Transmural Gradient Research Articles

Evaluating the Stress State and the Load-Bearing Fraction as Predicted by an In Vivo Parameter Identification Method for the Abdominal Aorta

Background: Arterial mechanics are crucial to cardiovascular functionality. The pressure–strain elastic modulus often delineates mechanical properties. Emerging methods use non-linear continuum mechanics and non-convex minimization to identify tissue-specific parameters in vivo. Reliability of these methods, particularly their accuracy in representing the in vivo stress state, is a significant concern. This study aims to compare the predicted stress state and the collagen-attributed load-bearing fraction with the stress state from in silico experiments. Methods: Our team has evaluated an in vivo parameter identification method through in silico experiments involving finite element models and demonstrated good agreement with the parameters of a healthy abdominal aorta. Results: The findings suggest that the circumferential stress state is well represented for an abdominal aorta with a low transmural stress gradient. Larger discrepancies are observed in the axial direction. The agreement deteriorates in both directions with an increasing transmural stress gradient, attributed to the membrane model’s inability to capture transmural gradients. The collagen-attributed load-bearing fraction is well predicted, particularly in the circumferential direction. Conclusions: These findings underscore the importance of investigating both isotropic and anisotropic aspects of the vessel wall. This evaluation advances the parameter identification method towards clinical application as a potential tool for assessing arterial mechanics.

Global, segmental, and layer-specific two-dimensional speckle tracking echocardiography immediately after acute myocardial infarction as a predictive tool to assess myocardial viability and scar size.

The identification of myocardial scar is key in clinical decision-making after acute myocardial infarction (AMI). However, the gold standard that is cardiac magnetic resonance imaging (CMR) encounters limitations in terms of availability. Two-dimensional speckle tracking echocardiography (2D-STE) may be an accessible alternative in detecting scar and assessing scar transmurality. We aim to evaluate the predictive value of 2D-STE, encompassing measures of global, segmental and layer-specific strain, with respect to myocardial viability and scar size at 6 months follow-up. In 43 patients admitted for primary AMI, we conducted a comparative analysis of strain parameters (including global longitudinal strain (GLS), segmental longitudinal strain (SLS), layer-specific GLS and SLS and the transmural strain gradient from endocardium to epicardium) in relation to conventional echocardiographic parameters at baseline in predicting for scar size and the transmurality index, as measured by CMR, 6 months post enrollment. We demonstrate a moderate correlation between both GLS and conventional echocardiographic parameters, and scar size as well as transmurality index. Wall motion score index exhibited superior predictive performance over GLS and left ventricular ejection fraction in anticipating scar formation. At a cut-off of -13.3% for any scar and -11.5% for transmural scar, SLS can predict scar formation. Layer-specific strain did not provide added predictive value. SLS, but not layer-specific strain, during admission after AMI is an easy and accessible quantitative tool for predicting scar formation and transmurality extent at 6 months follow-up. GLS correlates well with scar size, suggesting its potential utility as a predictive tool.

Significance of J wave with inverted ST-T polarity induced by ill-timed atrial premature beats and its association with Torsade de Pointes in patients with acute acquired long QT syndrome

Abstract Background When ventricular cardiomyocytes become depolarized during their relative refractory period (RRP), the amplitude of the action potential (AP) becomes lower than that of preceding AP, since some sodium channels are in their refractory state. If the membrane voltage does not reach a level high enough to activate voltage-dependent calcium channels, the AP duration becomes markedly shortened due to loss of AP dome. In patients with long QT syndrome (LQTS), intrinsic differences in AP duration and/or AP restitution kinetics exist between ventricular endocardium and epicardium. Thus, we hypothesized that atrial premature beats (APBs) can capture the RRP and amplify a transmural voltage gradient that manifests as a J wave with inverted ST-T polarity (APB-induced J wave). Purpose To investigate the prevalence of APB-induced J wave and examine the contribution to the development of Torsade de Pointes (TdP) in patients with acute acquired LQTS. Methods A total of 34 consecutive patients with acute acquired LQTS (14 men; median age, 69 years; median QTc, 645.5 ms) and documented TdP were enrolled. APBs were observed before the onset of TdP in 18 (52.9%) patients. The 34 patients were divided into 2 groups based on the presence or absence of APB-induced J wave with inverted ST-T polarity: APB-J wave group (n=8) and non-APB-J wave group (n=26). Results APB-J wave group constituted 23.5% (8/34) of the studied patients. There were no significant differences in clinical characteristics (sex, age and QTc) between the 2 groups. Macroscopic T-wave alternans was more frequently observed before TdP onset in APB-J wave group than non-APB-J wave group (75% vs 15.4%, p=0.003). The ill-timed APBs with J wave directly initiated TdP in all patients in APB-J wave group. APB-J wave group experienced TdP even after initiating conventional therapy more frequently than non-APB-J wave group (3.5 vs 1 event, p=0.04). Conclusions APB-induced J wave is observed in approximately one-fourth of acute acquired LQTS patients with TdP and is associated with an increased risk of TdP. Our observations suggest that APBs can amplify the transmural dispersion of repolarization manifested as a J wave.Figure1Figure2

The utility of novel STE parameters in echocardiographic assessment of single ventricle after Fontan palliation

Background and aims of the study A functionally single ventricle (FSV) refers to a group of congenital heart defects that are not amenable for biventricular correction. The Fontan operation is utilized as surgical treatment for most of FSV patients. The evaluation of FSV function is extremely difficult due to its unique pathophysiology. This study aimed to explore the efficacy of speckle tracking echocardiography (STE) parameters measured at rest and during exercise for comprehensive assessment of univentricular heart. MethodsWe enrolled 37 patients with a functionally single ventricle after the Fontan operation, hospitalized in the Department of Congenital Heart Defects between years 2019 and 2021.The echocardiographic stress tests were performed in the Echocardiography Laboratory of the Congenital Heart Defects Department. The study was conducted on a bicycle ergometer in a semi-recumbent position. The parameters obtained by speckle tracking echocardiography (STE): the longitudinal strain of the FSV free wall (Ɛ) and the longitudinal strain of myocardial layers: subendocardial, medial and subepicardial were analyzed. A transmural longitudinal strain gradient (TG) was calculated as the difference between longitudinal deformation of the subendocardial and subepicardial layers. Current results of cardiac magnetic resonance imaging (CMR) and cardio-pulmonary test (CPET) were also incorporated. Demographic data, past interventions, pharmacological treatment and comorbidities were extracted from medical records. ResultsƐ at rest and during exercise were not related to the parameters of physical capacity obtained on CPET nor to the CMR results. The transmural strain gradient was dependent on physical performance parameter- peak oxygen uptake- and related to the FSV ejection fraction calculated by magnetic resonance imaging. ConclusionsThe transmural strain gradient and FSV free wall strain are readily measurable and suitable for evaluating single ventricle function. The TG is positively correlated with peak oxygen uptake during the cardiopulmonary test and with the ejection fraction derived from cardiac magnetic resonance imaging. The applicability of these findings in patients undergoing the Fontan procedure warrants further exploration.

Alteration of transmural electrophysiological gradient in a rabbit model with a RyR2 mutation

Alteration of transmural electrophysiological gradient in a rabbit model with a RyR2 mutation

Repolarization gradient induces local depolarization abnormalities in Brugada Syndrome

Abstract Background Transmural voltage gradient in right ventricular outflow tract (RVOT) induces diagnostic ECG-phenotype in Brugada syndrome(BrS). Moreover, RVOT depolarization abnormalities have been described as contributors to BrS phenotype and arrhythmogenesis. Purpose To investigate the effect of ajmaline administration on J-elevation of RVOT unipolar signals in BrS patients. Moreover, we wanted to assess whether ajmaline-induced unipolar J-point elevation variations induced local depolarization abnormalities. Methods 21 BrS patients with spontaneous type-1 ECG pattern were enrolled. Due to the absence of BrS ECG pattern at the study, patients underwent RV endocardial mapping with the CARTO3 system, before (PRE) and after (POST) ajmaline administration. The PRE and POST data were exported from CARTO and converted into Matlab format using OpenEP. J-elevation for each point was calculated as the amplitude of the unipolar signal at J wave with respect to baseline. Activation time (AT) of each point was defined as the difference between local depolarization (minimum dV/dt of the unipolar signal) and surface ECG depolarization (time of the minimum signal on V2). With an automatic algorithm, corresponding PRE and POST points were selected. The difference between POST and PRE of each parameter was calculated to obtain the differential values delta-J and delta-AT. Differential values were then interpolated on the mesh of each subject to obtain 3D maps. The deltaJ map was divided into four intervals based on quartiles. We then selected a ROI 'IN' on a region with the greatest deltaJ variation, and a second ROI 'OUT' on the zone of lowest variation. The same ROIs were applied to the deltaAT map. The mean value of the respective differential parameters was extracted in each ROI. Results Greatest delta-J values were found in the RVOT/anterior wall. delta-J in the ROI 'IN' was greater than in the ROI 'OUT' (1.68 [1.11-2.28] vs 0.56 [0.38-0.93] mV, p<0.001). delta-AT in the ROI ‘IN’ was greater than in the ROI ‘OUT’ (27.96 [20.39-44.89] vs 7.62 [4.24-16.69] ms, p<0.001). A good correlation was found between delta-J and delta-AT, considering the data for the two ROIs together (Spearman R coefficient=0.71, p<0.001). Conclusions Our study shows that the repolarization gradient, evaluated by localized delta-J increase in RVOT, justifies BrS ECG phenotype and local depolarization abnormalities. A strong correlation was present in these RVOT areas between J-elevation variation and slow conducting zones.

REPOLARIZATION GRADIENT CAUSES LOCAL DEPOLARIZATION ABNORMALITIES IN BRUGADA SYNDROME

Abstract Background Transmural voltage gradient in RVOT induces ECG–phenotype in Brugada syndrome(BrS). Moreover,RVOT depolarization abnormalities have been described as contributors to BrS phenotype and arrhythmogenesis. Purpose To investigate the effect of ajmaline administration on J–elevation of RVOT unipolar signals in BrS patients. Moreover,we wanted to assess whether ajmaline–induced unipolar J–point elevation variations induced local depolarization abnormalities. Methods 21 BrS patients with spontaneous type–1 ECG pattern were enrolled. Due to the absence of BrS ECG pattern at the study, patients underwent RV endocardial mapping with the CARTO3 system, before (PRE) and after (POST) ajmaline administration. The data were exported from CARTO and converted into Matlab format using OpenEP. J–elevation for each point was calculated as the amplitude of the unipolar signal at J wave with respect to baseline. Activation time (AT) of each point was defined as the difference between local depolarization (minimum dV/dt of the unipolar signal) and surface ECG depolarization(time of the minimum signal on V2). With an automatic algorithm, corresponding PRE and POST points were selected. The difference between POST and PRE of each parameter was calculated to obtain the differential values delta–J and delta–AT. Differential values were then interpolated on the mesh of each subject to obtain 3D maps. The deltaJ map was divided into four intervals based on quartiles. We then selected a ROI ‘IN‘ on a region with the greatest deltaJ variation, and a second ROI ‘OUT‘ on the zone of lowest variation. The same ROIs were applied to the deltaAT map. The mean value of the respective differential parameters was extracted in each ROI. Results Greatest delta–J values were found in the RVOT/anterior wall. delta–J in the ROI ‘IN‘ was greater than in the ROI ‘OUT‘ (1.68 [1.11–2.28] vs 0.56 [0.38–0.93] mV, p<0.001). delta–AT in the ROI ‘IN’ was greater than in the ROI ‘OUT’ (27.96 [20.39–44.89] vs 7.62 [4.24–16.69] ms, p<0.001). A good correlation was found between delta–J and delta–AT, considering the data for the two ROIs together (Spearman R coefficient=0.71, p<0.001). Conclusions: Our study shows that the repolarization gradient, evaluated by localized delta–J increase in RVOT, justifies BrS ECG phenotype and local depolarization abnormalities. A strong correlation was present in these RVOT areas between J–elevation variation and slow conducting zones.

The value of speckle-tracking stratified strain combined with myocardial work measurement in evaluating left ventricular function in patients with heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is a highly prevalent progressive disease accompanied by poor quality of life, high utilization of medical resources, morbidity, and mortality. However, the role of left ventricular (LV) systolic dysfunction has yet to be well elaborated despite the preservation of the LV ejection fraction. This study aimed to explore the diagnostic value of speckle-tracking stratified strain combined with myocardial work (MW) measurement in evaluating LV systolic dysfunction in patients with HFpEF. A total of 125 study consecutive individuals, 64 HFpEF patients, and 61 controls were prospectively enrolled in the Fourth Affiliated Hospital of Harbin Medical University. In addition to the conventional echocardiographic parameters, LV stratified strain and MW parameters were statistically compared between the HFpEF and control groups. The global longitudinal strain (GLS) of the subendocardium, myocardium, and subepicardium (GLSendo, GLSmyo, and GLSepi); the transmural gradient (ΔGLS); the global myocardial work index (GWI), global myocardial work efficiency (GWE), global myocardial constructive work (GCW), and the global myocardial wasted work (GWW) were included. Area under the receiver operating characteristic curve analysis was used to evaluate the diagnostic performance of these univariate and multivariable logistic models in detecting impaired LV systolic function in HFpEF. Ten-fold cross-validation was used to evaluate the generalizability of the predictive model. Stratified strains values showed a gradient decline from GLSendo to GLSepi in both control and HFpEF patients. Compared with the control group, HFpEF patients had a significantly reduced GLSepi, GLSmyo, GLSendo, ΔGLS, GWI, GWE, and GCW and a significantly increased GWW (all P<0.001). In the derivation set, the optimal logistic model (combined stratified strain and MW variables) demonstrated the highest performance in predicting LV systolic function impairment in HFpEF patients. The best-performing model with a mean area under the curve (AUC) of 0.966 [95% confidence interval (CI): 0.88 to 1] accessed by 10-fold cross-validation. In the validation set, the AUC of the optimal logistic model was 0.933 (95% CI: 0.85 to 1), the sensitivity was 87%, and the specificity was 93%. Both speck-tracking stratified strain and MW measurement may sensitively detect impairment of LV myocardial function at an early stage for patients with HFpEF. Combining the two techniques may improve the quality of HFpEF diagnosis and may provide a reference value for the early diagnosis of HFpEF in the future.

Chronic fatigue syndrome and multiple sclerosis have reduced craniospinal compliance and dilated pressurized bridging cortical veins

Chronic fatigue syndrome (CFS) and multiple sclerosis (MS) share similarities regarding their epidemiology, symptomatology and craniospinal physiology. Indeed, the cardinal feature of CFS, fatigue, is also a major factor in the symptomatology of the majority of MS patients. Recently, we have found that there is a significant reduction in the craniospinal compliance in MS which affects both the stiffness of the walls of the spinal canal and the walls of the cerebral venous system. This change in compliance brings about an alteration in the effectiveness of the pulse wave dampening in the craniospinal system. The result is an impedance mismatch between the cortical veins and their draining sinuses, leading to dilatation of these upstream veins. We deduce this dilatation can only be brought about by an increase in the pressure gradient between the vein lumen and the subarachnoid space (i.e. the transmural pressure gradient). We hypothesise that given the similarities between MS and CFS, a similar mechanism underlies the physiology of CFS. We present two case studies to highlight the expected findings in CFS patients if this hypothesis were proven to be correct.

Biventricular intraventricular mechanical and electrical dyssynchrony in pulmonary arterial hypertension

BackgroundPulmonary arterial hypertension (PAH) leads to myocardial remodeling, manifesting as mechanical dyssynchrony (M-dys) and electrical dyssynchrony (E-dys), in both right (RV) and left ventricles (LV). However, the impacts of layer-specific intraventricular M-dys on biventricular functions and its association with E-dys in PAH remain unclear. MethodsSeventy-nine newly diagnosed patients with PAH undergoing cardiac magnetic resonance scanning were consecutively recruited between January 2011 and December 2017. The biventricular volumetric and layer-specific intraventricular M-dys were analyzed. The QRS duration z-scores were calculated after adjusting for age and sex. Results77.22 % of patients were female (mean age 30.30 ± 9.79 years; median follow-up 5.53 years). Further, 29 (36.71 %) patients succumbed to all-cause mortality by the end of the study. At the baseline, LV layer–specific intraventricular M-dys had apparent transmural gradients compared with RV in the radial and circumferential directions. However, deceased patients lost the transmural gradients. The LV longitudinal strain rate time to late diastolic peak in the myocardial region (LVmyoLSRTTLDPintra) predicted long-term survival. The Kaplan–Meier curve revealed that patients with PAH with LVmyoLSRTTLDPintra <20.01 milliseconds had a worse prognosis. Larger right ventricle (RV) intraventricular M-dys resulted in worse RV ejection fraction. However, larger LV intraventricular M-dys in the late diastolic phase indicated remarkable exercise capacity and higher LV stroke volume index. E-dys and intraventricular M-dys had no direct correlations. ConclusionsThe layer-specific intraventricular M-dys had varying impacts on biventricular functions in PAH. PAH patients with LVmyoLSRTTLDPintra <20.01 milliseconds had a worse prognosis. LV intraventricular M-dys in the late diastolic phase needs more attention to precisely evaluate LV function.

Heterogeneous cardiac sympathetic innervation gradients promote arrhythmogenesis in murine dilated cardiomyopathy.

Ventricular arrhythmias (VAs) in heart failure are enhanced by sympathoexcitation. However, radiotracer studies of catecholamine uptake in failing human hearts demonstrate a proclivity for VAs in patients with reduced cardiac sympathetic innervation. We hypothesized that this counterintuitive finding is explained by heterogeneous loss of sympathetic nerves in the failing heart. In a murine model of dilated cardiomyopathy (DCM), delayed PET imaging of sympathetic nerve density using the catecholamine analog [11C]meta-Hydroxyephedrine demonstrated global hypoinnervation in ventricular myocardium. Although reduced, sympathetic innervation in 2 distinct DCM models invariably exhibited transmural (epicardial to endocardial) gradients, with the endocardium being devoid of sympathetic nerve fibers versus controls. Further, the severity of transmural innervation gradients was correlated with VAs. Transmural innervation gradients were also identified in human left ventricular free wall samples from DCM versus controls. We investigated mechanisms underlying this relationship by in silico studies in 1D, 2D, and 3D models of failing and normal human hearts, finding that arrhythmogenesis increased as heterogeneity in sympathetic innervation worsened. Specifically, both DCM-induced myocyte electrical remodeling and spatially inhomogeneous innervation gradients synergistically worsened arrhythmogenesis. Thus, heterogeneous innervation gradients in DCM promoted arrhythmogenesis. Restoration of homogeneous sympathetic innervation in the failing heart may reduce VAs.

Modeling ventricular repolarization gradients in normal cases using the equivalent dipole layer

Background Electrical activity underlying the T-wave is less well understood than the QRS-complex. This study investigated the relationship between normal T-wave morphology and the underlying ventricular repolarization gradients using the equivalent dipole layer (EDL).Methods Body-surface-potential-maps (BSPM, 67‑leads) were obtained in nine normal cases. Subject specific MRI-based anatomical heart/torso-models with electrode positions were created. The boundary element method was used to account for the volume conductor effects. To simulate the measured T-waves, the EDL was used to apply different ventricular repolarization gradients: a) transmural, b) interventricular c) apico-basal and d) all three gradients (a-c) combined. The combined gradient (d) was optimized using an inverse procedure (Levenberg-Marquardt). Correspondence between simulated and measured T-waves was assessed using correlation coefficient (CC) and relative difference (RD).Results Realistic T-waves were simulated if repolarization times of: (a) the epicardium were smaller than the endocardium; (b) the left ventricle were smaller than the right ventricle and (c) the apex increased towards the base. The apico-basal gradient resulted in the highest correspondence between measured and simulated T-waves (CC = 0.84(0.81–0.91);RD = 0.68(0.60–0.71)) compared to a transmural gradient (CC = 0.77(0.71–0.80);RD = 1.46(0.82–1.75)) and an interventricular gradient (CC = 0.71(0.67–0.80);RD = 0.85(0.75–0.87)). All three gradients combined further improved the correspondence between measured and simulated T-waves (CC = 0.83(0.82–0.89);RD = 0.60(0.51–0.63)), especially after optimization (CC = 0.96(0.94–0.98);RD = 0.27(0.22–0.34)).Conclusion The application of all repolarization gradients combined resulted in the largest agreement between simulated and measured T-waves, followed by the apico-basal repolarization gradient. With these findings, we will optimize our EDL-based inverse procedure to assess repolarization abnormalities.

Localized cardiomyocyte lipid accumulation is associated with slowed epicardial conduction in rats.

Transmural action potential duration differences and transmural conduction gradients aid the synchronization of left ventricular repolarization, reducing vulnerability to transmural reentry and arrhythmias. A high-fat diet and the associated accumulation of pericardial adipose tissue are linked with conduction slowing and greater arrhythmia vulnerability. It is predicted that cardiac adiposity may more readily influence epicardial conduction (versus endocardial) and disrupt normal transmural activation/repolarization gradients. The aim of this investigation was to determine whether transmural conduction gradients are modified in a rat model of pericardial adiposity. Adult Sprague-Dawley rats were fed control/high-fat diets for 15 wk. Left ventricular 300 µm tangential slices were generated from the endocardium to the epicardium, and conduction was mapped using microelectrode arrays. Slices were then histologically processed to assess fibrosis and cardiomyocyte lipid status. Conduction velocity was significantly greater in epicardial versus endocardial slices in control rats, supporting the concept of a transmural conduction gradient. High-fat diet feeding increased pericardial adiposity and abolished the transmural conduction gradient. Slowed epicardial conduction in epicardial slices strongly correlated with an increase in cardiomyocyte lipid content, but not fibrosis. The positive transmural conduction gradient reported here represents a physiological property of the ventricular activation sequence that likely protects against reentry. The absence of this gradient, secondary to conduction slowing and cardiomyocyte lipid accumulation, specifically in the epicardium, indicates a novel mechanism by which pericardial adiposity may exacerbate ventricular arrhythmias.

Segmental and transmural motion of the rat myocardium estimated using quantitative ultrasound with new strategies for infarct detection.

Introduction: The estimation of myocardial motion abnormalities has great potential for the early diagnosis of myocardial infarction (MI). This study aims to quantitatively analyze the segmental and transmural myocardial motion in MI rats by incorporating two novel strategies of algorithm parameter optimization and transmural motion index (TMI) calculation. Methods: Twenty-one rats were randomly divided into three groups (n = 7 per group): sham, MI, and ischemia-reperfusion (IR) groups. Ultrasound radio-frequency (RF) signals were acquired from each rat heart at 1 day and 28 days after animal model establishment; thus, a total of six datasets were represented as Sham1, Sham28, MI1, MI28, IR1, and IR28. The systolic cumulative displacement was calculated using our previously proposed vectorized normalized cross-correlation (VNCC) method. A semiautomatic regional and layer-specific myocardium segmentation framework was proposed for transmural and segmental myocardial motion estimation. Two novel strategies were proposed: the displacement-compensated cross-correlation coefficient (DCCCC) for algorithm parameter optimization and the transmural motion index (TMI) for quantitative estimation of the cross-wall transmural motion gradient. Results: The results showed that an overlap value of 80% used in VNCC guaranteed a more accurate displacement calculation. Compared to the Sham1 group, the systolic myocardial motion reductions were significantly detected (p < 0.05) in the middle anteroseptal (M-ANT-SEP), basal anteroseptal (B-ANT-SEP), apical lateral (A-LAT), middle inferolateral (M-INF-LAT), and basal inferolateral (B-INF-LAT) walls as well as a significant TMI drop (p < 0.05) in the M-ANT-SEP wall in the MI1 rats; significant motion reductions (p < 0.05) were also detected in the B-ANT-SEP and A-LAT walls in the IR1 group. The motion improvements (p < 0.05) were detected in the M-INF-LAT wall in the MI28 group and the apical septal (A-SEP) wall in the IR28 group compared to the MI1 and IR1 groups, respectively. Discussion: Our results show that the MI-induced reductions and reperfusion-induced recovery in systolic myocardial contractility could be successfully evaluated using our method, and most post-MI myocardial segments could recover systolic function to various extents in the remodeling phase. In conclusion, the ultrasound-based quantitative estimation framework for estimating segmental and transmural motion of the myocardium proposed in our study has great potential for non-invasive, novel, and early MI detection.

Site-specific prolongation of repolarization prevents postmyocardial infarction tachycardia.

Site-specific prolongation of repolarization prevents postmyocardial infarction tachycardia.

The role transmural strain gradient in assessment of functionally single ventricle contractility

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The funds of the Ministry of Education and Science. Background Cardiac imaging in patients with FSV (functionally single ventricle) underwent the Fontan procedure is a challenge. One of the most difficult issue to be resolved in FSV patients is myocardial contractility. Thus, we sought for deformation parameters analysis by STE (Speckle Tracing Echocardiography), for haemodynamic and structural reason. We incorporated a novel STE (Speckle Tracing Echocardiography) parameter– TG (transmural strain gradient) representing the difference in strain between subendocardial and subepicardial layer to assess FSV contractile reserve. The role of TG in assessment of FSV after Fontan palliation has not been evaluated yet. Purpose The study aimed to introduce/evaluate transmural longitudinal strain gradient (TG) at rest and during exercise as marker of FSV contractility and exercise performace. Methods The group of 37 patients with FSV after Fontan palliation were enrolled in our study at least 12 months after Fontan operation and in sinus rhythm on ECG. We performed an transthoracic echocardiography at rest and during exercise on a semi-supine cycle ergometer. The apical-chamber views were registered for subsequent post-processing analysis. Due to heterogeneous FSV morphology and primary defects as well as accompanying intraventricular septum segments malformation in majority of cases, we decided to measure and analyse FSV free wall longitudinal strain only. The values of layer-specific: subendocardial and subepicardial longitudinal free wall systolic strain were assessed and the gradient between them was calculated. The TG at rest and during exercise were compared with the cardiopulmonary exercise test results, NYHA class, FSV systolic function studied by CMR (Cardiac Magnetic Resonance) and NT-proBNP concentration. Results The values of TG at rest and during exercise correlated with peak oxygen uptake during the cardio-pulmonary exercise test (p = ,012 for TG at rest, p = ,031). TG during exercise was negatively correlated with CMR-derived ejection fraction (p = ,031) . There was no relationship between TG and NYHA-class and NT-proBNP. Conclusion(s) TG is a promising parameter for FSV contractility assessment. Our preliminary study suggests that it can complete traditional imaging technics and derived parameters. TG is highly associated to exercise capacity. However, utility of TG requires further investigation.

Sex-specific repolarization heterogeneity in mouse left ventricle: Optical mapping combined with mathematical modeling predict the contribution of specific ionic currents.

Ventricular repolarization shows notable sex-specificity, with female sex being associated with longer QT-intervals in electrocardiography irrespective of the species studied. From a clinical point of view, women are at a greater risk for drug-induced torsade de pointes and symptomatic long-QT syndrome. Here, we present an optical mapping (OM) approach to reveal sex-specific action potential (AP) heterogeneity in a slice preparation of mouse hearts. Left ventricular epicardial repolarization in female versus male mice shows longer and, interindividually, more variable AP duration (APD), yielding a less prominent transmural APD gradient. By combining OM with mathematical modeling, we suggest a significant role of IKto,f and IKur in AP broadening in females. Other transmembrane currents, including INaL , only marginally affect basal APD. As in many cardiac pathophysiologies, increasing [Ca2+ ]i poses a risk for arrhythmia, the response of AP morphology to enhanced activation of L-type calcium channels (LTCC) was assessed in a sex-selective manner. Both APD and its variation increased significantly more in female versus male mice after pharmacological LTCC activation, which we hypothesize to be due to sex-specific INaL expression based on mathematical modeling. Altogether, we demonstrate a more delayed repolarization of LV epicardium, a leveled LV transmural APD gradient, and a more pronounced epicardial APD response to Ca2+ influx in females versus males. Mathematical modeling quantifies the relative contributions of selected ionic currents to sex-specific AP morphology under normal and pathophysiological conditions.

Multimodality Imaging and Biomarker Approach to Characterize the Pathophysiology of Heart Failure in Left Ventricular Non-Compaction with Preserved Ejection Fraction.

We enrolled 21 patients with LVNC and HFpEF and 21 HFpEF controls. For all patients, we performed CMR, speckle tracking echocardiography (STE), and biomarker assessment for HFpEF (NT-proBNP), for myocardial fibrosis (Galectin-3), and for endothelial dysfunction [ADAMTS13, von Willebrand factor, and their ratio]. By CMR, we assessed native T1 and extracellular volume (ECV) for each LV level (basal, mid, and apical). By STE, we assessed longitudinal strain (LS), globally and at each LV level, base-to-apex gradient, LS layer by layer, from epicardium to endocardium, and transmural deformation gradient. In the LVNC group, mean NC/C ratio was 2.9 ± 0.4 and the percentage of NC myocardium mass was 24.4 ± 8.7%. LVNC patients, by comparison with controls, had higher apical native T1 (1061 ± 72 vs. 1008 ± 40 ms), diffusely increased ECV (27.2 ± 2.9 vs. 24.4 ± 2.5%), with higher values at the apical level (29.6 ± 3.8 vs. 25.2 ± 2.8%) (all p < 0.01); they had a lower LS only at the apical level (-21.4 ± 4.4 vs. -24.3 ± 3.2%), with decreased base-to-apex gradient (3.8 ± 4.7 vs. 6.9 ± 3.4%) and transmural deformation gradient (3.9 ± 0.8 vs. 4.8 ± 1.0%). LVNC patients had higher NT-proBNP [237 (156-489) vs. 156 (139-257) pg/mL] and Galectin-3 [7.3 (6.0-11.5) vs. 5.6 (4.8-8.3) ng/mL], and lower ADAMTS13 (767.3 ± 335.5 vs. 962.3 ± 253.7 ng/mL) and ADAMTS13/vWF ratio (all p < 0.05). LVNC patients with HFpEF have diffuse fibrosis, which is more extensive at the apical level, explaining the decrease in apical deformation and overexpression of Galectin-3. Lower transmural and base-to-apex deformation gradients underpin the sequence of myocardial maturation failure. Endothelial dysfunction, expressed by the lower ADAMTS13 and ADAMTS13/vWF ratio, may play an important role in the mechanism of HFpEF in patients with LVNC.

P182 A STRANGE ELECTROCARDIOGRAM RECORDED AFTER A FALL TO THE GROUND

Abstract An 84–year–old man was found unconscious on the ground by his daughter. The patient had a medical history of arterial hypertension, dyslipidemia and type II diabetes mellitus complicated by peripheral neuropathy and has been experiencing frequent falls. The emergency services were alerted, and the man was taken to the emergency room. In the ER, an abnormal electrocardiogram was recorded, and an urgent cardiological consultation was requested. Upon reading the ECG, the cardiologist ordered the patient‘s body temperature to be measured, which was found to be 29.7°C. The recorded ECG showed signs of severe hypothermia, including an advanced atrioventricular block (in this case, III–degree AV block), a widening of the QRS complex with the appearance of the Osborn wave, and a prolonged QT interval. The Osborn wave is a positive deflection visible at the J point and it is an uncommon electrocardiographic finding that immediately suggests hypothermia, although it is not pathognomonic (it can also be found in acute myocardial ischemia, hypercalcemia, sepsis, and other non–hypothermic conditions). The electrophysiological basis of the Osborn wave lies in the Ito current, a transient current caused by the release of potassium ions from the ventricular myocardiocyte, which is responsible for a brief partial repolarization during phase 1 of the action potential. Hypothermia increases the amplitude and width of the action potential notch due to the Ito current in the epicardium much more than in the endocardium, creating a transmural voltage gradient that manifests on the surface ECG as the Osborn wave. The Osborn wave is initially more evident in the inferolateral leads; as the body temperature decreases, the wave gradually becomes visible in all 12 leads and, when the body temperature returns to normal, the wave progressively disappears. This potential difference also correlates with possible proarrhythmic effects and, when linked to acute myocardial ischemia, the Osborn wave is an adverse prognostic factor as it is associated with a higher risk of ventricular fibrillation. In this case, the patient had fallen during the night and remained on the ground for hours. He was hospitalized for short intensive observation, warmed up, and hydrated, with a rapid and complete resolution of the clinical and electrocardiographic abnormalities

INFLUENCE OF ATRIAL ELECTRICAL STIMULATION ON THE TRANSMURAL SEQUENCE OF DEPOLARIZATION OF VENTRICULAR WALLS IN RAT HEART UNDER ZOLETHYL-XYLAZINE ANESTHESIA

The transmural sequence of depolarization of the free walls of the ventricles of the heart of Wistar rats was studied with an increase in the heart rate under zoletyl- xylazine anesthesia. The increase in heart rate was caused by atrial electrical stimulation. Zoletyl-xylazine anesthesia with intramuscular injection at a dose of 0.15 mg/kg of zoletil and 3 mg/kg of xylazine caused a significant negative chronotropic effect with pronounced bradycardia, characterized by a decrease in heart rate from the initial two times. With a reduced sinoatrial rhythm with a frequency of 237 ± 34 beats/min, the subendocardial layers were initially depolarized, then the intramural and further subepicardial layers of the left and right free walls of the ventricles of the heart. The areas of the bases of the free walls of the ventricles depolarized later than the apical areas by approximately 2–4 ms, also by the movement of the activation wave from the endocardium to the epicardium. With an increase in heart rate, the sequence and transmural depolarization gradient did not change. At the same time, an increase in the stimulation frequency from 300 to 500 beats/min led to a decrease in the time of arrival of the depolarization wave to the subendocardial, intramural, and subepicardial layers of the walls of the left and right ventricles. Despite the depressive effect of zoletyl-xylazine anesthesia on the heart and its chronotropic function, at a high frequency of atrial electrical stimulation, the depolarization gradient from the endocardium to the epicardium and from the apex to the base of the ventricles was preserved, there were only minor changes in the duration of the process of transmural depolarization of the walls of the ventricles of the heart. This indicates the resistance of activation of the ventricles of the heart of Wistar rats to the toxic effect of zoletyl-xylazine anesthesia.