Paolo Della Bella

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.

Clinical and Genetic Heterogeneity of Right Bundle Branch Block and ST-Segment Elevation Syndrome A Prospective Evaluation of 52 Families

BackgroundThe ECG pattern of right bundle branch block and ST-segment elevation in leads V1 to V3 (Brugada syndrome) is associated with high risk of sudden death in patients with a normal heart. Current management and prognosis are based on a single study suggesting a high mortality risk within 3 years for symptomatic and asymptomatic patients alike. As a consequence, aggressive management (implantable cardioverter defibrillator) is recommended for both groups. Methods and ResultsSixty patients (45 males aged 40±15 years) with the typical ECG pattern were clinically evaluated. Events at follow-up were analyzed for patients with at least one episode of aborted sudden death or syncope of unknown origin before recognition of the syndrome (30 symptomatic patients) and for patients without previous history of events (30 asymptomatic patients). Prevalence of mutations of the cardiac sodium channel was 15%, demonstrating genetic heterogeneity. During a mean follow-up of 33±38 months, ventricular fibrillation occurred in 5 (16%) of 30 symptomatic patients and in none of the 30 asymptomatic patients. Programmed electrical stimulation was of limited value in identifying patients at risk (positive predictive value 50%, negative predictive value 46%). Pharmacological challenge with sodium channel blockers was unable to unmask most silent gene carriers (positive predictive value 35%). ConclusionsAt variance with current views, asymptomatic patients are at lower risk for sudden death. Programmed electrical stimulation identifies only a fraction of individuals at risk, and sodium channel blockade fails to unmask most silent gene carriers. This novel evidence mandates a reappraisal of therapeutic management.

Risk Stratification in Brugada Syndrome: Results of the PRELUDE (PRogrammed ELectrical stimUlation preDictive valuE) Registry

OBJECTIVES The PRELUDE (PRogrammed ELectrical stimUlation preDictive valuE) prospective registry was designed to assess the predictive accuracy of sustained ventricular tachycardia/ventricular fibrillation (VTs/VF) inducibility and to identify additional predictors of arrhythmic events in Brugada syndrome patients without history of VT/VF. BACKGROUND Brugada syndrome is a genetic disease associated with increased risk of sudden cardiac death. Even though its value has been questioned, inducibility of VTs/VF is widely used to select candidates to receive a prophylactic implantable defibrillator, and its accuracy has never been addressed in prospective studies with homogeneous enrolling criteria. METHODS Patients with a spontaneous or drug-induced type I electrocardiogram (ECG) and without history of cardiac arrest were enrolled. The registry included 308 consecutive individuals (247 men, 80%; median age 44 years, range 18 to 72 years). Programmed electrical stimulation was performed at enrollment, and patients were followed-up every 6 months. RESULTS During a median follow-up of 34 months, 14 arrhythmic events (4.5%) occurred (13 appropriate shocks of the implantable defibrillator, and 1 cardiac arrest). Programmed electrical stimulation performed with a uniform and pre-specified protocol induced ventricular tachyarrhythmias in 40% of patients: arrhythmia inducibility was not a predictor of events at follow-up (9 of 14 events occurred in noninducible patients). History of syncope and spontaneous type I ECG (hazard ratio [HR]: 4.20), ventricular refractory period <200 ms (HR: 3.91), and QRS fragmentation (HR: 4.94) were significant predictors of arrhythmias. CONCLUSIONS Our data show that VT/VF inducibility is unable to identify high-risk patients, whereas the presence of a spontaneous type I ECG, history of syncope, ventricular effective refractory period <200 ms, and QRS fragmentation seem useful to identify candidates for prophylactic implantable cardioverter defibrillator.

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.

Symbolic Dynamics of Heart Rate Variability A Probe to Investigate Cardiac Autonomic Modulation

Background—Sympathetic and parasympathetic systems are considered the principal rapidly reacting systems that control heart rate. Methods and Results—We propose a symbolic analysis series to quantify the prevalence of sympathetic or parasympathetic cardiac modulation. This analysis decomposes the heart rate variability series in patterns lasting 3 beats and classifies them into 3 categories: nonvariable, variable, and very variable patterns referred to as 0V, 1V, and 2V patterns. First, we applied this method to experimental and pharmacological conditions characterized by sympathetic activation (tilt test, handgrip, nitroprusside, and high-dose atropine administration) or parasympathetic activation (phenylephrine and low-dose atropine administration) in 60 healthy subjects. An increase in sympathetic modulation and a vagal withdrawal elicited a significant increase in 0V patterns and a decrease in 2V patterns, whereas parasympathetic dominance induced the opposite, reflecting a reciprocal sympathovagal balance. The second part of the study considered a series of 300 beats before the onset of major arrhythmic events in patients with an implantable cardioverter-defibrillator. Symbolic analysis detected an increase in the percentage of 0V patterns before the onset of major arrhythmias compared with baseline (41.6±3.9% and 24.4±2.9%, respectively; P<0.01), indicating a sympathetic prevalence. On the other hand, the 2V patterns did not decrease before major arrhythmias, suggesting the presence of nonreciprocal autonomic modulations. Conclusions—Symbolic analysis of 3 beat sequences takes into account the different time course of sympathetic and parasympathetic cardiac modulations and seems appropriate for elucidating the neural pathophysiological mechanisms occurring during the short periods that precede acute cardiac events.

Nonischemic ventricular tachycardia. Clinical course and long-term follow-up in patients without clinically overt heart disease.

This report describes the clinical, laboratory, and electrophysiologic features of 52 patients with ventricular tachycardia (VT) who had no clinical evidence of heart disease. The mean age of patients was 36 years, cardiovascular collapse occurred in 18 patients (35%), and exercise-related symptoms were present in 24 of 49 patients (49%). There were 20 patients with sustained monomorphic VT, 11 with incessant VT, and 21 with nonsustained VT. Abnormalities were present in 14 of 38 patients (37%) during echocardiography and in 21 of 47 patients (45%) who underwent cardiac catheterization. During baseline evaluation while patients were not receiving antiarrhythmic drugs, ambulatory monitoring and exercise testing showed an 88% and 57% incidence, respectively, of nonsustained or sustained monomorphic VT, whereas 31 of 50 patients (62%) had inducible VT (requiring an infusion of isoproterenol in 11 patients) during programmed electrical stimulation. The clinical VT (when a 12-lead electrocardiogram was available for analysis) had a left bundle branch block (LBBB) configuration in 20 of 33 patients (61%) and a right axis deviation in 17 of 33 patients (51%). The VT occurring during exercise testing and programmed electrical stimulation had the same configuration as the clinical VT in 22 of 22 patients. Three patients have received an antitachycardia pacemaker, and one patient underwent endocardial resection. Forty-eight patients (92%) were treated medically. One patient died of cancer; the remaining 47 patients were alive at a mean follow-up of 96 months after initial symptoms and 46 months after programmed electrical stimulation. We conclude that in patients without clinical evidence of heart disease, VT may be incessant, sustained, or nonsustained and that VT originates from the right ventricular outflow tract in more than 50% of patients. Although cardiac abnormalities may be found in more than 30% of patients, the exact significance of these abnormalities is unclear because of the absence of progressive changes and the excellent prognosis of this group of patients.

Hemofiltration as short-term treatment for refractory congestive heart failure

Hemofiltration has been suggested as a new therapeutic tool in refractory heart failure. In this study, 11 patients with primary or ischemic heart disease in New York Heart Association class IV, in whom there was no response to medical treatment, were subjected to hemofiltration. The pathophysiologic adjustments promoted by subtraction of plasma water were investigated, and guidelines for an appropriate use of this procedure in heart failure are provided. Fluid was removed from plasma at a rate of 500 ml/hour until either normalization of the right atrial pressure (which was increased in all cases) was achieved or the hematocrit exceeded 50 percent. According to these criteria, the duration of treatment ranged from four to six hours and the total amount of fluid removed was 2,000 to 3,000 ml. In each case, hemofiltration promoted relief of dyspnea and of clinical and radiographic evidence of lung congestion and pleural effusion, and substantially reduced the dependent edema and abdominal girth. These effects were paralleled by progressive decrease of the right (-70 percent) and left (-45 percent) ventricular filling pressures and of the pulmonary arterial pressure and arteriolar resistance, without significant variations in heart rate, aortic pressure, cardiac index, and systemic vascular resistance. Changes in the right atrial and wedge pulmonary pressures are interpreted as reflecting a combined effect of a decrease in pressure on the outside of the heart due to fluid reabsorption (from lung interstitial spaces and pericardial, pleural and abdominal cavities) and of intravascular volume subtraction. The arterial partial pressure of oxygen was raised, the partial pressure of carbon dioxide and pH were unchanged, and urinary output was substantially enhanced by the procedure. The study indicates that: hemofiltration may be a short-term treatment for refractory cardiac insufficiency with overhydration; a filtration rate of 500 ml/hour is effective and safe; and the central venous pressure may be a reliable guide to volume subtraction.

Epicardial Ablation for Ventricular Tachycardia A European Multicenter Study

Background— The purpose of this study was to describe the epicardial percutaneous ablation experience of 6 European high-volume ventricular tachycardia (VT) ablation centers. Methods and Results— Data from 218 patients with coronary artery disease (CAD, n=85 [39.0%]), idiopathic dilated of patients with idiopathic VT cardiomyopathy (IDCM, n=67 [30.7%]), arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARCD/C, n=13 [6%]), hypertrophic cardiomyopathy (HCM, n=5 [2.3%]), and absence of structural heart disease (n=48 [22%]) undergoing epicardial subxyphoid access for VT ablation were collected. The epicardial approach was attempted as first-line treatment in 78 patients (35.8%). Acute prevention of VT inducibility was obtained in 156 patients (71.6%). There were no procedure-related deaths. Cardiac tamponade occurred in 8 patients, and abdominal hemorrhage in 1 patient. Six patients died of electrical storm recurrence within 48 hours from the procedure. After a mean follow-up of 17.3±18.2 months, 60 patients (31.4%) presented with VT recurrence (39.3% of IDCM patients; 34.7% of CAD patients; 30.8% of ARVD/C patients; 25% of HCM patients; 17.1% of patients with idiopathic VT). Twenty patients (10.4%) died during follow-up (12 of heart failure, 2 of cardiac arrest, and 6 of extracardiac causes). Conclusions— In experienced centers, epicardial ablation of VT has an acceptable risk and favorable outcome. In selected patients, it is reasonable to consider as a first-line ablation approach.Background— The purpose of this study was to describe the epicardial percutaneous ablation experience of 6 European high-volume ventricular tachycardia (VT) ablation centers. Methods and Results— Data from 218 patients with coronary artery disease (CAD, n=85 [39.0%]), idiopathic dilated of patients with idiopathic VT cardiomyopathy (IDCM, n=67 [30.7%]), arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARCD/C, n=13 [6%]), hypertrophic cardiomyopathy (HCM, n=5 [2.3%]), and absence of structural heart disease (n=48 [22%]) undergoing epicardial subxyphoid access for VT ablation were collected. The epicardial approach was attempted as first-line treatment in 78 patients (35.8%). Acute prevention of VT inducibility was obtained in 156 patients (71.6%). There were no procedure-related deaths. Cardiac tamponade occurred in 8 patients, and abdominal hemorrhage in 1 patient. Six patients died of electrical storm recurrence within 48 hours from the procedure. After a mean follow-up of 17.3±18.2 months, 60 patients (31.4%) presented with VT recurrence (39.3% of IDCM patients; 34.7% of CAD patients; 30.8% of ARVD/C patients; 25% of HCM patients; 17.1% of patients with idiopathic VT). Twenty patients (10.4%) died during follow-up (12 of heart failure, 2 of cardiac arrest, and 6 of extracardiac causes). Conclusions— In experienced centers, epicardial ablation of VT has an acceptable risk and favorable outcome. In selected patients, it is reasonable to consider as a first-line ablation approach.

FREEDOM FROM RECURRENT VENTRICULAR TACHYCARDIA AFTER CATHETER ABLATION IS ASSOCIATED WITH IMPROVED SURVIVAL IN PATIENTS WITH STRUCTURAL HEART DISEASE: AN INTERNATIONAL VT ABLATION CENTER COLLABORATIVE GROUP STUDY

BACKGROUND The impact of catheter ablation of ventricular tachycardia (VT) on all-cause mortality remains unknown. OBJECTIVE The purpose of this study was to examine the association between VT recurrence after ablation and survival in patients with scar-related VT. METHODS Analysis of 2061 patients with structural heart disease referred for catheter ablation of scar-related VT from 12 international centers was performed. Data on clinical and procedural variables, VT recurrence, and mortality were analyzed. Kaplan-Meier analysis was used to estimate freedom from recurrent VT, transplant, and death. Cox proportional hazards frailty models were used to analyze the effect of risk factors on VT recurrence and mortality. RESULTS One-year freedom from VT recurrence was 70% (72% in ischemic and 68% in nonischemic cardiomyopathy). Fifty-seven patients (3%) underwent cardiac transplantation, and 216 (10%) died during follow-up. At 1 year, the estimated rate of transplant and/or mortality was 15% (same for ischemic and nonischemic cardiomyopathy). Transplant-free survival was significantly higher in patients without VT recurrence than in those with recurrence (90% vs 71%, P<.001). In multivariable analysis, recurrence of VT after ablation showed the highest risk for transplant and/or mortality [hazard ratio 6.9 (95% CI 5.3-9.0), P<.001]. In patients with ejection fraction <30% and across all New York Heart Association functional classes, improved transplant-free survival was seen in those without VT recurrence. CONCLUSION Catheter ablation of VT in patients with structural heart disease results in 70% freedom from VT recurrence, with an overall transplant and/or mortality rate of 15% at 1 year. Freedom from VT recurrence is associated with improved transplant-free survival, independent of heart failure severity.

Image integration increases efficacy of paroxysmal atrial fibrillation catheter ablation: Results from the CartoMerge™ italian Registry

AIMS The aim of this study was to investigate whether circumferential pulmonary vein (PV) isolation guided by image integration improves the procedural and clinical outcomes of atrial fibrillation (AF) ablation in comparison with segmental PV isolation and circumferential PV isolation guided by three-dimensional (3D) electroanatomical mapping alone. METHODS AND RESULTS Procedural and clinical outcomes of 573 patients who underwent their first catheter ablation for paroxysmal AF between January 2005 and April 2007 were collected from 12 centres. We evaluated three techniques: segmental ostial PV isolation (SOCA group, 240 patients), circumferential PV isolation guided by electroanatomical mapping (CARTO group, 107 patients), and circumferential PV isolation guided by electroanatomical mapping integrated with magnetic resonance/computed tomographic images of the left atrium (MERGE group, 226 patients). Procedure duration proved to be shorter in MERGE group patients than in CARTO group patients (P < 0.04), but longer than in SOCA group patients (P < 0.0001). During follow-up, atrial tachyarrhythmias relapsed more frequently in SOCA group patients (44.6%) and CARTO group patients (41.7%) than in MERGE group patients (22.6%; P < 0.0001). CONCLUSION In patients with paroxysmal AF, circumferential PV isolation guided by image integration significantly improves clinical outcome in comparison with both circumferential PV isolation guided by 3D mapping alone and with segmental electrophysiologically guided PV isolation.