Fady Dawoud

Inverse Solution Mapping of Epicardial Potentials Quantitative Comparison With Epicardial Contact Mapping

Background—Catheter ablation of ventricular tachycardia (VT) is still one of the most challenging procedures in cardiac electrophysiology, limited, in part, by unmappable arrhythmias that are nonsustained or poorly tolerated. Calculation of the inverse solution from body surface potential mapping (sometimes known as ECG imaging) has shown tremendous promise and can rapidly map these arrhythmias, but we lack quantitative assessment of its accuracy in humans. We compared inverse solution mapping with computed tomography–registered electroanatomic epicardial contact catheter mapping to study the resolution of this technique, the influence of myocardial scar, and the ability to map VT. Methods and Results—For 4 patients undergoing epicardial catheter mapping and ablation of VT, 120-lead body surface potential mappings were obtained during implantable defibrillator pacing, catheter pacing from 79 epicardial sites, and induced VT. Inverse epicardial electrograms computed using individualized torso/epicardial surface geometries extracted from computed tomography images were compared with registered electroanatomic contact maps. The distance between estimated and actual epicardial pacing sites was 13±9 mm over normal myocardium with no stimulus-QRS delay but increased significantly over scar (P=0.013) or was close to scar (P=0.014). Contact maps during right ventricular pacing correlated closely to inverse solution isochrones. Maps of inverse epicardial potentials during 6 different induced VTs indicated areas of earliest activation, which correlated closely with clinically identified VT exit sites for 2 epicardial VTs. Conclusions—Inverse solution maps can identify sites of epicardial pacing with good accuracy, which diminishes over myocardial scar or over slowly conducting tissue. This approach can also identify epicardial VT exit sites and ventricular activation sequences.Background— Catheter ablation of ventricular tachycardia (VT) is still one of the most challenging procedures in cardiac electrophysiology, limited, in part, by unmappable arrhythmias that are nonsustained or poorly tolerated. Calculation of the inverse solution from body surface potential mapping (sometimes known as ECG imaging) has shown tremendous promise and can rapidly map these arrhythmias, but we lack quantitative assessment of its accuracy in humans. We compared inverse solution mapping with computed tomography–registered electroanatomic epicardial contact catheter mapping to study the resolution of this technique, the influence of myocardial scar, and the ability to map VT. Methods and Results— For 4 patients undergoing epicardial catheter mapping and ablation of VT, 120-lead body surface potential mappings were obtained during implantable defibrillator pacing, catheter pacing from 79 epicardial sites, and induced VT. Inverse epicardial electrograms computed using individualized torso/epicardial surface geometries extracted from computed tomography images were compared with registered electroanatomic contact maps. The distance between estimated and actual epicardial pacing sites was 13±9 mm over normal myocardium with no stimulus-QRS delay but increased significantly over scar ( P =0.013) or was close to scar ( P =0.014). Contact maps during right ventricular pacing correlated closely to inverse solution isochrones. Maps of inverse epicardial potentials during 6 different induced VTs indicated areas of earliest activation, which correlated closely with clinically identified VT exit sites for 2 epicardial VTs. Conclusions— Inverse solution maps can identify sites of epicardial pacing with good accuracy, which diminishes over myocardial scar or over slowly conducting tissue. This approach can also identify epicardial VT exit sites and ventricular activation sequences.

Effect of the mitral valve on diastolic flow patterns

The leaflets of the mitral valve interact with the mitral jet and significantly impact diastolic flow patterns, but the effect of mitral valve morphology and kinematics on diastolic flow and its implications for left ventricular function have not been clearly delineated. In the present study, we employ computational hemodynamic simulations to understand the effect of mitral valve leaflets on diastolic flow. A computational model of the left ventricle is constructed based on a high-resolution contrast computed-tomography scan, and a physiological inspired model of the mitral valve leaflets is synthesized from morphological and echocardiographic data. Simulations are performed with a diode type valve model as well as the physiological mitral valve model in order to delineate the effect of mitral-valve leaflets on the intraventricular flow. The study suggests that a normal physiological mitral valve promotes the formation of a circulatory (or “looped”) flow pattern in the ventricle. The mitral valve leaflets also increase the strength of the apical flow, thereby enhancing apical washout and mixing of ventricular blood. The implications of these findings on ventricular function as well as ventricular flow models are discussed.

CT for Evaluation of Myocardial Cell Therapy in Heart Failure: A Comparison With CMR Imaging

OBJECTIVES The aim of this study was to use multidetector computed tomography (MDCT) to assess therapeutic effects of myocardial regenerative cell therapies. BACKGROUND Cell transplantation is being widely investigated as a potential therapy in heart failure. Noninvasive imaging techniques are frequently used to investigate therapeutic effects of cell therapies in the preclinical and clinical settings. Previous studies have shown that cardiac MDCT can accurately quantify myocardial scar tissue and determine left ventricular (LV) volumes and ejection fraction (LVEF). METHODS Twenty-two minipigs were randomized to intramyocardial injection of phosphate-buffered saline (placebo, n = 9) or 200 million mesenchymal stem cells (MSC, n = 13) 12 weeks after myocardial infarction (MI). Cardiac magnetic resonance and MDCT acquisitions were performed before randomization (12 weeks after MI induction) and at the study endpoint 24 weeks after MI induction. None of the animals received medication to control the intrinsic heart rate during first-pass acquisitions for assessment of LV volumes and LVEF. Delayed-enhancement MDCT imaging was performed 10 min after contrast delivery. Two blinded observers analyzed MDCT acquisitions. RESULTS MDCT demonstrated that MSC therapy resulted in a reduction of infarct size from 14.3 ± 1.2% to 10.3 ± 1.5% of LV mass (p = 0.005), whereas infarct size increased in nontreated animals (from 13.8 ± 1.3% to 16.5 ± 1.5%; p = 0.02) (placebo vs. MSC; p = 0.003). Both observers had excellent agreement for infarct size (r = 0.96; p < 0.001). LVEF increased from 32.6 ± 2.2% to 36.9 ± 2.7% in MSC-treated animals (p = 0.03) and decreased in placebo animals (from 33.3 ± 1.4% to 29.1 ± 1.5%; p = 0.01; at week 24: placebo vs. MSC; p = 0.02). Infarct size, end-diastolic LV volume, and LVEF assessed by MDCT compared favorably with those assessed by cardiac magnetic resonance acquisitions (r = 0.70, r = 0.82, and r = 0.902, respectively; p < 0.001). CONCLUSIONS This study demonstrated that cardiac MDCT can be used to evaluate infarct size, LV volumes, and LVEF after intramyocardial-delivered MSC therapy. These findings support the use of cardiac MDCT in preclinical and clinical studies for novel myocardial therapies.

Transmural Imaging of Ventricular Action Potentials and Post-Infarction Scars in Swine Hearts

The problem of using surface data to reconstruct transmural electrophysiological (EP) signals is intrinsically ill-posed without a unique solution in its unconstrained form. Incorporating physiological spatiotemporal priors through probabilistic integration of dynamic EP models, we have previously developed a Bayesian approach to transmural electrophysiological imaging (TEPI) using body-surface electrocardiograms. In this study, we generalize TEPI to using electrical signals collected from heart surfaces, and we test its feasibility on two pre-clinical swine models provided through the STACOM 2011 EP simulation Challenge. Since this new application of TEPI does not require whole-body imaging, there may be more immediate potential in EP laboratories where it could utilize catheter mapping data and produce transmural information for therapy guidance. Another focus of this study is to investigate the consistency among three modalities in delineating scar after myocardial infarction: TEPI, electroanatomical voltage mapping (EAVM), and magnetic resonance imaging (MRI). Our preliminary data demonstrate that, compared to the low-voltage scar area in EAVM, the 3-D electrical scar volume detected by TEPI is more consistent with anatomical scar volume delineated in MRI. Furthermore, TEPI could complement anatomical imaging by providing EP functional features related to both scar and healthy tissue.

Using inverse electrocardiography to image myocardial infarction—reflecting on the 2007 PhysioNet/Computers in Cardiology Challenge

The goal of the 2007 PhysioNet/Computers in Cardiology Challenge was to try to establish how well it is possible to characterize the location and extent of old myocardial infarcts using electrocardiographic evidence supplemented by anatomical imaging information. A brief overview of the challenge and how different challengers approached the competition is provided, followed by detailed response of the first author to integrate electrophysiologic and anatomical data. The first author used the provided 120-electrode body-surface potential mapping data and magnetic resonance imaging heart and torso images to calculate epicardial potentials on customized ventricular geometries. A method was developed to define the location and extent of scar tissue based on the morphology of computed epicardial electrograms. Negative Q-wave deflection followed by R-wave on the left ventricular surface seemed to correspond with the location of the scar as determined by the gadolinium-enhanced magnetic resonance imaging gold standard in the supplied data sets. The method shows promising results as a noninvasive imaging tool to quantitatively characterize chronic infarcts and warrants further investigation on a larger patient data set.

Using inverse electrocardiography to image myocardial infarction

We propose to use methods of inverse electrocardiography (iECG) to compete in the 2007 Computers in Cardiology Challenge, which aims to delineate the location and extent of old myocardial infarct from body-surface potential maps (BSPMs) combined with anatomical imaging information. The provided 120-electrode BSPM data and MRI images were used to calculate epicardial potentials and isochrones of activation. A method was used to define the location and extent of scar tissue based on the morphology of computed epicardial electrograms. Negative Q wave deflection followed by R wave on the left ventricular surface corresponded well with the location of the scar as determined by the gold standard in the two training cases. iECG shows promise as a non-invasive imaging tool to quantitatively characterize location and extent of chronic infarcts.

Noninvasive electrocardiographic imaging of chronic myocardial infarct scar.

BACKGROUND Myocardial infarction (MI) scar constitutes a substrate for ventricular tachycardia (VT), and an accurate delineation of infarct scar may help to identify reentrant circuits and thus facilitate catheter ablation. One of the recent advancements in characterization of a VT substrate is its volumetric delineation within the ventricular wall by noninvasive electrocardiographic imaging. This paper compares, in four specific cases, epicardial and volumetric inverse solutions, using magnetic resonance imaging (MRI) with late gadolinium enhancement as a gold standard. METHODS For patients with chronic MI, who presented at Glasgow Western Infirmary, delayed-enhancement MRI and 120-lead body surface potential mapping (BSPM) data were acquired and 4 selected cases were later made available to a wider community as part of the 2007 PhysioNet/Computers in Cardiology Challenge. These data were used to perform patient-specific inverse solutions for epicardial electrograms and morphology-based criteria were applied to delineate infarct scar on the epicardial surface. Later, the Rochester group analyzed the same data by means of a novel inverse solution for reconstructing intramural transmembrane potentials, to delineate infarct scar in three dimensions. Comparison of the performance of three specific inverse-solution algorithms is presented here, using scores based on the 17-segment ventricular division scheme recommended by the American Heart Association. RESULTS The noninvasive methods delineating infarct scar as three-dimensional (3D) intramural distribution of transmembrane action potentials outperform estimates providing scar delineation on the epicardial surface in all scores used for comparison. In particular, the extent of infarct scar (its percentage mass relative to the total ventricular mass) is rendered more accurately by the 3D estimate. Moreover, the volumetric rendition of scar border provides better clues to potential targets for catheter ablation. CONCLUSIONS Electrocardiographic inverse solution providing transmural distribution of ventricular action potentials is a promising tool for noninvasively delineating the extent and location of chronic MI scar. Further validation on a larger data set with detailed gold-standard data is needed to confirm observations reported in this study.

Non-invasive electromechanical activation imaging as a tool to study left ventricular dyssynchronous patients: Implication for CRT therapy.

AIMS Electromechanical de-coupling is hypothesized to explain non-response of dyssynchrony patient to cardiac resynchronization therapy (CRT). In this pilot study, we investigated regional electromechanical uncoupling in 10 patients referred for CRT using two non-invasive electrical and mechanical imaging techniques (CMR tissue tracking and ECGI). METHODS AND RESULTS Reconstructed regional electrical and mechanical activation captured delayed LBBB propagation direction from septal to anterior/inferior and finally to lateral walls as well as from LV apical to basal. All 5 responders demonstrated significantly delayed mechanical and electrical activation on the lateral LV wall at baseline compared to the non-responders (P<.05). On follow-up ECGI, baseline electrical activation patterns were preserved in native rhythm and global LV activation time was reduced with biventricular pacing. CONCLUSIONS The combination of novel imaging techniques of ECGI and CMR tissue tracking can be used to assess spatial concordance of LV electrical and mechanical activation to gain insight into electromechanical coupling.

Inverse solution electrocardiographic mapping of epicardial pacing correlates with three-dimensional electroanatomic mapping

We hypothesized that the calculation of epicardial potentials from body-surface potential maps (BSPMs) could aid ablation of ventricular tachycardia (VT). BSPMs were recorded during epicardial catheter mapping and pacing in 2 patients. Single-beat epicardial maps were calculated by inverse solution using customized torso/cardiac geometry, discretized from a CT scan. During pacing from 48 epicardial sites, we observed stimulus-QRS delay (Stim-QRS) of 27 plusmn 7 ms and a difference between known pacing locations and calculated sites of earliest potential minima of 1.6 plusmn 1.4 cm. Pacing in scar and scar-border zones had longer Stim-QRS delay (51 plusmn 24 ms and 35 plusmn 23 ms, respectively, p=0.004), and greater distances between known pacing sites and known locations (3.0 plusmn 1.6 cm and 4.6 plusmn 2.0 cm, respectively, p=0.0004). BSPM with inverse solution mapping can identify sites of earliest epicardial activation and thus could have clinical utility.

Estimation of ventricular fiber orientations in infarcted hearts for patient-specific simulations

Patient-specific modeling of the heart is limited by lack of technology to acquire myocardial fiber orientations in the clinic. To overcome this limitation, we recently developed an image-based methodology to estimate the fiber orientations. In this study, we test the efficacy of that methodology in infarcted hearts. To this end, we implemented a processing pipeline to compare estimated fiber orientations of infarcted hearts with measured ones, and quantify the effect of the estimation error on outcomes of electrophysiological simulations. The pipeline was applied to images that we acquired from three infarcted canine hearts. The new insights obtained from the project will pave the way for the development of patient-specific models of infarcted hearts that can aid physicians in personalized diagnosis and decisions regarding electrophysiological interventions.