasassociated with fewer cardiovascular hospitalizations (p ⬍ 0.01). One transient ischemicattack and 1 pericardial effusion occurred in the CPVA group; side effects of ADT wereobserved in 23 patients.
CONCLUSIONS Circumferential pulmonary vein ablation is more successful than ADT for prevention of PAF with few complications. Atrial fibrillation ablation warrants consideration in selected patientsin whom ADT had already failed and maintenance of sinus rhythm is desired. (A ControlledRandomized Trial of CPVA Versus Antiarrhythmic Drug Therapy in for Paroxysmal AF:APAF/01; NCT00340314) (J Am Coll Cardiol 2006;48: 2340 –7) 2006 by the American College of Cardiology Foundation Currently, antiarrhythmic drug therapy (ADT) is consid- study that confined the analysis to untreated patients with ered as first line therapy to prevent recurrent and symptom- an initial history of paroxysmal AF (PAF), who represent atic atrial fibrillation (AF), but antiarrhythmic drugs only a minority of the wide AF population. In another (AADs) are frequently ineffective and may be associated randomized study, Stabile et al. reported that ablation with serious adverse effects Atrial fibrillation ablation therapy combined with ADT was superior to ADT alone in has been demonstrated to be effective in patients with AF patients with paroxysmal or persistent AF. Recently, we and may be a realistic alternative to chronic ADT demonstrated that circumferential pulmonary vein ablation Recently, it has been reported in 3 randomized trials the (CPVA) is more effective than amiodarone in maintaining striking superiority of AF ablation strategy over ADT sinus rhythm (SR) at 1 year, even in patients with perma- The first study by Wazni et al. was a pilot nent AF Whether CPVA alone is superior to ADT inpatients with PAF is still unknown. Thus, we conducted a From the ⴱDivision of Cardiac Pacing and Electrophysiology, San Raffaele randomized controlled trial (the APAF [Ablation for Par- University Hospital, Milan, Italy; and the †Salvatore Maugeri Foundation, IRCCS, oxysmal Atrial Fibrillation] trial) to determine whether Telese Terme, Italy.
CPVA was superior to ADT for maintaining SR at 1 year Manuscript received August 2, 2006; revised manuscript received August 23, 2006, accepted August 28, 2006.
in patients with a long history of PAF.
JACC Vol. 48, No. 11, 2006 Pappone et al.
December 5, 2006:2340 –7 CPVA Versus Drug Therapy in Paroxysmal AF Table 1. Exclusion and Inclusion Criteria Abbreviations and Acronyms
Inclusion criteria AAD ⫽ antiarrhythmic drug Age ⬎18 or ⬍70 yrs ADT ⫽ antiarrhythmic drug therapy Creatinine concentration ⬍1.5 mg/dl ⫽ atrial fibrillation AF history ⬎6 months ⫽ atrial tachyarrhythmia AF burden ⬎2 episodes/month in the last 6 months* CPVA ⫽ circumferential pulmonary vein ablation Exclusion criteria ⫽ ejection fraction AF secondary to transient or correctable abnormality ⫽ paroxysmal atrial fibrillation Intra-atrial thrombus, tumor precluding catheter insertion LA diameter ⬎65 mmLeft ventricular ejection fraction ⬍35%HF symptoms ⬎ NYHA functional class IIPrior ADT therapy with amiodarone, flecainide, and sotalol Contraindication to beta-blocking therapyPatients with rheumatic mitral valve disease Study design. This study was designed to compare the
Unstable angina or acute or prior myocardial infarction (⬍6 months) relative efficacy of CPVA and ADT in the treatment of patients with PAF who have already failed AADs. Patients Renal or hepatic failure were randomized to another 3 widely used AADs (amioda- Implanted device (pacemaker or cardioverter-defibrillator) rone, flecainide, or sotalol, either as single drugs or in Need for antiarrhythmic therapy for arrhythmias other than AFContraindication to ADT† or anticoagulation with warfarin combination) at the maximum tolerable doses All History of a cerebrovascular accident consecutive patients with PAF referred to our electrophys- Prior attempt at catheter or surgical ablation for AF iology lab at the San Raffaele University Hospital starting *The AF burden was quantified before enrolment by review of patient charts.
from January 2005 were screened for inclusion and exclusion †Thyroid dysfunction, interstitial lung disease with DLCO ⬍70% of predicted or criteria At time of enrollment, patients were severe asthma, QT interval exceeding 400 ms, symptomatic sinus node or atrioven-tricular node dysfunction unless a pacemaker is implanted, or evidence of stress- randomized to 1 of 2 treatment arms: CPVA or long-term induced myocardial ischemia.
ADT The 198th patient was enrolled on May 11, ADT ⫽ antiarrhythmic drug therapy; AF ⫽ atrial fibrillation; DLCO ⫽ diffusion capacity of the lung for carbon monoxide; HF ⫽ heart failure; LA ⫽ left atrial; 2005. All patients signed a written informed consent, which NYHA ⫽ New York Heart Association.
was first approved by the institutional ethics and review Diamond Bar, California) or NavX (Endocardial Solutions board committees of the San Raffaele University Hospital.
Inc., St. Paul, Minnesota) Radiofrequency appli- CPVA therapy. The details of the CPVA procedure have
cations were done with either an 8-mm standard catheter been previously described Left atrial geometry (Navi-Star, Biosense-Webster or Livewire TC, St. Jude was constructed with either CARTO (Biosense-Webster, Medical, St. Paul, Minnesota) or an irrigated tip catheter
(3.5-mm Cool-Path, St. Jude Medical or Thermo-Cool
Navi-Star, Biosense-Webster); radiofrequency settings were
60 to 100 W, 50 to 65°C and 25 to 40 W, 35 to 40°C,
respectively. Completeness across mitral isthmus lines was
assessed as previously described Ablation at the
cavotricuspid isthmus to prevent isthmus-dependent atrial
flutter was performed in all patients. To reduce the proba-
bility of early recurrences of AF that could interfere with the
reverse remodeling process, patients were treated with ADT
for 6 weeks after catheter ablation; thereafter, a 12-month
follow-up started If there was a recurrence of atrial
tachyarrhythmias (AT) (including both AF and atrial tachy-
cardia) beyond the first 6 weeks after the ablation, then a
re-do procedure could be performed if the patient wished to
ADT. Oral flecainide was given at an initial dose of 100 mg
every 12 h, oral sotalol at an initial dose of 80 mg every 8 h,
and oral amiodarone at an initial loading of 600 mg/day for
the first week, 400 mg/day for the next week, after which a
daily maintenance dose of 200 mg a day was given. The
maximum tolerable dosage (up to 300 mg/day for flecainide
Figure 1. Study design. Enrolled patients were randomized to circumfer- and 320 mg/day for sotalol) was based on the clinical ential pulmonary vein ablation (CPVA) (n ⫽ 99) or antiarrhythmic drug response and/or the occurrence of side effects. Doses of each therapy (ADT) (n ⫽ 99). After 4 weeks of antiarrhythmic therapy (run-in drug were reduced if intolerable adverse reactions occurred, phase), patients proceeded to the randomized treatment (i.e., catheterablation or solely continuing ADT). AAD ⫽ antiarrhythmic drug.
and treatment was stopped if they persisted. Even with AF Pappone et al.
JACC Vol. 48, No. 11, 2006 CPVA Versus Drug Therapy in Paroxysmal AF December 5, 2006:2340 –7 Figure 2. Pre- and post-ablation bipolar voltage maps of the left atrium with either CARTO (A) or NavX systems (B) are shown.
recurrences, the patient could be maintained on the same tracings and echocardiograms were interpreted by 2 physi- drug and dose regimen if the investigator determined that cians blinded to the patient randomized arm. In the event of an acceptable clinical response was achieved based on the disagreement, the final interpretation was left to one of the duration and/or frequency of previous arrhythmia recur- authors, who were unaware of which group the patient rences. In case of failure of the first assigned drug at the belonged. An arrhythmia had to last ⬎5 s. Rhythm trans- maximum tolerable dosage, the choice of a second drug trial missions were available from all patients for 94 ⫾ 2% days was left to the primary physician, to be chosen from the of follow-up.
other 2 antiarrhythmic agents or a combination of 2 of the End point. The primary end point of this study was
3 agents used in this study; the minimum period after which freedom from documented recurrent AT during a 12- the second ADT trial was considered unsuccessful was set at month follow-up in patients who underwent CPVA and in 3 months. After 2 trials of ADT, patients could be consid- those receiving ADT. The end point was reached with the ered for crossover to CPVA first episode of AT, and cases with a second ADT or repeat Anticoagulant therapy. All patients were anticoagulated
ablation procedure were considered failures. Recurrence of with warfarin to maintain an international normalized ratio AT was defined as AT that lasted at least 30 s of 2.0 to 3.0. Anticoagulation was discontinued if SR was Monthly rhythm analysis according to different mapping maintained for ⬎6 weeks without any episodes of symp- systems and different catheters as well as number of hospi- tomatic or asymptomatic AF and in the absence of concur- talizations and complications in both groups were also rent indications.
Follow-up. All patients were seen in an outpatient clinic
Statistical analysis. Based on a conservative assumption
during the initial screening period before randomization and that SR would be maintained at 1 year in at least 75% of at 3, 6, and 12 months after randomization. At each visit, patients in the CPVA group and 50% of patients in the 12-lead electrocardiogram (ECG), 48-h Holter monitoring, control group a minimum of 85 patients was required and a transthoracic echocardiogram were obtained. Three in each group at a power of 90% to reach a 2-tailed alpha of months after randomization, thyroid function tests, hepatic 0.05. Considering the possibility of drop-outs, we planned panel, and serum chemical measurements were obtained.
to increase the number of patients by 15% for each group.
Chest X-ray and potential corneal deposits were also eval- Data are expressed as mean values ⫾ SD and analyzed using uated in patients receiving long-term amiodarone therapy.
the intention-to-treat method. Continuous variables were All patients were provided with an event monitor (Life compared by independent samples t test after checking with Watch, Buffalo Grove, Illinois) and were asked to record Levene's test for equality of variances and with the paired their rhythm 1 to 3 times daily and whenever they experi- samples t test, when appropriate. Categorical variables were enced symptoms suggestive of AT. All 1-min rhythm analyzed by chi-square test. Multivariate Cox regression JACC Vol. 48, No. 11, 2006 Pappone et al.
December 5, 2006:2340 –7 CPVA Versus Drug Therapy in Paroxysmal AF Table 2. Patient Characteristics of the blanking period; 5 were controlled by continuing ADT Group
ADT (flecainide in 4, sotalol in 1), whereas 6 required a (n 99)
(n 99)
repeat ablation session At this time, recovery ofconduction was documented in 5 left superior pulmonary veins, 4 right superior pulmonary veins, 2 left inferior pulmonary veins, and 1 left inferior pulmonary vein. After a Duration of AF (yrs) touch-up of the previous ablation lines, 5 patients stopped having AF (mean post-repeat ablation follow-up 6 months).
The use of an irrigated tip catheter had a better outcome than those ablated with an 8-mm catheter (p ⫽ 0.03). After ablation, asymptomatic AF was observed in 3 patients who Structural heart disease otherwise also reported symptomatic AF recurrences. In the Coronary artery disease CPVA group, the left atrial size was smaller at 12 months Valvular heart disease Congenital heart disease after (36 ⫾ 6 mm) than before (40 ⫾ 6 mm) ablation No. of previously ineffective (p ⬍ 0.01).
antiarrhythmic drugs No serious complications were observed in any patient CPVA ⫽ circumferential pulmonary vein ablation; LVEF ⫽ left ventricular ejection who underwent CPVA. Shortly after the procedure with an fraction; other abbreviations as in table 1.
8-mm catheter, 1 patient with a mild apical hypertrophic analysis was performed to determine the clinical predictors cardiomyopathy developed a spell transient ischemic attack, of freedom from recurrent AF. Observed event-free survival which resolved within a few seconds. Another patient who curves for both groups—presented as Kaplan-Meier plots— performed CPVA by the irrigated-tip catheter had a very were compared among them by 2-sample log-rank tests.
small pericardial effusion not due to cardiac perforation, A value of p ⬍ 0.05 indicated statistical significance. SPSS which otherwise did not require pericardiocentesis. Three 14.0.2 (SPSS Inc., Chicago, Illinois) was used for the patients in the CPVA group developed post-ablation atrial statistical analysis. The prevalence of SR and AT during tachycardia requiring activation mapping and ablation follow-up were also reported and compared on a monthly All patients underwent successful ablation after the basis. One rhythm recording in AT in a given month was index procedure, and no further ATs were detected after 5, sufficient to classify the patient as having suffered from AT 7, and 8 months of follow-up, respectively.
in that month.
ADT group. Of the 99 patients randomized to ADT, only
24 had their AF suppressed by a single AAD (amiodarone:
n ⫽ 12 of 33; flecainide: n ⫽ 7 of 33; sotalol: n ⫽ 5 of 33) Study population. Among 334 screened patients, 198 were
during the 12 months of follow-up. Of the 75 enrolled in the study and underwent randomization patients with AF recurrences, 20 (27%) had asymptomatic The most frequent reasons for the failure to enroll screened episodes; 49 were placed on combination therapy of 200 mg patients were previous ADT over the last 24 months with of flecainide and 200 mg of amiodarone daily and 26 on 200 amiodarone (46 patients), flecainide (35 patients), and mg of flecainide and 240 mg of sotalol; 11 patients were sotalol (25 patients) or combination of them (22 patients).
subsequently free from AF with the combination of flecain- Characteristics of the 2 randomized groups are shown in ide and amiodarone; 22 patients still had AF on combina- Most enrolled patients had received previous tion therapy although the arrhythmia was less frequent and treatment with propafenone, dysopiramide, and quinidine of short duration (amiodarone plus flecainide: n ⫽ 16; as single agents (140 patients) or in combination of digoxin flecainide plus sotalol: n ⫽ 6); the other 42 patients (7, 20, and verapamil (58 patients).
and 15 patients of the 3 subgroups, respectively) crossed Ablation group. Circumferential pulmonary vein ablation
over to CPVA Overall, amiodarone was given to was performed in 99 patients with a mean of 35 ⫾ 12 min 61 patients as a single drug (33 patients) or in combination of radiofrequency energy. The mean CPVA procedure time (28 patients). Amiodarone was as effective as flecainide and was 81 ⫾ 31 min. Inferior vena cava-tricuspid annulus sotalol (35%, 19%, and 11%, respectively, p ⫽ 0.11). No isthmus bidirectional block was successfully achieved in all change in atrial size was noted in patients who remained in patients. We performed CPVA by 8-mm catheter in 50 SR in the ADT group.
patients, and irrigated tip catheters were used in 49 patients.
Significant adverse events leading to permanent drug Six weeks after the procedure, no patients in the ablation withdrawal occurred in 23 patients. Pro-arrhythmia devel- group were on AAD therapy. During follow-up, 85 patients oped in 3 patients in the flecainide group (hypotensive wide remained free from AT and discontinued ADT; warfarin QRS tachycardia in 2 patients and 1:1 atrial flutter in 1); was also stopped in all but 3 having a mechanical mitral thyroid dysfunction occurred in 7 patients in the amioda- valve. Recurrent symptomatic AF was documented by rone group requiring drug discontinuation; and sexual transtelephonic ECG monitoring in 11 patients at the end impairment in 11 patients in the sotalol group.
Pappone et al.
JACC Vol. 48, No. 11, 2006 CPVA Versus Drug Therapy in Paroxysmal AF December 5, 2006:2340 –7 Figure 3. Flow of patients randomized to circumferential pulmonary vein ablation (CPVA) and antiarrhythmic drug therapy (ADT) groups. (A) After
ablation, stable sinus rhythm (SR) was obtained in 85 patients of whom 82 stopped oral anticoagulant therapy (OAT). Of the 11 patients with recurrent
atrial fibrillation (AF), 6 underwent a repeat procedure (REDO). Post-ablation atrial tachyarrhythmia (AT) developed in only 3 patients, and all had a
successful re-do procedure. (B) Among patients randomized to ADT, 42 patients crossed over to CPVA of whom only 6 had AF recurrence. By study
design, AF was considered under control if the patient had no more than 1 episode of AF in a 6-month period.
Primary end point. By Kaplan-Meier analysis, 86% of
from atrial arrhythmias as compared with the 35% in the patients randomized to CPVA were AT-free at the end of follow-up as compared with the 22% of patients randomized Predictors of freedom from PAF. Among the clinical
to ADT (p ⬍ 0.001) time 0 started at the end of parameters of age, gender, duration of AF (years), left atrial the 6-week blanking period.
size, left ventricular ejection fraction (EF), whether or not Follow-up. Among the 99 patients in the ADT group, 42
structural heart disease was present, and treatment assign- underwent CPVA after a mean of 5.8 months. At a mean of ment, CPVA was independently associated with SR main- 6.2 months of follow-up after crossover, 36 were free of tenance (hazard ratio 0.13, 95% confidence interval 0.07 to recurrent AF in the absence of ADT, whereas AF was 0.23, p ⬍ 0.001). Further analysis revealed that EF (hazard present in 6 (14%).
ratio 1.08, 95% confidence interval 1.03 to 1.13, p ⫽ 0.003), Hospital admissions. Among patients assigned to CPVA,
hypertension (hazard ratio 2.31, 95% confidence interval 9 summed up 24 hospital admissions for cardiovascular 1.34 to 3.97, p ⫽ 0.003), and AF duration (hazard ratio causes, including repeat procedures. In the ADT group, 167 1.03, 95% confidence interval 1.01 to 1.11, p ⫽ 0.015) were cardiovascular event-related hospital admissions occurred, independent predictors of drug failure in the ADT group.
not including the hospitalizations for crossover to CPVA (p No independent predictors of AF recurrences were found in ⬍ 0.001). Monthly rhythm analysis in the NavX versus the ablation group.
CARTO subgroups showed sinus rhythm in 95% and 87%at 1 year, respectively (p ⫽ 0.08) and in the 8-mm versus irrigated tip catheter groups 95% and 78% at 1 year,respectively (p ⫽ 0.03) By monthly rhythm Main findings. The results of the present study demon-
analysis that took into account also the outcome of the strate that a single CPVA procedure is more effective than second procedure and for patients controlled with combined ADT in preventing AF relapses in selected patients with therapy in ADT group, 93% of CPVA patients were free PAF. Ablation strategy resulted in maintenance of SR at 1 JACC Vol. 48, No. 11, 2006 Pappone et al.
December 5, 2006:2340 –7 CPVA Versus Drug Therapy in Paroxysmal AF Figure 4. Outcomes in the APAF (Ablation for Paroxysmal Atrial Fibrillation) trial. (A) By Kaplan-Meier analysis, 86% of patients randomized to
circumferential pulmonary vein ablation (CPVA) needed only a single procedure and were atrial tachyarrhythmia (AT)-free at the end of follow-up as
compared with the 22% of patients randomized to antiarrhythmic drug therapy (ADT) (p ⬍ 0.001) who did not require a second ADT and were AT-free
at the end of follow-up; time 0 started at the end of the 6-week blanking period for both groups. (B and C) Monthly rhythm analysis in the NavX versus
CARTO subgroups (95% and 87% at 1 year, respectively, p ⫽ 0.08) and in the 8-mm versus irrigated tip catheter groups (95% and 78% at 1 year,
respectively, p ⫽ 0.03). (D) By monthly rhythm analysis that also took into account the outcome of the second procedure and for patients controlled with
combined therapy in ADT group, 93% of CPVA patients were free from ATs as compared with the 35% in the ADT group. SR ⫽ sinus rhythm.
year without the need for continuing ADT in 86% of pulmonary vein isolation among patients with initial epi- patients as documented by intensive daily transtelephonic sodes of PAF may be superior to initial ADT at 1-year monitoring, whereas only 22% of patients in the ADT follow-up because 87% of ablated patients were AF-free group remained in SR at 1 year. Maintenance of SR after compared with 37% of patients who received ADT. A more ablation was associated with a reverse left atrial remodeling recent randomized trial by Stabile et al. also suggests and with fewer adverse events and hospital admissions due that AF ablation combined with ADT is superior to ADT to cardiovascular causes.
alone in preventing AF recurrences in patients with parox- AF ablation strategy versus ADT: efficacy to prevent
ysmal or persistent AF in whom ADT has already failed.
PAF. Fueled by dissatisfaction with pharmacologic therapy
The results of the present study demonstrate a striking and the explosive development in catheter-based technolo- superiority of the ablation strategy over ADT. Ablation was gies, AF ablation has matured from a purely investigational about 2.5 times more effective than amiodarone (86% vs.
technique to a preferred effective approach for treating AF 35%, respectively) in preventing AF recurrences in relatively Currently, there are few studies comparing ablation young patients with PAF of long duration in the absence of strategy with ADT in patients with PAF We major complications. During a 12-month follow-up by first reported in a non-randomized observational study the using an intense transtelephonic monitoring, asymptomatic striking superiority of AF ablation over ADT, which per- AF post-ablation was detected only in 3 patients in addition sisted up to 3 years after ablation We also reported that to symptomatic AF recurrences, similarly to those reported AF ablation was associated with significantly lower mortal- by Oral et al. on the contrary, asymptomatic episodes ity and adverse events compared with ADT in the long term were recorded in many patients (27%) in the ADT group.
In the first pilot randomized study by Wazni et al. The reports of these trials taken together indicate that AF who compared AF ablation with ADT, the authors, for the ablation strategy indeed warrants consideration as first-line first time, suggested that a strategy of using first-line therapy in selected patients in whom maintenance of SR is Pappone et al.
JACC Vol. 48, No. 11, 2006 CPVA Versus Drug Therapy in Paroxysmal AF December 5, 2006:2340 –7 desired. In the present study, the rate of AF recurrence in to hemodynamic instability were observed in 3 patients in the ADT group was higher than that reported in previous the flecainide group (hypotensive wide QRS tachycardia in studies but similar to that recently reported by Stabile et al.
2 and 1:1 atrial flutter in 1). Sexual dysfunction may be an and this in all probability was due to the same intensive important limitation especially in young patients, and in our monitoring strategy performed in both studies. Consistent series this complication occurred in 11 young patients with prior reports of the effect of CPVA on left atrial size during sotalol therapy.
there was a significant decrease in left atrial size Study limitations. The ablation procedures were per-
after CPVA. This is an important issue in patients with formed in a single highly specialized center with extensive increased left atrial dimensions because this can further experience in CPVA in patients most of whom were prevent atrial dilatation and disease progression. On the relatively young and healthy subjects. Therefore, these other hand, no left atrial remodeling was observed in the results cannot be generalized or applied to all AF patient group of patients assigned to ADT.
populations. Although ablation was more effective than AF ablation strategy versus ADT: complications. ABLA-
ADT at 1 year, maintenance of benefit and incidence of TION STRATEGY. The efficacy of AF ablation strategy is
adverse events over a much longer follow-up as compared superior to ADT, but the main concern and limitation of with ADT remain unknown. Indeed, most patients will any ablative procedure is the potential occurrence of major require ADT for many years, even decades, and thus would complications. Unlike ADT, previous studies have shown be subject to longer potential adverse effects of the drugs. It that complications of CPVA typically result in only acute is possible that this "early" end point biases our results and not long-term morbidity with no case of death toward ADT, for which longer-term adverse effects are a In the present study, a few transient complications concern. Finally, although every effort was made to avoid occurred in the CPVA group. Patients who underwent any potential bias excluding patients with previous treat- CPVA by using tip-irrigated catheters were less likely to ment with amiodarone, flecainide, and sotalol, we cannot have AF recurrences than those ablated with an 8-mm completely exclude that in this study some patients also had catheter. By introducing the modified CPVA approach that received these drugs over the past years. Even recognizing includes additional posterior lines, the incidence of AT has the limitations of the study, we believe that our results been lowered to 3.9% in this study, we corroborate the challenge the notion that multiple and different AADs requirement of these linear lesions even if gaps in ablation should be used life-long in patients with a long history of lesions, either circular or linear, can be arrhythmogenic.
Patients randomized to CPVA experienced less hospital Conclusions. Among selected patients with a long history
admissions for cardiovascular causes than those randomized of PAF, a single CPVA is more effective than ADT with 3 to ADT. This can be explained by the superior efficacy of AADs widely used as single agents or in combination.
CPVA over ADT in suppressing AF and by the fewer However, before translating the results of this study into adverse events reported in the CPVA group.
clinical practice, further multicenter randomized trials inolder patients with more extensive heart disease with longer ADT. In symptomatic patients with a long history of AF,
follow-up are required. Nevertheless, the results of our study usually ADT should be given for many years to prevent AF suggest that AF ablation strategy warrants consideration in recurrences. Unfortunately, current AADs have many lim- selected patients in whom ADT has already failed and itations in terms of adverse effects, which in some cases may maintenance of SR is desired.
be serious and may require drug discontinuation. Amioda-rone is well tolerated, but its chronic administration fre- Reprint requests and correspondence: Dr. Carlo Pappone, De-
quently is associated with thyroid dysfunction, as observed partment of Arrhythmology, San Raffaele University Hospital, Via in 7 patients in our series, which may further aggravate Olgettina 60, 20132—Milan, Italy. E-mail: episodes of PAF. In addition, the drug may induce pulmo- nary toxicity, but our study was relatively short (1 year), anddid not address the potential for this serious adverse effect.
Overall, in the present study, 23 patients (23%) discontin- 1. Fuster V, Ryden LE, Asinger RW, et al. ACC/AHA/ESC guidelines ued ADT because of adverse events, and these data compare for the management of patients with atrial fibrillation: executive well to the 11% to 28% reported in the AFFIRM (Atrial summary. A Report of the American College of Cardiology/American Fibrillation Follow-Up Investigation of Rhythm Manage- Heart Association Task Force on Practice Guidelines and the Euro-pean Society of Cardiology Committee for Practice Guidelines and ment), CTAF (Canadian Trial of Atrial Fibrillation), and Policy Conferences (Committee to Develop Guidelines for the Man- PIAF (Rhythm or Rate Control in Atrial Fibrillation- agement of Patients With Atrial Fibrillation): developed in collabo- Pharmacological Intervention in Atrial Fibrillation Ran- ration with the North American Society of Pacing and Electrophysi-ology. J Am Coll Cardiol 2001;38:1231– 66.
domised Trial) studies Thus, although more than 2. Wyse DG, Waldo AL, DiMarco JP, et al. A comparison of rate one-third of patients can be maintained in SR with 1 or control and rhythm control in patients with atrial fibrillation. N EnglJ Med 2002;347:1825–33.
more AAD, there is serious concern about the life-long use 3. Corley SD, Epstein AE, DiMarco JP, et al. Relationships between of these drugs to suppress AF. Proarrhythmic effects leading sinus rhythm, treatment, and survival in the Atrial Fibrillation JACC Vol. 48, No. 11, 2006 Pappone et al.
December 5, 2006:2340 –7 CPVA Versus Drug Therapy in Paroxysmal AF Follow-Up Investigation of Rhythm Management (AFFIRM) study.
centre, randomized, controlled study (Catheter Ablation For The Cure Circulation 2004;109:1509 –13.
Of Atrial Fibrillation Study). Eur Heart J 2006;27:216 –21.
4. Pappone C, Rosanio S, Augello G, et al. Mortality, morbidity, and 13. Oral H, Pappone C, Chugh A, et al. Circumferential pulmonary-vein quality of life after circumferential pulmonary vein ablation for atrial ablation for chronic atrial fibrillation. N Engl J Med 2006;354:934 – fibrillation: outcomes from a controlled nonrandomized long-term study. J Am Coll Cardiol 2003;42:185–97.
14. Pappone C, Santinelli V. The who, what, why, and how-to guide for 5. Pappone C, Santinelli V, Manguso F, et al. Pulmonary vein denerva- circumferential pulmonary vein ablation. J Cardiovasc Electrophysiol tion enhances long-term benefit after circumferential ablation for 2004;15:1226 –30.
paroxysmal atrial fibrillation. Circulation 2004;109:327–34.
15. Pappone C, Manguso F, Vicedomini G, et al. Prevention of iatrogenic 6. Nademanee K, McKenzie J, Kosar E, et al. A new approach for atrial tachycardia after ablation of atrial fibrillation: a prospective catheter ablation of atrial fibrillation: mapping of the electrophysi- randomized study comparing circumferential pulmonary vein ablation ologic substrate. J Am Coll Cardiol 2004;43:2044 –53.
with a modified approach. Circulation 2004;110:3036 – 42.
7. Oral H, Scharf C, Chugh A, et al. Catheter ablation for paroxysmal 16. The AFFIRM First Antiarrhythmic Drug Substudy Investigators.
atrial fibrillation: segmental pulmonary vein ostial ablation versus left Maintenance of sinus rhythm in patients with atrial fibrillation: anAFFIRM substudy of the first antiarrhythmic drug. J Am Coll Cardiol atrial ablation. Circulation 2003;108:2355– 60.
2003;42:20 –9.
8. Ouyang F, Bansch D, Ernst S, et al. Complete isolation of left atrium 17. Oral H, Veerareddy S, Good E, et al. Prevalence of asymptomatic surrounding the pulmonary veins: new insights from the double-Lasso recurrences of atrial fibrillation after successful radiofrequency catheter technique in paroxysmal atrial fibrillation. Circulation 2004;110: ablation. J Cardiovasc Electrophysiol 2004;15:920 – 4.
18. Pappone C, Oreto G, Rosanio S, et al. Atrial electroanatomic 9. Haissaguerre M, Hocini M, Sanders P, et al. Catheter ablation of remodeling after circumferential radiofrequency pulmonary vein abla- long-lasting persistent atrial fibrillation: clinical outcome and mecha- tion: efficacy of an anatomic approach in a large cohort of patients with nisms of subsequent arrhythmias. J Cardiovasc Electrophysiol 2005; atrial fibrillation. Circulation 2001;104:2539 – 44.
16:1138 – 47.
19. Lemola K, Sneider M, Desjardins B, et al. Effects of left atrial ablation 10. Pappone C, Santinelli V. Atrial fibrillation ablation: a realistic alter- of atrial fibrillation on size of the left atrium and pulmonary veins.
native to pharmacologic therapy. Nat Clin Pract Cardiovasc Med Heart Rhythm 2004;1:576 – 81.
2005;2:608 –9.
20. Roy D, Talajic M, Dorian P, et al. Amiodarone to prevent recurrence 11. Wazni OM, Marrouche NF, Martin DO, et al. Radiofrequency of atrial fibrillation. Canadian Trial of Atrial Fibrillation Investigators.
ablation vs antiarrhythmic drugs as first-line treatment of symptomatic N Engl J Med 2000;342:913–20.
atrial fibrillation: a randomized trial. JAMA 2005;293:2634 – 40.
21. Hohnloser SH, Kuck KH, Lilienthal J. Rhythm or rate control in atrial 12. Stabile G, Bertaglia E, Senatore G, et al. Catheter ablation treatment fibrillation—Pharmacological Intervention in Atrial Fibrillation in patients with drug-refractory atrial fibrillation: a prospective, multi- (PIAF): a randomised trial. Lancet 2000;356:1789 –94.


Faq for patients: deep brain stimulation for parkinson's disease

Frequently asked questions: Deep Brain Stimulation for Parkinson's Disease at UCSF Contents When should one consider surgical therapy? For patients with early Parkinson's disease, levodopa (sinemet) and other antiparkinsonian medications are usually effective for maintaining a good quality of life. As the disorder progresses, however, medications can produce disabling side effects. Many patients on long-term levodopa develop troublesome dyskinesias, excessive movements that often cause the limbs and body to writhe or jump. In addition, their dose

Heartjnl214031 6.14

Controversies in the cardiovascular management oftype 2 diabetes Lionel H Opie,1 Derek M Yellon,2 Bernard J Gersh3 1Hatter Cardiovascular Research low-density lipoprotein cholesterol (LDL-C) from Institute, Department of In patients with type 2 diabetes mellitus, intense control about 3.1 mmo/l (118 mg/dl) to 1.94 mmol/l Medicine, Faculty of Health of blood pressure, lipids and glucose, aiming at