Simone Sala

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.

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.

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.

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.

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}

Comparison of incidence and predictors of left bundle branch block after transcatheter aortic valve implantation using the CoreValve versus the Edwards valve.

Conduction disorders and permanent pacemaker implantation are common complications in patients who undergo transcatheter aortic valve implantation (TAVI). The aim of this study was to assess the incidence and clinical significance of new bundle branch block in patients who underwent TAVI with the Medtronic CoreValve Revalving System (MCRS) or the Edwards SAPIEN valve (ESV). Data from 238 patients with no previous pacemaker implantation, left bundle branch block (LBBB) or right bundle branch block at baseline electrocardiography who underwent TAVI with either MCRS (n = 87) or ESV (n = 151) bioprostheses from 2007 to 2011 were analyzed. New-onset LBBB occurred in 26.5% patients (n = 63): 13.5% with the ESV (n = 20) and 50.0% with the MCRS (n = 43) (p = 0.001). Permanent pacemaker implantation was required in 12.7% of patients (n = 8) because of complete atrioventricular block (ESV n = 2, MCRS n = 4), LBBB and first degree atrioventricular block (MCRS n = 1) and new-onset LBBB associated with sinus bradycardia (MCRS n = 1). At discharge, LBBB persisted in 8.6% of ESV patients (n = 13) and 32.2% of MCRS patients (n = 28) (p = 0.001). On multivariate analysis, the only predictor of LBBB was MCRS use (odds ratio 7.2, 95% confidence interval 2.9 to 17.4, p <0.001). Persistent new-onset LBBB at discharge was not associated with overall (log-rank p = 0.42) or cardiovascular (log-rank p = 0.46) mortality. New-onset right bundle branch block was documented in 4.6% of patients (n = 11), with no statistically significant differences between the ESV and MCRS. In conclusion, new-onset LBBB is a frequent intraventricular conduction disturbance after TAVI with a higher incidence with the MCRS compared with the ESV. LBBB persists in most patients, but in this cohort, it was not a predictor of overall or cardiovascular mortality or permanent pacemaker implantation.

Catheter ablation of ventricular arrhythmia in nonischemic cardiomyopathy: anteroseptal versus inferolateral scar sub-types.

Background—The aim was to relate distinct scar distributions found in nonischemic cardiomyopathy with ventricular tachycardia (VT) morphology, late potential distribution, ablation strategy, and outcome. Methods and Results—Eighty-seven patients underwent catheter ablation for drug-refractory VT. Based on endocardial unipolar voltage, 44 were classified as predominantly anteroseptal and 43 as inferolateral. Anteroseptal patients more frequently fulfilled diagnostic criteria for dilated cardiomyopathy (64% versus 36%), associated with more extensive endocardial unipolar scar (41 [22–83] versus 9 [1–29] cm2; P<0.001). Left inferior VT axis was predictive of anteroseptal scar (positive predictive value, 100%) and right superior axis for inferolateral (positive predictive value, 89%). Late potentials were infrequent in the anteroseptal group (11% versus 74%; P<0.001). Epicardial late potentials were common in the inferolateral group (81% versus 4%; P<0.001) and correlated with VT termination sites (&kgr;=0.667; P=0.014), whereas no anteroseptal patient had an epicardial VT termination (P<0.001). VT recurred in 44 patients (51%) during a median follow-up of 1.5 years. Anteroseptal scar was associated with higher VT recurrence (74% versus 25%; log-rank P<0.001) and redo procedure rates (59% versus 7%; log-rank P<0.001). After multivariable analysis, clinical predictors of VT recurrence were electrical storm (hazard ratio, 3.211; P=0.001) and New York Heart Association class (hazard ratio, 1.608; P=0.018); the only procedural predictor of VT recurrence was anteroseptal scar pattern (hazard ratio, 5.547; P<0.001). Conclusions—Unipolar low-voltage distribution in nonischemic cardiomyopathy allows categorization of scar pattern as inferolateral, often requiring epicardial ablation mainly based on late potentials, and anteroseptal, which frequently involves an intramural septal substrate, leading to a higher VT recurrence.Background— The aim was to relate distinct scar distributions found in nonischemic cardiomyopathy with ventricular tachycardia (VT) morphology, late potential distribution, ablation strategy, and outcome. Methods and Results— Eighty-seven patients underwent catheter ablation for drug-refractory VT. Based on endocardial unipolar voltage, 44 were classified as predominantly anteroseptal and 43 as inferolateral. Anteroseptal patients more frequently fulfilled diagnostic criteria for dilated cardiomyopathy (64% versus 36%), associated with more extensive endocardial unipolar scar (41 [22–83] versus 9 [1–29] cm2; P <0.001). Left inferior VT axis was predictive of anteroseptal scar (positive predictive value, 100%) and right superior axis for inferolateral (positive predictive value, 89%). Late potentials were infrequent in the anteroseptal group (11% versus 74%; P <0.001). Epicardial late potentials were common in the inferolateral group (81% versus 4%; P <0.001) and correlated with VT termination sites (κ=0.667; P =0.014), whereas no anteroseptal patient had an epicardial VT termination ( P <0.001). VT recurred in 44 patients (51%) during a median follow-up of 1.5 years. Anteroseptal scar was associated with higher VT recurrence (74% versus 25%; log-rank P <0.001) and redo procedure rates (59% versus 7%; log-rank P <0.001). After multivariable analysis, clinical predictors of VT recurrence were electrical storm (hazard ratio, 3.211; P =0.001) and New York Heart Association class (hazard ratio, 1.608; P =0.018); the only procedural predictor of VT recurrence was anteroseptal scar pattern (hazard ratio, 5.547; P <0.001). Conclusions— Unipolar low-voltage distribution in nonischemic cardiomyopathy allows categorization of scar pattern as inferolateral, often requiring epicardial ablation mainly based on late potentials, and anteroseptal, which frequently involves an intramural septal substrate, leading to a higher VT recurrence.

Noninducibility and Late Potential Abolition A Novel Combined Prognostic Procedural End Point for Catheter Ablation of Postinfarction Ventricular Tachycardia

Background— Successful late potential (LP) abolition and postprocedural ventricular tachycardia (VT) noninducibility constitute significant end points after catheter ablation for VT. We investigated the prognostic impact of a combined procedural end point of VT noninducibility and LP abolition in a large series of post–myocardial infarction patients with VT. Methods and Results— A total of 160 (154 men, 94% with implantable cardioverter defibrillators) consecutive post–myocardial infarction patients undergoing first-time ablation procedures from 2010 to 2012 were included. Of the 159 patients surviving the procedure, 137 (86%) were either inducible or in VT at baseline and 103 (65%) had baseline LP presence, of which 79 (77%) underwent successful LP abolition. The combined end point was assessable in 155 (97%) patients. There were 50 (32%) patients with VT recurrences and 17 (11%) cardiac deaths during follow-up. Patients who fulfilled the combined end point of VT noninducibility and LP abolition compared with inducible patients exhibited a significantly lower incidence of VT recurrence (16.4% versus 47.4%; log-rank P <0.001) and cardiac death (4.1% versus 42.1%; log-rank P <0.001). Among noninducible patients, those with additional LP abolition also had a lower incidence of VT recurrence (16.4% versus 46.0%; log-rank P <0.001). After multivariate analysis, the combined end point of VT noninducibility and LP abolition (hazard ratio, 0.205, P <0.001) was independently associated with VT recurrence and cardiac death (hazard ratio, 0.106; P =0.001). Conclusions— Achieving a combined catheter ablation procedural end point of VT noninducibility and LP abolition reduces VT recurrence rates to low levels (16%). The overall strategy was associated with a significant impact on cardiac survival.Background—Successful late potential (LP) abolition and postprocedural ventricular tachycardia (VT) noninducibility constitute significant end points after catheter ablation for VT. We investigated the prognostic impact of a combined procedural end point of VT noninducibility and LP abolition in a large series of post–myocardial infarction patients with VT. Methods and Results—A total of 160 (154 men, 94% with implantable cardioverter defibrillators) consecutive post–myocardial infarction patients undergoing first-time ablation procedures from 2010 to 2012 were included. Of the 159 patients surviving the procedure, 137 (86%) were either inducible or in VT at baseline and 103 (65%) had baseline LP presence, of which 79 (77%) underwent successful LP abolition. The combined end point was assessable in 155 (97%) patients. There were 50 (32%) patients with VT recurrences and 17 (11%) cardiac deaths during follow-up. Patients who fulfilled the combined end point of VT noninducibility and LP abolition compared with inducible patients exhibited a significantly lower incidence of VT recurrence (16.4% versus 47.4%; log-rank P<0.001) and cardiac death (4.1% versus 42.1%; log-rank P<0.001). Among noninducible patients, those with additional LP abolition also had a lower incidence of VT recurrence (16.4% versus 46.0%; log-rank P<0.001). After multivariate analysis, the combined end point of VT noninducibility and LP abolition (hazard ratio, 0.205, P<0.001) was independently associated with VT recurrence and cardiac death (hazard ratio, 0.106; P=0.001). Conclusions—Achieving a combined catheter ablation procedural end point of VT noninducibility and LP abolition reduces VT recurrence rates to low levels (16%). The overall strategy was associated with a significant impact on cardiac survival.

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.

LMNA-associated myopathies The Italian experience in a large cohort of patients

Objectives: Our aim was to conduct a comparative study in a large cohort of myopathic patients carrying LMNA gene mutations to evaluate clinical and molecular features associated with different phenotypes. Methods: We performed a retrospective cohort study of 78 myopathic patients with LMNA mutation and 30 familial cases with LMNA mutation without muscle involvement. We analyzed features characterizing the various forms of LMNA-related myopathy through correlation statistics. Results: Of the 78 patients, 37 (47%) had limb-girdle muscular dystrophy 1B (LGMD1B), 18 (23%) congenital muscular dystrophy (MDCL), 17 (22%) autosomal dominant Emery-Dreifuss muscular dystrophy 2 (EDMD2), and 6 (8%) an atypical myopathy. The myopathic phenotypes shared a similar cardiac impairment. Cardioverter defibrillator or pacemaker was implanted in 41 (53%) myopathic patients compared to 7 (23%) familial cases without muscle involvement (p = 0.005). Heart transplantation was performed in 8 (10.3%) myopathic patients and in none of the familial cases. Ten (12.8%) myopathic patients died; there were no deaths among the familial cases (p = 0.032). Missense mutations were found in 14 patients (82%) with EDMD2 and 14 patients (78%) with MDCL compared to 17 patients (45%) with LGMD1B and 4 (67%) atypical patients. Frameshift mutations were detected in 17 (45%) LGMD1B compared to 3 (18%) EDMD2, 1 (6%) MDCL, and 2 (33%) with atypical myopathy (p = 0.021). Furthermore, frameshift mutations were found in 30 of 73 patients (41%) with heart involvement compared to 4 of 35 (11%) without heart involvement (p = 0.004). Conclusions: Our data provided new insights in LMNA-related myopathies, whose natural history appears to be dominated by cardiac involvement and related complications.