Mechanism of tissue heating during high intensity focused ultrasound pulmonary vein isolation: implications for atrial fibrillation ablation efficacy and phrenic nerve protection.

INTRODUCTION: The purpose of this study was to examine tissue temperatures around pulmonary veins (PVs) during high intensity focused ultrasound (HIFU) balloon ablation for atrial fibrillation. The thermodynamics and extent of PV and phrenic nerve (PN) heating during HIFU ablation have not been established. METHODS AND RESULTS: Tissue temperatures were recorded from epicardial thermocouples at right superior (RS) PV orifice and PN in eight dogs undergoing 51 RSPV HIFU ablations (40 seconds, 40 W). Maximum tissue temperatures, reflected by 288 recording profiles, were negatively correlated with distance from balloon surface (r =-0.79, P < 0.001). Average maximum RSPV temperature was 56.8 +/- 16.8 degrees C (distance: 6.6 +/- 4.1 mm), resulting in full-thickness, circumferential PV isolation in 7 of 8 animals. Direct local mechanical heating restricted to the focused ultrasound zone showed temperature rise to > or =50 degrees C within 10 seconds to a maximum temperature of 82.6 +/- 8.9 degrees C (n = 31). Apparent conductive heating showed gradual heating patterns (<50 degrees C within 10 seconds) at greater distance. PN temperature at all recording sites was 45.0 +/- 11.3 degrees C (distance: 9.2 +/- 5.0 mm). Intentional PN injury (10 of 51 [19.6%] ablations), occurred at 63.7 +/- 16.0 degrees C with closest distance of 4.4 +/- 2.5 mm, which was closer than in PNs without injury (7.3 +/- 4.3 mm, P = 0.005). CONCLUSIONS: HIFU ablation is highly effective in generating temperatures needed for full-thickness, circumferential ablation through rapid direct mechanical heating. Gradual heating of surrounding tissue supports the presence of conductive heating. This study also discloses direct HIFU effects as the mechanism of PN injury occurring within 4-7 mm from balloon surface.

New generation of electro-anatomic mapping: full intracardiac ultrasound image integration.

Surrogate electro-anatomic-derived geometries are used as the three-dimensional (3D) basis for mapping of cardiac arrhythmias. While merged computed tomography (CT) imaging may provide stellar pulmonary vein (PV) and left atrial (LA) anatomy, the applied scans must be obtained prior to ablation, and may not reflect physiologic conditions at the time of intervention. Patient-specific, ultrasound-derived 3D imaging has been developed as an alternative basis for new generation electro-anatomic mapping. An electro-anatomic sensor positioned at the tip of the phased-array intracardiac ultrasound catheter, provides the means to specify both location and orientation of each image as the 'context' for creating the 3D volumes for co-registration with electro-anatomic mapping. Specific anatomic details such as the pulmonary veins, membranous fossa, papillary muscles, or valve structures derived from real-time imaging can also be integrated into each segmented volume. This presentation reviews the basis and methods for this novel multi-modality image fusion for the creation of robust, nearly real-time anatomic images for guiding electro-anatomic mapping and ablation without requiring pre-acquired CT image sets, with accompanying limitations.

A randomized trial of a strategy for increasing high-density lipoprotein cholesterol levels: effects on progression of coronary heart disease and clinical events.

BACKGROUND: The high-density lipoprotein (HDL) cholesterol level is a strong predictor of cardiovascular events in epidemiologic studies. Until recently, it has been less extensively studied as a therapeutic target. OBJECTIVE: To assess the angiographic and clinical effects of a pharmacologic strategy to increase HDL cholesterol levels. DESIGN: Randomized, double-blind, placebo-controlled trial conducted from 1993 to 1996. SETTING: Outpatient specialty clinic of a large U.S. military medical center. PARTICIPANTS: 143 military retirees younger than 76 years of age with low HDL cholesterol levels and angiographically evident coronary disease. INTERVENTION: Gemfibrozil, niacin, and cholestyramine or corresponding placebos, with aggressive dietary and lifestyle intervention at baseline. MEASUREMENTS: Change from baseline to 30 months and a composite measure of clinical events that included hospitalization for angina, myocardial infarction, transient ischemic attack and stroke, death, and cardiovascular procedures. RESULTS: At baseline, mean (+/-SD) lipid values were as follows: total cholesterol, 5.1 +/- 0.8 mmol/L (196 +/- 31 mg/dL); low-density lipoprotein (LDL) cholesterol, 3.3 +/- 0.7 mmol/L (128 +/- 27 mg/dL); and HDL cholesterol, 0.9 +/- 0.2 mmol/L (34 +/- 6 mg/dL). Compared with placebo, the pharmacologically treated group experienced a 20% (95% CI, 14.8% to 24.3%) decrease in total cholesterol level, a 36% (CI, 28.4% to 43.5%) increase in HDL cholesterol level, a 26% (CI, 19.1% to 33.7%) decrease in LDL cholesterol level, and a 50% (CI, 40.5% to 59.2%) reduction in triglyceride levels. Focal coronary stenosis increased by 1.4% in the placebo group but decreased by 0.8% in the drug group (difference, -2.2 percentage points [CI, -4.2 to -0.1 percentage points]). A composite cardiovascular event end point was reached in 26% of patients in the placebo group and 13% of those in the drug group (difference, 13.7 percentage points [CI, 0.9 to 26.5 percentage points]). Side effects, particularly flushing and gastrointestinal intolerance, were more common in the drug group but rarely led to withdrawal from the study. LIMITATIONS: The study was small and used a composite clinical outcome. Whether improvements in angiographic findings were due to reductions in LDL cholesterol or increases in HDL cholesterol was not established. Flushing may have led to inadvertent unblinding in patients who were randomly assigned to active study drugs. CONCLUSIONS: A combination regimen aimed at increasing HDL cholesterol levels improves cholesterol profiles, helps prevent angiographic progression of coronary stenosis, and may prevent cardiovascular events in some people who exercise regularly and eat low-fat diets.

Relation of QTc duration heterogeneity to mortality following orthotopic heart transplantation.

Studies of heart failure patients have demonstrated that serial QT prolongation and abnormally prolonged QT intervals are associated with greater mortality. Serial QT interval measurements in patients who undergo orthotopic heart transplantation (OHT) may quantify the degree of myocardial repolarization heterogeneity and serve as a marker of arrhythmogenic substrate. In this study, the mean survival for those with "stable" QT(c) intervals (a change of -10 to 10 ms/year) was 124 +/- 8 months versus 63 +/- 25 months in those with annual QT(c) changes of >10 ms (p = 0.009). Ventricular repolarization heterogeneity may serve as a marker of identifying high-risk patients after OHT.

Quantitative modeling of the accuracy in registering preoperative patient-specific anatomic models into left atrial cardiac ablation procedures.

PURPOSE: In cardiac ablation therapy, accurate anatomic guidance is necessary to create effective tissue lesions for elimination of left atrial fibrillation. While fluoroscopy, ultrasound, and electroanatomic maps are important guidance tools, they lack information regarding detailed patient anatomy which can be obtained from high resolution imaging techniques. For this reason, there has been significant effort in incorporating detailed, patient-specific models generated from preoperative imaging datasets into the procedure. Both clinical and animal studies have investigated registration and targeting accuracy when using preoperative models; however, the effect of various error sources on registration accuracy has not been quantitatively evaluated. METHODS: Data from phantom, canine, and patient studies are used to model and evaluate registration accuracy. In the phantom studies, data are collected using a magnetically tracked catheter on a static phantom model. Monte Carlo simulation studies were run to evaluate both baseline errors as well as the effect of different sources of error that would be present in a dynamic in vivo setting. Error is simulated by varying the variance parameters on the landmark fiducial, physical target, and surface point locations in the phantom simulation studies. In vivo validation studies were undertaken in six canines in which metal clips were placed in the left atrium to serve as ground truth points. A small clinical evaluation was completed in three patients. Landmark-based and combined landmark and surface-based registration algorithms were evaluated in all studies. In the phantom and canine studies, both target registration error and point-to-surface error are used to assess accuracy. In the patient studies, no ground truth is available and registration accuracy is quantified using point-to-surface error only. RESULTS: The phantom simulation studies demonstrated that combined landmark and surface-based registration improved landmark-only registration provided the noise in the surface points is not excessively high. Increased variability on the landmark fiducials resulted in increased registration errors; however, refinement of the initial landmark registration by the surface-based algorithm can compensate for small initial misalignments. The surface-based registration algorithm is quite robust to noise on the surface points and continues to improve landmark registration even at high levels of noise on the surface points. Both the canine and patient studies also demonstrate that combined landmark and surface registration has lower errors than landmark registration alone. CONCLUSIONS: In this work, we describe a model for evaluating the impact of noise variability on the input parameters of a registration algorithm in the context of cardiac ablation therapy. The model can be used to predict both registration error as well as assess which inputs have the largest effect on registration accuracy.

Surface electrocardiography and histologic rejection following orthotopic heart transplantation.

BACKGROUND: Intraventricular conduction delay and QT interval dispersion may be related to electrical instability and the risk of ventricular arrhythmogenesis. The interlead variability of the QT interval on a surface 12-lead electrocardiogram (ECG) has been associated with an increased likelihood of sudden death in patients with long QT syndromes, in patients recovering from myocardial infarction, and dilated cardiomyopathy. We sought to determine the incidence of increased QT(c) dispersion (QT(c-d)) relative to biopsy grade of severity of rejection. METHODS: Records of patients having undergone orthotopic heart transplantation (OHT) were reviewed focusing specifically on surface ECGs performed in temporal proximity to endomyocardial biopsy. RESULTS: Seventy-five patients were evaluated on 1573 occasions, to include 999 surface ECGs, and 847 endomyocardial biopsies. There were 269 interpretable surface ECGs and endomyocardial biopsies performed within 1.1 +/- 4.6 days. There were no identifiable trends in atrioventricular or intraventricular conduction abnormalities (to include right bundle branch block) when comparing those with and without significant rejection on endomyocardial biopsy. The mean QT(c-d) of those with none (n = 34), mild (n = 194), moderate (n = 39), and severe (n = 2) rejection was 49 +/- 29, 49 +/- 35, 57 +/- 38, 81 +/- 7 ms, respectively (P = 0.28 by ANOVA of means). When comparing those with significant rejection so as to change management there was a trend toward increased dispersion (no to mild rejection, 49 +/- 34 ms vs moderate to severe rejection, 59 +/- 37 ms, P = 0.09). CONCLUSIONS: In this study investigating noninvasive ventricular depolarization/repolarization and correlation to histologic manifestation of rejection, there was suggestion, but no statistical significance, of QT(c-d) and severity of rejection. QT(c-d) should not be considered a sensitive marker for OHT rejection.