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Cardiac resynchronization therapy is a valuable tool to restore left ventricular function in patients experiencing dyssynchronous ventricular activation. However, the non-responder rate is still as high as 40%. Recent studies suggest that left ventricular torsion or specifically the lack thereof might be a good predictor for the response of cardiac resynchronization therapy. Since left ventricular torsion is governed by the muscle fiber orientation and the heterogeneous electromechanical activation of the myocardium, understanding the relation between these components and the ability to measure them is vital. To analyze if locally altered electromechanical activation in heart failure patients affects left ventricular torsion, we conducted a simulation study on 27 personalized left ventricular models. Electroanatomical maps and late gadolinium enhanced magnetic resonance imaging data informed our in-silico model cohort. The angle of rotation was evaluated in every material point of the model and averaged values were used to classify the rotation as clockwise or counterclockwise in each segment and sector of the left ventricle. 88% of the patient models (n = 24) were classified as a wringing rotation and 12% (n = 3) as a rigid-body-type rotation. Comparison to classification based on in vivo rotational NOGA XP maps showed no correlation. Thus, isolated changes of the electromechanical activation sequence in the left ventricle are not sufficient to reproduce the rotation pattern changes observed in vivo and suggest that further patho-mechanisms are involved.

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INTRODUCTION: Cell therapy has the potential to improve symptoms and clinical outcomes in refractory angina (RFA). Further analyses are needed to evaluate factors influencing its therapeutic effectiveness. AIM: Assessment of electromechanical (EM) parameters of the left ventricle (LV) and investigation of correlation between EM parameters of the myocardium and response to CD133+ cell therapy. MATERIAL AND METHODS: Thirty patients with RFA (16 active and 14 placebo individuals) enrolled in the REGENT-VSEL trial underwent EM evaluation of the LV with intracardiac mapping system. The following parameters were analyzed: unipolar voltage (UV), bipolar voltage (BV), local linear shortening (LLS). Myocardial ischemia was evaluated with single-photon emission computed tomography (SPECT). The median value of each EM parameter was used for intra-group comparisons. RESULTS: Global EM parameters (UV, BV, LLS) of LV in active and placebo groups were 11.28 mV, 3.58 mV, 11.12%, respectively; 13.00 mV, 3.81 mV, 11.32%, respectively. EM characteristics analyzed at global and segmental levels did not predict response to CD133+ cell therapy in patients with RFA (Global UV, BV and LLS at rest R = -0.06; R = 0.2; R = -0.1 and at stress: R = 0.07, R = 0.09, R = -0.1, respectively; Segmental UV, BV, LLS at rest R = -0.2, R = 0.03, R = -0.4 and at stress R = 0.02, R = 0.2, R = -0.2, respectively). Multiple linear regression of the treated segments showed that only pre-injection SPECT levels were significantly correlated with post-injection SPECT, either at rest or stress (p < 0.05). CONCLUSIONS: Electromechanical characteristics of the left ventricle do not predict changes of myocardial perfusion by SPECT after cell therapy. Baseline SPECT results are only predictors of changes of myocardial ischemia observed at 4-month follow-up.

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Many cardiac catheter interventions require accurate discrimination between healthy and infarcted myocardia. The gold standard for infarct imaging is late gadolinium-enhanced MRI (LGE-MRI), but during cardiac procedures electroanatomical or electromechanical mapping (EAM or EMM, respectively) is usually employed. We aimed to improve the ability of EMM to identify myocardial infarction by combining multiple EMM parameters in a statistical model. From a porcine infarction model, 3D electromechanical maps were 3D registered to LGE-MRI. A multivariable mixed-effects logistic regression model was fitted to predict the presence of infarct based on EMM parameters. Furthermore, we correlated feature-tracking strain parameters to EMM measures of local mechanical deformation. We registered 787 EMM points from 13 animals to the corresponding MRI locations. The mean registration error was 2.5 ± 1.16 mm. Our model showed a strong ability to predict the presence of infarction (C-statistic = 0.85). Strain parameters were only weakly correlated to EMM measures. The model is accurate in discriminating infarcted from healthy myocardium. Unipolar and bipolar voltages were the strongest predictors.

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OBJECTIVES: This study sought to test the accuracy of strain measurements based on anatomo-electromechanical mapping (AEMM) measurements compared with magnetic resonance imaging (MRI) tagging, to evaluate the diagnostic value of AEMM-based strain measurements in the assessment of myocardial viability, and the additional value of AEMM over peak-to-peak local voltages. BACKGROUND: The in vivo identification of viable tissue, evaluation of mechanical contraction, and simultaneous left ventricular activation is currently achieved using multiple complementary techniques. METHODS: In 33 patients, AEMM maps (NOGA XP, Biologic Delivery Systems, Division of Biosense Webster, a Johnson & Johnson Company, Irwindale, California) and MRI images (Siemens 3T, Siemens Healthcare, Erlangen, Germany) were obtained within 1 month. MRI tagging was used to determine circumferential strain (Ecc) and delayed enhancement to obtain local scar extent (%). Custom software was used to measure Ecc and local area strain (LAS) from the motion field of the AEMM catheter tip. RESULTS: Intertechnique agreement for Ecc was good (R2 = 0.80), with nonsignificant bias (0.01 strain units) and narrow limits of agreement (-0.03 to 0.06). Scar segments showed lower absolute strain amplitudes compared with nonscar segments: Ecc (median [first to third quartile]: nonscar -0.10 [-0.15 to -0.06] vs. scar -0.04 [-0.06 to -0.02]) and LAS (-0.20 [-0.27 to -0.14] vs. -0.09 [-0.14 to -0.06]). AEMM strains accurately discriminated between scar and nonscar segments, in particular LAS (area under the curve: 0.84, accuracy = 0.76), which was superior to peak-to-peak voltages (nonscar 9.5 [6.5 to 13.3] mV vs. scar 5.6 [3.4 to 8.3] mV; area under the curve: 0.75). Combination of LAS and peak-to-peak voltages resulted in 86% accuracy. CONCLUSIONS: An integrated AEMM approach can accurately determine local deformation and correlates with the scar extent. This approach has potential immediate application in the diagnosis, delivery of intracardiac therapies, and their intraprocedural evaluation.

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For cardiac regenerative therapy intramyocardial catheter guided cell transplantations are targeted to the infarct border zone (IBZ) i.e. the closest region of viable myocardium in the vicinity of the infarct area. For optimal therapeutic effect this area should be accurately identified. However late gadolinium enhanced magnetic resonance imaging (LGE-MRI) is the gold standard technique to determine the infarct size and location, electromechanical mapping (EMM) is used to guide percutaneous intramyocardial injections to the IBZ. Since EMM has a low spatial resolution, we aim to develop a practical and accurate technique to fuse EMM with LGE-MRI to guide intramyocardial injections. LGE-MRI and EMM were obtained in 17 pigs with chronic myocardial infarction created by balloon occlusion of LCX and LAD coronary arteries. LGE-MRI and EMM datasets were registered using our in-house developed 3D CartBox image registration software toolbox to assess: (1) the feasibility of the 3D CartBox toolbox, (2) the EMM values measured in the areas with a distinct infarct transmurality (IT), and (3) the highest sensitivity and specificity of the EMM to assess IT and define the IBZ. Registration of LGE-MRI and EMM resulted in a mean error of 3.01 ± 1.94 mm between the LGE-MRI mesh and EMM points. The highest sensitivity and specificity were found for UV <9.4 mV and bipolar voltage <1.2 mV to respectively identify IT of ≥5 and ≥97.5 %. The 3D CartBox image registration toolbox enables registration of EMM data on pre-acquired MRI during the EMM guided procedure and allows physicians to easily guide injections to the most optimal injection location for cardiac regenerative therapy and harness the full therapeutic effect of the therapy.

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The use of transendocardial (TE) injection as a validated method for delivering therapeutic agents to the diseased heart is increasing. Of the catheter systems currently available, TE injections guided by electromechanical mapping are attractive due to their minimal use of fluoroscopy and three-dimensional reconstruction capabilities that allow precise targeting of injections. We propose a method of cardiac sampling that takes advantage of the spatial accuracy of this system. Our preclinical experience with this methodology has yielded encouraging results, allowing a thorough examination of the injected areas through limited sampling.

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BACKGROUND: We analyzed electromechanical mismatch (EMM) and its relationship to ventricular repolarization in patients with nonischemic dilated cardiomyopathy (DCM). METHODS AND RESULTS: In 39 DCM patients with left ventricular ejection fraction (LVEF) <40% and New York Heart Association functional class ≥III, electroanatomic mapping was used to quantify areas of EMM. High-resolution electrocardiograph was used to measure heart rate variability (HRV) and QT variability index (QTVI). EMM was present in 22 patients (56%, group 1), whereas 17 patients presented no mismatched segments (44%, group 2). The groups did not differ in age (56 ± 10 years in group 1 vs 57 ± 7 years in group 2; P = .82), sex (male: 82% vs 94%; P = .40), LVEF (27 ± 8% vs 25 ± 6%; P = .18), or N-terminal pro-B-type natriuretic peptide (2,350 pg/mL vs 2,831 pg/mL; P = .32). Although heart rate and HRV were similar in both groups (rate: 80 ± 20 beats/min in group 1 vs 74 ± 19 beats/min in group 2 [P = .47]; standard deviation of normal-to normal RR intervals: 106 ± 79 vs 88 ± 115 [P = .61]), we found significantly higher QTVI values in patients from group 1 (-1.15 ± 0.46 vs -1.62 ± 0.51 in group 2; P = .005). In patients with implantable cardioverter-defibrillators, ventricular arrhythmias recorded ≤1 year before enrollment were more frequent in group 1 than in group 2 (58% vs 13%; P = .02). CONCLUSIONS: EMM is present in a majority of patients with DCM and is associated with ventricular repolarization instability.

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The objective of this study was to determine the safety and feasibility of performing transendocardial electromechanical mapping and mesenchymal precursor stem cell injections after left ventricular assist device (LVAD) implantation in a sheep model of acute myocardial infarction. Six sheep were assigned to either an acute or chronic group. Then we created an acute myocardial infarction in each by occluding the distal left anterior descending coronary artery with a balloon for 90 minutes. All the sheep underwent LVAD implantation 30 days later. On the same day, sheep in the acute group underwent transendocardial cell injections and were euthanized. Sheep in the chronic group received cell injections 2 weeks after LVAD implantation and were euthanized 30 days later. The presence of the LVAD or the use of chest-closure wires did not interfere with electromechanical mapping. Furthermore, no adverse events were observed during electromechanical mapping or the stem cell injections. In all sheep, the LVAD flow rate was approximately 4 L/min during mapping and the injections, and no adjustments were required. Histologic analysis confirmed that the mesenchymal precursor stem cells were successfully delivered. No differences were observed between the acute and chronic groups. In conclusion, our study showed that transendocardial electromechanical mapping and stem cell injections are safe and feasible in the presence of an LVAD. Surgically implanted metal devices, including the LVAD, steel chest-closure wire, and skin staples, were compatible with the electromechanical mapping system.

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Ischemic heart disease, despite advances in treatment, remains the major cause of mortality worldwide. NOGA 3D left ventricular electromechanical mapping allows accurate determination of cardiac function and precise identification of sites of injury. In a porcine model of ischemia-reperfusion injury, we validate the use of the NOGA mapping system for assessment of cardiac function along with the Myostar injection catheter for directed delivery of therapeutics to localized target sites in the setting of acute myocardial injury.

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BACKGROUND AND OBJECTIVE: Left ventricular electromechanical mapping (EMM) determines myocardial viability on the basis of endocardial electrograms. The aim of the present study was to validate EMM in differentiating infarcted myocardium from viable myocardium by histopathological analysis. METHODS: Sixty days after implanting an ameroid constrictor over the left circumflex artery to create chronic ischemia in 19 pigs, EMM was performed to construct unipolar voltage (UPV), bipolar voltage (BPV) and linear local shortening (LLS) maps. Noninfarcted and infarcted myocardium were identified by histopathology. Threshold determinations comparing noninfarcted tissue with scarred tissue were made by measuring the area under the receiver operating characteristic curves. RESULTS: From the 19 hearts, 149 myocardial segments were divided into noninfarcted myocardium (n=128) and transmural infarct (n=21). UPV, BPV and LLS values (4.7+/-1.2 mV, 2.8+/-2.5 mV and 10.0+/-5.1%, respectively) of infarcted segments were significantly lower than those in noninfarcted myocardium (10.9+/-3.4 mV, 4.5+/-2.4 mV and 15.7+/-9.5%, respectively; P<0.01 for each comparison). The threshold values of UPV, BPV and LLS differentiating noninfarcted from infarcted myocardium were 6.2 mV (98% sensitivity, 95% specificity, 97% accuracy), 2.8 mV (80% sensitivity, 72% specificity, 79% accuracy) and 12.3% (68% sensitivity, 67% specificity, 68% accuracy), respectively. The relative dispersion of voltage was lower for UPV versus BPV. CONCLUSION: UPV can accurately differentiate infarcted from noninfarcted tissue in the chronic ischemic heart of pigs; however, BPV and LLS results were less accurate.