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

Measurement of coronary calcium scores by electron beam computed tomography or exercise testing as initial diagnostic tool in low-risk patients with suspected coronary artery disease

We determined the efficiency of a screening protocol based on coronary calcium scores (CCS) compared with exercise testing in patients with suspected coronary artery disease (CAD), a normal ECG and troponin levels. Three-hundred-and-four patients were enrolled in a screening protocol including CCS by electron beam computed tomography (Agatston score), and exercise testing. Decision-making was based on CCS. When CCS≥400, coronary angiography (CAG) was recommended. When CCS<10, patients were discharged. Exercise tests were graded as positive, negative or nondiagnostic. The combined endpoint was defined as coronary event or obstructive CAD at CAG. During 12±4 months, CCS≥400, 10–399 and <10 were found in 42, 103 and 159 patients and the combined endpoint occurred in 24 (57%), 14 (14%) and 0 patients (0%), respectively. In 22 patients (7%), myocardial perfusion scintigraphy was performed instead of exercise testing due to the inability to perform an exercise test. A positive, nondiagnostic and negative exercise test result was found in 37, 76 and 191 patients, and the combined endpoint occurred in 11 (30%), 15 (20%) and 12 patients (6%), respectively. Receiver-operator characteristics analysis showed that the area under the curve of 0.89 (95% CI: 0.85–0.93) for CCS was superior to 0.69 (95% CI: 0.61–0.78) for exercise testing (P<0.0001). In conclusion, measurement of CCS is an appropriate initial screening test in a well-defined low-risk population with suspected CAD

Strain analysis is superior to wall thickening in discriminating between infarcted myocardium with and without microvascular obstruction

Objectives: The aim of the present study was to evaluate the diagnostic performances of strain and wall thickening analysis in discriminating among three types of myocardium after acute myocardial infarction: non-infarcted myocardium, infarcted myocardium without microvascular obstruction (MVO) and infarcted myocardium with MVO. Methods: Seventy-one patients with a successfully treated ST-segment elevation myocardial infarction underwent cardiovascular magnetic resonance imaging at 2-6 days after reperfusion. The imaging protocol included conventional cine imaging, myocardial tissue tagging and late gadolinium enhancement. Regional circumferential and radial strain and associated strain rates were analyzed in a 16-segment model as were the absolute and relative wall thickening. Results: Hyperenhancement was detected in 418 (38%) of 1096 segments and was accompanied by MVO in 145 (35%) of hyperenhanced segments. Wall thickening, circumferential and radial strain were all significantly diminished in segments with hyperenhancement and decreased even further if MVO was also present (all p < 0.001). Peak circumferential strain (CS) surpassed all other strain and wall thickening parameters in its ability to discriminate between hyperenhanced and non-enhanced myocardium (all p < 0.05). Furthermore, CS was superior to both absolute and relative wall thickening in differentiating infarcted segments with MVO from infarcted segments without MVO (p = 0.02 and p = 0.001, respectively). Conclusions: Strain analysis is superior to wall thickening in differentiating between non-infarcted myocardium, infarcted myocardium without MVO and

Determinants of myocardial energetics and efficiency in symptomatic hypertrophic cardiomyopathy

Next to hypertrophy, hypertrophic cardiomyopathy (HCM) is characterized by alterations in myocardial energetics. A small number of studies have shown that myocardial external efficiency (MEE), defined by external work (EW) in relation to myocardial oxidative metabolism (MVO2), is reduced. The present study was conducted to identify determinants of MEE in patients with HCM by use of dynamic positron emission tomography (PET) and cardiovascular magnetic resonance imaging (CMR). Twenty patients with HCM (12 men, mean age: 55.2 +/- 13.9 years) and 11 healthy controls (7 men, mean age: 48.1 +/- 10 years) were studied with [C-11]acetate PET to assess MVO2. CMR was performed to determine left ventricular (LV) volumes and mass (LVM). Univariate and multivariate analyses were employed to determine independent predictors of myocardial efficiency. Between study groups, MVO2 (controls: 0.12 +/- 0.04 ml center dot min(-1)center dot g(-1), HCM: 0.13 +/- 0.05 ml center dot min(-1)center dot g(-1), p = 0.64) and EW (controls: 9,139 +/- 2,484 mmHg center dot ml, HCM: 9,368 +/- 2,907 mmHg center dot ml, p = 0.83) were comparable, whereas LVM was significantly higher (controls: 99 +/- 21 g, HCM: 200 +/- 76 g, p < 0.001) and MEE was decreased in HCM patients (controls: 35 +/- 8%, HCM: 21 +/- 10%, p < 0.001). MEE was related to stroke volume (SV), LV outflow tract gradient, NH2-terminal pro-brain natriuretic peptide (NT-proBNP) and serum free fatty acid levels (all p < 0.05). Multivariate analysis revealed that SV ( = 0.74, p < 0.001) and LVM ( = -0.43, p = 0.013) were independently related to MEE. HCM is characterized by unaltered MVO2, impaired EW generation per gram of myocardial tissue and subsequent deteriorated myocardial efficiency. Mechanical external efficiency could independently be predicted by SV and LVM