Basis and applicability of noninvasive inverse electrocardiography: a comparison between cardiac source models.

The body surface electrocardiogram (ECG) is a direct result of electrical activity generated by the myocardium. Using the body surface ECGs to reconstruct cardiac electrical activity is called the inverse problem of electrocardiography. The method to solve the inverse problem depends on the chosen cardiac source model to describe cardiac electrical activity. In this paper, we describe the theoretical basis of two inverse methods based on the most commonly used cardiac source models: the epicardial potential model and the equivalent dipole layer model. We discuss similarities and differences in applicability, strengths and weaknesses and sketch a road towards improved inverse solutions by targeted use, sequential application or a combination of the two methods.

High-rate pacing suppresses Torsade de Pointes arrhythmias and reduces spatial dispersion of repolarization in the chronic AV-block dog model.

Background: An electrical storm of Torsade de Pointes arrhythmias (TdP) can be reproducibly induced in the anesthetized chronic AV-block (CAVB) dog by infusion of the IKr-blocker dofetilide. Earlier studies showed that these arrhythmias 1) arise from locations with high spatial dispersion in repolarization (SDR) and 2) can be suppressed by high-rate pacing. We examined whether suppression of TdP by high-rate pacing is established through a decrease in SDR in the CAVB dog. Methods: Dofetilide (25 µg/kg in 5 min) was administered to 5 anesthetized CAVB dogs to induce TdP arrhythmias. During the experiments, animals were continuously paced from the right ventricular apex at 50 beats/minute (RVA50). Upon TdP occurrence and conversion, RVA pacing was consecutively set to 100, 80 and 60 beats/minute for 2 min, referred to as pacing blocks. To determine the additional anti-arrhythmic effects of HRP over defibrillation alone, the number of arrhythmic events and SDR at RVA100 were compared to data from three previously conducted experiments, in which dogs underwent the same experimental protocol but were paced at RVA60 upon TdP occurrence (RVA60retro). In all experiments, recordings included surface electrocardiogram and mapping by 56 intramural needles, each recording four electrograms, evenly inserted into the ventricular walls and septum. For each pacing block, the number of ectopic beats (EB), and TdP severity were scored. SDR was quantified as the average difference in repolarization time within four squared needles (SDRcubic). Results: In 4 out of 5 animals, pacing at RVA100 suppressed TdP occurrence. One dog could not be converted by defibrillation after the initial TdP. Compared to RVA50, pacing at RVA100, but not RVA80 and RVA60, significantly reduced the TdP score (78 ± 33 vs. 0 ± 0, p < 0.05 and vs. 12.5 ± 25 and 25 ± 50, both p > 0.05). The reduction in TdP score was reflected by a significant decrease in SDRcubic (125 ± 46 ms before TdP vs. 49 ± 18 ms during RVA100, p < 0.05), and SDR was smaller than in the RVA60retro animals (101 ± 52 ms, p < 0.05 vs. RVA100). Conclusion: In CAVB dogs, high-rate pacing effectively suppresses TdP, which, at least in part, results from a spatial homogenization of cardiac repolarization, as reflected by a decrease in SDR.

Steep repolarization time gradients in pig hearts cause distinct changes in composite electrocardiographic T-wave parameters.

BACKGROUND: The T wave of the electrocardiogram (ECG) reflects ventricular repolarization. Repolarization heterogeneity is associated with reentrant arrhythmias. Several T-wave markers (including QT interval) have been associated with ventricular arrhythmias, but studies linking such markers to underlying local repolarization time (RT) inhomogeneities are lacking. We aimed to investigate the relation of several T-wave markers to controlled drug-induced regional RT gradients in intact pig hearts. METHODS: Repolarization time gradients were created by regional infusion of dofetilide and pinacidil in four atrially paced porcine Langendorff-perfused hearts placed inside a torso tank. From the 12-lead ECG on the torso tank, the mean, maximum, and dispersion (max-min) of QTtime , JTtime , Tpeak-end , Twidth , TQratio , dV/dtmax , Tarea , Tamp , and T-upslope duration were determined, as well as upslope end difference between leads V1 and V6 . RESULTS: Temporal T-wave parameters Tpeak-end , Twidth, and TQratio show a significant and high correlation with RT gradient, best reflected by mean value. Tarea (mean, max and dispersion) and dV/dtmax dispersion show only a moderate significant correlation. T-upslope duration shows a significant correlation in particular for mean values. Mean, maximum, or dispersion of QTtime and V1 -V6 upslope end difference were not significantly correlated with RT gradient. CONCLUSION: Composite 12-lead ECG T-wave parameters Tpeak-end , Twidth , TQratio , upslope duration, and Tarea show a good correlation with underlying RT heterogeneity, whereas standard clinical metrics such as QTtime do not reflect local RT heterogeneity. The composite T-wave metrics may thus provide better insights in arrhythmia susceptibility than traditional QTtime metrics.

Ex vivo Validation of Noninvasive Epicardial and Endocardial Repolarization Mapping.

Background: The detection and localization of electrophysiological substrates currently involve invasive cardiac mapping. Electrocardiographic imaging (ECGI) using the equivalent dipole layer (EDL) method allows the noninvasive estimation of endocardial and epicardial activation and repolarization times (AT and RT), but the RT validation is limited to in silico studies. We aimed to assess the temporal and spatial accuracy of the EDL method in reconstructing the RTs from the surface ECG under physiological circumstances and situations with artificially induced increased repolarization heterogeneity. Methods: In four Langendorff-perfused pig hearts, we simultaneously recorded unipolar electrograms from plunge needles and pseudo-ECGs from a volume-conducting container equipped with 61 electrodes. The RTs were computed from the ECGs during atrial and ventricular pacing and compared with those measured from the local unipolar electrograms. Regional RT prolongation (cooling) or shortening (pinacidil) was achieved by selective perfusion of the left anterior descending artery (LAD) region. Results: The differences between the computed and measured RTs were 19.0 ± 17.8 and 18.6 ± 13.7 ms for atrial and ventricular paced beats, respectively. The region of artificially delayed or shortened repolarization was correctly identified, with minimum/maximum RT roughly in the center of the region in three hearts. In one heart, the reconstructed region was shifted by ~2.5 cm. The total absolute difference between the measured and calculated RTs for all analyzed patterns in selectively perfused hearts (n = 5) was 39.6 ± 27.1 ms. Conclusion: The noninvasive ECG repolarization imaging using the EDL method of atrial and ventricular paced beats allows adequate quantitative reconstruction of regions of altered repolarization.

Critical repolarization gradients determine the induction of reentry-based torsades de pointes arrhythmia in models of long QT syndrome.

BACKGROUND: Torsades de pointes arrhythmia is a potentially lethal polymorphic ventricular tachyarrhythmia (pVT) in the setting of long QT syndrome. Arrhythmia susceptibility is influenced by risk factors modifying repolarization. OBJECTIVE: The purpose of this article was to characterize repolarization duration and heterogeneity in relation to pVT inducibility and maintenance. METHODS: Sotalol was infused regionally or globally in isolated Langendorff blood-perfused pig hearts (N = 7) to create repolarization time (RT) heterogeneities. Programmed stimulation and epicardial activation and repolarization mapping were performed. The role of RT (heterogeneities) was studied in more detail using a computer model of the human heart. RESULTS: pVTs (n = 11) were inducible at a critical combination of RT and RT heterogeneities. The pVT cycle lengths were similar in the short and long RT regions. Short-lasting pVTs were maintained by focal activity while longer-lasting pVTs by reentry wandering along the interface between the 2 regions. Local restitution curves from the long and short RT regions crossed. This was associated with T-wave inversion at coupling intervals at either side of the crossing point. These experimental observations were confirmed by the computer simulations. CONCLUSION: pVTs are inducible within a critical range of RT and RT heterogeneities and are maintained by reentry wandering along the repolarization gradient. Double potentials localize at the core of the reentrant circuit and reflect phase singularities. RT gradient and T waves invert with short-coupled premature beats in the long RT region as a result of the crossing of the restitution curves allowing reentry initiation.

In silico validation of electrocardiographic imaging to reconstruct the endocardial and epicardial repolarization pattern using the equivalent dipole layer source model.

The solution of the inverse problem of electrocardiology allows the reconstruction of the spatial distribution of the electrical activity of the heart from the body surface electrocardiogram (electrocardiographic imaging, ECGI). ECGI using the equivalent dipole layer (EDL) model has shown to be accurate for cardiac activation times. However, validation of this method to determine repolarization times is lacking. In the present study, we determined the accuracy of the EDL model in reconstructing cardiac repolarization times, and assessed the robustness of the method under less ideal conditions (addition of noise and errors in tissue conductivity). A monodomain model was used to determine the transmembrane potentials in three different excitation-repolarization patterns (sinus beat and ventricular ectopic beats) as the gold standard. These were used to calculate the body surface ECGs using a finite element model. The resulting body surface electrograms (ECGs) were used as input for the EDL-based inverse reconstruction of repolarization times. The reconstructed repolarization times correlated well (COR > 0.85) with the gold standard, with almost no decrease in correlation after adding errors in tissue conductivity of the model or noise to the body surface ECG. Therefore, ECGI using the EDL model allows adequate reconstruction of cardiac repolarization times. Graphical abstract Validation of electrocardiographic imaging for repolarization using forward calculated body surface ECGs from simulated activation-repolarization sequences.