A priori model independent inverse potential mapping: the impact of electrode positioning

__Introduction:__ In inverse potential mapping, local epicardial potentials are computed from recorded body surface potentials (BSP). When BSP are recorded with only a limited number of electrodes, in general biophysical a priori models are applied to facilitate the inverse computation. This study investigated the possibility of deriving epicardial potential information using only 62 torso electrodes in the absence of an a priori model. __Methods:__ Computer simulations were used to determine the optimal in vivo positioning of 62 torso electrodes. Subsequently, three different electrode configurations, i.e., surrounding the thorax, concentrated precordial (30 mm inter-electrode distance) and super-concentrated precordial (20 mm inter-electrode distance) were used to record BSP from three healthy volunteers. Magnetic resonance imaging (MRI) was performed to register the electrode positions with respect to the anatomy of the patient. Epicardial potentials were inversely computed from the recorded BSP. In order to determine the reconstruction quality, the super-concentrated electrode configuration was applied in four patients with an implanted MRI-conditional pacemaker system. The distance between the position of the ventricular lead tip on MRI and the inversely reconstructed pacing site was determined. __Results:__ The epicardial potential distribution reconstructed using the super-concentrated electrode configuration demonstrated the highest correlation (R = 0.98; p < 0.01) with the original epicardial source model. A mean localization error of 5.3 mm was found in the pacemaker patients. __Conclusion:__ This study demonstrated the feasibility of deriving detailed anterior epicardial potential information using only 62 torso electrodes without the use of an a priori model

Integrated whole-heart computational workflow for inverse potential mapping and personalized simulations

Background: Integration of whole-heart activation simulations and inverse potential mapping (IPM) could benefit the guidance and planning of electrophysiological procedures. Routine clinical application requires a fast and adaptable workflow. These requirements limit clinical translation of existing simulation models. This study proposes a comprehensive finite element model (FEM) based whole-heart computational workflow suitable for IPM and simulations. Methods: Three volunteers and eight patients with premature ventricular contractions underwent body surface potential (BSP) acquisition followed by a cardiac MRI (CMR) scan. The cardiac volumes were segmented from the CMR images using custom written software. The feasibility to integrate tissue-characteristics was assessed by generating meshes with virtual edema and scar. Isochronal activation maps were constructed by identifying the fastest route through the cardiac volume using the Möller-Trumbore and Floyd-Warshall algorithms. IPM's were reconstructed from the BSP's. Results: Whole-heart computational meshes were generated within seconds. The first point of atrial activation on IPM was located near the crista terminalis of the superior vena cave into the right atrium. The IPM demonstrated the ventricular epicardial breakthrough at the attachment of the moderator band with the right ventricular free wall. Simulations of sinus rhythm were successfully performed. The conduction through the virtual edema and scar meshes demonstrated delayed activation or a complete conductional block respectively. Conclusion: The proposed FEM based whole-heart computational workflow offers an integrated platform for cardiac electrical assessment using simulations and IPM. This workflow can incorporate patient-specific electrical parameters, perform whole-heart cardiac activation simulations and accurately reconstruct cardiac activation sequences from BSP's

Non-invasive focus localization, right ventricular epicardial potential mapping in patients with an MRI-conditional pacemaker system ‐ a pilot study

Abstract Background With the advent of magnetic resonance imaging (MRI) conditional pacemaker systems, the possibility of performing MRI in pacemaker patients has been introduced. Besides for the detailed evaluation of atrial and ventricular volumes and function, MRI can be used in combination with body surface potential mapping (BSPM) in a non-invasive inverse potential mapping (IPM) strategy. In non-invasive IPM, epicardial potentials are reconstructed from recorded body surface potentials (BSP). In order to investigate whether an IPM method with a limited number of electrodes could be used for the purpose of non-invasive focus localization, it was applied in patients with implanted pacing devices. Ventricular paced beats were used to simulate ventricular ectopic foci. Methods Ten patients with an MRI-conditional pacemaker system and a structurally normal heart were studied. Patientspecific 3D thorax volume models were reconstructed from the MRI images. BSP were recorded during ventricular pacing. Epicardial potentials were inversely calculated from the BSP. The site of epicardial breakthrough was compared to the position of the ventricular lead tip on MRI and the distance between these points was determined. Results For all patients, the site of earliest epicardial depolarization could be identified. When the tip of the pacing lead was implanted in vicinity to the epicardium, i.e. right ventricular (RV) apex or RV outflow tract, the distance between lead tip position and epicardial breakthrough was 6.0±1.9 mm. Conclusions In conclusion, the combined MRI and IPM method is clinically applicable and can identify sites of earliest depolarization with a clinically useful accuracy

Variable cardiac myosin binding protein-C expression in the myofilaments due to MYBPC3 mutations in hypertrophic cardiomyopathy

Background: Mutations in MYBPC3 are the most common cause of hypertrophic cardiomyopathy (HCM). These mutations produce dysfunctional protein that is quickly degraded and not incorporated in the myofilaments. Most patients are heterozygous and allelic expression differs between cells. We hypothesized that this would lead to cell-to-cell variation in cardiac myosin binding protein-C (cMyBP-C, encoded by MYBPC3 gene) protein levels. Methods: Twelve HCM patients were included (six had no sarcomere mutations (HCMsmn) and served as the control group and six harbored mutations in the MYBPC3 gene (MYBPC3mut). Western blot and RNA sequencing analysis of cardiac tissue lysates were performed to detect overall cMyBP-C protein and mRNA levels. Cellular expression of cMyBP-C and α-actin was obtained by immunofluorescence staining. Quantification of cell-to-cell variation of cMyBP-C expression between cardiomyocytes was measured by determining the ratio of cMyBP-C:α-actin stained area of each cell. Results: Protein and mRNA analysis revealed significantly reduced cMyBP-C levels in MYBPC3mut patients compared with HCMsmn patients (0.73 ± 0.09 vs. 1.0 ± 0.15, p <.05; 162.3 ± 16.4 vs. 326.2 ± 41.9 RPKM, p =.002), without any sign of truncated proteins. Immunofluorescence staining of individual cardiomyocytes in HCMsmn patients demonstrated homogenous and equal cMyBP-C:α-actin staining ratio. In contrast, MYBPC3mut patients demonstrated inhomogeneous staining patterns with a large intercellular variability per patient. Coefficient of variance for cMyBP-C/α-actin staining for each patient showed a significant difference between both groups (17.30 ± 4.08 vs. 5.18 ± 0.65% in MYBPC3mut vs. HCMsmn, p =.02). Conclusion: This is the first study to demonstrate intercellular variation of myofilament cMyBP-C protein expression within the myocardium from HCM patients with heterozygous MYBPC3 mutations

Determinants of coronary microvascular dysfunction in symptomatic hypertrophic cardiomyopathy

Impaired hyperemic myocardial blood flow (MBF) in hypertrophic cardiomyopathy (HCM), despite normal epicardial coronary arteries, results in microvascular dysfunction. The aim of the present study was to determine the relative contribution of extravascular compressive forces to microvascular dysfunction in HCM. Eighteen patients with symptomatic HCM and normal coronary arteries and 10 age-matched healthy volunteers were studied with PET to quantify resting and hyperemic MBF at a subendocardial and subepicardial level. In HCM patients, MRI was performed to determine left ventricular (LV) mass index (LVMI) and volumes, echocardiography to assess diastolic perfusion time, heart catheterization to measure LV outflow tract gradient (LVOTG) and LV pressures, and serum NH2-terminal pro-brain natriuretic peptide (NT-proBNP) as a biochemical marker of LV wall stress. Hyperemic MBF was blunted in HCM vs. controls (2.26 ± 0.97 vs. 2.93 ± 0.64 ml·min-1·g-1, P < 0.05). In contrast to controls (1.38 ± 0.15 to 1.25 ± 0.19, P = not significant), the endocardial-to-epicardial MBF ratio decreased significantly in HCM during hyperemia (1.20 ± 0.11 to 0.88 ± 0.18, P < 0.01). This pattern was similar for hypertrophied septum and lateral wall. Hyperemic MBF was inversely correlated with LVOTG, NT-proBNP, left atrial volume index, and LVMI (all P < 0.01). Multivariate regression analysis, however, revealed that only LVMI and NT-proBNP were independently related to hyperemic MBF, with greater impact at the subendocardial myocardial layer. Hyperemic MBF is more severely impaired at the subendocardial level in HCM patients. The level of impairment is related to markers of increased hemodynamic LV loading conditions and LV mass. These observations suggest that, in addition to reduced capillary density caused by hypertrophy, extravascular compressive forces contribute to microvascular dysfunction in HCM patients. Copyrigh

Tachyarrhythmia in patients with congenital heart disease: Inevitable destiny?

The prevalence of patients with congenital heart disease (CHD) has increased over the last century. As a result, the number of CHD patients presenting with late, postoperative tachyarrhythmias has increased as well. The aim of this review is to discuss the present knowledge on the mechanisms underlying both atrial and ventricular tachyarrhythmia in patients with CHD and the advantages and disadvantages of the currently available invasive treatment modalities