Absence of Arrhythmogenicity with Biphasic Pulsed Electric Fields Delivered to Porcine Airways.

Pulsed electric field (PEF) technologies treat many types of tissue. Many systems mandate synchronization to the cardiac cycle to avoid the induction of cardiac arrhythmias. Significant differences between PEF systems make the assessment of cardiac safety from one technology to another challenging. A growing body of evidence suggests that shorter duration biphasic pulses obviate the need for cardiac synchronization, even when delivered in a monopolar fashion. This study theoretically evaluates the risk profile of different PEF parameters. It then tests a monopolar, biphasic, microsecond-scale PEF technology for arrhythmogenic potential. PEF applications of increasing likelihood to induce an arrhythmia were delivered. The energy was delivered throughout the cardiac cycle, including both single and multiple packets, and then with concentrated delivery on the t-wave. There were no sustained changes to the electrocardiogram waveform or to the cardiac rhythm, despite delivering energy during the most vulnerable phase of the cardiac cycle, and delivery of multiple packets of PEF energy across the cardiac cycle. Only isolated premature-atrial contractions (PAC) were observed. This study provides evidence that certain varieties of biphasic, monopolar PEF delivery do not require synchronized energy delivery to prevent harmful arrhythmias.

Feasibility of real-time magnetic resonance imaging for catheter guidance in electrophysiology studies.

BACKGROUND: Compared with fluoroscopy, the current imaging standard of care for guidance of electrophysiology procedures, magnetic resonance imaging (MRI) provides improved soft-tissue resolution and eliminates radiation exposure. However, because of inherent magnetic forces and electromagnetic interference, the MRI environment poses challenges for electrophysiology procedures. In this study, we sought to test the feasibility of performing electrophysiology studies with real-time MRI guidance. METHODS AND RESULTS: An MRI-compatible electrophysiology system was developed. Catheters were targeted to the right atrium, His bundle, and right ventricle of 10 mongrel dogs (23 to 32 kg) via a 1.5-T MRI system using rapidly acquired fast gradient-echo images (approximately 5 frames per second). Catheters were successfully positioned at the right atrial, His bundle, and right ventricular target sites of all animals. Comprehensive electrophysiology studies with recording of intracardiac electrograms and atrial and ventricular pacing were performed. Postprocedural pathological evaluation revealed no evidence of thermal injury to the myocardium. After proof of safety in animal studies, limited real-time MRI-guided catheter mapping studies were performed in 2 patients. Adequate target catheter localization was confirmed via recording of intracardiac electrograms in both patients. CONCLUSIONS: To the best of our knowledge, this is the first study to report the feasibility of real-time MRI-guided electrophysiology procedures. This technique may eliminate patient and staff radiation exposure and improve real-time soft tissue resolution for procedural guidance.

The benefit of upgrading chronically right ventricle-paced heart failure patients to resynchronization therapy demonstrated by strain rate imaging.

BACKGROUND: RV pacing induces conduction delay (CD), mechanical dyssynchrony, and increased morbidity in patients with HF. CRT improves HF symptoms and survival, but sparse data exist on its direct effect on chronically RV-paced HF patients. OBJECTIVES: To assess the benefit of cardiac resynchronization therapy (CRT) in chronically right ventricle (RV)-paced heart failure (HF) patients. METHODS: We studied 12 consecutive patients with class III HF who had a previously implanted pacemaker or implantable cardioverter-defibrillator. These individuals were chronically RV paced and referred for upgrade to a biventricular device by their primary cardiologists. Tissue Doppler and strain rate imaging (TDI and SRI, respectively) were performed immediately before each upgrade and 4-6 weeks afterward to quantify changes in regional wall motion and synchrony with CRT. RESULTS: CRT significantly reduced the mean QRS duration (205 ms to 156 ms; P<.0001), and it increased the ejection fraction (30.7%+/-5.1% to 35.8%+/-5.1%; P<.01). Left ventricular end-systolic and end-diastolic dimensions were also significantly reduced. Clinically, patients improved by an average of one New York Heart Association (NYHA) functional class after upgrade (P = .006). The parameter exhibiting greatest improvement was the coefficient of variation (CoV: standard deviation/mean) of time to peak systolic strain rate, a marker of ventricular dyssynchrony, which decreased from 34.3%+/-13.0% to 19.0%+/-6.6% (P<.01). Reduction in CoV of time to peak systolic strain rate was maximally seen in the midventricle (38.2%+/-19.6% to 16.5%+/-9.7%; P<.01). CONCLUSIONS: Upgrading chronically RV-paced HF patients to CRT improves global and regional systolic function. TDI and SRI provide compelling evidence that this benefit parallels that seen in HF patients with CD unrelated to RV pacing, which implies that biventricular pacing synchronizes mechanical activation in different myocardial regions in patients upgraded from RV pacing as well.

Magnetic resonance assessment of the substrate for inducible ventricular tachycardia in nonischemic cardiomyopathy.

BACKGROUND: Patients with left ventricular dysfunction have an elevated risk of sudden cardiac death. However, the substrate for ventricular arrhythmia in patients with nonischemic cardiomyopathy remains poorly understood. We hypothesized that the distribution of scar identified by MRI is predictive of inducible ventricular tachycardia. METHODS AND RESULTS: Short-axis cine steady-state free-precession and postcontrast inversion-recovery gradient-echo MRI sequences were obtained before electrophysiological study in 26 patients with nonischemic cardiomyopathy. Left ventricular ejection fraction was measured from end-diastolic and end-systolic cine images. The transmural extent of scar as a percentage of wall thickness (percent scar transmurality) in each of 12 radial sectors per slice was calculated in all myocardial slices. The percentages of sectors with 1% to 25%, 26% to 50%, 51% to 75%, and 76% to 100% scar transmurality were determined for each patient. Predominance of scar distribution involving 26% to 75% of wall thickness was significantly predictive of inducible ventricular tachycardia and remained independently predictive in the multivariable model after adjustment for left ventricular ejection fraction (odds ratio, 9.125; P=0.020). CONCLUSIONS: MR assessment of scar distribution can identify the substrate for inducible ventricular tachycardia and may identify high-risk patients with nonischemic cardiomyopathy currently missed by ejection fraction criteria.

Modern pacemaker and implantable cardioverter/defibrillator systems can be magnetic resonance imaging safe: in vitro and in vivo assessment of safety and function at 1.5 T.

BACKGROUND: MRI has unparalleled soft-tissue imaging capabilities. The presence of devices such as pacemakers and implantable cardioverter/defibrillators (ICDs), however, is historically considered a contraindication to MRI. These devices are now smaller, with less magnetic material and improved electromagnetic interference protection. Our aim was to determine whether these modern systems can be used in an MR environment. METHODS AND RESULTS: We tested in vitro and in vivo lead heating, device function, force acting on the device, and image distortion at 1.5 T. Clinical MR protocols and in vivo measurements yielded temperature changes <0.5 degrees C. Older (manufactured before 2000) ICDs were damaged by the MR scans. Newer ICD systems and most pacemakers, however, were not. The maximal force acting on newer devices was <100 g. Modern (manufactured after 2000) ICD systems were implanted in dogs (n=18), and after 4 weeks, 3- to 4-hour MR scans were performed (n=15). No device dysfunction occurred. The images were of high quality with distortion dependent on the scan sequence and plane. Pacing threshold and intracardiac electrogram amplitude were unchanged over the 8 weeks, except in 1 animal that, after MRI, had a transient (<12 hours) capture failure. Pathological data of the scanned animals revealed very limited necrosis or fibrosis at the tip of the lead area, which was not different from controls (n=3) not subjected to MRI. CONCLUSIONS: These data suggest that certain modern pacemaker and ICD systems may indeed be MRI safe. This may have major clinical implications for current imaging practices.

Prognostic usefulness of marginal troponin T elevation.

Marginal elevations of troponin T among patients with chest pain are often considered to be insignificant. We sought to define the prognostic value of marginal troponin T elevations in patients presenting to the emergency department with suspected myocardial ischemia. Four hundred twenty-eight consecutive patients presenting to the emergency department with ongoing chest pain were evaluated, followed through their hospital course, and contacted for follow-up 4 months after discharge. Two hundred ninety-nine patients had undetectable troponin T levels (<0.01 microg/L), 76 had marginal troponin T elevations (0.01 to 0.09 microg/L), and 53 had frank troponin T elevations (> or =0.1 microg/L). Patients with either marginally or frank elevated troponin levels were older and more likely to be men, but did not differ from patients with undetectable troponin levels with regard to the prevalence of coronary artery disease risk factors, history of coronary disease, or race. While in the hospital, the undetectable and marginal troponin groups were referred for cardiac testing in equal proportions (58% and 59%, respectively), whereas 87% of the elevated group underwent further testing. After adjustment for possible confounders, a significantly increased rate of death/myocardial infarction/revascularization was observed in the marginal troponin group compared with the undetectable troponin group (p = 0.004). Marginal elevations of troponin T identified a currently underevaluated high-risk subgroup of patients with suspected myocardial ischemia who are more likely to have adverse clinical outcomes than those with undetectable troponin levels.

Chest pain relief by nitroglycerin does not predict active coronary artery disease.

BACKGROUND: The belief that chest pain relief with nitroglycerin indicates the presence of active coronary artery disease is common. However, this hypothesis has not been tested. OBJECTIVE: To define the diagnostic and prognostic value of chest pain relief with nitroglycerin. DESIGN: Prospective observational cohort study. SETTING: Urban community teaching hospital. PATIENTS: 459 consecutive patients with chest pain admitted through the emergency department who received nitroglycerin from emergency services personnel or an emergency department nurse. Follow-up was obtained by telephone contact at 4 months. MEASUREMENTS: Chest pain relief was defined as a decrease of at least 50% in patients' self-reported pain within 5 minutes of the initial dose of sublingual or spray nitroglycerin. Active coronary artery disease was defined as any elevated serum enzyme levels, coronary angiography demonstrating a 70% or greater stenosis, or a positive exercise test result. RESULTS: Nitroglycerin relieved chest pain in 39% of patients (181 of 459). In patients with active coronary artery disease as the likely cause of their chest pain, 35% (49 of 141) had chest pain relief with nitroglycerin. In contrast, in patients without active coronary artery disease, 41% (113 of 275) had chest pain relief (P > 0.2). Four-month clinical outcomes were similar in patients with or without chest pain relief with nitroglycerin (P > 0.2). CONCLUSIONS: These data suggest that, in a general population admitted for chest pain, relief of pain after nitroglycerin treatment does not predict active coronary artery disease and should not be used to guide diagnosis.

Initial experience with a novel focused ultrasound ablation system for ring ablation outside the pulmonary vein.

INTRODUCTION: Atrial fibrillation has been shown to initiate from triggers within pulmonary veins. Several studies have documented that electrical isolation of those triggers can lead to maintenance of sinus rhythm. The complication of pulmonary vein stenosis has limited the utility of delivering ablation energy within the pulmonary vein. We utilize a focused ultrasound catheter ablation system for delivery of transmural ablation lines proximal to the pulmonary vein ostium. METHODS: Nine dogs (weight 30-39 kg) were anesthetized and ventilated. Through a transseptal approach, pulmonary veins were engaged with the focused balloon ultrasound catheter. Ultrasound power was delivered at 40 acoustic watts outside the pulmonary vein ostium, focused 2 mm off the balloon surface, with a depth of approximately 6 mm, for 30-120 seconds. Following ablation, lesions were histopathologically analyzed. RESULTS: Of nine animals studied, fourteen pulmonary veins were ablated. We found successful delivery of near circumferential and transmural ablation lines in 6/14 pulmonary veins. In each of the six circumferential ablations, successful alignment of the ultrasound transducer along the longitudinal axis of the parabolic balloon occurred. The final four ablations were conducted with an enhanced catheter design that assured axial alignment. Of these ablations, all four were circumferential. The remaining 8 pulmonary veins had incomplete delivery of lesions. In each of these veins the ultrasound transducer was misaligned with the balloon axis when therapy was delivered. CONCLUSION: Focused ultrasound ablation is a new means of performing pulmonary vein isolation. This method provides delivery of lesions outside the vein, limiting the risk of pulmonary vein stenosis for the treatment of atrial fibrillation.