Ramya Vijayakumar

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.

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.

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.

Electrophysiologic Substrate in Congenital Long QT Syndrome Noninvasive Mapping With Electrocardiographic Imaging (ECGI)

Background— Congenital Long QT syndrome (LQTS) is an arrhythmogenic disorder that causes syncope and sudden death. Although its genetic basis has become well-understood, the mechanisms whereby mutations translate to arrhythmia susceptibility in the in situ human heart have not been fully defined. We used noninvasive ECG imaging to map the cardiac electrophysiological substrate and examine whether LQTS patients display regional heterogeneities in repolarization, a substrate that promotes arrhythmogenesis. Methods and Results— Twenty-five subjects (9 LQT1, 9 LQT2, 5 LQT3, and 2 LQT5) with genotype and phenotype positive LQTS underwent ECG imaging. Seven normal subjects provided control. Epicardial maps of activation, recovery times, activation-recovery intervals, and repolarization dispersion were constructed. Activation was normal in all patients. However, recovery times and activation–recovery intervals were prolonged relative to control, indicating delayed repolarization and abnormally long action potential duration (312±30 ms versus 235±21 ms in control). Activation–recovery interval prolongation was spatially heterogeneous, with repolarization gradients much steeper than control (119±19 ms/cm versus 2.0±2.0 ms/cm). There was variability in steepness and distribution of repolarization gradients between and within LQTS types. Repolarization gradients were steeper in symptomatic patients (130±27 ms/cm in 12 symptomatic patients versus 98±19 ms/cm in 13 asymptomatic patients; P <0.05). Conclusions— LQTS patients display regions with steep repolarization dispersion caused by localized action potential duration prolongation. This defines a substrate for reentrant arrhythmias, not detectable by surface ECG. Steeper dispersion in symptomatic patients suggests a possible role for ECG imaging in risk stratification. # CLINICAL PERSPECTIVE {#article-title-34}Background— Congenital Long QT syndrome (LQTS) is an arrhythmogenic disorder that causes syncope and sudden death. Although its genetic basis has become well-understood, the mechanisms whereby mutations translate to arrhythmia susceptibility in the in situ human heart have not been fully defined. We used noninvasive ECG imaging to map the cardiac electrophysiological substrate and examine whether LQTS patients display regional heterogeneities in repolarization, a substrate that promotes arrhythmogenesis. Methods and Results— Twenty-five subjects (9 LQT1, 9 LQT2, 5 LQT3, and 2 LQT5) with genotype and phenotype positive LQTS underwent ECG imaging. Seven normal subjects provided control. Epicardial maps of activation, recovery times, activation-recovery intervals, and repolarization dispersion were constructed. Activation was normal in all patients. However, recovery times and activation–recovery intervals were prolonged relative to control, indicating delayed repolarization and abnormally long action potential duration (312±30 ms versus 235±21 ms in control). Activation–recovery interval prolongation was spatially heterogeneous, with repolarization gradients much steeper than control (119±19 ms/cm versus 2.0±2.0 ms/cm). There was variability in steepness and distribution of repolarization gradients between and within LQTS types. Repolarization gradients were steeper in symptomatic patients (130±27 ms/cm in 12 symptomatic patients versus 98±19 ms/cm in 13 asymptomatic patients; P<0.05). Conclusions— LQTS patients display regions with steep repolarization dispersion caused by localized action potential duration prolongation. This defines a substrate for reentrant arrhythmias, not detectable by surface ECG. Steeper dispersion in symptomatic patients suggests a possible role for ECG imaging in risk stratification.

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 real-time mapping of an incomplete pulmonary vein isolation using electrocardiographic imaging

Establishing entrance and exit block from pulmonary veins is an endpoint for pulmonary vein isolation (PVI) procedures (1). Reestablished pulmonary vein connection is a common cause of atrial fibrillation (AF) recurrence in patients who have previously undergone PVI. Here we provide images from a noninvasive cardiac electrophysiology imaging system (ECGI) performed during PVI. The ECGI procedure has been described previously (2) (3). 250 carbon electrodes were applied to the patient’s torso before a pre-procedural contrast-enhanced CT scan, which provided torso-electrode positions and atrial geometry in the same reference frame. The electrodes were removed, then replaced on the day of the PVI procedure in the same configuration, and remained on the patient throughout the procedure. ECGI performed during the procedure noninvasively generated epicardial isochrone activation maps. After circumferential ablation around the antrum of the right pulmonary veins, a lasso catheter in the right inferior pulmonary vein (RIPV) demonstrated entrance block. However, high-output pacing from within the RIPV captured the atrium, revealing incomplete exit block. Panel A displays the real-time ECGI isochrone map during RIPV pacing, showing earliest activation in the superior-posterior antrum of the RIPV (red is earliest), with radial spread across the posterior LA. A 60-ms delay is seen from the pacing breakthrough (red) to posterior LA (green) activation, consistent with incomplete line of block created by the ablation. The invasive electroanatomic map (Panel B) shows the final ablation lesion set and the additional ablation necessary for exit block from the RIPV (pink marker). This location on the invasive electroanatomic map corresponds closely to the exit site determined by ECGI in Panel A. Panel C shows an ECGI isochrone map during high-output pacing from within the RIPV after the complete ablation. Pacing failed to capture the atrium, and the earliest LA activation in sinus rhythm was near Bachmann’s bundle (red). Posterior LA activation is limited superiorly and inferiorly with lines of block (white dotted lines) corresponding to the ablation lines on the LA roof and posterior wall seen in panel B. Three PV’s also demonstrate electrical isolation (blue). Although the RSPV in Panel C appears to have electrical connection in sinus rhythm, the appearance of activation is due to far-field signal from the posterior right atrium in close proximity. Invasive testing of the RSPV demonstrated entrance and exit block. Rigorous prospective study is needed, but if real-time ECGI can accurately identify areas of incomplete PVI isolation, it may shorten procedure time and improve long-term success rates by pinpointing sites of incomplete linear ablation.

The Electrophysiologic Cardiac Ventricular Substrate in Patients after Myocardial Infarction: Noninvasive Characterization with ECG Imaging (ECGI)

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.

Electrophysiologic Substrate in Congenital Long QT SyndromeCLINICAL PERSPECTIVE

Background— Congenital Long QT syndrome (LQTS) is an arrhythmogenic disorder that causes syncope and sudden death. Although its genetic basis has become well-understood, the mechanisms whereby mutations translate to arrhythmia susceptibility in the in situ human heart have not been fully defined. We used noninvasive ECG imaging to map the cardiac electrophysiological substrate and examine whether LQTS patients display regional heterogeneities in repolarization, a substrate that promotes arrhythmogenesis. Methods and Results— Twenty-five subjects (9 LQT1, 9 LQT2, 5 LQT3, and 2 LQT5) with genotype and phenotype positive LQTS underwent ECG imaging. Seven normal subjects provided control. Epicardial maps of activation, recovery times, activation-recovery intervals, and repolarization dispersion were constructed. Activation was normal in all patients. However, recovery times and activation–recovery intervals were prolonged relative to control, indicating delayed repolarization and abnormally long action potential duration (312±30 ms versus 235±21 ms in control). Activation–recovery interval prolongation was spatially heterogeneous, with repolarization gradients much steeper than control (119±19 ms/cm versus 2.0±2.0 ms/cm). There was variability in steepness and distribution of repolarization gradients between and within LQTS types. Repolarization gradients were steeper in symptomatic patients (130±27 ms/cm in 12 symptomatic patients versus 98±19 ms/cm in 13 asymptomatic patients; P <0.05). Conclusions— LQTS patients display regions with steep repolarization dispersion caused by localized action potential duration prolongation. This defines a substrate for reentrant arrhythmias, not detectable by surface ECG. Steeper dispersion in symptomatic patients suggests a possible role for ECG imaging in risk stratification. # CLINICAL PERSPECTIVE {#article-title-34}Background— Congenital Long QT syndrome (LQTS) is an arrhythmogenic disorder that causes syncope and sudden death. Although its genetic basis has become well-understood, the mechanisms whereby mutations translate to arrhythmia susceptibility in the in situ human heart have not been fully defined. We used noninvasive ECG imaging to map the cardiac electrophysiological substrate and examine whether LQTS patients display regional heterogeneities in repolarization, a substrate that promotes arrhythmogenesis. Methods and Results— Twenty-five subjects (9 LQT1, 9 LQT2, 5 LQT3, and 2 LQT5) with genotype and phenotype positive LQTS underwent ECG imaging. Seven normal subjects provided control. Epicardial maps of activation, recovery times, activation-recovery intervals, and repolarization dispersion were constructed. Activation was normal in all patients. However, recovery times and activation–recovery intervals were prolonged relative to control, indicating delayed repolarization and abnormally long action potential duration (312±30 ms versus 235±21 ms in control). Activation–recovery interval prolongation was spatially heterogeneous, with repolarization gradients much steeper than control (119±19 ms/cm versus 2.0±2.0 ms/cm). There was variability in steepness and distribution of repolarization gradients between and within LQTS types. Repolarization gradients were steeper in symptomatic patients (130±27 ms/cm in 12 symptomatic patients versus 98±19 ms/cm in 13 asymptomatic patients; P<0.05). Conclusions— LQTS patients display regions with steep repolarization dispersion caused by localized action potential duration prolongation. This defines a substrate for reentrant arrhythmias, not detectable by surface ECG. Steeper dispersion in symptomatic patients suggests a possible role for ECG imaging in risk stratification.

Electrophysiologic Substrate in Congenital Long QT SyndromeCLINICAL PERSPECTIVE: Noninvasive Mapping With Electrocardiographic Imaging (ECGI)

Background— Congenital Long QT syndrome (LQTS) is an arrhythmogenic disorder that causes syncope and sudden death. Although its genetic basis has become well-understood, the mechanisms whereby mutations translate to arrhythmia susceptibility in the in situ human heart have not been fully defined. We used noninvasive ECG imaging to map the cardiac electrophysiological substrate and examine whether LQTS patients display regional heterogeneities in repolarization, a substrate that promotes arrhythmogenesis. Methods and Results— Twenty-five subjects (9 LQT1, 9 LQT2, 5 LQT3, and 2 LQT5) with genotype and phenotype positive LQTS underwent ECG imaging. Seven normal subjects provided control. Epicardial maps of activation, recovery times, activation-recovery intervals, and repolarization dispersion were constructed. Activation was normal in all patients. However, recovery times and activation–recovery intervals were prolonged relative to control, indicating delayed repolarization and abnormally long action potential duration (312±30 ms versus 235±21 ms in control). Activation–recovery interval prolongation was spatially heterogeneous, with repolarization gradients much steeper than control (119±19 ms/cm versus 2.0±2.0 ms/cm). There was variability in steepness and distribution of repolarization gradients between and within LQTS types. Repolarization gradients were steeper in symptomatic patients (130±27 ms/cm in 12 symptomatic patients versus 98±19 ms/cm in 13 asymptomatic patients; P <0.05). Conclusions— LQTS patients display regions with steep repolarization dispersion caused by localized action potential duration prolongation. This defines a substrate for reentrant arrhythmias, not detectable by surface ECG. Steeper dispersion in symptomatic patients suggests a possible role for ECG imaging in risk stratification. # CLINICAL PERSPECTIVE {#article-title-34}Background— Congenital Long QT syndrome (LQTS) is an arrhythmogenic disorder that causes syncope and sudden death. Although its genetic basis has become well-understood, the mechanisms whereby mutations translate to arrhythmia susceptibility in the in situ human heart have not been fully defined. We used noninvasive ECG imaging to map the cardiac electrophysiological substrate and examine whether LQTS patients display regional heterogeneities in repolarization, a substrate that promotes arrhythmogenesis. Methods and Results— Twenty-five subjects (9 LQT1, 9 LQT2, 5 LQT3, and 2 LQT5) with genotype and phenotype positive LQTS underwent ECG imaging. Seven normal subjects provided control. Epicardial maps of activation, recovery times, activation-recovery intervals, and repolarization dispersion were constructed. Activation was normal in all patients. However, recovery times and activation–recovery intervals were prolonged relative to control, indicating delayed repolarization and abnormally long action potential duration (312±30 ms versus 235±21 ms in control). Activation–recovery interval prolongation was spatially heterogeneous, with repolarization gradients much steeper than control (119±19 ms/cm versus 2.0±2.0 ms/cm). There was variability in steepness and distribution of repolarization gradients between and within LQTS types. Repolarization gradients were steeper in symptomatic patients (130±27 ms/cm in 12 symptomatic patients versus 98±19 ms/cm in 13 asymptomatic patients; P<0.05). Conclusions— LQTS patients display regions with steep repolarization dispersion caused by localized action potential duration prolongation. This defines a substrate for reentrant arrhythmias, not detectable by surface ECG. Steeper dispersion in symptomatic patients suggests a possible role for ECG imaging in risk stratification.

The Electrophysiological Cardiac Ventricular Substrate in Patients After Myocardial Infarction

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.