Phillip S. Cuculich

Noninvasive Characterization of Epicardial Activation in Humans With Diverse Atrial Fibrillation Patterns

Background— Various mechanisms of atrial fibrillation (AF) have been demonstrated experimentally. Invasive methods to study these mechanisms in humans have limitations, precluding continuous mapping of both atria with sufficient resolution. In this article, we present continuous biatrial epicardial activation sequences of AF in humans using noninvasive electrocardiographic imaging (ECGI). Methods and Results— In the testing phase, ECGI accuracy was evaluated by comparing ECGI with coregistered CARTO images during atrial pacing in 6 patients. Additionally, correlative observations from catheter mapping and ablation were compared with ECGI in 3 patients. In the study phase, ECGI maps during AF in 26 patients were analyzed for mechanisms and complexity. ECGI noninvasively imaged the low-amplitude signals of AF in a wide range of patients (97% procedural success). Spatial accuracy for determining initiation sites from pacing was 6 mm. Locations critical to maintenance of AF identified during catheter ablation were identified by ECGI; ablation near these sites restored sinus rhythm. In the study phase, the most common patterns of AF were multiple wavelets (92%), with pulmonary vein (69%) and non–pulmonary vein (62%) focal sites. Rotor activity was seen rarely (15%). AF complexity increased with longer clinical history of AF, although the degree of complexity of nonparoxysmal AF varied widely. Conclusions— ECGI offers a noninvasive way to map epicardial activation patterns of AF in a patient-specific manner. The results highlight the coexistence of a variety of mechanisms and variable complexity among patients. Overall, complexity generally increased with duration of AF.

Noninvasive Electroanatomic Mapping of Human Ventricular Arrhythmias with Electrocardiographic Imaging

Noninvasive imaging of cardiac electrical activity during ventricular arrhythmias enables superior diagnosis and treatment. A New View of the Beating Heart Just as a tree’s shadow is an oversimplification of branches and foliage, the electrocardiogram, a decades-old tool for measuring the electrical activity of the heart, captures only an approximate view of the heartbeat, distorted by the intervening tissues between the heart and the few electrodes on the skin. This poses a problem when trying to treat heart diseases such as dangerous ventricular arrhythmias, which destabilize the heartbeat and can lead to sudden cardiac death. Now, with a technique called electrocardiographic imaging (ECGI), Wang and colleagues have married multiple electrical recordings from the skin of patients who have ventricular tachycardia (VT) with detailed computerized axial tomography (CAT) scans of the anatomy of their torso. From these data, the authors can back calculate what is happening, electrically speaking, on the surface of the misbehaving hearts, yielding an individual portrait of that patient’s beating heart so that treatment can be more effectively deployed. Twenty-five patients with VT were scheduled to undergo electrical mapping of their hearts and then ablation of heart tissue to correct the electrical defect with an invasive catheter. The authors augmented this standard treatment by creating an image of their beating hearts with noninvasive ECGI, before the standard procedure. The ECGI and standard procedure identified the same origination point of the tachycardia in almost all of the patients, and ECGI was able to correctly categorize both focal and reentrant mechanisms of VT. The time resolution of ECGI enabled the authors to follow the response of the heart to different patterns of stimulation (or pacing), revealing presystolic activation near the site of origin. They could see variable beat-to-beat conduction patterns and showed that the abnormal conduction patterns often began in regions of scar tissue, relics of previous heart attacks. ECGI yields information comparable to the current procedure for mapping abnormal heart activity with a catheter-fed electrode, repeatedly placed on the heart surface. But it has significant advantages over the current approach: The spatial resolution of the ventricular arrhythmia on the heart surface is high, and it takes into account patient-to-patient variability in body size and shape. Further, it is noninvasive and can map single heartbeats, allowing unprecedented visualization of the anatomy of the electrical activation and beat-to-beat variability. These advantages should enable more effective diagnosis of VT and more appropriate drug or ablation therapy, which can now be directed to the specific characteristics of the patient’s heart instead of a simplified shadow. The rapid heartbeat of ventricular tachycardia (VT) can lead to sudden cardiac death and is a major health issue worldwide. Efforts to identify patients at risk, determine mechanisms of VT, and effectively prevent and treat VT through a mechanism-based approach would all be facilitated by continuous, noninvasive imaging of the arrhythmia over the entire heart. Here, we present noninvasive real-time images of human ventricular arrhythmias using electrocardiographic imaging (ECGI). Our results reveal diverse activation patterns, mechanisms, and sites of initiation of human VT. The spatial resolution of ECGI is superior to that of the routinely used 12-lead electrocardiogram, which provides only global information, and ECGI has distinct advantages over the currently used method of mapping with invasive catheter-applied electrodes. The spatial resolution of this method and its ability to image electrical activation sequences over the entire ventricular surfaces in a single heartbeat allowed us to determine VT initiation sites and continuation pathways, as well as VT relationships to ventricular substrates, including anatomical scars and abnormal electrophysiological substrate. Thus, ECGI can map the VT activation sequence and identify the location and depth of VT origin in individual patients, allowing personalized treatment of patients with ventricular arrhythmias.

Poor prognosis for patients with chronic kidney disease despite ICD therapy for the primary prevention of sudden death.

Introduction: Chronic kidney disease (CKD) has been independently associated with increased cardiovascular mortality. Little is known about the benefit of implantable cardioverter defibrillator (ICD) therapy for prevention of sudden death in this large, high‐risk population. We sought to evaluate the impact of CKD on survival in patients who received an ICD for primary prevention of sudden death.

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.

Short and long-term outcomes of percutaneous left atrial appendage suture ligation: Results from a US multicenter evaluation

BACKGROUND Published studies of epicardial ligation of left atrial appendage (LAA) have reported discordant results. OBJECTIVE The purpose of this study was to delineate the safety and efficacy of LAA closure with the LARIAT device. METHODS This is a multicenter registry of 712 consecutive patients undergoing LAA ligation with LARIAT at 18 US hospitals. The primary end point was successful suture deployment, no leak by intraprocedural transesophageal echocardiography (TEE), and no major complication (death, stroke, cardiac perforation, and bleeding requiring transfusion) at discharge. A leak of 2-5 mm on follow-up TEE was the secondary end point. RESULTS LARIAT was successfully deployed in 682 patients (95.5%). A complete closure was achieved in 669 patients (98%), while 13 patients (1.8%) had a trace leak (<2 mm). There was 1 death related to the procedure. Ten patients (1.44%) had cardiac perforation necessitating open heart surgery, while another 14 (2.01%) did not need surgery. The risk of cardiac perforation decreased significantly after the introduction of a micropuncture (MP) needle for pericardial access. Delayed complications (pericarditis requiring >2 weeks of treatment with nonsteroidal anti-inflammatory drugs/colchicine and pericardial and pleural effusion after discharge) occurred in 34 (4.78%) patients, and the risk decreased significantly with the periprocedural use of colchicine. Follow-up TEE (n = 480) showed a leak of 2-5 mm in 6.5% and a thrombus in 2.5%. One patient had a leak of >5 mm. CONCLUSION LARIAT effectively closes the LAA and has acceptable procedural risks with the evolution of the use of the micropuncture needle for pericardial access and the use of colchicine for mitigating the postinflammatory response associated with LAA ligation and pericardial access.

The Electrophysiological Cardiac Ventricular Substrate in Patients After Myocardial Infarction: Noninvasive Characterization With Electrocardiographic Imaging

OBJECTIVES The aim of this study was to noninvasively image the electrophysiological (EP) substrate of human ventricles after myocardial infarction and define its characteristics. BACKGROUND Ventricular infarct border zone is characterized by abnormal cellular electrophysiology and altered structural architecture and is a key contributor to arrhythmogenesis. The ability to noninvasively image its electrical characteristics could contribute to understanding of mechanisms and to risk-stratification for ventricular arrhythmia. METHODS Electrocardiographic imaging, a noninvasive functional EP imaging modality, was performed during sinus rhythm (SR) in 24 subjects with infarct-related myocardial scar. The abnormal EP substrate on the epicardial aspect of the scar was identified, and its location, size, and morphology were compared with the anatomic scar imaged by other noninvasive modalities. RESULTS Electrocardiographic imaging constructs epicardial electrograms that have characteristics of reduced amplitude (low voltage) and fractionation. Electrocardiographic imaging colocalizes the epicardial electrical scar to the anatomic scar with a high degree of accuracy (sensitivity 89%, specificity 85%). In nearly all subjects, SR activation patterns were affected by the presence of myocardial scar. Late potentials could be identified and were almost always within ventricular scar. CONCLUSIONS Electrocardiographic imaging accurately identifies areas of anatomic scar and complements standard anatomic imaging by providing scar-related EP characteristics of low voltages, altered SR activation, electrogram fragmentation, and presence of late potentials.

Predictors and Risk of Pacemaker Implantation After the Cox-Maze IV Procedure

BACKGROUND The incidence of and causes for permanent pacemaker implantation (PPM) after surgical arrhythmia procedures remain poorly understood because of the varied lesion patterns and energy sources reported in small series. This study characterized the incidence, indications, and risk factors for PPM after the Cox-maze IV (CMIV) procedure when performed as either a lone or a concomitant procedure. METHODS A retrospective analysis of 340 patients undergoing a CMIV as either a lone (n = 112) or a concomitant (n = 228) procedure was conducted. The incidence, indication, and variables associated with PPM implantation within 1 year of the operation were assessed. Follow-up was conducted at 30 days and 1 year and was 90% complete. RESULTS The incidence of PPM after a lone CMIV procedure was 5%. Patients with concomitant cardiac operations had a nonsignificant increase in PPM insertion at 30 days (11% vs 5%, p = 0.14) and 1 year (15% vs 6%, p = 0.06) when compared with lone CMIV patients. Of patients who required pacemakers, sinus node dysfunction was present in 79% (35/44) of patients in the entire series and in 88% (8/9) after lone CMIV. After PPM, 84% (37/44) of patients remained paced at last follow-up. Multivariate analysis identified age (odds ratio = 1.10 [1.06-1.14], p < 0.001) as the only variable associated with higher risk of a PPM after any CMIV procedure. CONCLUSIONS The risk of PPM implantation after a lone CMIV is 5% and increases with age. The need for a PPM after a CMIV is largely due to SA node dysfunction, which appears unlikely to recover. These data should help physicians counsel patients regarding the perioperative risks associated with the CMIV.

Methodology Considerations in Phase Mapping of Human Cardiac Arrhythmias.

Background—Phase analysis of cardiac arrhythmias, particularly atrial fibrillation, has gained interest because of the ability to detect organized stable drivers (rotors) and target them for therapy. However, the lack of methodology details in publications on the topic has resulted in ongoing debate over the phase mapping technique. By comparing phase maps and activation maps, we examined advantages and limitations of phase mapping. Methods and Results—Seven subjects were enrolled. We generated phase maps and activation maps from electrocardiographic imaging–reconstructed epicardial unipolar electrograms. For ventricular signals, phase was computed with (1) pseudoempirical mode decomposition detrending and (2) a novel Moving Average (MVG) detrending approach. For atrial fibrillation signals, MVG was modified to incorporate dynamic cycle length (DCL) changes (MVG-DCL). Phase maps were visually analyzed to study phase singularity points and rotors. Results show that phase is sensitive to cycle length choice, a limitation that was addressed by the MVG-DCL algorithm. MVG-DCL was optimal for atrial fibrillation analysis. Phase maps helped to highlight high-curvature wavefronts and rotors. However, for some activation patterns, phase generated nonrotational singularity points and false rotors. Conclusions—Phase mapping computes singularity points and visually highlights rotors. As such, it can help to provide a clearer picture of the spatiotemporal activation characteristics during atrial fibrillation. However, it is advisable to incorporate electrogram characteristics and the time-domain activation sequence in the analysis, to prevent misinterpretation and false rotor detection. Therefore, for mapping complex arrhythmias, a combined time-domain activation and phase mapping with variable cycle length seems to be the most reliable method.

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.)

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).