Daniel H. Cooper

Cardiac Electrophysiological Substrate Underlying the ECG Phenotype and Electrogram Abnormalities in Brugada Syndrome Patients

Background— Brugada syndrome (BrS) is a highly arrhythmogenic cardiac disorder, associated with an increased incidence of sudden death. Its arrhythmogenic substrate in the intact human heart remains ill-defined. Methods and Results— Using noninvasive ECG imaging, we studied 25 BrS patients to characterize the electrophysiological substrate and 6 patients with right bundle-branch block for comparison. Seven healthy subjects provided control data. Abnormal substrate was observed exclusively in the right ventricular outflow tract with the following properties (in comparison with healthy controls; P<0.005): (1) ST-segment elevation and inverted T wave of unipolar electrograms (2.21±0.67 versus 0 mV); (2) delayed right ventricular outflow tract activation (82±18 versus 37±11 ms); (3) low-amplitude (0.47±0.16 versus 3.74±1.60 mV) and fractionated electrograms, suggesting slow discontinuous conduction; (4) prolonged recovery time (381±30 versus 311±34 ms) and activation-recovery intervals (318±32 versus 241±27 ms), indicating delayed repolarization; (5) steep repolarization gradients (&Dgr;recovery time/&Dgr;x=96±28 versus 7±6 ms/cm, &Dgr;activation-recovery interval/&Dgr;x=105±24 versus 7±5 ms/cm) at right ventricular outflow tract borders. With increased heart rate in 6 BrS patients, reduced ST-segment elevation and increased fractionation were observed. Unlike BrS, right bundle-branch block had delayed activation in the entire right ventricle, without ST-segment elevation, fractionation, or repolarization abnormalities on electrograms. Conclusions— The results indicate that both slow discontinuous conduction and steep dispersion of repolarization are present in the right ventricular outflow tract of BrS patients. ECG imaging could differentiate between BrS and right bundle-branch block.

Early repolarization associated with sudden death: insights from noninvasive electrocardiographic imaging.

Early repolarization (significant elevation of the QRS-ST junction in the inferior or lateral ECG leads), thought previously to be a benign entity, was recently shown1,2 to be more prevalent in patients with a history of idiopathic ventricular fibrillation. Electrocardiographic Imaging (ECGI)3,4,6 is a novel noninvasive imaging modality that generates electroanatomic maps of epicardial activation and repolarization.

Noninvasive Cardiac Radiation for Ablation of Ventricular Tachycardia

BACKGROUND Recent advances have enabled noninvasive mapping of cardiac arrhythmias with electrocardiographic imaging and noninvasive delivery of precise ablative radiation with stereotactic body radiation therapy (SBRT). We combined these techniques to perform catheter‐free, electrophysiology‐guided, noninvasive cardiac radioablation for ventricular tachycardia. METHODS We targeted arrhythmogenic scar regions by combining anatomical imaging with noninvasive electrocardiographic imaging during ventricular tachycardia that was induced by means of an implantable cardioverter–defibrillator (ICD). SBRT simulation, planning, and treatments were performed with the use of standard techniques. Patients were treated with a single fraction of 25 Gy while awake. Efficacy was assessed by counting episodes of ventricular tachycardia, as recorded by ICDs. Safety was assessed by means of serial cardiac and thoracic imaging. RESULTS From April through November 2015, five patients with high‐risk, refractory ventricular tachycardia underwent treatment. The mean noninvasive ablation time was 14 minutes (range, 11 to 18). During the 3 months before treatment, the patients had a combined history of 6577 episodes of ventricular tachycardia. During a 6‐week postablation “blanking period” (when arrhythmias may occur owing to postablation inflammation), there were 680 episodes of ventricular tachycardia. After the 6‐week blanking period, there were 4 episodes of ventricular tachycardia over the next 46 patient‐months, for a reduction from baseline of 99.9%. A reduction in episodes of ventricular tachycardia occurred in all five patients. The mean left ventricular ejection fraction did not decrease with treatment. At 3 months, adjacent lung showed opacities consistent with mild inflammatory changes, which had resolved by 1 year. CONCLUSIONS In five patients with refractory ventricular tachycardia, noninvasive treatment with electrophysiology‐guided cardiac radioablation markedly reduced the burden of ventricular tachycardia. (Funded by Barnes–Jewish Hospital Foundation and others.)

Repolarization changes underlying long-term cardiac memory due to right ventricular pacing: noninvasive mapping with electrocardiographic imaging.

Background— Cardiac memory refers to the observation that altered cardiac electrical activation results in repolarization changes that persist after the restoration of a normal activation pattern. Animal studies, however, have yielded disparate conclusions, both regarding the spatial pattern of repolarization changes in cardiac memory and the underlying mechanisms. The present study was undertaken to produce 3-dimensional images of the repolarization changes underlying long-term cardiac memory in humans. Methods and Results— Nine adult subjects with structurally normal hearts and dual-chamber pacemakers were enrolled in the study. Noninvasive electrocardiographic imaging was used before and after 1 month of ventricular pacing to reconstruct epicardial activation and repolarization patterns. Eight subjects exhibited cardiac memory in response to ventricular pacing. In all subjects, ventricular pacing resulted in a prolongation of the activation recovery interval (a surrogate for action potential duration) in the region close to the site of pacemaker-induced activation from 228.4±7.6 ms during sinus rhythm to 328.3±6.2 ms during cardiac memory. As a consequence, increases are observed in both apical-basal and right-left ventricular gradients of repolarization, resulting in a significant increase in the dispersion of repolarization. Conclusions— These results demonstrate that electrical remodeling in response to ventricular pacing in human subjects results in action potential prolongation near the site of abnormal activation and a marked dispersion of repolarization. This dispersion of repolarization is potentially arrhythmogenic and, intriguingly, was less evident during continuous right ventricular pacing, suggesting the novel possibility that continuous right ventricular pacing at least partially suppresses pacemaker-induced cardiac memory.Background— Cardiac memory refers to the observation that altered cardiac electrical activation results in repolarization changes that persist after the restoration of a normal activation pattern. Animal studies, however, have yielded disparate conclusions, both regarding the spatial pattern of repolarization changes in cardiac memory and the underlying mechanisms. The present study was undertaken to produce 3-dimensional images of the repolarization changes underlying long-term cardiac memory in humans. Methods and Results— Nine adult subjects with structurally normal hearts and dual-chamber pacemakers were enrolled in the study. Noninvasive electrocardiographic imaging was used before and after 1 month of ventricular pacing to reconstruct epicardial activation and repolarization patterns. Eight subjects exhibited cardiac memory in response to ventricular pacing. In all subjects, ventricular pacing resulted in a prolongation of the activation recovery interval (a surrogate for action potential duration) in the region close to the site of pacemaker-induced activation from 228.4±7.6 ms during sinus rhythm to 328.3±6.2 ms during cardiac memory. As a consequence, increases are observed in both apical-basal and right-left ventricular gradients of repolarization, resulting in a significant increase in the dispersion of repolarization. Conclusions— These results demonstrate that electrical remodeling in response to ventricular pacing in human subjects results in action potential prolongation near the site of abnormal activation and a marked dispersion of repolarization. This dispersion of repolarization is potentially arrhythmogenic and, intriguingly, was less evident during continuous right ventricular pacing, suggesting the novel possibility that continuous right ventricular pacing at least partially suppresses pacemaker-induced cardiac memory.

Electrophysiologic Scar Substrate in Relation to VT: Noninvasive High-Resolution Mapping and Risk Assessment with ECGI

Ischemic cardiomyopathy (ICM) can provide the substrate for ventricular tachycardia (VT).

Continuous ECGI mapping of spontaneous VT initiation, continuation, and termination with antitachycardia pacing

A 40-year-old woman with nonischemic cardiomyopathy and a left ventricular (LV) ejection fraction of 35% was referred for recurrent ventricular tachycardia (VT). She experienced 248 VT episodes treated by antitachycardia pacing (ATP) over 14 days. In 2005, she received an implantable cardioverter defibrillator for an episode of syncope and nonsustained VT. She later underwent an invasive electrophysiology study (EPS) with inducible VT and an ablation of the AV nodal reentrant tachycardia. Since then, she experienced symptomatic VT, terminated by ATP. Her VT was unresponsive to sotalol and mexiletine. Two EPS in early 2010 failed to induce VT despite intravenous isoproterenol and triple extrastimuli at two right ventricular (RV) sites; therefore, no ablations were performed.

Catheter ablation of atrial fibrillation: long-term outcomes

Evaluation of: Weerasooriya R, Khairy P, Litalien J et al. Catheter ablation for arial fibrillation; are results maintained at 5 years of follow-up? J. Am. Coll. Cardiol. 57, 160–166 (2011). Atrial fibrillation is the most common arrhythmia faced in clinical practice with a substantial impact on morbidity, mortality, and heathcare expenditures. Patients with atrial fibrillation in which a rhythm control strategy is desired to improve quality of life have had limited options. The discovery of the role of pulmonary vein triggers has led to the development of catheter ablation techniques that have shown promising short-term success rates. Long-term outcomes were until recently, lacking. These results confirm the inherently recurrent nature of atrial fibrillation and the need for multiple procedures to achieve reasonable long-term successful maintenance of sinus rhythm.

Repolarization Changes Underlying Long-Term Cardiac Memory Due to Right Ventricular Pacing: Noninvasive Mapping with ECGI

Background— Cardiac memory refers to the observation that altered cardiac electrical activation results in repolarization changes that persist after the restoration of a normal activation pattern. Animal studies, however, have yielded disparate conclusions, both regarding the spatial pattern of repolarization changes in cardiac memory and the underlying mechanisms. The present study was undertaken to produce 3-dimensional images of the repolarization changes underlying long-term cardiac memory in humans. Methods and Results— Nine adult subjects with structurally normal hearts and dual-chamber pacemakers were enrolled in the study. Noninvasive electrocardiographic imaging was used before and after 1 month of ventricular pacing to reconstruct epicardial activation and repolarization patterns. Eight subjects exhibited cardiac memory in response to ventricular pacing. In all subjects, ventricular pacing resulted in a prolongation of the activation recovery interval (a surrogate for action potential duration) in the region close to the site of pacemaker-induced activation from 228.4±7.6 ms during sinus rhythm to 328.3±6.2 ms during cardiac memory. As a consequence, increases are observed in both apical-basal and right-left ventricular gradients of repolarization, resulting in a significant increase in the dispersion of repolarization. Conclusions— These results demonstrate that electrical remodeling in response to ventricular pacing in human subjects results in action potential prolongation near the site of abnormal activation and a marked dispersion of repolarization. This dispersion of repolarization is potentially arrhythmogenic and, intriguingly, was less evident during continuous right ventricular pacing, suggesting the novel possibility that continuous right ventricular pacing at least partially suppresses pacemaker-induced cardiac memory.Background— Cardiac memory refers to the observation that altered cardiac electrical activation results in repolarization changes that persist after the restoration of a normal activation pattern. Animal studies, however, have yielded disparate conclusions, both regarding the spatial pattern of repolarization changes in cardiac memory and the underlying mechanisms. The present study was undertaken to produce 3-dimensional images of the repolarization changes underlying long-term cardiac memory in humans. Methods and Results— Nine adult subjects with structurally normal hearts and dual-chamber pacemakers were enrolled in the study. Noninvasive electrocardiographic imaging was used before and after 1 month of ventricular pacing to reconstruct epicardial activation and repolarization patterns. Eight subjects exhibited cardiac memory in response to ventricular pacing. In all subjects, ventricular pacing resulted in a prolongation of the activation recovery interval (a surrogate for action potential duration) in the region close to the site of pacemaker-induced activation from 228.4±7.6 ms during sinus rhythm to 328.3±6.2 ms during cardiac memory. As a consequence, increases are observed in both apical-basal and right-left ventricular gradients of repolarization, resulting in a significant increase in the dispersion of repolarization. Conclusions— These results demonstrate that electrical remodeling in response to ventricular pacing in human subjects results in action potential prolongation near the site of abnormal activation and a marked dispersion of repolarization. This dispersion of repolarization is potentially arrhythmogenic and, intriguingly, was less evident during continuous right ventricular pacing, suggesting the novel possibility that continuous right ventricular pacing at least partially suppresses pacemaker-induced cardiac memory.

The Electrophysiological Substrate of Early Repolarization Syndrome: Noninvasive Mapping in Patients

Background The early repolarization (ER) pattern is a common ECG finding. Recent studies established a definitive clinical association between ER and fatal ventricular arrhythmias. However, the arrhythmogenic substrate of ER in the intact human heart has not been characterized. Objectives To map the epicardial electrophysiological (EP) substrate in ER syndrome patients using noninvasive Electrocardiographic Imaging (ECGI), and to characterize substrate properties that support arrhythmogenicity. Methods Twenty-nine ER syndrome patients were enrolled, 17 of which had a malignant syndrome. Characteristics of the abnormal EP substrate were analyzed using data recorded during sinus rhythm. The EP mapping data were analyzed for electrogram morphology, conduction and repolarization. Seven normal subjects provided control data. Results The abnormal EP substrate in ER syndrome patients has the following properties: (1) Abnormal epicardial electrograms characterized by presence of J-waves in localized regions; (2) Absence of conduction abnormalities, including delayed activation, conduction block, or fractionated electrograms; (3) Marked abbreviation of ventricular repolarization in areas with J-waves. The action potential duration (APD) was significantly shorter than normal (196±19 vs. 235±21 ms, p<0.05). Shortening of APD occurred heterogeneously, leading to steep repolarization gradients compared to normal control (45±17 vs.7±5 ms/cm, p<0.05). Premature ventricular contractions (PVCs) were recorded in 2 patients. The PVC sites of origin were closely related to the abnormal EP substrate with J-waves and steep repolarization gradients. Conclusions Early Repolarization is associated with steep repolarization gradients caused by localized shortening of APD. Results suggest association of PVC initiation sites with areas of repolarization abnormalities. Conduction abnormalities were not observed.

Pericardial invasion: lessons learned from surgical and transcatheter aortic valve replacement.

Atrial fibrillation is the most common arrhythmic complication observed after cardiac surgery. The reported incidence of post-operative atrial fibrillation (POAF) after cardiac surgery ranges from 10% to 65% [(1)][1]. The wide range of incidence is driven by myriad factors, including differences in