Endocardial impedance mapping during circumferential pulmonary vein ablation of atrial fibrillation differentiates between atrial and venous tissue.

BACKGROUND: Circumferential pulmonary vein ablation (CPVA) is an effective treatment for atrial fibrillation (AF). Accurate left atrial (LA) mapping is essential for creating lesions at the LA-pulmonary vein (PV) junction, avoiding PV stenosis. OBJECTIVES: The purpose of this study was to establish whether endocardial impedance varies within the LA and PVs and whether it is a useful tool for mapping and ablation. METHODS: Pilot Phase: Three-dimensional LA maps were created using CARTO. Impedance (Z) was measured using a radiofrequency generator at multiple points in the LA, PV ostia (PVO), and deep PVs in 79 patients undergoing their first AF ablation (group 1) and 29 patients undergoing repeat CPVA (group 2). Prospective Phase: In an additional 20 patients, using pilot phase data, one operator defined catheter tip location as either LA or PVO based on CARTO and fluoroscopy. A second operator blinded to CARTO simultaneously did the same based on impedance at 15 +/- 4 points per patient. RESULTS: Group 1: Z(LA) was 99.4 +/- 9.0 omega. Z(PVO) was higher (109.2 +/- 8.5 omega), rising further as the catheter advanced into deep PV (137 omega +/- 18). Z(PVO) differed from Z(LA) by 9 +/- 4 omega. Group 2 had a lower Z(LA) and Z(PVO) compared with group 1 (P <.05). Impedance monitoring differentiated between LA and PVO, with 91% specificity and sensitivity, 96% positive predictive value, and 81% negative predictive value. At 3-month follow-up, no patients had evidence of PV stenosis on magnetic resonance imaging. CONCLUSION: Impedance mapping reliably identifies the LA-PV transitional zone, facilitating AF ablation, and its use is associated with a low incidence of PV stenosis.

Radiofrequency ablation in children with asymptomatic Wolff-Parkinson-White syndrome.

BACKGROUND: Ventricular fibrillation can be the presenting arrhythmia in children with asymptomatic Wolff-Parkinson-White syndrome. Deaths due to this arrhythmia are potentially preventable. METHODS: We performed a randomized study in which prophylactic radiofrequency catheter ablation of accessory pathways was compared with no ablation in asymptomatic children (age range, 5 to 12 years) with the Wolff-Parkinson-White syndrome who were at high risk for arrhythmias. The primary end point was the occurrence of arrhythmic events during follow-up. RESULTS: Of the 165 eligible children, 60 were determined to be at high risk for arrhythmias. After randomization, but before any ablation had been performed, the parents withdrew 13 children from the study. Of the remaining children, 20 underwent prophylactic ablation and 27 had no treatment. The characteristics of the two groups were similar. There were three ablation-related complications, one of which led to hospitalization. During follow-up, 1 child in the ablation group (5 percent) and 12 in the control group (44 percent) had arrhythmic events. Two children in the control group had ventricular fibrillation, and one died suddenly. The cumulative rate of arrhythmic events was lower among children at high risk who underwent ablation than among those at high risk who did not. The reduction in risk associated with ablation remained significant after adjustment in a Cox regression analysis. In both the ablation and the control groups, the independent predictors of arrhythmic events were the absence of prophylactic ablation and the presence of multiple accessory pathways. CONCLUSIONS: In asymptomatic, high-risk children with the Wolff-Parkinson-White syndrome, prophylactic catheter ablation performed by an experienced operator reduces the risk of life-threatening arrhythmias.

Cardiac contractility modulation by non-excitatory electrical currents. The new frontier for electrical therapy of heart failure.

Heart failure (HF) may complicate ischemic heart disease in both its acute and chronic manifestations, representing a prevalent health problem throughout the world. Development of therapies to improve heart function, relieve symptoms, reduce hospitalizations and improve survival is a high priority in cardiovascular medicine. The available pharmacological strategies, including angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists, beta-blockers, and aldosterone receptor antagonists have recently been complemented by new electrical therapy, including implantable cardioverter-defibrillators for "MADIT II" patients and cardiac resynchronization for the 30% of HF patients with concomitant intraventricular conduction delay. The wide variety of available HF medications provides ample evidence that we have not yet succeeded in this effort. Safe and effective inotropic electrical therapy could be a useful addition to our therapeutic armamentarium in an attempt to correct Ca2+ fluxes abnormalities during the cardiac action potential. Cardiac contractility modulation (CCM) by means of non-excitatory electrical currents delivered during the action potential plateau has been shown to acutely enhance systolic function in humans with HF. Herewith, we report on our preliminary experience with CCM therapy for patients with HF, providing fundamental notions to characterize the rationale of this novel form of therapy. Briefly, CCM therapy appears to be safe and feasible. Proarrhythmic effects of this novel therapy seem unlikely. Preliminary data indicate that CCM gradually and significantly improves systolic performance, symptoms and functional status. The technique would appear to be attractive as an additive treatment for severe HF. Controlled randomized studies are needed to validate this novel concept.

First human chronic experience with cardiac contractility modulation by nonexcitatory electrical currents for treating systolic heart failure: mid-term safety and efficacy results from a multicenter study.

INTRODUCTION: Conventional electrical therapies for heart failure (HF) encompass defibrillation and ventricular resynchronization for patients at high risk for lethal arrhythmias and/or with inhomogeneous ventricular contraction. Cardiac contractility modulation (CCM) by means of nonexcitatory electrical currents delivered during the action potential plateau has been shown to acutely enhance systolic function in humans with HF. The aim of this multicenter study was to assess the chronic safety and preliminary efficacy of an implantable device delivering this novel form of electrical therapy. METHODS AND RESULTS: Thirteen patients with drug-resistant HF (New York Heart Association [NYHA] class III) were consecutively implanted with a device (OPTIMIZER II) delivering CCM biphasic square-wave pulses (20 ms, 5.8-7.7 V, 30 ms after detection of local activation) through two right ventricular leads screwed into the right aspect of the interventricular septum. CCM signals were delivered 3 hours daily over 8 weeks (3-hour phase) and 7 hours daily over the next 24 weeks (7-hour phase). Safety and feasibility of this novel therapy were regarded as primary endpoints. Preliminary clinical efficacy, -as expressed by changes in ejection fraction (EF), NYHA class, 6-minute walking test (6-MWT), peak O(2) uptake (peak VO(2)), and Minnesota Living with HF Questionnaire (MLWHFQ), was assessed at baseline and at the end of each phase. At the end of follow-up (8.8 +/- 0.2 months), all patients were alive, without heart transplantation or need for left ventricular assist device. Serial 24-hour Holter analysis revealed no proarrhythmic effect. No devices malfunctioned or failed for any reason other than end-of-battery life. Throughout the two study phases, EF improved from 22.7 +/- 7% to 28.7 +/- 7% and 37 +/- 13% (P = 0.004), 6-MWT from 418 +/- 99 m to 477 +/- 96 m and 510 +/- 107 m (P = 0.002), MLWHFQ from 36 +/- 21 to 18 +/- 12 and 7 +/- 6 (P = 0.002), peak VO(2) from 13.7 +/- 1.1 to 14.9 +/- 1.9 to 16.2 +/- 2.4 (P = 0.037), and NYHA class from 3 to 1.8 +/- 0.4 to 1.5 +/- 0.7 (P < 0.001). CONCLUSION: CCM therapy appears to be safe and feasible. Proarrhythmic effects of this novel therapy seem unlikely. Preliminary data indicate that CCM gradually and significantly improves systolic performance, symptoms, and functional status. CCM therapy for 7 hours per day is associated with greater dispersion near the mean, emphasizing the need to individually tailor CCM delivery duration. The technique appears to be attractive as an additive treatment for severe HF. Controlled randomized studies are needed to validate this novel concept.

A randomized study of prophylactic catheter ablation in asymptomatic patients with the Wolff-Parkinson-White syndrome.

BACKGROUND: Young age and inducibility of atrioventricular reciprocating tachycardia or atrial fibrillation during invasive electrophysiological testing identify asymptomatic patients with a Wolff-Parkinson-White pattern on the electrocardiogram as being at high risk for arrhythmic events. We tested the hypothesis that prophylactic catheter ablation of accessory pathways would provide meaningful and durable benefits as compared with no treatment in such patients. METHODS: From 1997 to 2002, among 224 eligible asymptomatic patients with the Wolff-Parkinson-White syndrome, patients at high risk for arrhythmias were randomly assigned to radio-frequency catheter ablation of accessory pathways (37 patients) or no treatment (35 patients). The end point was the occurrence of arrhythmic events over a five-year follow-up period. RESULTS: Patients assigned to ablation had base-line characteristics that were similar to those of the controls. Two patients in the ablation group (5 percent) and 21 in the control group (60 percent) had arrhythmic events. One control patient had ventricular fibrillation as the presenting arrhythmia. The five-year Kaplan-Meier estimates of the incidence of arrhythmic events were 7 percent among patients who underwent ablation and 77 percent among the controls (P<0.001 by the log-rank test); the risk reduction with ablation was 92 percent (relative risk, 0.08; 95 percent confidence interval, 0.02 to 0.33; P<0.001). CONCLUSIONS: Prophylactic accessory-pathway ablation markedly reduces the frequency of arrhythmic events in asymptomatic patients with the Wolff-Parkinson-White syndrome who are at high risk for such events.

Cardiac contractility modulation by electric currents applied during the refractory period in patients with heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

We assessed the feasibility of cardiac contractility modulation (CCM) by electric currents applied during the refractory period in patients with heart failure (HF). Extracellular electric currents modulating action potential and calcium transients have been shown to potentiate myocardial contractility in vitro and in animal models of chronic HF. CCM signals were biphasic square-wave pulses with adjustable amplitude, duration, and time delay from sensing of local electric activity. Signals were applied to the left ventricle through an epicardial vein (in 12 patients) or to the right ventricular (RV) aspect of the septum endocardially (in 6 patients). Simultaneous left ventricular (LV) and aortic pressure measurements were performed using a Millar catheter (Millar Instruments, Houston, Texas). Hemodynamics during RV temporary dual-chamber pacing was regarded as the control condition. Both LV and RV CCM stimulation increased dP/dt(max) to a similar degree (9.1 +/- 4.5% and 7.1 +/- 0.8%, respectively; p <0.01 vs controls), with associated aortic pulse pressure changes of 10.3 +/- 7.2% and 10.8 +/- 1.1% (p <0.01 vs controls). Regional systolic wall motion assessed quantitatively by color kinesis echocardiography was markedly enhanced near the CCM electrode, and the area of increased contractility involved 4.6 +/- 1.2 segments per patient. In 6 patients with HF with left bundle branch block, CCM signals delivered during biventricular pacing (BVP) produced an additional 16.1 +/- 3.7% increase in dP/dt(max) and a 17.0 +/- 7.5% increase in pulse pressure compared with BVP alone (p <0.01). CCM stimulation in patients with HF enhanced regional and global measures of LV systolic function, regardless of the varied delivery chamber or whether modulation was performed during RV pacing or BVP.