Ablation of CTI-dependent flutter using different ablation technologies: acute and long-term outcome from the LEONARDO study.

BACKGROUND: A novel ablation catheter has been released to map and ablate the cavo-tricuspid isthmus (CTI) in patients with atrial flutter (AFL), improving ablation efficiency. METHODS: We evaluated the acute and long-term outcome of CTI ablation aiming at bidirectional conduction block (BDB) in a prospective, multicenter cohort study enrolling 500 patients indicated for typical AFL ablation. Patients were grouped on the basis of the AFL ablation method (linear anatomical approach, Conv group n = 425, or maximum voltage guided, MVG group, n = 75) and ablation catheter (mini-electrodes technology, MiFi group, n = 254, or a standard 8-mm ablation catheter, BLZ group, n = 246). RESULTS: Complete BDB according to both validation criteria (sequential detailed activation mapping or mapping only the ablation site) was achieved in 443 patients (88.6%). The number of RF applications needed to achieve BDB was lower in the MiFi MVG group vs both the MiFi Conv group and the BLZ Conv group (3.2 ± 2 vs 5.2 ± 4 vs 9.3 ± 5, p < 0.0001 for all comparisons). Fluoroscopy time was similar among groups, whereas we observed a reduction in the procedure duration from the BLZ Conv group (61.9 ± 26min) to the MiFi MVG group (50.6 ± 17min, p = 0.048). During a mean follow-up of 548 ± 304 days, 32 (6.2%) patients suffered an AFL recurrence. No differences were found according to BDB achieved by both validation criteria. CONCLUSIONS: Ablation was highly effective in achieving acute CTI BDB and long-term arrhythmia freedom irrespective of the ablation strategy or the validation criteria for CTI chosen by the operator. The use of an ablation catheter equipped with mini-electrodes technology seems to improve ablation efficiency. CLINICAL TRIAL REGISTRATION: Atrial Flutter Ablation in a Real World Population. (LEONARDO). CLINICALTRIALS: gov Identifier: NCT02591875.

Transcatheter ablation of the atrioventricular junction in refractory atrial fibrillation: A clinicopathological study.

BACKGROUND: Catheter ablation of the specialized atrioventricular junction (AVJ) with a right-side approach is an effective therapy for refractory atrial fibrillation with fast ventricular rate. Our aim is to assess the efficacy of the procedure in a single center experience and investigate the histologic findings of AVJ after catheter ablation. METHODS: A) Analysis of AVJ ablation efficacy in a consecutive series of patients with refractory atrial fibrillation; B) Histopathologic study of the conduction system by serial section technique and clinical-electrophysiologic correlation in four patients who underwent AVJ ablation. RESULTS: A) Right-sided AVJ ablation was successful in all 87 consecutive patients (mean procedural time 19.2±17.9 min). Energy applications ranged from 1 to 27 (mean 5.8±5.1) with eight patients (9%) requiring > 15 applications. B) Fibrotic disruption of atrioventricular (AV) node and/or His bundle interruption was found in three cases with previous AVJ ablation. In the case requiring a left side approach, the compact AV node and common His bundle appeared undamaged whereas extensive fibrosis of the summit of the ventricular septum, branching His bundle and proximal bundle branches was found. Noteworthy, a continuity between the septal and anterior tricuspid valve leaflets was present. CONCLUSION: Our data confirm that the ideal site for ablation of the specialized AVJ is the AV node. In selected cases with unsuccessful AV node ablation, a shift towards the His bundle is needed. A continuity between the septal and anterior leaflets of the tricuspid valve may protect the His bundle as to require multiple shocks and prolong the procedure.

Prediction of mortality in patients with implantable defibrillator using CHADS2 score: data from a prospective observational investigation.

BACKGROUND: CHADS2 (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, previous stroke/TIA) score has been validated as a risk stratification score to predict stroke in patients with atrial fibrillation (AF). The objective of this analysis was to assess whether patient risk factors, in particular CHADS2 score, identified patients at risk of mortality. METHODS: 821 patients with an implantable cardioverter defibrillator were prospectively followed-up in 11 cardiology centers. Patients were grouped in 3 groups according to pre-specified risk classes: low (CHADS2 = 0), moderate (CHADS2 = 1, 2), and high (CHADS2 = 3-6). Information on clinical status and events, were collected during scheduled and unscheduled follow-up visits. Deaths were retrieved from medical records, or through the Regional Office of Vital Statistics. RESULTS: Over a mean follow-up of 44±26 months, 135 deaths occurred in the overall population: 6 (7.7%) in the low-risk population, 69 (13.8%) in moderate-risk patients and 60 (24.6%) in high-risk patients. Kaplan-Meier estimated of patient survival were significantly different in 3 patients groups (93.0%, 90.1%, 78.5% in low, moderate and high risk patients respectively, at 4 years P<0.001). A sub-analysis on patients without history of AF showed similar results. Multivariate regression analysis adjusted for baseline characteristics confirmed the high risk status (HR 1.88, 95% CI 1.27-2.80; P = 0.002) as an independent predictor of mortality adjusted for the baseline characteristics. CONCLUSIONS: In our multicenter research, the long-term mortality was higher in patients with high CHADS2 score than in those with lower risk score regardless the presence of history of AF. CHADS2 score could be considered a toll to predict all causes mortality.

Ventricular antitachycardia pacing therapy in patients with heart failure implanted with a cardiac resynchronization therapy defibrillator device: Efficacy, safety, and impact on mortality.

BACKGROUND: Cardiac resynchronization therapy defibrillator can terminate ventricular tachycardia (VT) and fast VT (FVT) via antitachycardia pacing (ATP). OBJECTIVES: We evaluated efficacy and safety of ATP, whether ATP induces ventricular arrhythmias after inappropriate ATP or atrial fibrillation (AF) after appropriate ATP, and whether ATP is associated with mortality. METHODS: A total of 1404 patients with a cardiac resynchronization therapy defibrillator were followed in a prospective multicenter observational research. All-cause mortality rates were estimated in patient subgroups in order to uncouple the trigger (VT/FVT or other rhythms causing inappropriate detections) from ATP therapy. RESULTS: Over a median follow-up of 31 months, 2938 VT/FVT episodes were treated with ATP in 360 patients. The adjusted ATP success rate was 63% (95% confidence interval [CI] 57%-69%) on FVTs and 68% (95% CI 62%-74%) on VTs. Acceleration occurred in 55 (1.87%) and syncope in 4 (0.14%) of all ATP-treated episodes. In 14 true VT/FVT episodes in 5 patients, AF followed ATP therapy. In 4 episodes in 2 patients, VT followed ATP inappropriately applied during AF. Death rate per 100 patient-years was 5.6 (95% CI 4.3-7.5) in patients with appropriate ATP and 1.5 (95% CI 0.4-6.1) in patients with inappropriate ATP (P = .045). CONCLUSION: ATP was effective in terminating VT/FVT episodes and displayed a good safety profile. ATP therapies by themselves did not increase death risk; prognosis was indeed better in patients without arrhythmic episodes, even if they received inappropriate ATP, than in patients with ATP on VT/FVT episodes. Adverse outcomes observed in patients receiving implantable cardioverter-defibrillator therapies are probably related to the arrhythmia itself, a marker of disease progression, rather than to adverse effects of ATP.

Efficacy of low interatrial septum and right atrial appendage pacing for prevention of permanent atrial fibrillation in patients with sinus node disease: results from the electrophysiology-guided pacing site selection (EPASS) study.

BACKGROUND: The role of pacing sites and atrial electrophysiology on the progression of atrial fibrillation (AF) to the permanent form in patients with sinus node dysfunction (SND) has never been investigated. The aim of the study was to investigate the relationship between atrial electrophysiology and the efficacy of atrial pacing at the low interatrial septum (IAS) or at the right atrial appendage (RAA) to prevent persistent/permanent AF in patients with SND. METHODS AND RESULTS: The Electrophysiology-Guided Pacing Site Selection (EPASS) Study was a prospective, controlled, randomized study. Atrial refractoriness, basal and incremental conduction times from the RAA to the coronary sinus ostium were measured before implantation, and the difference (ΔCTos) was calculated. Patients with ΔCTos ≥ 50 ms (study group) and those with ΔCTos <50 ms (control group) were randomly assigned to RAA or IAS with algorithms for continuous atrial stimulation "on." The primary end point was time to development of permanent or persistent AF within a 2-year follow-up in the study group, IAS versus RAA. Data were analyzed by intention to treat. One hundred two patients (77 ± 7 years, 44 mol/L) were enrolled, 69 (68%) in the study group and 33 (32%) in the control group. Of these, 97 ended the study, respectively, randomly assigned: 29 IAS versus 36 RAA and 18 IAS versus 14 RAA. After a mean follow-up of 15 ± 7 (median, 17) months, 11 (16.6%) patients in the study group met the primary end point: 2 IAS versus 9 RAA (log rank=3.93, P=0.047). CONCLUSIONS: In patients with SND and intra-atrial conduction delay, low IAS pacing was superior to RAA pacing in preventing progression to persistent or permanent AF. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00239226.

Three-dimensional electroanatomical voltage mapping and histologic evaluation of myocardial substrate in right ventricular outflow tract tachycardia.

OBJECTIVES: We tested whether 3-dimensional electroanatomical voltage mapping (EVM) may help in the differential diagnosis between idiopathic right ventricular outflow tract (RVOT) tachycardia and arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D). BACKGROUND: Right ventricular EVM has been demonstrated to reliably identify low-voltage regions ("electroanatomical scar"), which in patients with ARVC/D correspond to areas of fibrofatty myocardial replacement. METHODS: The study population comprised 27 patients (15 men and 12 women, age 33.9 +/- 8 years) with RVOT tachycardia and no echocardiographic/angiographic evidence of right ventricular (RV) dilation/dysfunction, who underwent EVM and endomyocardial biopsy (EMB) for characterization of ventricular tachycardia (VT) substrate before catheter ablation. RESULTS: Electroanatomical voltage mapping was normal in 20 of 27 patients (74%, group A), with electrogram voltage >1.5 mV throughout the RV. The other 7 patients (26%, group B) showed >/=1 (1.4 +/- 07) RV electroanatomical scar area(s) (bipolar voltage <0.5 mV) that correlated with fibrofatty myocardial replacement at EMB (p < 0.001). Clinical predictors of RV scar were right precordial QRS prolongation (p < 0.001) and VT inducibility (p = 0.001). Catheter ablation successfully eliminated VT in 18 of 20 patients (90%). During a follow-up of 41 +/- 8 months, 3 of 7 patients (43%) from group B received an implantable defibrillator because of life-threatening ventricular arrhythmias, compared with no patients from group A (p = 0.016). CONCLUSIONS: An early/minor form of ARVC/D may mimic idiopathic RVOT tachycardia. Electroanatomical voltage mapping is able to identify RVOT tachycardia due to concealed ARVC/D by detecting RVOT electroanatomical scars that correlate with fibrofatty myocardial replacement at EMB and predispose to sudden arrhythmic death.

Prevalence of conduction delay of the right atrium in patients with SSS: implications for pacing site selection.

OBJECTIVES: To evaluate the prevalence of severe right atrial conduction delay in patients with sinus node dysfunction (SND) and atrial fibrillation (AF) and the effects of pacing in the right atrial appendage (RAA) and in the inter-atrial septum (IAS). METHODS: Forty-two patients (15 male, 72 +/- 7 years) underwent electrophysiologic study to measure the difference between the conduction time from RAA to coronary sinus ostium during stimulation at 600 ms and after extrastimulus (DeltaCTos). Patients were classified as group A if DeltaCTos > 60 ms and group B if < 60 ms. Each Group was randomized to RAA/IAS pacing and algorithms ON/OFF. RESULTS: Fifteen patients (36%, group A) had DeltaCTos = 76 +/- 11 ms and 27 patients (64%, group B) had DeltaCTos = 36 +/- 20 ms. Twenty-two patients were paced at the RAA and 20 at the IAS. During the study, no AF recurrences were reported in 11 of 42 (26%) patients, independently of RAA or IAS pacing. Patients from group A and RAA pacing had 0.79 +/- 0.81 episodes of AF/day during DDD, which increased to 1.52 +/- 1.41 episodes of AF/day during DDDR + Alg (P = 0.046). Those with IAS pacing had 0.5 +/- 0.24 episodes of AF/day during DDD, which decreased to 0.06 +/- 0.08 episodes of AF/day during DDDR + Alg (P = 0.06). In group B, no differences were reported between pacing sites and pacing modes. CONCLUSIONS: Severe right atrial conduction delay is present in one-third of patients with SND and AF: continuous pacing at the IAS is superior to RAA for AF recurrences. In patients without severe conduction delay, no differences between pacing site or mode were observed.

Transesophageal echocardiographic follow-up of pulmonary veins in patients undergoing ostial radiofrequency catheter ablation for atrial fibrillation.

BACKGROUND: Ostial radiofrequency catheter ablation (RFCA) of pulmonary veins (PVs) is a promising invasive approach for the non-pharmacologic treatment of atrial fibrillation, but PV stenosis has been reported as a possible complication of this intervention. The aim of this study was to assess PV anatomy and stenosis (i.e. number and progression) by means of transesophageal echocardiography (TEE) during the follow-up of patients undergoing RFCA. METHODS: Twenty-three consecutive patients with refractory and highly symptomatic atrial fibrillation underwent ostial radiofrequency isolation of arrhythmogenic triggers/foci, localized into the PVs, by an electroanatomic approach (CARTO system) or circular mapping with a multipolar catheter (LASSO) placed under radioscopic guidance. All patients were investigated using TEE and magnetic resonance angiography before radiofrequency application to evaluate PV anatomy. TEE examination was repeated after 2 months of follow-up and, in the presence of a stenosis, 1 year later. RESULTS: TEE allowed to identify 100% of the left and right superior PVs, 96% of right inferior PVs, and 74% of the left inferior PVs. Anatomic variants were detected at TEE in 33% of patients against 37% at magnetic resonance angiography (95% of concordance). After ostial RFCA, TEE disclosed a significant reduction in the mean diameters of the left superior PV (14.1 +/- 3.2 vs 12.0 +/- 2.7 mm, p < 0.01), left inferior PV (11.2 +/- 2.3 vs 9.8 +/- 2.2 mm, p = 0.05) and right superior PV (14.2 +/- 2.6 vs 12.9 +/- 2.7 mm, p < 0.05), and an increase in the mean peak velocities of the left superior PV (69.8 +/- 14.8 vs 91 +/- 42.4 cm/s, p < 0.05) and left inferior PV (59.2 +/- 18.1 vs 79.3 +/- 40.5 cm/s, p < 0.05). From a total of 88 PVs treated, 7 (7.9%) showed a higher significant stenosis in patients treated using the LASSO than the CARTO system (31.3 vs 2.8% respectively, p < 0.01). After 1-year follow-up there was no progression of PV stenosis. CONCLUSIONS: TEE was successful to evaluate PV anatomy and stenosis of patients undergoing ostial RFCA for atrial fibrillation. This complication is not rare and seems to be strictly related to the method of ablation, in particular when circular mapping and disconnection of triggers/foci was carried out by only a circular multipolar catheter without an electroanatomic approach.

Three-dimensional electroanatomic voltage mapping increases accuracy of diagnosing arrhythmogenic right ventricular cardiomyopathy/dysplasia.

BACKGROUND: Three-dimensional electroanatomic voltage mapping offers the potential to identify low-voltage areas that correspond to regions of right ventricular (RV) myocardial loss and fibrofatty replacement in patients with arrhythmogenic RV cardiomyopathy/dysplasia (ARVC/D). METHODS AND RESULTS: Thirty-one consecutive patients (22 men and 9 women; mean age, 30.8+/-7 years) who fulfilled the criteria of the Task Force of the European Society of Cardiology and International Society and Federation of Cardiology (ESC/ISFC) for ARVC/D diagnosis after noninvasive clinical evaluation underwent further invasive study including RV electroanatomic voltage mapping and endomyocardial biopsy (EMB) to validate the diagnosis. Multiple RV endocardial, bipolar electrograms (175+/-23) were sampled during sinus rhythm. Twenty patients (group A; 65%) had an abnormal RV electroanatomic voltage mapping showing > or =1 area (mean 2.25+/-0.7) with low-voltage values (bipolar electrogram amplitude <0.5 mV), surrounded by a border zone (0.5 to 1.5 mV) that transitioned into normal myocardium (>1.5 mV). Low-voltage electrograms appeared fractionated with significantly prolonged duration and delayed activation. In 11 patients (group B; 35%), electroanatomic voltage mapping was normal, with preserved electrogram voltage (4.4+/-0.7 mV) and duration (37.2+/-0.9 ms) throughout the RV. Low-voltage areas in patients from group A corresponded to echocardiographic/angiographic RV wall motion abnormalities and were significantly associated with myocyte loss and fibrofatty replacement at EMB (P<0.0001) and familial ARVC/D (P<0.0001). Patients from group B had sporadic disease and histopathological evidence of inflammatory cardiomyopathy (P<0.0001). During the time interval from onset of symptoms to the invasive study, 11 patients (55%) with electroanatomic low-voltage regions received an implantable cardioverter/defibrillator because of life-threatening ventricular arrhythmias, whereas all but 1 patient with a normal voltage map remained stable on antiarrhythmic drug therapy (P=0.02). CONCLUSIONS: Three-dimensional electroanatomic voltage mapping enhanced accuracy for diagnosing ARVC/D (1) by demonstrating low-voltage areas that were associated with fibrofatty myocardial replacement and (2) by identifying a subset of patients who fulfilled ESC/ISFC Task Force diagnostic criteria but showed a preserved electrogram voltage, an inflammatory cardiomyopathy mimicking ARVC/D, and a better arrhythmic outcome.

Comparison between anatomical and integrated approaches to atrial fibrillation ablation: adjunctive role of electrical pulmonary vein disconnection.

INTRODUCTION: The aim of this study was to compare the outcome of anatomical pulmonary vein (PV) radiofrequency (RF) ablation with that of an integrated approach (anatomical with electrophysiological confirmation of PV disconnection). METHODS: Sixty consecutive patients affected by drug-refractory paroxysmal (39), persistent (13), and permanent (8) atrial fibrillation (AF) were assigned to an anatomical (group A: 30 patients; 25 male, 5 female, mean age: 55 +/- 7 years) or integrated approach (group B: 30 patients; 26 male, 4 female, mean age: 52 +/- 9 years). In all cases, RF ablation was performed by means of the Carto system in order to anatomically create circumferential lines around PVs. In group B, the persistence of PV potentials was then assessed with a multipolar circular catheter. If PV potentials persisted, RF pulses targeting the electrophysiological breakthroughs were delivered to disconnect PVs. RESULTS: Total procedure duration, fluoroscopy time, and RF delivery time were similar in both groups: 227 +/- 43, 50 +/- 23, and 43 +/- 16 minutes (group A); 232 +/- 32, 55 +/- 15, and 42 +/- 10 minutes (group B), respectively (ns). One asymptomatic PV stenosis and one pericardial effusion occurred in group A and B, respectively. After 15.4 +/- 7.4 months, 17 (57%) group A patients and 25 (83%) group B patients were in stable sinus rhythm (P = 0.02) (RR 1.78; 95% CI: 1.7-2.9). CONCLUSIONS: PV ablation by means of an integrated anatomical and electrophysiological approach seems more effective than a purely anatomical RF ablation approach. Electrophysiological confirmation of PV disconnection could be a useful marker of successful RF treatment of AF.

Implantable cardioverter-defibrillator therapy for prevention of sudden death in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a condition associated with the risk of sudden death (SD). METHODS AND RESULTS: We conducted a multicenter study of the impact of the implantable cardioverter-defibrillator (ICD) for prevention of SD in 132 patients (93 males and 39 females, age 40+/-15 years) with ARVC/D. Implant indications were a history of cardiac arrest in 13 patients (10%), sustained ventricular tachycardia in 82 (62%), syncope in 21 (16%), and other in 16 (12%). During a mean follow-up of 39+/-25 months, 64 patients (48%) had appropriate ICD interventions, 21 (16%) had inappropriate interventions, and 19 (14%) had ICD-related complications. Fifty-three (83%) of the 64 patients with appropriate interventions received antiarrhythmic drug therapy at the time of first ICD discharge. Programmed ventricular stimulation was of limited value in identifying patients at risk of tachyarrhythmias during the follow-up (positive predictive value 49%, negative predictive value 54%). Four patients (3%) died, and 32 (24%) experienced ventricular fibrillation/flutter that in all likelihood would have been fatal in the absence of the device. At 36 months, the actual patient survival rate was 96% compared with the ventricular fibrillation/flutter-free survival rate of 72% (P<0.001). Patients who received implants because of ventricular tachycardia without hemodynamic compromise had a significantly lower incidence of ventricular fibrillation/flutter (log rank=0.01). History of cardiac arrest or ventricular tachycardia with hemodynamic compromise, younger age, and left ventricular involvement were independent predictors of ventricular fibrillation/flutter. CONCLUSIONS: In patients with ARVC/D, ICD therapy provided life-saving protection by effectively terminating life-threatening ventricular arrhythmias. Patients who were prone to ventricular fibrillation/flutter could be identified on the basis of clinical presentation, irrespective of programmed ventricular stimulation outcome.

Noninvasive risk stratification in arrhythmogenic right ventricular cardiomyopathy.

The natural history of arrhythmogenic right ventricular cardiomyopathy is determined by the electrical instability of the dystrophic myocardium, which can precipitate arrhythmic cardiac arrest any time during the course of the disease and by the progressive myocardial loss that results in ventricular dysfunction and heart failure. Sudden death accounts for the majority of the fatal events but its occurrence is mostly unpredictable. There are no prospective and controlled studies assessing clinical markers that can predict the occurrence of life-threatening ventricular arrhythmias. However, the noninvasive risk profile, which emerges from retrospective analysis of clinical and pathologic series, is characterized by history of syncope, physical exercise, spontaneous ventricular tachycardia or ventricular fibrillation, right ventricular dysfunction, left ventricular involvement, right precordial negative T wave, right bundle branch block, QT-QRS dispersion, right precordial ST-segment elevation and late potentials. At present only QRS dispersion, history of syncope and right and/or left ventricular abnormalities at radionuclide angiography proved to be independent noninvasive predictors of sudden death.

Screening for ryanodine receptor type 2 mutations in families with effort-induced polymorphic ventricular arrhythmias and sudden death: early diagnosis of asymptomatic carriers.

OBJECTIVES: We sought to establish the role of genetic screening for ryanodine receptor type 2 (RyR2) gene mutations in families with effort-induced polymorphic ventricular arrhythmia (PVA), syncope and juvenile sudden death. BACKGROUND: The RyR2 mutations have been associated with PVA, syncope and sudden death in response to physical or emotional stress. METHODS: We studied 81 subjects (39 males and 42 females; mean age 31 +/- 20 years) belonging to eight families with pathogenic RyR2 mutations. All subjects underwent screening for RyR2 mutations, electrocardiography (ECG), 24-h Holter monitoring, signal-averaged electrocardiography (SAECG), two-dimensional echocardiography and exercise stress testing. Electrophysiologic (EP) study was performed in nine patients. RESULTS: Six different RyR2 mutations were found in eight families. Forty-three family members carried the gene mutation. Of these, 28 (65%) showed effort-induced arrhythmic symptoms or signs and one died suddenly during follow-up. Family history revealed 19 juvenile cases of sudden death during effort or emotion. In two families sharing the same mutation, no subject presented with PVA during the stress test; thus, sudden death and syncope were the only clinical manifestations. The 12-lead ECG was normal in all but two subjects, whereas five patients showed positive late potentials on the SAECG. In 17 (39.5%) of 43 subjects, the two-dimensional echocardiogram revealed localized kinetic abnormalities and mild structural alterations of the right ventricle. The EP study was not able to induce PVA. CONCLUSIONS: The absence of symptoms and PVA on the stress test in more than one-third of carriers of RyR2 mutations, as well as the lack of PVA inducibility by the EP study, underlies the importance of genetic screening for the early diagnosis of asymptomatic carriers and prevention of sudden death.