Research ArticleCardiovascular Disease

Noninvasive Electroanatomic Mapping of Human Ventricular Arrhythmias with Electrocardiographic Imaging

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Science Translational Medicine  31 Aug 2011:
Vol. 3, Issue 98, pp. 98ra84
DOI: 10.1126/scitranslmed.3002152

Abstract

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.

Introduction

Ventricular arrhythmias in the heart are a major cause of death and disability. In the past several decades, implantable and wearable defibrillator technologies have been developed to terminate ventricular tachycardia (VT), a life-threatening regular and repetitive fast heart rhythm, and ventricular fibrillation (VF), an irregular fast heart rhythm that is even more lethal (13). In addition, anti-arrhythmic drugs have been developed to prevent VT, but these have had limited success. Invasive procedures to modify the arrhythmic ventricular tissue to prevent VT have also been used, beginning with cardiac surgery to resect areas of scar (46). More recently, substrate modification has been achieved with radio-frequency ablation delivered at the tip of a steerable catheter inserted into the heart through a blood vessel (710). Nevertheless, invasive catheter mapping and ablation of the arrhythmic substrate is not a widely available procedure, and successful long-term outcomes from the procedure have been modest. Sudden death from ventricular arrhythmias remains a leading cause of death worldwide. Reasons for this include inability of current diagnostic tools to accurately identify patients at risk for sudden death, the limitations of invasive techniques for intracardiac mapping of cardiac electrical activation during arrhythmia, and incomplete knowledge about how and why VT and VF occur in a particular patient at a particular point in time.

Current routine noninvasive detection and diagnosis of the cardiac electrical activity is performed with a 12-lead electrocardiogram (ECG), a widely used test that is part of routine medical care. However, this century-old technology measures the reflection of cardiac electrical activity on the surface of the body, not on the heart itself. Therefore, it has limited spatial resolution for determining regional cardiac electrical activity and limited ability to locate regions of arrhythmic activity in the heart. These limitations are highlighted when the ECG is compared to currently available cardiac imaging tools, such as echocardiography, computed tomography (CT), and magnetic resonance imaging (MRI). A similar noninvasive method that provides high spatial resolution maps of abnormal electrical activity on the heart surface (rather than on the body surface) could contribute greatly to our understanding of the mechanisms of ventricular arrhythmias and to the diagnosis and treatment of cardiac rhythm disorders in patients. It could also help to identify patients at risk of sudden cardiac death and to develop mechanism-based therapy and guide patient-specific treatments. Here, we present such a noninvasive imaging method [electrocardiographic imaging (ECGI)] for electroanatomic mapping of cardiac electrical activation, as applied in a series of 25 patients undergoing catheter ablation procedures for various forms of VT.

Results

ECGI (Fig. 1) combines body surface electrical potentials and heart-torso anatomical geometry to noninvasively determine the local electrical signals of the heart (electrograms) over the entire surface of both the left and the right ventricles (1113). Using the relative timing of the constructed electrograms, activation sequences (isochrones) can be constructed in color-coded maps, and the propagation of activation wavefronts can be depicted in animated movies. ECGI images are constructed continuously and do not require the accumulation of data from multiple beats.

Fig. 1

ECGI methodology. Two hundred and fifty carbon electrodes mounted in strips are applied to the patient’s torso before a pre-procedural thoracic CT scan, which provides cardiac geometry and torso-electrode positions in the same reference frame. The electrodes are connected to a multichannel mapping system. The electrical and anatomical data are processed mathematically to obtain noninvasive ECGI epicardial images that include potential maps, electrograms, isochronal activation sequences, and repolarization patterns. An ECGI movie of normal epicardial activation is provided in the Supplementary Material as reference (control) for the VT data (movie S1).

Twenty-five patients were referred for evaluation of symptomatic VT or premature ventricular contractions (PVCs). One patient underwent two different studies several months apart, for a total of 26 ECGIs performed. This group of patients participated in a total of 23 catheter-based electrophysiology studies (EPSs) in which we planned to initiate the ventricular arrhythmia, map its origin and circuit (if possible), and ablate the necessary tissue to render the arrhythmia noninducible. We performed noninvasive ECGI before the invasive EPS in those patients who demonstrated spontaneous abnormal ventricular rhythms (18 patients, 19 studies). ECGI was performed during the EPS in other patients (four patients). Nine patients were imaged during sustained VT; the remaining patients were imaged during PVCs.

Patients were identified on the basis of their VT localization: RVX for patient X with right ventricular (RV) localization, and LVX for patient X with left ventricular (LV) localization. Pertinent medical records are summarized in Table 1. The mean age for the cohort was 54 years (range, 21 to 81 years). Results of the corresponding EPS, including 12-lead ECG morphology, cycle length, and information regarding induction, testing, and ablation of the tachycardia, are detailed in the Supplementary Material (compiled in table S2).

Table 1

Patient population. Patients are identified on the basis of VT localization: RVX for patient X with right ventricular localization, and LVX for patient X with left ventricular localization. PVC, premature ventricular complex; VT, ventricular tachycardia.

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We used ECGI to characterize each tachycardia on the basis of analysis of the isochrone (color-coded map depicting the location of the activation wavefront over time), potential, local electrogram, and wavefront propagation information. A three-step process, created from previously validated findings (1113), was used for each patient: (i) localize the site of origin (SOO) of the arrhythmia from isochrone and potential maps; (ii) evaluate the mechanism by observing the three-dimensional propagation pattern and its relationship to the myocardial substrate; and (iii) approximate the myocardial depth of the origin with local electrograms (pure Q wave for epicardial origin, rS complex for intramural or endocardial origin). Representative examples of specific instances of cardiac physiology are shown in the text. Detailed maps of ventricular arrhythmias for all ECGI studies are shown in the Supplementary Material, comprising a collection of noninvasively mapped human VTs (figs. S2 to S27). Movies of electrical activation are provided for a subset of representative cases (movies S2 to S13). The Supplementary Material also includes a map and movie of a normal ventricular activation pattern for reference (fig. S1 and movie S1).

Location of VT initiation

On the basis of the invasive EPS, 11 patients had an SOO in the RV, including 9 patients in which the SOO was in the RV outflow tract. Twelve patients had an SOO in the LV. When we compared the results from ECGI to those from invasive EPS (Table 2), ECGI correctly identified the LV or RV SOO 100% of the time (23 of 23). When we compared the specific locations within each ventricle, noninvasive ECGI SOO was in agreement with invasive EPS SOO in 10 of 11 RV sites (91%) and in 11 of 12 LV sites (92%). Examples of ECGI localization can be found in Fig. 2.

Table 2

Comparison of noninvasive ECGI with invasive EP study. Patients are identified on the basis of VT localization: RVX for patient X with right ventricular localization, and LVX for patient X with left ventricular localization. Discrepancies between ECGI and EPS are in bold. Because of the thin tissue in the outflow tract, patients with outflow tract SOO were excluded from myocardial depth analysis. Arrhythmias starting from a focal origin and spreading radially in the ECGI activation map are classified as “radial,” because ECGI cannot differentiate between focal mechanism and micro-reentry. LV, left ventricle; RV, right ventricle; RVOT, right ventricular outflow tract; N/A, not available.

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Fig. 2

Examples of noninvasive ECGI isochrone maps for localization of VT site of origin. Epicardial isochrone maps are shown for four patients, with earliest epicardial activation marked with an asterisk (see Supplementary Material for detailed description of activation sequences). EP study–determined sites of origin are indicated under the ECGI maps. Yellow arrows point to VT origin on a representative CT scan. RA, right atrium; LA, left atrium; AO, aorta; LAD, left anterior descending coronary artery; LV, left ventricle; RVOT, right ventricular outflow tract.

For the two patients with discrepancies between invasive EPS and noninvasive ECGI (patients RV10 and LV11), the discrepant locations were in proximity to each other. For patient RV10, ECGI imaged the right posterolateral base as the SOO, whereas EPS suggested the right posteroseptal base as the SOO. This patient had undergone previous ablations of a right posteroseptal accessory pathway and a right atriofascicular pathway in the posterolateral base. We suspect that the previous ablations in these locations may have played a role in the differences between ECGI and EPS. For patient LV11, ECGI imaged the mid-anterior LV as the SOO, whereas EPS suggested a more apical LV location as the SOO. This patient had a large LV apical aneurysm and had several different VT morphologies. It is possible that ECGI and EPS imaged two different VTs.

Mechanisms of VT

During the invasive EPS, the arrhythmia mechanism can be characterized on the basis of the heart’s response to ventricular pacing at a faster rate than the tachycardia and resetting of the VT, a process known as entrainment. On the basis of invasive EPS, 18 patients were found to have focal VT (activation starting from a focal site and inability to reproducibly entrain the tachycardia with ventricular pacing), whereas 5 patients had a reentrant mechanism (activation forming a rotational wave comprising nearly all of the tachycardia cycle length and successful entrainment of the tachycardia with stable return cycle lengths after cessation of pacing). For the patients with focal VTs, noninvasive ECGI activation maps uniformly showed a radial activation pattern from the SOO (18 of 18). In all the patients with a reentrant mechanism, noninvasive ECGI showed a rotational wavefront with a high degree of curvature (five of five), with the wavefront returning to the initiation site. Examples of these two distinct propagation patterns are shown in Fig. 3. Detailed descriptions and selected movies of activation are in the Supplementary Material. It should be emphasized that the five reentrant VTs imaged by ECGI involved a macro-reentry circuit (a long, looping path of continuous electrical activation). It is not known whether ECGI can differentiate mechanistically between micro-reentry and focal activation.

Fig. 3

ECGI imaged propagation patterns, origins, and local electrograms for VT. Isochrone maps for six patients, with earliest epicardial activation marked with an asterisk (see Supplementary Material for detailed descriptions of activation sequences). (Top) Focal propagation patterns. Tachycardias that were determined to be focal during EP studies demonstrate a radial spread (white arrows) away from the early activation point (asterisk). Yellow arrows indicate later phases of ventricular activation. (Bottom) Reentrant propagation patterns. Tachycardias that were determined to be reentrant during EP studies show a rotational activation pattern (white arrows). Thick black lines indicate conduction block. Purple arrows indicate later phases of ventricular activation. (Insets) Several epicardial electrograms from sites of earliest activation are shown in blue, highlighting the presence or absence of r wave. Pure Q morphology indicates epicardial origin; rS morphology indicates intramural origin. Description under each image indicates the location of VT initiation and identifies the displayed view of the heart. LAO, left anterior oblique.

The use of ECGI during induction of VT by programmed stimulation in the EP lab allowed us to visualize arrhythmogenesis in a closed-chest human heart. An example is Fig. 4, in which programmed ventricular stimulation initiated sustained VT. Figure 4A shows baseline pacing (cycle length = 600 ms) from a catheter placed in the RV apex, marked with +. A line of conduction block through which the wavefront cannot directly pass is seen in the lateral LV (thick black line). Figure 4B shows premature pacing (S1 − S2 = 280 ms) from the same location, which resulted in functional extension of the line of block. Figure 4C demonstrates the first beat of induced VT, marked with *, which originated from the last area that was activated by the premature paced beat in Fig. 4B, suggesting triggered activity as the mechanism (14). The delayed activation of this region by premature pacing promotes recovery and capture of adjacent myocardium by the first beat of VT excitation. In this case, during the invasive EPS, the VT had variable responses to pacing entrainment maneuvers, which is more characteristic of focal triggered activity than reentrant mechanism.

Fig. 4

Example ECGI of focal VT induced by programmed electrical stimulation (patient LV1). (A) Epicardial activation sequence during drive train (S1) pacing at a cycle length (CL) of 600 ms. RAO, right anterior oblique. White arrows show direction of wavefront propagation. Thick black line indicates conduction block. Earliest epicardial activation site is marked by + and corresponds to the underlying endocardial pacing site. ECGI epicardial electrogram from this site is shown at the left (blue), with rS complex consistent with endocardial activation. (Right) Twelve-lead surface ECG during VT. (B) Premature (S2) pacing at 280-ms coupling interval from the same pacing site. The major wavefront is forced to pivot around the extended line of conduction block. There is some fusion with an intramural transseptal front (small white arrow). (Right) Recording from a single-lead ECG. All S1 beats (blue) are similar, as are the two S2 beats (black) and all the VT beats (red). (C) VT. The earliest epicardial activation site is marked by an asterisk. ECGI electrogram from the VT origin site is shown (blue), with a pure Q wave, indicative of epicardial origin. (Right) Invasive LV endocardial activation map (CARTO) of the VT in the left anterior oblique projection (red is early). ECGI epicardial activation movies are in the Supplementary Material (movie S5).

In addition to VT initiation, ECGI provided images of VT maintenance. As shown in the activation movies S5 and S6, local presystolic activation was often imaged 5 to 10 ms before the subsequent beats of both reentry and focal VT. The presystolic activation was always near the SOO of the VT and was often consistent from beat to beat. This finding was apparent on ECGI of patients with VT of both epicardial origin (1:02 and 1:13 in movie S5) and endocardial origin (0:14, 0:27, and 0:50 in movie S6).

For all five patients with reentrant VT, the VT activation pattern was related to areas of ventricular scar, as shown in the example of Fig. 5. Figure 5B shows ECGI during VT, where the earliest activation is in the inferior basal septum (red). The wavefront initially exits this area at the start of the VT beat and completes the beat by reentering this area (arrows). Local presystolic activation was imaged at the scar border immediately before each VT beat, indicating exit sites of slowly propagating wavefronts through the scar (see movie S6). Figure 5C (left) shows results from the clinical nuclear myocardial perfusion images [single-photon emission computed tomography (SPECT)]. For this study, technetium-99m was administered intravenously and was incorporated into living cardiac myocytes. Imaging the absence of this isotope in regions of the heart allowed identification of scar tissue, most often a result of a myocardial infarction. In Fig. 5C (left), the area of the scar from a previous infarction is located in the inferior septum (dark blue). Invasive catheter mapping (Fig. 5C, right) during tachycardia confirmed the origin of VT in the inferior septum. Pacing entrainment maneuvers confirmed a reentrant mechanism, and radio-frequency ablation, applied through the tip of a catheter in this region (red marks), terminated the tachycardia.

Fig. 5

Example ECGI of reentrant VT from inferobasal scar (patient LV2). (A) Four views of activation sequence during a sinus capture (SC) beat (blue on the V2 ECG). Arrows indicate direction of the activation wavefronts. (B) Activation sequence during VT beats (red on the V2 ECG). White arrows indicate a clockwise lateral loop (left lateral and left anterior oblique inferior views); purple arrows show propagation into the RV in a counterclockwise fashion. (C) (Left) SPECT images showing a scar at the inferobasal LV region (blue). (Right) Limited invasive endocardial map of VT activation (red, early; blue, late). ECGI epicardial activation movies, including early activation of a region near the inferior scar border, are in the Supplementary Material (movie S6). (Right column) (Top) Twelve-lead surface ECG during VT. (Lower) Ablation catheter signals. The earliest electrogram signal is seen at the inferoseptal border zone, 50 ms before the onset of the surface QRS. ABL d, bipolar electrogram at the distal ablation catheter; HIS, AV junction/His bundle; CS, coronary sinus; RVa d, right ventricular apex.

Although monomorphic VT is thought to arise from a single location, localized beat-to-beat changes in the ventricular activation pattern can be seen with ECGI. This may be a result of different exit points from a ventricular scar (Fig. 6) or functional changes related to ventricular excitation and recovery properties, as shown in movie S9. Figure 6 shows ECGI during a monomorphic VT from an infiltrative cardiomyopathy in the lateral LV. Figure 6A shows activation patterns for three consecutive VT beats (T1, T2, and T3) in three views. ECGI identified two distinct areas of early epicardial activation (white asterisks), which differed slightly from beat to beat. The propagation pattern varied depending on the relative contribution of the two sources, but for all beats, the wavefront turned clockwise and propagated toward the LV lateral base with a high degree of curvature, where it reached a line of block in the inferolateral base. ECGI movies of this phenomenon are available online (movie S7). Figure 6B shows a gadolinium-enhanced MRI image, which revealed a patch of myocardial enhancement in the lateral LV (white arrows), consistent with a focal myocarditis or cardiac sarcoid. Figure 6C shows the invasive electroanatomic map created during the presenting VT (Tx). The region of earliest activation is white (black arrows). Figure 6D shows the invasive electroanatomic map created during a different VT (Ty) after initial ablation at the site of earliest activation. The earliest activation site (black arrows) is shifted more apically. Twelve-lead surface ECGs of the two VT morphologies (Tx and Ty) are shown. In this example, noninvasive ECGI was able to accurately identify the spontaneous, dynamic, beat-to-beat transitions of VT activation patterns, which were not easily recognized on the 12-lead ECG. Examples of similar beat-to-beat changes during VT, imaged by ECGI, can be found in the Supplementary Material (figs. S17, S21, and S25 and movies S9 and S12).

Fig. 6

Example of ECGI of reentrant VT in lateral wall infiltrative cardiomyopathy (patient LV3). (A) ECGI isochrone map. Activation patterns for three consecutive VT beats (T1, T2, and T3). ECGI identified two distinct areas of early epicardial activation (white asterisks), which differed from beat to beat. The propagation pattern varied somewhat depending on the relative contribution of the two sources, but for all beats, the wavefront turned clockwise and propagated to the LV lateral base with a high degree of curvature, where it reached a line of block in the inferolateral base. The corresponding movie is available in the Supplementary Material. (B) A gadolinium-enhanced MRI revealed a patch of myocardial enhancement in the lateral LV (white arrows), consistent with a focal myocarditis or cardiac sarcoid. (C) Invasive electroanatomic map created during the presenting VT (arbitrarily named Tx). The region of earliest activation is shown by black arrows. (D) Invasive electroanatomic map created during a different VT (arbitrarily named Ty) after initial ablation at the site of earliest activation. The earliest activation (black arrows) is shifted more apically. (Right) Twelve-lead surface ECGs of two VT morphologies (Tx and Ty). AP, anterior-posterior view; SR1, first sinus rhythm beat after VT.

Myocardial depth

Invasive EPS findings were compared with ECGI for determining epicardial or intramural locations of VT. Because of the thin tissue in the outflow tract, patients with outflow tract SOO were excluded. Of the 13 remaining patients, the invasive EPS determined the SOO to be endocardial in 6, epicardial in 5, and mid-myocardial in 2. All five patients with epicardial SOO had a pure Q wave on the noninvasive ECGI electrogram at the site of earliest activation (100%), indicative of epicardial origin (15). Of the patients with a nonepicardial SOO, the local noninvasive ECGI electrogram at the earliest site demonstrated a small r wave in seven of eight (88%), indicative of an intramural initiation site (15).

Discussion

This paper reports the use of a noninvasive, three-dimensional electroanatomic mapping system, ECGI, in a series of patients undergoing catheter ablation for a broad range of VTs. Our findings reveal a large diversity of human VT with respect to activation patterns, mechanisms, and sites of initiation (shown individually, including movies of dynamic progression, in the Supplementary Material). Over a wide range of VT locations and mechanisms, the noninvasive ECGI results were consistent with those of invasive catheter mapping.

In the clinical setting, ECGI has several advantages. It overcomes the main limitation of the standard body surface 12-lead ECG by providing high spatial resolution maps of ventricular arrhythmias on the heart surface. Where the 12-lead ECG requires interpretation of body surface data in terms of cardiac activity, assuming a “standard” heart shape and size in a “standard” torso, ECGI uses the patient’s specific heart-torso geometry to identify the location of the arrhythmia and map its sequence on the heart. Additionally, ECGI offers distinct advantages over invasive catheter mapping, a technique in which the tip of a catheter is maneuvered inside the heart to hundreds of locations, and information about the continuing arrhythmia is gathered sequentially from each site. ECGI’s advantages include its noninvasive nature and the ability to map the entire tachycardia in a single beat. The spatial resolution and ability to image continuously and simultaneously the activation sequences over the entire ventricular surfaces allowed us to make observations beyond the ability of current tools regarding VT initiation and continuation (Fig. 4) and regarding the relationship of the VT activation wavefront to the ventricular substrate (Figs. 5 and 6), including anatomical scars and abnormal electrophysiological substrate (lines of block, slow conduction). With the single beat, continuous mapping that ECGI provides, we were able to detect beat-to-beat dynamic changes in the origin and sequence of VT (Fig. 6).

The results suggest that ECGI can play a clinically useful role. From a treatment perspective, potential clinical advantages include the ability to assist in guiding the choice of medication on the basis of VT mechanism or pointing to the most effective strategy for catheter ablation. An example illustrates the potential benefit. Currently, when a patient has recurrent VT, especially when it is refractory to anti-arrhythmic medications, an EP mapping study with ablation is offered. An endocardial approach in which an electrode is inserted through veins to map the electrical activity of the heart is almost exclusively used as a first procedure; then, the operator tries to induce the arrhythmia with pacing and intravenous medications. The VT can be mapped accurately only if it is sustained over time. Mapping is a meticulous process in which electrical information is collected from the tip of a roving catheter on a point-by-point basis and that lasts for several hours. Ideally, for obtaining a detailed map of the arrhythmia, the mapping is performed during sustained VT. However, most patients in sustained VT have life-threatening low blood pressure, which does not allow the time for detailed mapping. Additionally, sustained VT can have deleterious cardiovascular effects. If at the end of mapping, or after unsuccessful endocardial ablation (performed by heating the tip of the catheter to eliminate electrical conduction of the diseased tissue), the operator deems the VT to be epicardial in origin, the procedure is halted, and a separate procedure to target the epicardium is scheduled at a later date. In contrast, if ECGI is used, the location and depth of the VT SOO can be determined in a single beat of arrhythmia, either during or before the procedure. The treating physician could then direct the catheter-based ablation procedure toward that area in a more focused and time-efficient manner. It is probable that the alternative ECGI-directed treatment would yield improved patient safety and beneficial treatment outcomes, although this will require evaluation in a randomized clinical trial in a large population of VT patients.

The results presented here provide the basis for noninvasive arrhythmia diagnosis. Technologies such as high-frequency ultrasound (16, 17) and gamma knife radiosurgery (18) are being developed for noninvasive ablation of cardiac tissue, paving the way for completely noninvasive diagnosis and treatment of VTs. The noninvasive nature of ECGI would also allow its use in testing the outcomes of treatment (by ablation or drugs) and examining heart activity changes over time.

There are several limitations to the clinical applicability of ECGI at this time. ECGI is still a research tool, and its limited availability precludes large-scale multicenter clinical studies at present. Further technical developments are needed to facilitate rapid application of the many body surface electrodes in the clinical setting, to automate the data analysis and map generation and display, and to build a user-friendly interface for the clinical operator. The body surface electrodes, placed with high density on the torso surface, often compete for skin area needed to place other clinical monitoring systems during the EP study. Finally, previous ECGI validation studies show accuracy of 4 to 6 mm in determining activation initiation sites. Future algorithm developments may allow for more precise mapping.

The most significant weakness to the current study involves the variable contributions of the endocardium and epicardium to the tachycardia circuits (1922). As demonstrated in open chest mapping, the earliest epicardial activation of VT may not accurately identify the location of an endocardial circuit, although our data show close correlation between invasive endocardial mapping and noninvasive ECGI epicardial imaging. Additionally, because the ECGI-imaged activation sequence uses only the QRS complex for analysis, it does not image continuously during one cycle of tachycardia, known as cycle length. Slow, discontinuous diastolic conduction inside the scar (reflected in early activation detected by ECGI at the scar border zone; see example in movie S6) and intramural activation (ECGI is limited to the epicardium) likely continue during the time that ECGI does not image. Finally, analysis of the ECGI data collected in the EP lab (4 of the 26 cases) was subject to the bias of the investigator knowing the outcome of the EPS.

Materials and Methods

All protocols were approved by the Institutional Review Board at Washington University in St. Louis, and informed consent was obtained from all patients. ECGI methodology was described previously (1113). ECGI has been validated extensively under different physiological and pathological conditions in animal models (13, 15, 2326) and in human studies (11, 12, 2742). Two hundred and fifty-six carbon electrodes on strips were applied to the patient’s torso. Small radio-opaque markers were attached to each electrode. All strips were connected to a portable mapping system (BioSemi). After electrode application, patients underwent thoracic non–contrast-gated CT scan with axial resolution of 3 mm. Scans were gated at 70% of the R-R interval (ventricular diastole) if patients were in sinus rhythm. For patients who underwent continued ECGI mapping during a subsequent EP study, the 256 carbon electrodes were kept in the same position. Patient-specific ventricular epicardial surface geometry and body surface electrode positions were labeled and digitized from CT images.

The 256 channels of body surface potentials were sampled at 1-ms intervals, and the data were saved on a laptop computer. Body surface potentials were acquired during sinus rhythm, VT, and programmed electrical stimulation, when available.

The body surface potential and geometrical information (torso-heart geometrical relationship) were combined by ECGI algorithms to noninvasively construct epicardial electrograms, activation sequences (isochrones), potential maps, and repolarization patterns (11, 12). ECGI was constructed on a beat-by-beat basis and did not require accumulating data from many identical beats. Activation times were determined by the maximal negative slope of the epicardial electrograms. Activation movies for several consecutive beats were constructed by animating the activation wavefront on the patient-specific CT-derived epicardial surface. On the basis of the isochrone map, lines or regions of block (thick black lines in the map) were inferred if activation times in adjacent areas differed by more than 50 ms. Slow conduction is represented by crowded isochrones. The earliest site of epicardial activation was determined from the isochrone map and from the earliest potential minimum in the epicardial potential map (13).

The results of ECGI were processed independently from the results of the EP study. Additionally, EP operators did not have access to ECGI results before the procedure. Clinical cardiac testing results, such as invasive three-dimensional electroanatomic maps, gadolinium-enhanced cardiac MRI, and SPECT, were obtained retrospectively for each patient.

Supplementary Material

www.sciencetranslationalmedicine.org/cgi/content/full/3/98/98ra84/DC1

The complete data set of ECGI-imaged human ventricular tachycardia.

Fig. S1. Normal ventricular epicardial activation (see movie S1).

Fig. S2. Patient RV1: ECGI of an anterior-left RVOT tachycardia.

Fig. S3. Patient RV2: ECGI of a mid-septal RVOT tachycardia.

Fig. S4. Patient RV3: ECGI of a mid-septal RVOT tachycardia.

Fig. S5. Patient RV4: ECGI of a posterior-right RVOT tachycardia.

Fig. S6. Patient RV5: ECGI of an anterior-left RVOT tachycardia (noninducible during EPS).

Fig. S7. Patient RV6: ECGI of a free wall RVOT tachycardia.

Fig. S8. Patient RV7: ECGI of a mid-septal RVOT tachycardia (see movie S2).

Fig. S9. Patient RV8: ECGI of a free wall RVOT tachycardia.

Fig. S10. Patient RV9: ECGI of a mid-septal RVOT tachycardia (see movie S3).

Fig. S11. Patient RV10: ECGI of an RV base tachycardia.

Fig. S12. Patient RV11: ECGI of a posterior-right RVOT tachycardia (see movie S4).

Fig. S13. Patient LV1: ECGI of a focal ventricular tachycardia induced by programmed electrical stimulation (with movie S5).

Fig. S14. Patient LV2: ECGI of reentrant VT from inferobasal scar (with movie S6).

Fig. S15. Patient LV3: ECGI of a reentrant VT from mid-lateral LV (lateral wall infiltrative cardiomyopathy) (with movie S7).

Fig. S16. Patient LV4: ECGI of left posterior fascicular VT (with movie S8).

Fig. S17. Patient LV5: ECGI of a left fascicular VT (with movie S9).

Fig. S18. Patient LV6: ECGI of an epicardial anterior basal focal VT.

Fig. S19. Patient LV7: ECGI of tachycardia originating in the left coronary cusp of the aorta.

Fig. S20. Patient LV8: ECGI of a basal mitral annular PVC.

Fig. S21. Patient LV9: ECGI of an inferior septal VT.

Fig. S22. Patient LV10: ECGI of an inferior lateral mitral annular PVC.

Fig. S23. Patient LV11: ECGI of apical scar–related reentrant VT (with movie S10).

Fig. S24. Patient LV12: ECGI of an inferior basal LV PVC (with movie S11).

Fig. S25. Patient LV13: ECGI of pleomorphic PVCs from the posterolateral LV (with movie S12).

Fig. S26. Patient LV14: ECGI of a VT from the anterior-apical LV in a patient with an apical aneurysm (with movie S13).

Fig. S27. Patient LV15: ECGI of a VT from the anterior interventricular vein/distal coronary sinus.

Table S1. Results from EP studies.

Movie S1. Normal: Normal ventricular activation pattern.

Movie S2. Patient RV7 activation pattern.

Movie S3. Patient RV9 activation pattern.

Movie S4. Patient RV11 activation pattern.

Movie S5. Patient LV1 activation pattern.

Movie S6. Patient LV2 activation pattern.

Movie S7. Patient LV3 activation pattern.

Movie S8. Patient LV4 activation pattern.

Movie S9. Patient LV5 activation pattern.

Movie S10. Patient LV11 activation pattern.

Movie S11. Patient LV12 activation pattern.

Movie S12. Patient LV13 activation pattern.

Movie S13. Patient LV14 activation pattern.

Footnotes

  • * These authors contributed equally to this work.

References and Notes

  1. Acknowledgments: We thank T. Street and S. Ghosh for their help in this study. Funding: This study was supported by NIH–National Heart, Lung, and Blood Institute grants R01-HL-033343-26 and R01-HL-049054-18 (to Y.R.) and grants 1 UL1 RR024992-01, 1 TL1 RR024995-01, and 1 KL2 RR 024994-01 from the National Center for Research Resources of the NIH. Y.R. is the Fred Saigh Distinguished Professor at Washington University in St. Louis. Author contributions: Y.W., P.S.C., and Y.R. devised the experiments. Y.W., P.S.C., J.Z., K.A.D., R.V., J.C., M.N.F., B.D.L., and T.W.S. performed the experiments. Y.W., P.S.C., J.Z., K.A.D., R.V., and Y.R. performed data analysis. Y.W., P.S.C., and Y.R. wrote the manuscript. All authors reviewed and edited the manuscript. Y.R. provided funding. Competing interests: Y.R. co-chairs the scientific advisory board of and holds equity in CardioInsight Technologies. CardioInsight Technologies does not support any research conducted by Y.R., including that presented here. B.D.L. is a member of the scientific advisory board of CardioInsight Technologies. The following patents are related to ECGI technology and owned by the university where the research was conducted: U.S. patent number 6772004, “System and Method for Non-invasive Electrocardiographic Imaging,” Case Western Reserve University; U.S. patent number 6975900, “Systems and Methods for Determining Surface Geometry,” Case Western Reserve University; U.S. patent number 7016719 “System and Method for Non-invasive Electrocardiographic Imaging (ECGI) Using Generalized Minimum Residual (GMRes),” Case Western Reserve University; U.S. patent number 7471973, “Determining a Surface Geometry of an Object,” Case Western Reserve University; “System and Methods for On-site and Real Time Electrocardiographic Imaging (ECGI),” submitted to Washington University; “A Fast, Mesh-Free Numerical Method for Noninvasive Electrocardiographic Imaging,” submitted to Washington University.
  • Citation: Y. Wang, P. S. Cuculich, J. Zhang, K. A. Desouza, R. Vijayakumar, J. Chen, M. N. Faddis, B. D. Lindsay, T. W. Smith, Y. Rudy, Noninvasive Electroanatomic Mapping of Human Ventricular Arrhythmias with Electrocardiographic Imaging. Sci. Transl. Med. 3, 98ra84 (2011).

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