Gaetano Fassini

Periprocedural Stroke and Bleeding Complications in Patients Undergoing Catheter Ablation of Atrial Fibrillation With Different Anticoagulation Management Results From the Role of Coumadin in Preventing Thromboembolism in Atrial Fibrillation (AF) Patients Undergoing Catheter Ablation (COMPARE) Randomized Trial

Background— Periprocedural thromboembolic and hemorrhagic events are worrisome complications of catheter ablation for atrial fibrillation (AF). The periprocedural anticoagulation management could play a role in the incidence of these complications. Although ablation procedures performed without warfarin discontinuation seem to be associated with lower thromboembolic risk, no randomized study exists. Methods and Results— This was a prospective, open-label, randomized, parallel-group, multicenter study assessing the role of continuous warfarin therapy in preventing periprocedural thromboembolic and hemorrhagic events after radiofrequency catheter ablation. Patients with CHADS2 score ≥1 were included. Patients were randomly assigned in a 1:1 ratio to the off-warfarin or on-warfarin arm. The incidence of thromboembolic events in the 48 hours after ablation was the primary end point of the study. The study enrolled 1584 patients: 790 assigned to discontinue warfarin (group 1) and 794 assigned to continuous warfarin (group 2). No statistical difference in baseline characteristics was observed. There were 39 thromboembolic events (3.7% strokes [n=29] and 1.3% transient ischemic attacks [n=10]) in group 1: two events (0.87%) in patients with paroxysmal AF, 4 (2.3%) in patients with persistent AF, and 33 (8.5%) in patients with long-standing persistent AF. Only 2 strokes (0.25%) in patients with long-standing persistent AF were observed in group 2 (P<0.001). Warfarin discontinuation emerged as a strong predictor of periprocedural thromboembolism (odds ratio, 13; 95% confidence interval, 3.1–55.6; P<0.001). Conclusion— This is the first randomized study showing that performing catheter ablation of AF without warfarin discontinuation reduces the occurrence of periprocedural stroke and minor bleeding complications compared with bridging with low-molecular-weight heparin. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01006876.

Left Mitral Isthmus Ablation Associated with PV Isolation: Long-Term Results of a Prospective Randomized Study

Background: The deployment of an ablation line connecting the left inferior PV to the mitral annulus (mitral isthmus line [MIL]) enhances the efficacy of pulmonary vein disconnection (PVD) in preventing atrial fibrillation (AF) recurrences.

Periprocedural Stroke and Bleeding Complications in Patients undergoing Catheter Ablation of Atrial Fibrillation with Different Anticoagulation Management: Results from the "COMPARE" Randomized Trial

Background— Periprocedural thromboembolic and hemorrhagic events are worrisome complications of catheter ablation for atrial fibrillation (AF). The periprocedural anticoagulation management could play a role in the incidence of these complications. Although ablation procedures performed without warfarin discontinuation seem to be associated with lower thromboembolic risk, no randomized study exists. Methods and Results— This was a prospective, open-label, randomized, parallel-group, multicenter study assessing the role of continuous warfarin therapy in preventing periprocedural thromboembolic and hemorrhagic events after radiofrequency catheter ablation. Patients with CHADS2 score ≥1 were included. Patients were randomly assigned in a 1:1 ratio to the off-warfarin or on-warfarin arm. The incidence of thromboembolic events in the 48 hours after ablation was the primary end point of the study. The study enrolled 1584 patients: 790 assigned to discontinue warfarin (group 1) and 794 assigned to continuous warfarin (group 2). No statistical difference in baseline characteristics was observed. There were 39 thromboembolic events (3.7% strokes [n=29] and 1.3% transient ischemic attacks [n=10]) in group 1: two events (0.87%) in patients with paroxysmal AF, 4 (2.3%) in patients with persistent AF, and 33 (8.5%) in patients with long-standing persistent AF. Only 2 strokes (0.25%) in patients with long-standing persistent AF were observed in group 2 (P<0.001). Warfarin discontinuation emerged as a strong predictor of periprocedural thromboembolism (odds ratio, 13; 95% confidence interval, 3.1–55.6; P<0.001). Conclusion— This is the first randomized study showing that performing catheter ablation of AF without warfarin discontinuation reduces the occurrence of periprocedural stroke and minor bleeding complications compared with bridging with low-molecular-weight heparin. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01006876.

Electrophysiological characteristics and outcome in patients with idiopathic right ventricular arrhythmia compared with arrhythmogenic right ventricular dysplasia

Background: Idiopathic right ventricular arrhythmias (IRVA) are responsive to medical and ablative treatment and have a benign prognosis. Arrhythmias caused by right ventricular dysplasia (ARVD) are refractory to treatment and may cause sudden death. It is difficult to distinguish between these two types of arrhythmia. Objective: To differentiate patients with IRVA and ARVD by a conventional electrophysiological study. Methods: 56 patients with a right ventricular arrhythmia were studied. They had no history or signs of any cardiac disease other than right ventricular dysplasia. They were classified as having IRVA (n = 41) or ARVD (n = 15) on the basis of family history, ECG characteristics, and various imaging techniques. They were further investigated by standard diagnostic electrophysiology. Results: The two groups were clearly distinguished by the electrophysiological study in the following ways: inducibility of ventricular tachycardia by programmed electrical stimulation with ventricular extrastimuli (IRVA 3% v ARVD 93%, p < 0.0001); presence of more than one ECG morphology during tachycardia (IRVA 0% v ARVD 73%, p < 0.0001); and fragmented diastolic potentials during ventricular arrhythmia (IRVA 0% v ARVD 93%, p < 0.0001). Data from the clinical follow up in these patients supported the diagnosis derived from the electrophysiological study. Conclusions: Patients with IRVA or ARVD can be distinguished by specific electrophysiological criteria. A diagnosis of ARVD can be made reliably on the basis of clinical presentation, imaging techniques, and an electrophysiological study.

Percutaneous cardiopulmonary support for catheter ablation of unstable ventricular arrhythmias in high-risk patients.

Background and Purpose:In patients with severe cardiomyopathy, recurrent episodes of nontolerated ventricular tachycardia (VT) or electrical storm (ES) frequently cause acute heart failure and cardiac death; the suppression of the arrhythmia is therefore lifesaving, but feasibility of catheter ablation (CA) is precluded by the adverse hemodynamic conditions together with the characteristics of the arrhythmia that interdicts efficacious mapping. The use of the percutaneous cardiopulmonary support (CPS) for circulatory assistance may allow patient’s stabilization and enhance efficacy and safety of CA in this emergency setting.Patients and Methods:19 patients (19 males; mean age 61 ± 6 years; chronic ischemic cardiomyopathy, eleven patients; primary dilated cardiomyopathy, six patients; arrhythmogenic right ventricular dysplasia/ cardiomyopathy, two patients) with recurrent nontolerated VT episodes undergoing CPS-assisted CA were retrospectively evaluated. Twelve patients had acute hemodynamic failure refractory to inotropic agents and ventilatory assistance, seven patients had undergone a failing nonconventional CA procedure. 14 patients presented with ES, and in twelve the procedure was undertaken under emergency conditions within 24 h from admission. Patients were ventilated under general anesthesia and assisted by a multidisciplinary team. The CPS system consisted in a Medtronic Bio-Medicus centrifugal pump and in a Maxima Plus oxygenator, a 15-F arterial cannula, and a 17-F venous cannula.Results:Flows between 2 and 3 l/min were activated after induction of 56/62 forms of nontolerated VT, achieving hemodynamic stabilization in all patients. CA was mainly guided by conventional activation mapping and was effective in abolishing 45/56 supported VTs; in 10/19 patients all clinical VTs were suppressed by CA. Mean procedural time was 4 h and 20 min. Complete stabilization was achieved in 13 patients (68%) without VT recurrence during a 7-day in-hospital monitoring. A significant clinical improvement was observed in two patients (11%); one patient (5%) with persistent VT episodes acutely died after heart transplant. At a mean follow-up of 42 months (range 15–60 months), 5/18 patients (28%) were free from VT recurrence, 7/18 (39%) had a clear clinical improvement with reduced implantable cardioverter defibrillator interventions. 5/14 patients (36%) had ES recurrence; among them, three died because of acute heart failure. No serious CPS-related complications were observed.Conclusion:The CPS warrants acceptable hemodynamic stabilization and efficacious mapping in highrisk patients undergoing CA for unstable VT in the emergency setting. Safety and efficacy of this technique translate into significant clinical improvement in the majority of patients. Even if only relatively invasive, CPS should be reserved to patients with ES or intractable arrhythmia causing acute heart failure; moreover, the need for an experienced team of multidisciplinary operators implies that its use is restricted to selected high-competency institutions.ZusammenfassungHintergrund und Fragestellung:Bei Patienten mit schwerer Kardiomyopathie verursachen rezidivierende Episoden nicht tolerierter ventrikulärer Tachykardie (VT) oder eines elektrischen Sturms (ES) häufig akutes Herzversagen und plötzlichen Herztod; die Suppression der Arrhythmie ist daher lebensrettend, jedoch stehen der Durchführbarkeit der Katheterablation (KA) ungünstige hämodynamische Verhältnisse sowie die Charakteristika der Arrhythmie, die ein effizientes Mapping verhindert, entgegen. Der Einsatz des perkutanen kardiopulmonalen Supports (KPS) zur Kreislaufunterstützung kann zur Stabilisierung des Patienten beitragen und die Effizienz und Sicherheit der KA in diesem Notfallszenario erhöhen.Patienten und Methodik:19 Patienten (19 Männer; Durchschnittsalter 61 ± 6 Jahre; chronische ischämische Kardiomyopathie, elf Patienten; primäre dilatative Kardiomyopathie, sechs Patienten; arrhythmogene rechtsventrikuläre Dysplasie/Kardiomyopathie, zwei Patienten) mit rezidivierenden nicht tolerierten VT-Episoden, die einer KPS-unterstützten KA unterzogen wurden, wurden retrospektiv evaluiert. Zwölf Patienten hatten ein akutes, gegenüber inotropen Agenzien und assistierter Beatmung refraktäres hämodynamisches Versagen. Sieben Patienten hatten sich einem frustranen nichtkonventionellen KA-Verfahren unterzogen. 14 Patienten hatten ES, und bei zwölf wurde das Verfahren innerhalb von 24 h nach der Aufnahme unter Notfallbedingungen durchgeführt. Die Patienten wurden unter Vollnarkose beatmet und von einem multidisziplinären Team unterstützt. Das KPS-System bestand aus einer Medtronic-Bio-Medicus-Zentrifugalpumpe und einem Maxima-Plus-Oxygenator, einer arteriellen Kanüle (15 F) und einer venösen Kanüle (17 F).Ergebnisse:Nach der Induktion von 56/62 Formen nicht tolerierter VT wurden Flussraten zwischen 2 und 3 l/min eingestellt, so dass bei allen Patienten eine hämodynamische Stabilisierung erreicht wurde. Die KA wurde hauptsächlich durch konventionelles Aktivierungsmapping geführt, und sie war effizient bei der Beseitigung von 45/56 VT mit KPS; bei 10/19 Patienten wurden alle klinischen VT durch KA supprimiert. Die mittlere Eingriffszeit betrug 4 h und 20 min. Bei 13 Patienten (68%) wurde eine völlige Stabilisierung ohne rezidivierende VT während einer 7-tägigen stationären Überwachung erreicht. Bei zwei Patienten (11%) wurde eine erhebliche klinische Verbesserung beobachtet; ein Patient (5%) mit persistierenden VT-Episoden verstarb akut nach einer Herztransplantation. Nach einem mittleren Beobachtungszeitraum von 42 Monaten (Range 15–60 Monate) waren 5/18 Patienten (28%) in Bezug auf die VT rezidivfrei und 7/18 (39%) zeigten eine deutliche klinische Verbesserung mit weniger ICD-Interventionen (implantierbarer Kardioverter-Defibrillator). 5/14 Patienten (36%) hatten ES-Rezidive; davon starben drei aufgrund von akutem Herzversagen. Es wurden keine schweren, mit dem KPS im Zusammenhang stehenden Komplikationen beobachtet.Schlussfolgerung:Der KPS garantiert eine akzeptable hämodynamische Stabilisierung und effizientes Mapping bei Hochrisikopatienten, die sich notfallmäßig aufgrund einer instabilen VT einer KA unterziehen. Die Sicherheit und Effizienz dieser Technik führen bei der Mehrheit der Patienten zu einer erheblichen klinischen Verbesserung. Selbst wenn der KPS nur relativ invasiv ist, sollte er beschränkt sein auf Patienten mit ES oder hartnäckiger Arrhythmie, die akutes Herzversagen verursacht. Ferner impliziert die Notwendigkeit eines erfahrenen multidisziplinären Teams einen limitierten Einsatz in ausgewählten Einrichtungen mit hoher Fachkompetenz.

Value of analysis of ST segment changes during tachycardia in determining type of narrow QRS complex tachycardia.

OBJECTIVES Repolarization changes during narrow QRS complex tachycardia were analyzed to differentiate the tachycardia mechanism and to guide the preliminary location of the accessory pathway. BACKGROUND Noninvasive determination of the mechanism of tachycardia is becoming increasingly important in view of the role of catheter ablation techniques for the cure of supraventricular tachycardia. METHODS We analyzed 159 12-lead electrocardiograms during narrow QRS complex tachycardia to evaluate 1) the tachycardia cycle; and 2) ST segment depression or T wave inversion, or both. Each patient underwent a complete electrophysiologic evaluation. RESULTS There were 13 atrial tachycardias, 57 atrioventricular (AV) node reentrant tachycardias and 89 AV reciprocating tachycardias. The mean RR cycle did not differ among types of tachycardia. ST segment depression >2 mm or T wave inversion, or both, was present more often in AV reciprocating tachycardia (57%) than in AV node tachycardia (25%). The magnitude of ST segment depression was greater in AV reciprocating tachycardia than in AV node tachycardia (mean +/- SD 1.3 +/- 1.6 vs. 0.7 +/- 0.8 mm, p < 0.005). In AV reciprocating tachycardia distinct patterns of repolarization changes and P wave configuration were associated with different sites of the accessory pathway. CONCLUSIONS The presence of ST segment depression >2 mm or T wave inversion, or both, during narrow QRS complex tachycardia suggests that AV reentry using an accessory pathway is the mechanism of the tachycardia. The phenomenon may be the consequence of a distinct pattern of retrograde atrial activation. Analysis of repolarization changes can guide preliminary localization of the accessory pathway even in the absence of ventricular preexcitation.

Catheter ablation of atrial fibrillation in hypertrophic cardiomyopathy: long-term outcomes and mechanisms of arrhythmia recurrence.

Background—Pulmonary vein (PV) antrum isolation in patients with hypertrophic cardiomyopathy and atrial fibrillation (AF) has been reported to have satisfactory results at the mid- and short-term follow-up. We determined the outcomes at the long-term follow-up of PV antrum isolation in these patients. Methods and Results—We enrolled 43 patients with hypertrophic cardiomyopathy and AF (28% paroxysmal AF). PV antrum isolation (paroxysmal AF) and posterior wall isolation with complex fractionated atrial electrogram ablation (persistent and longstanding persistent AF) were the end points at the time of the index procedure and for repeat procedures during the first year of follow-up. In case of recurrent arrhythmia >1 year, high-dose isoproterenol challenge was used to disclose non-PV trigger sites. During the first year, the success rate reached 91% (mean of 1.6 procedures). After a median follow-up of 42 months (range, 38–48 months), 49% of the patients remained free from AF/atrial tachycardia. All patients underwent an additional procedure. PV antrum and posterior wall remained isolated in 82% of the cases, and extra-PV triggers were documented in all patients and targeted for ablation. After a median follow-up of 15 months (range, 8–19 months) subsequent to the last procedure, 94% of the patients remained free from AF/atrial tachycardia off antiarrhythmic drugs. Conclusions—PV isolation in patients with hypertrophic cardiomyopathy is feasible and safe, although is not effective in preventing late (≥1 year) AF recurrences in ≈50% of patients. Non-PV triggers seem to be responsible of late recurrences, which supports the appropriateness of a more extensive ablation beyond PV isolation to improve the long-term arrhythmia-free survival.Background— Pulmonary vein (PV) antrum isolation in patients with hypertrophic cardiomyopathy and atrial fibrillation (AF) has been reported to have satisfactory results at the mid- and short-term follow-up. We determined the outcomes at the long-term follow-up of PV antrum isolation in these patients. Methods and Results— We enrolled 43 patients with hypertrophic cardiomyopathy and AF (28% paroxysmal AF). PV antrum isolation (paroxysmal AF) and posterior wall isolation with complex fractionated atrial electrogram ablation (persistent and longstanding persistent AF) were the end points at the time of the index procedure and for repeat procedures during the first year of follow-up. In case of recurrent arrhythmia >1 year, high-dose isoproterenol challenge was used to disclose non-PV trigger sites. During the first year, the success rate reached 91% (mean of 1.6 procedures). After a median follow-up of 42 months (range, 38–48 months), 49% of the patients remained free from AF/atrial tachycardia. All patients underwent an additional procedure. PV antrum and posterior wall remained isolated in 82% of the cases, and extra-PV triggers were documented in all patients and targeted for ablation. After a median follow-up of 15 months (range, 8–19 months) subsequent to the last procedure, 94% of the patients remained free from AF/atrial tachycardia off antiarrhythmic drugs. Conclusions— PV isolation in patients with hypertrophic cardiomyopathy is feasible and safe, although is not effective in preventing late (≥1 year) AF recurrences in ≈50% of patients. Non-PV triggers seem to be responsible of late recurrences, which supports the appropriateness of a more extensive ablation beyond PV isolation to improve the long-term arrhythmia-free survival.

Biomarkers of myocardial injury with different energy sources for atrial fibrillation catheter ablation

BACKGROUND Our study aims to compare acute myocardial injury biomarker rise after atrial fibrillation ablation performed with different technologies. METHODS AND RESULTS One hundred and ten patients were treated with pulmonary vein isolation with 4 different technologies: open-irrigated tip radiofrequency (RF) catheter in35 patients (Group A), cryoballoon in 35 patients (Group B), visually guided laser balloon in 20 patients (Group C), open-irrigated tip RF catheter with contact-force-sensing technology in 20 patients (Group D). Post-procedure samples of cardiac troponin I (cTnI) and creatinine kinase-MB (CK-MB) were collected at 19 ± 3 h and 43 ± 3 h after ablation. At the first postprocedural sample, cTnI and CK-MB levels were found elevated in all 110 patients with a median value of 2.11 ng/mL and 8.95 ng/mL, respectively. Group B showed cTnI levels increased (median 5.96 ng/mL) compared to other groups (median Group A: 1.72 ng/mL, Group C: 1.54 ng/mL, Group D: 2.0 ng/mL; p < 0.001). Also CK-MB levels resulted higher in cryoablation (median 26.4 ng/mL) compared to other groups (median Group A: 6.40 ng/mL, Group C: 7.15 ng/mL, Group D: 6.50 ng/mL; p < 0.001). No significant association was observed between biomarker levels and recurrences of atrial fibrillation after a mean follow-up of 369 ± 196 days. CONCLUSIONS Highest markers for myocardial injury were observed in the cryoballoon group. It is possible that a longer delivery energy duration and other factors affecting lesion size resulted in higher amount of cardiac injury in cryoablation. The higher levels of cardiac biomarkers did not translate into a better outcome and its physiologic significance is unknown.

Feasibility of combined unipolar and bipolar voltage maps to improve sensitivity of endomyocardial biopsy

Background—Endomyocardial biopsy (EMB) has a low sensitivity. Electroanatomic voltage mapping (EVM) is effective in guiding EMB thanks to its ability in identifying and locating low-voltage regions. The analysis of unipolar EVM can correlate with epicardial pathological involvement. We evaluated the unipolar EVM in EMB areas to determine whether it can increase EMB sensitivity in diagnosing epicardial diseases. Methods and Results—We performed endocardial bipolar EVM-guided EMBs in 29 patients and we analyzed unipolar EVM at withdrawal sites. Eighty myocardial samples were collected (mean, 2.8±0.9; median, 3 fragments per patient) and 60 were suitable for histological analysis. Ten specimens (17%) were collected from an area with discordant normal bipolar/low-voltage unipolar EVM and they were diagnostic or suggestive for arrhythmogenic right ventricular dysplasia/cardiomyopathy in 6 patients, for myocarditis and sarcoidosis in 1 patient each. Six samples (10%) were collected from an area with discordant low-voltage bipolar/normal unipolar EVM and they showed nonspecific features. The sensitivity of unipolar EVMs for a diagnostic biopsy finding EMB was significantly higher compared with bipolar EVMs analyzed according to samples (P<0.01) and patients (P=0.008). The specificity of unipolar EMB was better than bipolar EMB when analyzed for all samples (P=0.0014) but the difference did not reach statistical significance when analyzed by patient (P=0.083). The diagnostic yield was 63.3% for the bipolar and 83.3% for the unipolar EVM. Conclusions—These findings suggest that use of a combined bipolar/unipolar map may be able to improve the diagnostic yield of endomyocardial ventricular biopsy.

Rationale and design of the NO-PARTY trial: near-zero fluoroscopic exposure during catheter ablation of supraventricular arrhythmias in young patients

INTRODUCTION Radiofrequency catheter ablation is the mainstay of therapy for supraventricular tachyarrhythmias. Conventional radiofrequency catheter ablation requires the use of fluoroscopy, thus exposing patients to ionising radiation. The feasibility and safety of non-fluoroscopic radiofrequency catheter ablation has been recently reported in a wide range of supraventricular tachyarrhythmias using the EnSite NavX™ mapping system. The NO-PARTY is a multi-centre, randomised controlled trial designed to test the hypothesis that catheter ablation of supraventricular tachyarrhythmias guided by the EnSite NavX™ mapping system results in a clinically significant reduction in exposure to ionising radiation compared with conventional catheter ablation. METHODS The study will randomise 210 patients undergoing catheter ablation of supraventricular tachyarrhythmias to either a conventional ablation technique or one guided by the EnSite NavX™ mapping system. The primary end-point is the reduction of the radiation dose to the patient. Secondary end-points include procedural success, reduction of the radiation dose to the operator, and a cost-effectiveness analysis. In a subgroup of patients, we will also evaluate the radiobiological effectiveness of dose reduction by assessing acute chromosomal DNA damage in peripheral blood lymphocytes. CONCLUSIONS NO-PARTY will determine whether radiofrequency catheter ablation of supraventricular tachyarrhythmias guided by the EnSite NavX™ mapping system is a suitable and cost-effective approach to achieve a clinically significant reduction in ionising radiation exposure for both patient and operator.