Right Ventricular Endocardium Research Articles

Three-Dimensional Echocardiography Right Ventricular Volumes and Ejection Fraction Reference Values in Children: A North American Multicentre Study.

Three-dimensional echocardiography (3DE) evaluation of right ventricular (RV) volumes and ejection fraction (EF) is increasingly used for clinical serial assessments and management in children. This study aims to generate sex-specific reference values and z-score equations for RV volumetric parameters, independent of age and body size indices, derived from multiple populations across North America. We prospectively recruited 455 healthy children (ages 0 to 18 years) from 5 centres. 3DE of the RV were acquired using various vendors with analyses performed offline using vendor-independent software. 3DE datasets with all walls of the RV endocardium visible were included. We reported data on RV EF, and generated z scores for end-systolic volumes (ESV), end-diastolic volumes (EDV) and stroke volume (SV). Differences between the sexes were explored. Of 455 3DE datasets, 312 (68%) met imaging criteria for analysis. Median age was 10.1 years (interquartile ratio [IQR]: 5.6, 14.0) with 17% being younger than 3 years of age. The mean and standard deviation for RV EDV, ESV, and SV for male and female patients were reported. We provided a downloadable z-score calculator with height and weight as independent variables to facilitate clinical utility. Although statistically significant differences between male and female RVEF was present (female 52.9 ± 3.9% vs male 51.6 ± 3.5%, P= 0.006), after adjusting for age, height, and weight, the magnitude of difference was clinically insignificant. Sex-specific reference values for pediatric RV volumes and EF, and z-score equations were derived from children 3DE datasets across 5 centres in North America.

Isolated critical epicardial arrhythmogenic substrate abnormalities in patients with arrhythmogenic right ventricular cardiomyopathy and ventricular tachycardia.

Ventricular tachycardia (VT) substrate abnormalities in arrhythmogenic right ventricular cardiomyopathy (ARVC) typically involve both the right ventricular (RV) endocardium (ENDO) and epicardium (EPI). The purpose of this study was to examine the prevalence, electrophysiological features, and outcomes of catheter ablation of VT in patients with isolated epicardial substrate (IES) abnormalities. We studied 71 consecutive patients with VT who met Task Force criteria for ARVC and underwent detailed ENDO and EPI mapping. Patients with critical IES demonstrated (1) confluent EPI bipolar abnormal electrograms (EGMs) and (2) no or minor (<5.0 cm2) RV ENDO low bipolar voltage. Induced VTs were localized using activation mapping, entrainment mapping, and/or pacemapping. Twelve patients (17%) had IES. Extensive EPI bipolar low-voltage area (Bi-LVA; 74 ± 40 cm2) and EGM abnormalities were identified in all patients. Uni-ENDO LVA (<5.5 mV) was seen in 11 of 12 patients (92%) (41 ± 25 cm2) and corresponded to EPI RV bipolar abnormalities. A median of 2 VTs (range 1-7; cycle length 288 ± 68 ms) were induced and localized to the EPI. EPI ablation resulted in noninducibility of all targeted VTs. Preablation cardiac magnetic resonance (CMR) imaging was performed in 10 of 12 patients with RV dyskinesis and/or late gadolinium enhancement in only 4 of 10 patients. During follow-up of 56 ± 46 months, 9 of 12 patients (75%) remained VT-free. In patients with ARVC and VT, substrate abnormalities can uncommonly be isolated to the RV EPI. Detection of critical IES may be limited with CMR imaging but suggested by ENDO unipolar EGM abnormalities. EPI ablation eliminates VT in these patients and typically results in long-term VT-free survival.

Upgrade of cardiac resynchronization therapy by utilizing additional His-bundle pacing in a patient with lamin A/C cardiomyopathy: an autopsy case report.

Abstract Background A number of heart failure patients (HF) do not fully benefit from cardiac resynchronization therapy (CRT). Although His bundle pacing (HBP) have been developed as an alternative strategy, its role for treating advanced cardiomyopathy remains unclear. Case summary We previously reported a patient with lamin A/C cardiomyopathy (Eur Heart J Case Rep. 2020; 4:1-9). He had turned non-response to conventional biventricular pacing (BVP), and an upgrade to CRT combining para-His bundle pacing (HBP) and left ventricular (LV) pacing had markedly improved his HF status. In the present report, we assessed the autopsy and histological findings of this patient. A histological examination of both the LV and right ventricular (RV) apex pacing regions exhibited extensive scarring. Although a distinct conduction system was not identified in the alternative para-HBP region, the RV endocardium had more viable myocytes in this region. Discussion In patients with advanced cardiomyopathy accompanied by extensive fibrosis, RV apex pacing, delivered from scar tissue, can render conventional BVP ineffective. Additionally, HBP alone can not provide adequate resynchronization under the presence of diffuse injury of the His-Purkinje system. In these circumstances, combined para-HB and LV pacing may facilitate electrical and mechanical resynchronization of the ventricles and may be attributed to favourable CRT response in advanced HF, even if para-HBP fails to directly capture the conduction system.

Reconstruction of three-dimensional biventricular activation based on the 12-lead electrocardiogram via patient-specific modelling.

AimsNon-invasive imaging of electrical activation requires high-density body surface potential mapping. The nine electrodes of the 12-lead electrocardiogram (ECG) are insufficient for a reliable reconstruction with standard inverse methods. Patient-specific modelling may offer an alternative route to physiologically constraint the reconstruction. The aim of the study was to assess the feasibility of reconstructing the fully 3D electrical activation map of the ventricles from the 12-lead ECG and cardiovascular magnetic resonance (CMR).Methods and resultsVentricular activation was estimated by iteratively optimizing the parameters (conduction velocity and sites of earliest activation) of a patient-specific model to fit the simulated to the recorded ECG. Chest and cardiac anatomy of 11 patients (QRS duration 126–180 ms, documented scar in two) were segmented from CMR images. Scar presence was assessed by magnetic resonance (MR) contrast enhancement. Activation sequences were modelled with a physiologically based propagation model and ECGs with lead field theory. Validation was performed by comparing reconstructed activation maps with those acquired by invasive electroanatomical mapping of coronary sinus/veins (CS) and right ventricular (RV) and left ventricular (LV) endocardium. The QRS complex was correctly reproduced by the model (Pearson’s correlation r = 0.923). Reconstructions accurately located the earliest and latest activated LV regions (median barycentre distance 8.2 mm, IQR 8.8 mm). Correlation of simulated with recorded activation time was very good at LV endocardium (r = 0.83) and good at CS (r = 0.68) and RV endocardium (r = 0.58).ConclusionNon-invasive assessment of biventricular 3D activation using the 12-lead ECG and MR imaging is feasible. Potential applications include patient-specific modelling and pre-/per-procedural evaluation of ventricular activation.

P1710 Reverse right ventricular remodeling using right ventricular strain and strain rate after mitral clip implantation in functional mitral regurgitation, an echocardiographic study

Abstract Funding Acknowledgements none OnBehalf none Background Chronic mitral regurgitation (MR) leads to right ventricular dysfunction because of volume and pressure overload over a long time. Mitral valve repair with a mitral clip will reduce the (MR) but how much its effect on the right ventricle. Aim The aim of the present study is to assess the impact of Mitral Valve Clipping on right ventricular (RV) remodeling (RV strain and strain rate) at med term after Mitral Clip implantation in high-risk surgical patients with severe functional mitral regurgitation (MR). Methods Study population included 62 patients with severe functional MR. All the patients underwent full echocardiographic evaluation before MV clip, and at 12-month follow-up. RV systolic function was assessed using tissue Doppler and TAPSE. Using Tom-Tec software the RV endocardium is traced in the apical 4 chamber view to get the RV strain and strain rate. RV after load was evaluated using systolic pulmonary artery pressure. Results In our cohort, 62 patients had percutaneous mitral valve clip and completed at least 12 months of follow-up. The average age was 60.56 years, 24.19 were females, 50% were diabetic, 46.77 were hypertensive, 12.90 had ESRD and 11.29 % had anemia. Coronary artery disease (CAD) was present in 59.41 %, prior CABG in 11.67% and prior PCI in 35.48%. All parameters value was compared pre MV clip and 12 ± 4.6 months after MV clip. The RV longitudinal strain was -12.4 ± 2.6% and improved to -14.6 ± 3.1% (P 0.005) (Figure A and B). The RV strain rate was -1.1 ± 0.41 and improved to -1.3 ± 0.57 (P 0.004) (Figure C and D). The tricuspid annulus plane systolic excursion (TAPSE) was 1.76 ±0.57 mm, and improved to 1.82 ±0.63 mm (P 0.4). The systolic velocity at the tricuspid annulus was 9.50 ±2.33cm/sec and improved to 9.64 ±2.72 cm/sec (P 0.269). The systolic pulmonary artery pressure (SPAP) was 50.49 ±13.92 and improved to 42.33 (P 0.036). Conclusion Mitral Clip implantation induces a significant reverse remodeling of RV. It produces significant improvement in the hemodynamics of the right side indicated by the significant reduction in SPAP and a significant increase in longitudinal RV strain and strain rate. Those changes could be a direct reflection of the concomitant reduction in LV filling pressure produced by the significant reverse remodeling of the LV caused by Mitral Clipping. Abstract P1710 Figure.

P99 Rapid ventricular stimulation induces augmented conduction delay in Brugada syndrome patients

Abstract Background The exact mechanism for Brugada Syndrome (BrS) is still not clear. There are two main physiologic hypotheses that have been suggested: the repolarization and the depolarization disorder models. Right ventricular (RV) activation delay was verified by echocardiography, conduction time in an explanted heart or in computer simulation. Verification of prolonged longitudinal activation time in human RV of only 5 patients of type-1 BrS and 5 controls was reported in 2008. Methods Bidirectional longitudinal activation times were assessed between RV outflow tract (RVot) and RV-apex (RVa) by stimulating and mapping RV endocardium in BrS patients. Conduction velocity was calculated considering ventricle size and distance between catheters. Results The studies were performed in controls (n = 18) and BrS patients (n = 6). There was no statistical difference in RP interval and QRS duration (PR 146 ± 21.7 vs 167 ± 45.2 ms, p = 0.325; QRS 102 ± 28.2 vs 122 ± 32.2 ms, p = 0.163). There was no difference of longitudinal activation time on stimulation at 500 ms (RVa to RVot: 63 ± 14.3 versus 80 ± 34.2 ms, p = 0.290; RVot to RVa: 50 ± 12.2 versus 76 ± 35.1 ms, p = 0.122). The BrS patients had longer longitudinal activation time on stimulation at 400 ms (RVa to RVot: 61 ± 15.2 versus 87 ± 28.7 ms, p = 0.009; RVot to RVa: 52 ± 11.1 versus 76 ± 35.3 ms, p = 0.029). The difference was not significant when isoproterenol was infused. Conclusions BrS patients display bidirectional longitudinal conduction delay when rapid stimulation. These findings support that BrS might be partly attributable to depolarization abnormality.

Abstract 17250: Underestimation of RV Volume by 3D Echocardiography in Patients With Severe PAH

Background: Right ventricular (RV) volume is a significant predictor of mortality in pulmonary arterial hypertension (PAH). RV volume measured by 3D echocardiography (3DE) an attractive imaging modality because it is faster and cheaper than cardiac MRIs. However, newer semi-automated speckle tracking 3DE has not been validated against cardiac MRI (CMR) in patients with severe PAH and dilated RVs. This study investigated the feasibility of 3DE to measure RV volumes in a prevalent cohort of patients with severe PAH. Methods: Patients with severe PAH with a 3DE and CMR within 30 days were included. RV endocardial contours were performed using TomTec 4D RV analysis© for 3DE and Circle Cardiovascular Imaging 42© for CMR. Results: Patients (n = 11) had severe PAH as classified as having high sPAP (66.4±5.0 mmHg), and reduced RV ejection fraction as measured by CMR (37.7±2.9%). In two patients, 3DE was not obtainable due to suboptimal definition of ventricular walls. In the remaining patients, there were systematic underestimation of volumes by 3DE (EDV bias: -71.5 LOA: 63.7; ESV -58.7: LOA: 72.7) and appears to be volume dependent (Fig 1A ). Lack of agreement seemed to possibly be related to extrapolation of poorly defined lateral wall RV endocardium by 3DE in patients with a large right ventricle (Fig 1B). Conclusion: Lack of agreement between CMR and 3DE derived RV volumes suggests the need for further validation of 3DE in patients with severe PAH.

Evaluating the roles of detailed endocardial structures on right ventricular haemodynamics by means of CFD simulations.

Computational modelling plays an important role in right ventricular (RV) haemodynamic analysis. However, current approaches use smoothed ventricular anatomies. The aim of this study is to characterise RV haemodynamics including detailed endocardial structures like trabeculae, moderator band, and papillary muscles. Four paired detailed and smoothed RV endocardium models (2 male and 2 female) were reconstructed from ex vivo human hearts high-resolution magnetic resonance images. Detailed models include structures with ≥1 mm2 cross-sectional area. Haemodynamic characterisation was done by computational fluid dynamics simulations with steady and transient inflows, using high-performance computing. The differences between the flows in smoothed and detailed models were assessed using Q-criterion for vorticity quantification, the pressure drop between inlet and outlet, and the wall shear stress. Results demonstrated that detailed endocardial structures increase the degree of intra-ventricular pressure drop, decrease the wall shear stress, and disrupt the dominant vortex creating secondary small vortices. Increasingly turbulent blood flow was observed in the detailed RVs. Female RVs were less trabeculated and presented lower pressure drops than the males. In conclusion, neglecting endocardial structures in RV haemodynamic models may lead to inaccurate conclusions about the pressures, stresses, and blood flow behaviour in the cavity.

Compartmentalized Structure of the Moderator Band Provides a Unique Substrate for Macroreentrant Ventricular Tachycardia

Background Papillary muscles are an important source of ventricular tachycardia (VT). Yet little is known about the role of the right ventricular (RV) endocavity structure, the moderator band (MB). The aim of this study was to determine the characteristics of the MB that may predispose to arrhythmia substrates. Methods Ventricular wedge preparations with intact MBs were studied from humans (n=2) and sheep (n=15; 40-50 kg). RV endocardium was optically mapped, and electrical recordings were measured along the MB and septum. S1S2 pacing of the RV free wall, MB, or combined S1-RV S2-MB sites were assessed. Human (n=2) and sheep (n=4) MB tissue constituents were assessed histologically. Results The MB structure was remarkably organized as 2 excitable, yet uncoupled compartments of myocardium and Purkinje. In humans, action potential duration heterogeneity between MB and RV myocardium was found (324.6±12.0 versus 364.0±8.4 ms; P<0.0001). S1S2-MB pacing induced unidirectional propagation via MB myocardium, permitting sustained macroreentrant VT. In sheep, the incidence of VT for RV, MB, and S1-RV S2-MB pacing was 1.3%, 5.1%, and 10.3%. Severing the MB led to VT termination, confirming a primary arrhythmic role. Inducible preparations had shorter action potential duration in the MB than RV (259.3±45.2 versus 300.7±38.5 ms; P<0.05), whereas noninducible preparations showed no difference (312.0±30.3 versus 310.0±24.6 ms, respectively). Conclusions The MB presents anatomic and electrical compartmentalization between myocardium and Purkinje fibers, providing a substrate for macroreentry. The vulnerability to sustain VT via this mechanism is dependent on MB structure and action potential duration gradients between the RV free wall and MB.

Computational Platform Based on Deep Learning for Segmenting Ventricular Endocardium in Long-axis Cardiac MR Imaging.

This paper presents an automated computational platform based on deep learning (DL) approach for left ventricular (LV) and right ventricular (RV) endocardium segmentation in long-axis cine cardiovascular magnetic resonance (CMR). The proposed method uses modified deep U-Net convolutional networks. We trained our model using 4800 images from 40 human subjects (20 healthy volunteers, 20 patients with various cardiac diseases) and validated the technique in 6000 images from 50 subjects (10 healthy volunteers, 40 patients). An average Dice metric of 0.929 ± 0.036 along with an average Jaccard index of 0.869 ± 0.059 were achieved for all the studied subjects. In addition, a high level of correlation and agreement with the ground truth contours for LV ejection fraction (R=0.975), LV fractional area change (R=0.959 to 0.971), and RV fractional area change (R=0.927) were observed. The proposed DL-based segmentation process took less than 3 seconds per subject (or < 30 milliseconds per image over 120 images for each subject). Therefore, our proposed framework offers a promising means to achieve fully automated and rapid segmentation for both LV and RV endocardium in long-axis cine CMR images using an appropriately trained deep convolutional neural network.

Quantification of Right Ventricular Size and Function from Contrast-Enhanced Three-Dimensional Echocardiographic Images

Three-dimensional (3D) echocardiography directly assesses right ventricular (RV) volumes without geometric assumptions, despite the complex shape of the right ventricle, and accordingly is more accurate and reproducible than the two-dimensional methodology, which is able to measure only surrogate parameters of RV function. Volumetric analysis has been hampered by frequent inability to clearly visualize RV endocardium, especially the RV free wall, in 3D echocardiographic images. The aim of this study was to test the hypothesis that RV contrast enhancement during 3D echocardiographic imaging would improve the accuracy of RV volume and function analysis. Thirty patients with a wide range of RV size and function and image quality underwent transthoracic 3D echocardiography with and without contrast enhancement and cardiovascular magnetic resonance imaging on the same day. RV end-diastolic and end-systolic volumes and ejection fraction were measured from contrast-enhanced and nonenhanced 3D echocardiographic images and compared with cardiovascular magnetic resonance reference values using linear regression and Bland-Altman analyses. Blinded repeated measurements were performed to assess measurement variability. RV contrast enhancement was feasible in all patients. RV volumes obtained both with and without contrast enhancement correlated highly with cardiovascular magnetic resonance (end-diastolic volume, r=0.90 and r=0.92; end-systolic volume, r=0.92 and r=0.94, respectively), but the correlation for ejection fraction was better with contrast (r=0.87 vs r=0.70). Biases were smaller with contrast for all three parameters (end-diastolic volume, -16±23 vs -36±25mL; end-systolic volume, -10±16 vs -23±18mL; ejection fraction, -0.7±5.5% vs -2.7±8.1% of the mean measured values), reflecting improved accuracy. Also, measurement reproducibility was improved by contrast enhancement. Contrast enhancement improves the visualization of RV endocardial borders, resulting in more accurate and reproducible 3D echocardiographic measurements of RV size and function. This approach may be particularly useful in patients with suboptimal image quality.

Right Ventricular Deformation Analyses Using a Three-Dimensional Speckle-Tracking Echocardiographic System Specialized for the Right Ventricle

Given the complex morphologic nature of the right ventricle, three-dimensional (3D) approaches would be more appropriate for assessing right ventricular (RV) function than two-dimensional approaches. Thus, the investigators have developed a novel 3D speckle-tracking echocardiographic (STE) system specialized for the right ventricle. The aim of this study was to assess the characteristics of RV global and regional deformation as well as changes on stress tests using the 3D STE system in experimental studies. In 10 sheep, sonomicrometry crystals were implanted to validate 3D STE data in the RV endocardium of seven RV segments, including the basal and mid anterior, lateral and inferior wall, and outflow free wall. Full-volume 3D STE data sets and sonomicrometric data were acquired at baseline, during pulmonary artery banding (PAB)-induced moderate (peak RV pressure>40mmHg) and severe (peak RV pressure>60mmHg) RV pressure increases, and during propranolol infusion. The 3D STE area change ratio (ACR), longitudinal strain (LS), and circumferential strain (CS) were measured, and RV global and all segmental deformation data were compared between baseline and stress tests. To assess clinical feasibility, 30 control subjects and 11 patients with pulmonary arterial hypertension were enrolled. All combined 3D STE data were significantly correlated with the sonomicrometric data (ACR, R(2)=0.88; LS, R(2)=0.84; CS, R(2)=0.82; P<.001). In all seven segments, the 3D STE data correlated with the sonomicrometric data (R(2)=0.72-0.90, P<.001). Global ACR and LS data showed significant differences among baseline, moderate PAB, and severe PAB; however, CS differed only between baseline and severe PAB. The magnitudes of segmental deformation in the free wall were larger than those in the septum and apex under all conditions (P<.05) except LS during severe PAB. Segmental analyses also showed similar responses during stress tests; the ACR in each segment differed significantly between conditions. In all but the apical segments, LS showed significant reductions from moderate PAB; in contrast, CS was significantly reduced with severe PAB in all segments. In this clinical study, the acquisition rate of adequate images for analysis of the RV outflow tract was lower (75.6%) compared with the rate in other segments (from 85.4% to 100%). However, the pulmonary arterial hypertension group had lower RV global deformation values than the control group (ACR and LS, P<.001; CS, P=.003), the ACR and LS in basal and middle segments differed significantly between groups, and the outflow and apex did not differ. A novel 3D STE system specialized for the right ventricle is reliable for RV deformation analyses and may provide additional information about RV global and segmental function. The clinical feasibility of this system is acceptable.

Right Ventricular Systolic and Diastolic Function as Assessed by Speckle-Tracking Echocardiography Improve with Long-Term Left Ventricular Assist Device Support

Right ventricular (RV) failure is a major cause of morbidity and mortality after left ventricular assist device (LVAD) implantation. As a LVAD primarily supports the left ventricle, it is unknown whether RV pathology progresses over time leading to deterioration in RV function among patients chronically supported with a LVAD. RV longitudinal strain and strain rate as measured by speckle-tracking echocardiography provide a more sensitive, reproducible, and quantitative assessment of RV systolic and diastolic function than conventional echocardiography. Since LVADs decrease left sided filling pressure, reduce pulmonary pressure, and reduce RV afterload we hypothesized that RV systolic and diastolic function would remain stable or even improve after prolonged continuous-flow LVAD support. Echocardiograms were retrospectively reviewed from before and after implantation of a HeartMate II LVAD between 2006 and 2013 at a single center. Patients who had a baseline echocardiogram before LVAD that was performed off inotropes and a follow up echocardiogram after at least 2 months of LVAD support were included in the analysis. Patients were excluded if they required a RV assist device, had a LVAD malfunction, or had poor echocardiographic visualization of the RV endocardium. The speckle-tracking analysis software Velocity Vector Imaging (Siemens Medical) was used to calculate global RV longitudinal systolic strain, strain rate, and diastolic strain rate. Paired t-tests compared measures at baseline before LVAD to the time of maximal follow up after LVAD implantation. Of the 75 LVAD patients screened, 32 had a baseline echocardiogram off inotropes before LVAD along with a paired echocardiogram at least 2 months after LVAD implantation. 15 patients met exclusion criteria, leaving an analysis cohort of 17 patients with a mean duration of LVAD support at the time of the follow up echocardiogram of 271±129 days. Global RV longitudinal strain improved in 12 of 17 patients (70%) with the average RV strain decreasing from -7.9±2.3% before to -9.8±3.4% after LVAD (p=0.034). Similarly, RV longitudinal systolic strain rate improved in 11 patients (64%) with the average RV systolic strain rate decreasing from -0.67±0.24%/sec before to -0.99±0.35%/sec after LVAD (p=0.002). Finally RV longitudinal diastolic strain rate improved in 14 patients (82%) with the average RV diastolic strain rate increasing from 0.77±0.33%/sec before to 0.99±0.33%/sec after LVAD (p=0.029). Among LVAD patients who did not require a RV assist device, RV systolic and diastolic function as determined by speckle-tracking echocardiography improved in the majority of patients during chronic LVAD support. This suggests that LVADs prevent progression of RV dysfunction in this group of patients and emphasizes the need for strategies for temporary support of the failing RV in the initial period after LVAD implantation to allow for long term stabilization and improvement in RV function.

Three-Dimensional Modeling of the Right Ventricle from Two-Dimensional Transthoracic Echocardiographic Images: Utility of Knowledge-Based Reconstruction in Pulmonary Arterial Hypertension

Right ventricular (RV) volume and functional assessments are essential in the management of pulmonary arterial hypertension but are often difficult to perform. Three-dimensional (3D) echocardiography is limited by acoustic dropout of the RV free wall in dilated ventricles. The aim of this study was to test the hypothesis that knowledge-based reconstruction, a novel method for 3D modeling of RV endocardium from two-dimensional echocardiographic images, could provide accurate measurements of RV volumes and systolic function. Twenty-seven patients with pulmonary arterial hypertension were prospectively recruited for same-day echocardiography and cardiovascular magnetic resonance (CMR), which was used as a reference standard. Two-dimensional transthoracic echocardiographic images were acquired with 3D spatial localization equipment to allow 3D reconstruction. Image analysis was performed with dedicated software to obtain end-diastolic volume (EDV) and end-systolic volume (ESV) and RV ejection fraction (EF). The method of disks was used to determine RV volumes on CMR. Echocardiographic RV volumes correlated well with CMR (EDV, R= 0.87; ESV, R= 0.88; EF, R= 0.75). For interobserver analyses, coefficients of variability were 7.8 ± 7.0% for EDV, 10.2 ± 8.0% for ESV, and 15.4 ± 13.8% for EF. For intraobserver analyses, coefficients of variability were 7.1 ± 5.1% for EDV, 8.3 ± 7.0% for ESV, and 10.9 ± 9.2% for EF. On Bland-Altman analyses, volumes obtained on transthoracic echocardiography (TTE) were slightly larger than those obtained by CMR (ΔEDVTTE-CMR, 5.8 ± 33.7 mL; ΔESVTTE-CMR, 3.5 ± 27.8 mL), whereas EFs tended to be slightly higher by CMR (ΔEFCMR-TTE, 0.5 ± 6.5%). Knowledge-based reconstruction provides accurate and reproducible measurements of RV volumes in patients with pulmonary arterial hypertension. Larger studies are needed to confirm these results and to determine the practicality of this approach in daily practice and as an end point in clinical trials.

Right ventricular arrhythmogenesis in failing human heart: the role of conduction and repolarization remodeling

Increased dispersion of repolarization has been suggested to underlie increased arrhythmogenesis in human heart failure (HF). However, no detailed repolarization mapping data were available to support the presence of increased dispersion of repolarization in failing human heart. In the present study, we aimed to determine the existence of enhanced repolarization dispersion in the right ventricular (RV) endocardium from failing human heart and examine its association with arrhythmia inducibility. RV free wall preparations were dissected from five failing and five nonfailing human hearts, cannulated and coronary perfused. RV endocardium was optically mapped from an ∼6.3 × 6.3 cm(2) field of view. Action potential duration (APD), dispersion of APD, and conduction velocity (CV) were quantified for basic cycle lengths (BCL) ranging from 2,000 ms to the functional refractory period. We found that RV APD was significantly prolonged within the failing group compared with the nonfailing group (560 ± 44 vs. 448 ± 39 ms, at BCL = 2,000 ms, P < 0.05). Dispersion of APD was increased in three failing hearts (161 ± 5 vs. 86 ± 19 ms, at BCL = 2,000 ms). APD alternans were induced by rapid pacing in these same three failing hearts. CV was significantly reduced in the failing group compared with the nonfailing group (81 ± 11 vs. 98 ± 8 cm/s, at BCL = 2,000 ms). Arrhythmias could be induced in two failing hearts exhibiting an abnormally steep CV restitution and increased dispersion of repolarization due to APD alternans. Dispersion of repolarization is enhanced across the RV endocardium in the failing human heart. This dispersion, together with APD alternans and abnormal CV restitution, could be responsible for the arrhythmia susceptibility in human HF.

Impact of the permanent ventricular pacing site on left ventricular function in children: a retrospective multicentre survey

BackgroundChronic right ventricular (RV) pacing is associated with deleterious effects on cardiac function.ObjectiveIn an observational multicentre study in children with isolated atrioventricular (AV) block receiving chronic ventricular pacing, the importance...

Regional variations in action potential alternans in isolated murine Scn5a+/− hearts during dynamic pacing

clinical observations suggest that alternans in action potential (AP) characteristics presages breakdown of normal ordered cardiac electrical activity culminating in ventricular arrhythmogenesis. We compared such temporal nonuniformities in monophasic action potential (MAP) waveforms in left (LV) and right ventricular (RV) epicardia and endocardia of Langendorff-perfused murine wild-type (WT), and Scn5a(+/-) hearts modelling Brugada syndrome (BrS) for the first time. a dynamic pacing protocol imposed successively incremented steady pacing rates between 5.5 and 33 Hz. A signal analysis algorithm detected sequences of >10 beats showing alternans. Results were compared before and following the introduction of flecainide (10 microm) and quinidine (5 microm) known to exert pro- and anti-arrhythmic effects in BrS. sustained and transient amplitude and duration alternans were both frequently followed by ventricular ectopic beats and ventricular tachycardia or fibrillation. Diastolic intervals (DIs) that coincided with onsets of transient (tr) or sustained (ss) alternans in MAP duration (DI*) and amplitude (DI') were determined. Kruskal-Wallis tests followed by Bonferroni-corrected Mann-Whitney U-tests were applied to these DI results sorted by recording site, pharmacological conditions or experimental populations. WT hearts showed no significant heterogeneities in any DI. Untreated Scn5a (+/-) hearts showed earlier onsets of transient but not sustained duration alternans in LV endocardium compared with RV endocardium or LV epicardium. Flecainide administration caused earlier onsets of both transient and sustained duration alternans selectively in the RV epicardium in the Scn5a (+/-) hearts. these findings in a genetic model thus implicate RV epicardial changes in the arrhythmogenicity produced by flecainide challenge in previously asymptomatic clinical BrS.

Acute ischemia of canine interventricular septum produces asymmetric suppression of conduction

Acute ischemia depresses tissue excitability more rapidly in the epicardium than in the endocardium of the canine left ventricular (LV) free wall. However, the effects of acute ischemia on conduction in the interventricular septum (IVS), which is composed of right ventricular (RV) and LV endocardium and midmyocardium without epicardium, are less known. The purpose of this study was to evaluate the hypothesis that the IVS exhibits transseptal differences in local tissue response to acute ischemia. Isolated canine IVS preparations were perfused through the septal branch of the anterior descending coronary artery, and conduction on the cut-exposed transseptal surfaces was optically mapped before and after two sequential episodes of 8 minutes of global ischemia (separated by >60 minutes of reperfusion). The preparations were paced alternately between the RV endocardium and LV endocardium at cycle lengths of 250, 300, and 1,500 ms. Prior to ischemia, transseptal conduction was radial and symmetric during either RV endocardial or LV endocardial pacing at all cycle lengths. Eight minutes of ischemia depressed conduction velocity more in the RV half than in the LV half of the IVS and caused local conduction block in the sub-RV endocardium, especially during rapid pacing. The K(ATP) channel blocker glibenclamide (10 micromol/L) prevented development of this transseptal asymmetry and conduction block during ischemia. Acute global ischemia increased transseptal heterogeneity and induced sub-RV endocardial block of conduction via activation of the ATP-sensitive potassium current. Such changes could contribute to initiation of arrhythmia in patients with septal infarction.

Transmural temporospatial left ventricular activation during pacing from different sites: potential implications for optimal pacing

Previous studies showed that right ventricular (RV) endocardial pacing can be deleterious even in individuals with initially normal left ventricular (LV) function. The mechanism(s) by which RV endocardial pacing may cause LV dysfunction is unknown. This study compares the temporospatial LV transmyocardial activation profiles during sinus rhythm with normal His/Purkinje conduction vs. currently utilized and proposed cardiac pacing sites. Mongrel dogs were instrumented with transmural electrodes that tracked transmyocardial activation sequences at five sites in the LV. Pacing/recording catheters were positioned in the RV apex and on the RV and LV sides of the ventricular septum. An epicardial pacing electrode was also sewn to the mid-lateral LV epicardium. Electrograms were recorded during sinus rhythm and pacing from the RV endocardium, LV septum, LV epicardium and during biventricular pacing. Compared to normal sinus/His/Purkinje rhythm (NSR), RV endocardial pacing significantly (P < 0.05) prolonged transmural activation (NSR endocardium 6.1 +/- 1 ms vs. RV endocardium 23.0 +/- 2.6 ms). The highly ordered temporospatial pattern of transmural activation during sinus rhythm was replaced with dispersion and intermingling of endo-, mid-, and epicardial activation. LV epicardial and biventricular pacing did not correct these abnormalities. Only LV septal pacing achieved the transmural and transseptal activation sequences similar to sinus rhythm. Clinically utilized pacing modalities, including biventricular pacing, cause abnormal transmyocardial activation. LV septal pacing results in transmyocardial activation patterns that closely resemble those seen in sinus rhythm.

Steeper restitution slopes across right ventricular endocardium in patients with cardiomyopathy at high risk of ventricular arrhythmias

Steep action potential duration (APD) restitution slopes (>1) and spatial APD restitution heterogeneity provide the substrate for ventricular fibrillation in computational models and experimental studies. Their relationship to ventricular arrhythmia vulnerability in human cardiomyopathy has not been defined. Patients with cardiomyopathy [left ventricular (LV) ejection fraction <40%] and no history of ventricular arrhythmias underwent risk stratification with programmed electrical stimulation or T wave alternans (TWA). Low-risk patients (n = 10) had no inducible ventricular tachycardia (VT) or negative TWA, while high-risk patients (n = 8) had inducible VT or positive TWA. Activation recovery interval (ARI) restitution slopes were measured simultaneously from 10 right ventricular (RV) endocardial sites during an S1-S2 pacing protocol. ARI restitution slope heterogeneity was defined as the coefficient of variation of slopes. Mean ARI restitution slope was significantly steeper in the high-risk group compared with the low-risk group [1.16 (SD 0.31) vs. 0.59 (SD 0.19), P = 0.0002]. The proportion of endocardial recording sites with a slope >1 was significantly larger in the high-risk patients [47% (SD 35) vs. 13% (SD 21), P = 0.022]. Spatial heterogeneity of ARI restitution slopes was similar between the two groups [29% (SD 16) vs. 39% (SD 34), P = 0.48]. There was an inverse linear relationship between the ARI restitution slope and the minimum diastolic interval (P < 0.001). In cardiomyopathic patients at high risk of ventricular arrhythmias, ARI restitution slopes along the RV endocardium are steeper, but restitution slope heterogeneity is similar compared with those at low risk. Steeper ARI restitution slopes may increase the propensity for ventricular arrhythmias in patients with impaired left ventricular function.