Giuseppe Ciconte

The Natural History of Asymptomatic Ventricular Pre-Excitation A Long-Term Prospective Follow-Up Study of 184 Asymptomatic Children

OBJECTIVES The aim of this study was to describe the natural history of asymptomatic ventricular pre-excitation in children and to determine predictors of potentially life-threatening arrhythmic events. BACKGROUND Sudden death can be the first clinical manifestation in asymptomatic children with ventricular pre-excitation, but reduction of its incidence by prophylactic ablation requires the identification of subjects at high risk. METHODS Between 1995 and 2005 we prospectively collected clinical and electrophysiologic data from 184 children (66% male; median age 10 years; range 8 to 12 years) with asymptomatic ventricular pre-excitation on the electrocardiogram. After electrophysiologic testing, subjects were followed as outpatients taking no medications. The primary end point of the study was the occurrence of arrhythmic events. Predictors of potentially life-threatening arrhythmias were analyzed. RESULTS Over a median follow-up of 57 months (min/max 32/90 months) after electrophysiologic testing, 133 children (mean age 10 years; range 8 to 12 years) did not experience arrhythmic events, remaining totally asymptomatic, while 51 children had within 20 months (min/max 8/60 months) a first arrhythmic event, which was potentially life-threatening in 19 of them (mean age 10 years; range 10 to 14 years). Life-threatening tachyarrhythmias resulted in cardiac arrest (3 patients), syncope (3 patients), atypical symptoms (8 patients), or minimal symptoms (5 patients). Univariate analysis identified tachyarrhythmia inducibility (p < 0.001), anterograde refractory period of accessory pathways (APERP) </=240 ms (p < 0.001), and multiple accessory pathways (p < 0.001) as risk factors for potentially life-threatening arrhythmic events. Independent predictors by multivariate analysis were APERP (p = 0.001) and multiple accessory pathway (p = 0.001). CONCLUSIONS These findings are potentially relevant in terms of early identification of high-risk asymptomatic children with ventricular pre-excitation. Subjects with short APERPs and multiple pathways are at higher risk of developing life-threatening arrhythmic events and are the best candidates for prophylactic ablation.

Second-generation cryoballoon ablation for paroxysmal atrial fibrillation: 1-year follow-up.

BACKGROUND The novel cryoballoon Advance (CB-A) has proven to achieve significantly lower temperatures and faster pulmonary vein isolation (PVI) times in comparison with the first-generation device. Although acutely very effective, to the best of our knowledge, data on mid-term clinical follow-up is lacking. AIMS The aim of the study was to analyse the freedom from recurrence of atrial fibrillation (AF) on a 1-year follow-up period, in a series of consecutive patients having undergone PVI with the CB-A for paroxysmal AF (PAF). METHODS AND RESULTS Forty-two patients [30 male (71%); mean age: 57.9 ± 21.1 years] were included. All patients underwent a procedure with the large 28 mm CB-A. A total 168 PVs were depicted on the pre-procedural computed tomography scan. All PVs (100%) could be isolated with the CB only. The freedom from AF off-antiarrhythmic drug treatment after a single procedure was 78% of patients at a mean 11.6 ± 2.0 months follow-up. If considering a blanking period (BP) of 3 months, success rate was 83%. Phrenic nerve palsy (PNP) was the most frequent complication occurring in 19% of individuals. CONCLUSION The CB-A is very effective in producing PVI and affords freedom from AF at 12 months follow-up in 83% of patients affected by drug-resistant PAF following a 3-month BP. The most frequent complication observed was PNP which occurred in 19% of patients. All PNP reverted during follow-up.

Atrial fibrillation progression and management: A 5-year prospective follow-up study

BACKGROUND Few data on atrial fibrillation (AF) progression from the first paroxysmal episode are available. OBJECTIVE The purpose of this study was to assess the progression of AF not due to potentially reversible causes in patients treated according to current guidelines recommendations that also include catheter ablation. METHODS Among 402 screened patients with first AF, 106 patients (mean age 57.5 years) were selected and followed for 5 years. Of these patients, 54 had lone AF and 52 had comorbidities. RESULTS Fifty patients (61.1% with lone AF) had no further recurrence after 5 years. The remaining 56 patients within 19 months after the first episode developed recurrent paroxysmal AF requiring long-term antiarrhythmic drug therapy, which was continued in 45 patients and was stopped because of intolerance/failure in 11 patients who underwent catheter ablation. AF became persistent in 24 of the 45 patients on antiarrhythmic drug therapy and then permanent in 16, of whom 6 had refused catheter ablation at the time of persistence. No AF recurrences or AF progression occurred after ablation. Kaplan-Meier curves demonstrated that patients with comorbidities were more likely to progress than were those with lone AF (P <.001) and that patients who underwent catheter ablation were at lower risk for progression to permanent AF than were those on antiarrhythmic drug therapy (P = .029). Age, diabetes, and heart failure (P <.001) predict final progression to permanent AF. CONCLUSION Patients with first AF and comorbidities are at higher risk for rapid progression to permanent AF, and age, diabetes, and heart failure are independent predictors. Catheter ablation rather than antiarrhythmic drug therapy is beneficial in eliminating recurrences delaying arrhythmia progression.

Implantable Cardioverter-Defibrillator Therapy in Brugada Syndrome: A 20-Year Single-Center Experience

BACKGROUND Patients with Brugada syndrome and aborted sudden cardiac death or syncope have higher risks for ventricular arrhythmias (VAs) and should undergo implantable cardioverter-defibrillator (ICD) placement. Device-based management of asymptomatic patients is controversial. ICD therapy is associated with high rates of inappropriate shocks and device-related complications. OBJECTIVES The objective of this study was to investigate clinical features, management, and long-term follow-up of ICD therapy in patients with Brugada syndrome. METHODS Patients presenting with spontaneous or drug-induced Brugada type 1 electrocardiographic findings, who underwent ICD implantation and continuous follow-up at a single institution, were eligible for this study. RESULTS A total of 176 consecutive patients were included. During a mean follow-up period of 83.8 ± 57.3 months, spontaneous sustained VAs occurred in 30 patients (17%). Eight patients (4.5%) died. Appropriate ICD shocks occurred in 28 patients (15.9%), and 33 patients (18.7%) had inappropriate shocks. Electrical storm occurred in 4 subjects (2.3%). Twenty-eight patients (15.9%) experienced device-related complications. In multivariate Cox regression analysis, aborted sudden cardiac death and VA inducibility on electrophysiologic studies were independent predictors of appropriate shock occurrence. CONCLUSIONS ICD therapy was an effective strategy in Brugada syndrome, treating potentially lethal arrhythmias in 17% of patients during long-term follow-up. Appropriate shocks were significantly associated with the presence of aborted sudden cardiac death but also occurred in 13% of asymptomatic patients. Risk stratification by electrophysiologic study may identify asymptomatic patients at risk for arrhythmic events and could be helpful in investigating syncope not related to VAs. ICD placement is frequently associated with device-related complications, and rates of inappropriate shocks remain high regardless of careful device programming.

Comparison between radiofrequency with contact force-sensing and second-generation cryoballoon for paroxysmal atrial fibrillation catheter ablation: a multicentre European evaluation

AIMS Whether pulmonary vein isolation (PVI) for paroxysmal atrial fibrillation (PAF) using contact force (CF)-guided radiofrequency (RF) or second-generation cryoballoon (CB) present similar efficacy and safety remains uncertain. METHODS AND RESULTS We performed a multicentre study comparing procedural safety and arrhythmia recurrence after standardized PVI catheter ablation for PAF using CF-guided RF ablation (Thermocool(®) SmartTouch™, Biosense Webster; or Tacticath™, St Jude Medical) (CF group) with second-generation CB ablation (Arctic Front Advance™, Medtronic) (CB group). Overall, 376 patients (mean age 59.8 ± 10.4 years, 280 males) were enrolled in 4 centres: 198 in CF group and 178 in CB group. Procedure was shorter for CB group than for CF group (109.6 ± 40 vs. 122.5 ± 40.7 min, P = 0.003), but fluoroscopy duration and X-ray exposure were not statistically different (P = 0.1 and P = 0.22, respectively). Overall complication rate was similar in both groups: 14 (7.1%) in the CF group vs. 13 (7.3%) in the CB group (P = 0.93). However, transient right phrenic nerve palsy occurred only in CB group (10 patients, 5.6%; P = 0.001 vs. CF group) and severe non-lethal complications (embolic event, tamponade, or oesophageal injury) occurred only in CF group (5 patients, 2.5%; P = 0.03 vs. CB group). No periprocedural death occurred in either group. Single-procedure freedom from any atrial arrhythmias at 18 months post-ablation was comparable in CF group and CB group (76 vs. 73.3%, respectively, log rank P = 0.63). CONCLUSION Pulmonary vein isolation using CF-guided RF and second-generation CB leads to comparable single-procedure arrhythmia-free survival at up to 18 months with similar overall complication rate.

Asymptomatic Ventricular Preexcitation: A Long-Term Prospective Follow-Up Study of 293 Adult Patients

Background—Sudden cardiac death can be the first clinical presentation of asymptomatic ventricular preexcitation. Methods and Results—From 1995 to 2005, we prospectively collected clinical and electrophysiological data among 293 adults with asymptomatic ventricular preexcitation (61.4% males; median age, 36 years; interquartile range [IQR], 28 to 47.5). After electrophysiological testing, patients were prospectively followed, taking no drugs. The primary end point of the study was the occurrence of a first arrhythmic event. Predictors of arrhythmic events were analyzed by univariate and multivariate Cox models. Over a median follow-up of 67 months (minimum to maximum, 8 to 90), after electrophysiological testing, 262 patients (median age, 37 years; IQR, 30 to 48) did not experience arrhythmic events, remaining totally asymptomatic, whereas 31 patients (median age, 25 years; IQR, 22 to 29; median follow-up, 27 months; minimum to maximum, 8 to 55) had a first arrhythmic event, which was potentially life-threatening in 17 of them (median age, 24 years; IQR, 20 to 28.5; median follow-up, 25 months; minimum to maximum, 9 to 55). Potentially life-threatening tachyarrhythmias resulted in resuscitated cardiac arrest (1 patient), presyncope (7 patients) syncope (4 patients), or dizziness (5 patients). In multivariate analysis age (P =0.004), inducibility (P =0.001) and anterograde effective refractory period of the accessory pathway ≤250 ms (P =0.001) predicted potentially life-threatening arrhythmias. Conclusions—These results indicate that prognosis of adults who present with asymptomatic ventricular preexcitation is good, and the risk of a significant event is small. Short anterograde effective refractory period of the accessory pathway and inducibility at baseline are independent predictors of potentially life-threatening arrhythmic events, and the risk decreases with increasing age.Background— Sudden cardiac death can be the first clinical presentation of asymptomatic ventricular preexcitation. Methods and Results— From 1995 to 2005, we prospectively collected clinical and electrophysiological data among 293 adults with asymptomatic ventricular preexcitation (61.4% males; median age, 36 years; interquartile range [IQR], 28 to 47.5). After electrophysiological testing, patients were prospectively followed, taking no drugs. The primary end point of the study was the occurrence of a first arrhythmic event. Predictors of arrhythmic events were analyzed by univariate and multivariate Cox models. Over a median follow-up of 67 months (minimum to maximum, 8 to 90), after electrophysiological testing, 262 patients (median age, 37 years; IQR, 30 to 48) did not experience arrhythmic events, remaining totally asymptomatic, whereas 31 patients (median age, 25 years; IQR, 22 to 29; median follow-up, 27 months; minimum to maximum, 8 to 55) had a first arrhythmic event, which was potentially life-threatening in 17 of them (median age, 24 years; IQR, 20 to 28.5; median follow-up, 25 months; minimum to maximum, 9 to 55). Potentially life-threatening tachyarrhythmias resulted in resuscitated cardiac arrest (1 patient), presyncope (7 patients) syncope (4 patients), or dizziness (5 patients). In multivariate analysis age ( P =0.004), inducibility ( P =0.001) and anterograde effective refractory period of the accessory pathway ≤250 ms ( P =0.001) predicted potentially life-threatening arrhythmias. Conclusions— These results indicate that prognosis of adults who present with asymptomatic ventricular preexcitation is good, and the risk of a significant event is small. Short anterograde effective refractory period of the accessory pathway and inducibility at baseline are independent predictors of potentially life-threatening arrhythmic events, and the risk decreases with increasing age. Received October 10, 2008; accepted January 27, 2009. # CLINICAL PERSPECTIVE {#article-title-2}

Pulmonary vein isolation as index procedure for persistent atrial fibrillation: One-year clinical outcome after ablation using the second-generation cryoballoon

BACKGROUND No data are available about the clinical outcome of pulmonary vein isolation (PVI) as an index procedure for persistent atrial fibrillation (PersAF) ablation using the second-generation cryoballoon (CB-Adv). OBJECTIVE The purpose of this study was to assess the 1-year efficacy of PVI as an index procedure for PersAF ablation using the novel CB-Adv. METHODS Sixty-three consecutive patients (45 male [71.4%], mean age 62.7 ± 9.7 years) with drug-refractory PersAF undergoing PVI using the novel CB-Adv were enrolled. Follow-up was based on outpatient clinic visits including Holter ECGs. Recurrence of atrial tachyarrhythmias (ATas) was defined as a symptomatic or documented episode >30 seconds. RESULTS A total of 247 PVs were identified and successfully isolated with a mean of 1.7 ± 0.4 freezes. Mean procedural and fluoroscopy times were 87.1 ± 38.2 minutes and 14.9 ± 6.1 minutes, respectively. Among 26 of 63 patients (41.3%) presenting with AF at the beginning of the procedure, 7 of 26 (26.9%) converted to sinus rhythm during ablation. Phrenic nerve palsy occurred in 4 of 63 patients (6.3%). At 1-year follow-up, after a 3-month blanking period (BP), 38 of 63 patients (60.3%) were in sinus rhythm. Because of ATa recurrences, 9 patients underwent a second procedure with radiofrequency ablation showing a pulmonary vein reconnection in 4 right-sided PVs (44.4%) and 3 left-sided PVs (33.3%). Multivariate analysis demonstrated that PersAF duration (P = .01) and relapses during BP (P = .04) were independent predictors of AT recurrences. CONCLUSION At 1-year follow-up, freedom from ATas following PersAF ablation with the novel CB-Adv is 60%. Phrenic nerve palsy is the most common complication. PersAF duration and relapses during the BP appear to be significant predictors of arrhythmic recurrences.

Circumferential pulmonary vein isolation as index procedure for persistent atrial fibrillation: a comparison between radiofrequency catheter ablation and second-generation cryoballoon ablation

AIMS To assess the 1 year efficacy of pulmonary vein isolation (PVI) as index procedure for persistent atrial fibrillation (PersAF) comparing conventional radiofrequency irrigated-tip catheter ablation (RFCA) using contact-force technology and ablation using the second-generation cryoballoon (CB-AdvA). METHODS AND RESULTS One hundred consecutive patients (74 male, 74%; mean age 62.4 ± 9.6 years) with drug-refractory PersAF undergoing PVI using RFCA and CB-AdvA were enrolled. Follow-up was based on outpatient clinic visits including Holter-electrocardiograms. Recurrence of atrial tachyarrhythmias (ATas) was defined as a symptomatic or documented episode >30 s. Among 100 patients, 50 underwent RFCA whereas 50 CB-AdvA. Mean procedure and fluoroscopy times were 90.5 ± 41.7 vs. 140.2 ± 46.9 min and 14.5 ± 6.6 vs. 19.8 ± 6.8 min in the CB-Adv and in the RFCA group, respectively (P < 0.01). At 1 year follow-up, after a 3 months blanking period (BP), freedom from ATas off-drugs after a single procedure was 60% (28/50 patients) in the CB-Adv and 56% (27/50 patients) in the RFCA group (P = 0.71). Multivariate analysis demonstrated that PersAF duration (P = 0.01) and relapses during BP (P = 0.02) were independent predictors of ATa recurrences following the index procedure. CONCLUSION Freedom from ATas following PersAF ablation with RFCA and CB-Adv is comparable at 1 year follow-up after a single procedure. Ablation with the CB-Adv is associated with shorter procedure time and radiation exposure as compared with RFCA. Atrial tachyarrhythmias occurrence during BP and longer time of PersAF seem to be significant predictors of arrhythmia recurrences after the index procedure.

Drug-Induced Brugada Syndrome in Children: Clinical Features, Device-Based Management, and Long-Term Follow-Up

OBJECTIVES The goal of this study was to investigate the clinical features, management, and long-term follow-up of children with drug-induced Brugada syndrome (BS). BACKGROUND Patients with BS <12 years of age with a spontaneous type I electrocardiogram have a higher risk of arrhythmic events. Data on drug-induced BS in patients <12 years of age are lacking. METHODS Among 505 patients with ajmaline-induced BS, subjects ≤12 years of age at the time of diagnosis were considered as children and eligible for this study. RESULTS Forty children (60% male; age 8 ± 2.8 years) were included. Twenty-four children (60%) had a family history of sudden death. Two (5%) had a previous episode of aborted sudden death, and 8 (20%) had syncope. Children experienced more frequent episodes of sinus node dysfunction (SND) compared with older subjects (7.5% vs. 1.5%; p = 0.04) and had a comparable incidence of atrial tachyarrhythmias. Children more frequently experienced episodes of ajmaline-induced sustained ventricular arrhythmias (VAs) compared with older patients (10.0% vs. 1.3%; p = 0.005). Twelve children (30%) received an implantable cardioverter-defibrillator (ICD). After a mean follow-up time of 83 ± 51 months, none of the children died suddenly. Spontaneous sustained VAs were documented in 1 child (2%). Among children with ICD, 1 (8%) experienced an appropriate shock, 4 (33%) had inappropriate ICD shocks, and 4 (33%) experienced device-related complications. CONCLUSIONS Drug-induced BS is associated with atrial arrhythmias and SND. Children are at higher risk of ajmaline-induced VAs. The rate of device-related complications, leading to lead replacement or inappropriate shocks, is considerable and even higher than with appropriate interventions. Based on these findings, the optimal management of BS in childhood should remain individualized, taking into consideration the patients clinical history and familys wishes.

New-onset atrial fibrillation as first clinical manifestation of latent Brugada syndrome: prevalence and clinical significance

AIMS To evaluate the prevalence, clinical significance, and prognosis of latent Brugada syndrome (BrS) in patients with new-onset atrial fibrillation (AF) unmasked by class 1C antiarrhythmic drugs. METHODS AND RESULTS Between January 2000 and June 2008, all consecutive patients with new-onset AF, who after flecainide exhibited typical Brugada ECG pattern, underwent electrophysiologic, pharmacologic, and genetic testing. Among 346 patients [median age 53 years; interquartile range (IQR), 15], 11 (3.2%; median age 51 years; IQR, 19) diagnosed as lone AF exhibited typical Brugada ECG pattern. Genetic testing was negative. Ventricular tachycardia/ventricular fibrillation (VT/VF) was induced by electrophysiologic testing (five patients) or during flecainide infusion (one patient). Six patients with type 1 ECG pattern and inducible VT/VF underwent ICD implantation. During a median follow-up of 31.5 months (range: 10-85) after ICD implantation, three patients developed BrS and one of them experienced VF. Patients without ICD (five patients) remained asymptomatic during a median follow-up of 74 months. Persistent type 1 pattern occurred only in the three patients who developed BrS. CONCLUSION This study, for the first time, reveals the prevalence of latent BrS in patients with new-onset lone AF, which may precede VT/VF. Persistence of type 1 and ventricular tachyarrhythmias inducibility represents a marker of electrical instability leading to sudden death.