Endocardial Layers Research Articles

Intracardiac echocardiography techniques to identify ventricular arrhythmia substrate.

Intracardiac echocardiography (ICE) is increasingly used to facilitate catheter ablation of ventricular arrhythmias (VA). It allows intraprocedural recognition of myocardial substrate, optimization of catheter-tissue contact, identification of anatomical barriers to ablation, and early recognition of complications. In the era where the 3-dimensionality of substrate for VA is increasingly recognized, ICE is invaluable in identifying scar topography in the endocardial, midmyocardial, and epicardial layers. ICE assists in identifying endocavitary structures that are a common source of VA in idiopathic and structural heart disease. Furthermore, as substrate imaging of the right ventricle has not been optimized with other imaging modalities, ICE offers a unique opportunity to visualize substrate in this chamber. Real-time substrate identification can be particularly useful where there are contraindications to use of other imaging modalities or the images are obscured by artefact in the presence of cardiac device leads. In this review we provide a step-by-step guide in the techniques used to image ventricular arrhythmia substrate with ICE. We also discuss the benefits and limitations of this technique in comparison to other imaging modalities.

Left ventricular noncompaction: a disorder with genotypic and phenotypic heterogeneity-a narrative review.

Background and ObjectiveLeft ventricular noncompaction (LVNC) is a cardiomyopathy characterized by excessive trabecular formation and deep recesses in the ventricular wall, with a bilaminar structure consisting of an endocardial noncompaction layer and an epicardial compacted layer. Although genetic variants have been reported in patients with LVNC, understanding of LVNC and its pathogenesis has not yet been fully elucidated. We addressed the latest findings on genes reported to be associated with LVNC morphogenesis and possible pathologies to understand the diverse spectrum between genotype and phenotype in LVNC. Also, the latest findings and issues related to the diagnosis of LVNC were summarized.MethodsThis article is written as a commentary narrative review and will provide an update on the current literature and available data on common forms of LVNC published in the past 30 years in English through to May 2022 using PubMed.Key Content and FindingsFamilial forms of LVNC are frequent, and autosomal dominant mode of inheritance has been predominantly observed. Several of the candidate causative genes are also mutated in other cardiomyopathies, suggesting a possible shared molecular and/or cellular etiology. The most common gene functions were sarcomere function whereas genes in mice LVNC models were involved in heart development. Echocardiography and cardiac magnetic resonance imaging (CMR) are useful for diagnosis although there are no unified criteria due to overdiagnosis of imaging, poor consistency between techniques, and lack of association between trabecular severity and adverse clinical outcomes.ConclusionsThis review reflects the current lack of clarity regarding the pathogenesis and significance of LVNC and showed the complexity of imaging diagnostic criteria, interpretation of the role of LVNC as a cause, and uncertainty regarding the specific genetic basis of LVNC.

High-Spatiotemporal-Resolution Visualization of Myocardial Strains Through Vector Doppler Estimation: A Small-Animal Study.

High-frequency ultrasound (HFUS) imaging is extensively used for cardiac diseases in small animals due to its high spatial resolution. However, there is a lack of a system that can provide a 2-D high-spatiotemporal dynamic visualization of mouse myocardial strains. In this article, a dynamic HFUS (40 MHz) high-resolution strain imaging was developed through the vector Doppler imaging. Following in vitro tests using a rubber balloon phantom, in vivo experiments were performed on wild-type (WT) and myocardial infarction (MI) mice. High-resolution dynamic images of myocardial strains were obtained in the longitudinal, radial, and circumferential directions at a frame rate of 1 kHz. Global peak strain values for WT mice were -19.3% ± 1.3% (longitudinal), 31.4% ± 1.7% (radial in the long axis), -19.9% ±.8% (circumferential), and 34.4% ± 1.9% (radial in the short axis); those for the MI mice were -16.1% ±.9% (longitudinal), 26.8% ± 2.9% (radial in the long axis), -15.2% ± 2.7% (circumferential), and 21.6% ± 4.8% (radial in the short axis). These results indicate that the strains for MI mice are significantly lower than those for WT mice. Regional longitudinal strain curves in the epicardial, midcardial, and endocardial layers were measured and the peak strain values for WT mice were -22.% and -16.8% in the endocardial and epicardial layers, respectively. However, no significant difference in the layer-based values was noted for the MI mice. Regional analysis results revealed obvious myocardial strain variation in the apical anterior region in the MI mice. The experimental results demonstrate that the proposed dynamic cardiac strain imaging can be useful in high-performance imaging of small-animal cardiac diseases.

Associations between perfusion defects, tissue changes and myocardial deformation in hypertrophic cardiomyopathy, uncovered by a cardiac magnetic resonance segmental analysis

BackgroundMicrovascular dysfunction is an often overlooked feature of hypertrophic cardiomyopathy (HCM). Our aim was to assess the association between microvascular dysfunction, wall thickness, tissue characteristics and myocardial deformation in HCM patients, by analyzing individual myocardial segments. MethodsProspective assessment including cardiac magnetic resonance to assess wall thickness, T1 and T2 mapping, extracellular volume, late gadolinium enhancement (LGE) and stress perfusion. Results were stratified according to the 16 American Heart Association segments. ResultsSeventy-five patients were recruited (1200 segments), 63% male, mean age 54.6±14.8 years, maximal wall thickness of 20.22±4.6 mm. Among the 424 segments (35%) with perfusion defects, 24% had defects only in the endocardial layer and 12% in both endocardial and epicardial layers. Perfusion defects were more often detected in hypertrophied segments (64%). Among the 660 segments with normal wall thickness, 19% presented perfusion defects. Independently of wall thickness, segments with perfusion defects had a higher T1 (β-estimate 30.28, p<0.001), extracelluar volume (β-estimate 1.50, p<0.001) and T2 (β-estimate 0.73, p<0.001) and had late gadolinium enhancement more frequently (odds ratio 4.16, p<0.001). Higher values of circumferential strain (lower deformation) and lower values of radial strain were found in segments with perfusion defects (β-estimate 2.76, p<0.001; and β-estimate -10.39, p<0.001, circumferential and radial strain, respectively). ConclusionWhile microvascular dysfunction was more prevalent in more hypertrophied segments, it also had a major presence in segments without hypertrophy. In this segmental analysis, we found an association between the presence of ischemia and tissue abnormalities, replacement fibrosis as well as impaired strain, independently of the segmental wall thickness.

P307 POST–COVID–19 SYNDROME: CAN IT BE CAUSED BY MYOCARDIAL INVOLVEMENT?

ObjectivesThe main aim of this work is the evaluation of the myocardial activity in recovered SARS–COV–2 patients using echocardiography.Methods64 recovered SARS–COV–2 patients (28 men and 36 women) were checked within our premises because of persistent symptoms after the peak phase of the infection. EchocoloDoppler has been exploited for each patient to determine the following indicators of left ventricular activity: Biplane Ejection fraction; Myocardial function by means of global longitudinal strain (GLS), global radial strain (GRS) global circonferential strain (GCS), Analysis of longitudinal and circumferential tracking at the level of the three endocardial, middle and epicardial layers and radial at the basal, middle and apical level; Myocardial Work (MW): Global Work Index (GWI), Global Constructive Work (GCW), Global Work Efficency (GWE) e Global Work Waste (GWW); assessment of the mitral E/A and E/E’ diastolic function.OutcomesIn 4 out of 64 patients (3 women and 1 man) a myocardial dysfunction of the left ventricle was highlighted. In 2 out of 64 patients an EF reduction was discovered, while a reduction of GLS GCS GWE and an increase of the GWW was detected in every patient involved in the study. We did not encountered variations of the tracking gradient concerning the layers of the layers with lower valuesat the level of the epicardial layer and higher values at the level of the endocardial one. Every patient involved in the study was affected by a diastolic dysfunction of 1° grade with E/A < 1 and E/E’ < 12 and they did not present significant stenosis after CT scan or angiography. Two of the 4 patients mentioned above had fibrosis areas as detected through RMN.ConclusionsWe confirm that for patients with persistent symptoms after SARS–COV–2 recovery echocardiography assessment is recommended to exclude potential damages. Assessing the functioning status by strain analysis is important to confirm damages, mainly for patients where the EF activity is not significantly varied. The identification of early or soft myocardial damages is key to start treatments and schedule follow–up analysis.

Spatial distribution and network morphology of epicardial, endocardial, interstitial, and Purkinje cell-associated elastin fibers in porcine left ventricle.

Cardiac extracellular matrices (ECM) play crucial functional roles in cardiac biomechanics. Previous studies have mainly focused on collagen, the major structural ECM in heart wall. The role of elastin in cardiac mechanics, however, is poorly understood. In this study, we investigated the spatial distribution and microstructural morphologies of cardiac elastin in porcine left ventricles. We demonstrated that the epicardial elastin network had location- and depth-dependency, and the overall epicardial elastin fiber mapping showed certain correlation with the helical heart muscle fiber architecture. When compared to the epicardial layer, the endocardial layer was thicker and has a higher elastin-collagen ratio and a denser elastin fiber network; moreover, the endocardial elastin fibers were finer and more wavy than the epicardial elastin fibers, all suggesting various interface mechanics. The myocardial interstitial elastin fibers co-exist with the perimysial collagen to bind the cardiomyocyte bundles; some of the interstitial elastin fibers showed a locally aligned, hinge-like structure to connect the adjacent cardiomyocyte bundles. This collagen-elastin combination reflects an optimal design in which the collagen provides mechanical strength and elastin fibers facilitate recoiling during systole. Moreover, cardiac elastin fibers, along with collagen network, closely associated with the Purkinje cells, indicating that this ECM association could be essential in organizing cardiac Purkinje cells into “fibrous” and “branching” morphologies and serving as a protective feature when Purkinje fibers experience large deformations in vivo. In short, our observations provide a structural basis for future in-depth biomechanical investigations and biomimicking of this long-overlooked cardiac ECM component.

Isoprenaline induced Takotsubo syndrome: Histopathological analyses of female rat hearts.

BackgroundTakotsubo syndrome (TTS) is a stress-induced disorder affecting mostly postmenopausal women. The aim of the study was to evaluate isoprenaline (ISO) dependent female rat model and histopathological characteristics in TTS.MethodsForty-nine Sprague Dawley female rats, 12 weeks old, were injected intraperitoneally with a single dose of ISO at doses 50 (n = 8), 75 (n = 6), 100 (n = 3), 150 (n = 27) and 200 (n = 5) mg/kg body weight (bw). The control group (n = 6) was injected with physiological saline. The echocardiographic examination to assess wall motion abnormalities took place 24, 48, 72 h, and 7 days post-ISO. Histopathological analysis was performed on the basis of hematoxylin-eosin staining.ResultsThe total mortality rate was 3/49 (6.12%). The optimum dose of ISO to induce TTS was 150 mg/kg bw and 21/27 (77.77%) rats showed apical ballooning. Histopathological analysis revealed focal necrosis/apoptosis of cardiomyocytes with inflammatory and fibroblast-like cell infiltration. Foci were the most numerous in the central muscle layer with apical-basal gradient 24, 48, 72 h post-ISO (p < 0.05). Significant differences were noted 48 h post-ISO in the central layer in apical vs basal segments (p = 0.0032), in the endocardial layer in apical vs basal segments (0.00024) and in mid-cavital vs. basal segments (p = 0.0483). The number of foci in endocardium of apical region differ 48 h post-ISO in rats with a dose of 150 vs. 200 mg/kg bw (p = 0.0084).ConclusionsThe ISO female rat model of TTS is associated with higher optimum dose and lower mortality in comparison with the male TTS model. TTS presents as a singles cardiomyocyte disorder, foci concerned mainly central muscle layer with apical-basal gradient.

In vivo Evaluation of Non-viral NICD Plasmid-Loaded PLGA Nanoparticles in Developing Zebrafish to Improve Cardiac Functions.

In the era of the advanced nanomaterials, use of nanoparticles has been highlighted in biomedical research. However, the demonstration of DNA plasmid delivery with nanoparticles for in vivo gene delivery experiments must be carefully tested due to many possible issues, including toxicity. The purpose of the current study was to deliver a Notch Intracellular Domain (NICD)-encoded plasmid via poly(lactic-co-glycolic acid) (PLGA) nanoparticles and to investigate the toxic environmental side effects for an in vivo experiment. In addition, we demonstrated the target delivery to the endothelium, including the endocardial layer, which is challenging to manipulate gene expression for cardiac functions due to the beating heart and rapid blood pumping. For this study, we used a zebrafish animal model and exposed it to nanoparticles at varying concentrations to observe for specific malformations over time for toxic effects of PLGA nanoparticles as a delivery vehicle. Our nanoparticles caused significantly less malformations than the positive control, ZnO nanoparticles. Additionally, the NICD plasmid was successfully delivered by PLGA nanoparticles and significantly increased Notch signaling related genes. Furthermore, our image based deep-learning analysis approach evaluated that the antibody conjugated nanoparticles were successfully bound to the endocardium to overexpress Notch related genes and improve cardiac function such as ejection fraction, fractional shortening, and cardiac output. This research demonstrates that PLGA nanoparticle-mediated target delivery to upregulate Notch related genes which can be a potential therapeutic approach with minimum toxic effects.

Alterations in multi-layer strain in AL amyloidosis

Background Cardiac involvement in AL amyloidosis portends a poor prognosis. 2D-speckle tracking echocardiography (2D-STE) strain can identify subclinical cardiac involvement. This study performed multilayer and multiplanar 2D-STE myocardial strain analysis. Methods We compared 75 AL amyloidosis patients to 49 hypertensive patients and 49 healthy controls. Longitudinal strain was obtained from epicardial, mid-myocardial and endocardial layers; segmental strain was measured from mid-myocardial basal, mid and apical segments. Results Global longitudinal strain was reduced in epicardial (−14.3 ± −4.0% vs. −17.4 ± 2.2% vs. −17.5 ± −2.0%, p < .001), mid–myocardial (−16.3 ± −4.5% vs. −19.7 ± 2.5% vs. −19.7 ± −2.2%, p < .001) and endocardial layers (−18.7 ± −4.9% vs. −22.2 ± 3.0% vs. −22.3 ± −2.6%, p < .001) in amyloid patients compared to hypertensive and healthy controls. Segmental strain confirmed significant reduction in basal (−11.2 ± −3.9% vs. −17.6 ± 2.7% vs. −20.9 ± −3.4%, p < .001) and mid (−14.8 ± −4.3% vs. −19.2 ± 2.5% vs. −19.6 ± −2.2%, p < .001) LV segments in the AL amyloid group. Receiver operating curve analysis demonstrated that an optimal cut-off of −16% for basal segmental strain better differentiated AL amyloid from hypertensive group (sensitivity 96%, specificity 70%, AUC 0.93), compared to relative apical sparing (AUC of 0.85). Conclusion Strain demonstrated myocardial involvement in all layers in AL amyloidosis, with reduced basal segmental longitudinal strain a likely marker of early disease.

Serial changes of layer-specific myocardial function according to chemotherapy regimen in patients with breast cancer.

AimsChemotherapy-induced cardiotoxicity (CIC) is a significant complication, meanwhile myocardial damage might differ depending on chemotherapy agents and their timing. The aim of this study was to evaluate serial changes of layer-specific myocardial function in patients with breast cancer and their differences by the development time of CIC and chemotherapy agent.Methods and resultsA total of 105 consecutive patients with breast cancer (age: 52.3 ± 9.3 years) were enrolled. Chemotherapy-induced cardiotoxicity occurred in 20 (19%) patients during 6 months. Endocardial and midmyocardial functions decreased in patients with or without CIC, with patients with CIC showing greater decreases during follow-up. Global longitudinal strain (GLS) change at 3 months was the most sensitive parameter to detect CIC. When new development of CIC was analysed at 6 months, GLS was reduced earlier than the decrease of left ventricular ejection fraction. In patients with CIC who were treated with anthracycline-based regimen for 3 months, endocardial GLS markedly decreased at 3 months and continued to decrease until 6 months. Patients with CIC who received trastuzumab therapy after anthracycline therapy showed further reduction in endocardial GLS at the 6-month follow-up, which was not shown in patients with CIC who received taxane therapy subsequently.ConclusionMyocardial function assessed by strain decreased in all patients with breast cancer receiving chemotherapy. The endocardial layer was the most vulnerable to chemotherapy-induced myocardial damage. Functional impairment was more profound in patients with CIC who received sequential anthracycline-trastuzumab chemotherapy. Thus, early evaluation of left ventricular function might be necessary for all patients with breast cancer to detect CIC.

Segmental analysis of microvascular dysfunction and tissue characterization in hypertrophic cardiomyopathy by magnetic resonance imaging

Abstract Funding Acknowledgements Type of funding sources: None. Background While left ventricular hypertrophy (LVH) and myocardial fibrosis are frequently evaluated in hypertrophic cardiomyopathy (HCM), microvascular dysfunction is often overlooked. The aim of this study was to assess the association between wall thickness, microvascular dysfunction and tissue characteristics in HCM patients (P), comparing individual myocardial segments. Methods Prospective evaluation of adult P with HCM (P with "end-stage" HCM, prior septal reduction therapy or epicardial coronary artery disease were excluded). All underwent a cardiac magnetic resonance (CMR) protocol (1.5-T), from which the following parameters were analysed: maximal LV wall thickness (MLVWT), T1 and T2 mapping, extracellular volume (ECV), late gadolinium enhancement (LGE) and stress perfusion. Results were stratified according to the 16 American Heart Association segments. Multivariate regression analyses for perfusion defects and tissue characteristics were performed. Results 75 P (total of 1200 myocardial segments analysed), 63% male, mean age 55 ± 15 years, MLVWT of 20 ± 4.5mm (61% asymmetric septal LVH, 29% apical LVH and 8% concentric LVH). 28% presented LV outflow tract obstruction. MLVWT was greater in the basal and mid septum (table 1). Among the 424 segments (35.3%) with a perfusion defect, 286 (23.8%) had a defect only in the endocardial layer and 138 (11.5%) in both endocardial and epicardial layers with defects more often detected in hypertrophied segments. This association was verified in segments with MLVWT 12-14mm and MLVWT ≥15mm (OR 7.83, 95% CI 5.75-10.67, p &amp;lt; 0.001) (table 2). Among the 660 segments with normal MLVWT (≤11mm), 123 (19%) presented perfusion defects. A perfusion defect was more frequent in segments of obstructive HCM P (OR 1.48, 95% CI 1.13-1.92, p = 0.004). Microvascular dysfunction was associated with changes in tissue characteristics. For the same thickness, segments with perfusion defects had a higher T1 mapping (β-estimate 20.91, 95% CI 16.87-24.96, p &amp;lt; 0.001) and T2 mapping mean values than those without. Furthermore, regardless of MLVWT, segments with perfusion defects had LGE more often (OR 4.16, 95% CI 3.19-5.41, p &amp;lt; 0.001) and a higher ECV. On the other hand, among the 424 segments with a perfusion defect, 115 (27%) did not present LGE. MLVWT was associated with tissue characteristics. Comparing to non-hypertrophied segments, T1 mapping mean value was higher in segments with MLVWT 12-14mm and with ≥15mm (β-estimate 37.71, 95% CI 31.2-44.21, p &amp;lt; 0.001). Segments with MLVWT ≥15mm showed a significantly superior ECV mean value comparing to non-hypertrophied segments. LGE was more frequent in the more hypertrophied segments: MLVWT 12-14mm and ≥15mm (OR 9.02, 95% CI 6.42-12.67, p &amp;lt; 0.001) (Table 2). Conclusion Microvascular dysfunction is more prevalent in obstructive HCM, particularly in the more hypertrophied segments. The presence of microvascular dysfunction is associated with diffuse tissue abnormalities and replacement fibrosis. Abstract Table 1: Characteristics of AHA segments Abstract Table 2: Multivariable analyses

Vasodilator Strain Stress Echocardiography in Suspected Coronary Microvascular Angina.

Background: In patients with Ischemia and non-obstructive coronary artery stenosis (INOCA) wall motion is rarely abnormal during stress echocardiography (SE). Our aim was to determine if patients with INOCA and reduced coronary flow velocity reserve (CVFR) have altered cardiac mechanics using two-dimensional speckle-tracking echocardiography (2DSTE) during SE. Methods: In a prospective, multicenter, international study, we recruited 135 patients with INOCA. Overall, we performed high dose (0.84 mg/kg) dipyridamole SE with combined assessment of CVFR and 2DSTE. The population was divided in patients with normal CVFR (>2, group 1, n = 95) and abnormal CVFR (≤2, group 2, n = 35). Clinical and 2DSTE parameters were compared between groups. Results: Feasibility was high for CFVR (98%) and 2DSTE (97%). A total of 130 patients (mean age 63 ± 12 years, 67 women) had complete flow and strain data. The two groups showed similar 2DSTE values at rest. At peak SE, Group 1 patients showed lower global longitudinal strain (p < 0.007), higher mechanical dispersion (p < 0.0005), lower endocardial (p < 0.001), and epicardial (p < 0.0002) layer specific strain. Conclusions: In patients with INOCA, vasodilator SE with simultaneous assessment of CFVR and strain is highly feasible. Coronary microvascular dysfunction is accompanied by an impairment of global and layer-specific deformation indices during stress.

A case of Takotsubo cardiomyopathy with apical hypertrophic cardiomyopathy-like morphological changes during recovery.

Objective: Few cases of Takotsubo cardiomyopathy with apical hypertrophic cardiomyopathy (APH)-like morphological changes during the recovery process have been reported.Patient: A 56-year-old woman diagnosed with Takotsubo cardiomyopathy showed a morphology similar to that of APH during recovery. We examined this patient using 2D speckle-tracking echocardiography based on the method used for hypertrophic cardiomyopathy, which suggested that the circumferential strain (CS) of the middle wall indicated myocardial function of the left ventricle, and the CS of the inner wall was associated with left ventricular chamber function.Results: We measured the CS of the endocardial, middle, and epicardial layers and found that the apical inner layer CS (CSinner), middle layer CS, and outer layer CS were all decreased at the onset. CSinner showed a strong tendency to recover on echocardiography performed when APH-like morphology was observed.Conclusion: The morphology of the apex in our case likely contributed to the maintenance of chamber function.

BUNDLE BRANCH BLOCKS SIMULATIONS IN VENTRICULAR MODEL WITH REALISTIC GEOMETRY AND CONDUCTION SYSTEM

The goal of the study was to design a model of cardiac ventricles with realistic geometry that enables simulation of the ventricular activation with normal conduction system functions, as well as with bundle branch blocks. In ventricles, electrical activation propagates from the His bundle to the left and right bundle branches and continues to the fascicles and branching fibers of the Purkinje system. The role of these parts of the conduction system is to lead the activation rapidly and synchronously to the left and right ventricle. The velocity of propagation in the conduction system is several times higher than in the surrounding ventricular myocardium. If the conduction system works normally, QRS duration representing the total activation time of the ventricles lies in the physiological range of about 80 to 120 ms but it is more than 120 ms in the case of bundle branch blocks. In our study, the realistic geometry of the ventricles was constructed on the base of a patient CT scan, defining epicardial and endocardial surfaces. The first part of the conduction system (fast-conducting bundle branches, fascicles in the left ventricle and initial parts of the Purkinje fibers) was modeled as polyline pathways isolated from the surrounding ventricular tissue. The remaining part of the Purkinje system was modeled as an endocardial layer with higher conduction velocity. The propagation of the electrical activation in the ventricular model was modeled using reaction-diffusion (RD) equations, except for the first part of the conduction system, where the activation times were evaluated algebraically with respect to predefined velocity of propagation and estimated distance between the His bundle and particular entry point to the layer with higher conduction velocity. Propagation of activation in cardiac ventricles was numerically solved in Comsol Multiphysics environment. Several configurations of the first part of the conduction system with different number of polyline pathways and entry points were proposed and tested to achieve realistic activation propagation. For the model with 9 starting points, realistic total activation time (TAT) of the whole ventricles of about 108 ms was obtained for the model with normal conduction system, and realistic TAT of 126 ms and 149 ms were obtained for the right and left bundle branch block (RBBB, LBBB), respectively. Very similar TAT was found also for the model with 7 starting points, but unrealistically long TAT was obtained in LBBB simulation for the model with only 5 starting points.

A proposed strategy for anticoagulation therapy in noncompaction cardiomyopathy.

Noncompaction cardiomyopathy (NCCM) is a rare condition characterized by prominent trabeculae, deep intertrabecular recesses, and a left ventricular myocardium with a two‐layered structure, characterized by a spongy endocardial layer and a thinner and compacted epicardial one. NCCM can be isolated or associated with other congenital heart diseases and complex syndromes involving neuromuscular disorders and facial dysmorphisms. To date, more than 40 genes coding for sarcomeric, cytoskeletal, ion channels, and desmosomal proteins have been identified. Clinical presentation is also highly variable, ranging from no symptoms to end‐stage heart failure (HF), lethal arrhythmias, sudden cardiac death, or thromboembolic events. In particular, the prevalence of thromboembolism in NCCM patients appears to be higher than that of a similar, age‐matched population without NCCM. Thromboembolism has a multifactorial aetiology, which is linked to genetic, as well as traditional cardiovascular risk factors. In previous studies, atrial fibrillation (AF) was observed in approximately 25–30% of adult NCCM patients and embolism had a cardiac source in ~63–69% of cases; therefore, AF represents a strong predictor of adverse events, especially if associated to HF and neuromuscular disorders. Left ventricular dysfunction is another risk factor for thromboembolism, as a result of blood stagnation and local myocardial injury. Moreover, it is not completely clarified if the presence of deep intertrabecular recesses causing stagnant blood flow can constitute per se a thrombogenic substrate even in absence of ventricular dysfunction. For the clinical management of NCCM patients, an appropriate stratification of the thromboembolic risk is of utmost importance for a timely initiation of anticoagulant therapy. The aim of the present study is to review the available literature on NCCM with particular attention on thromboembolic risk stratification and prevention and the current evidence for oral anticoagulation therapy. The use of direct oral anticoagulants vs. vitamin K antagonists is also discussed with important implications for patient treatment and prognosis.

108 Atrial fibrillation effects on coronary perfusion across the different myocardial layers: a computational analysis

Abstract Aims Atrial fibrillation (AF) patients may present ischaemic chest pain in the absence of classical obstructive coronary disease. Among the possible causes, the direct haemodynamic effect exerted by the irregular arrhythmia has not been studied in detail. Methods and results A computational fluid dynamics analysis was performed by means of a 1D-0D multiscale model of the entire human cardiovascular system, characterized by a detailed mathematical modelling of the coronary arteries and their downstream distal microcirculatory districts (subepicardial, midwall, and subendocardial layers). Three mean ventricular rates were simulated in both sinus rhythm (SR) and AF: 75, 100, 125 b.p.m. We conducted inter-layer and inter-frequency analysis of the ratio between mean beat-to-beat blood flow in AF compared to SR (Q¯AP/Q¯SR Inter-layer analysis showed that, for each simulated ventricular rate, Q¯AP/Q¯SR progressively decreased from the epicardial to the endocardial layer in the distal left coronary artery districts (P-values &amp;lt; 0.001 for both left anterior descending artery—LAD, and left circumflex artery—LCx), while this was not the case for the distal right coronary artery (RCA) district. Inter-frequency analysis showed that, focusing on each myocardial layer, Q¯AP/Q¯SR progressively worsened as the ventricular rates increased in all investigated microcirculatory districts (LAD, LCx, and RCA) (P-values &amp;lt; 0.001 for all layer-specific comparisons). Conclusions AF exerts direct haemodynamic consequences on the coronary microcirculation, causing a reduction in microvascular coronary flow particularly at higher ventricular rates; the most prominent reduction was seen in the subendocardial layers perfused by left coronary arteries (LAD and LCx).

Multilayer global longitudinal strain assessment of subclinical myocardial dysfunction related to insulin resistance

Abstract Myocardial tissue is sensitive to insulin resistance (IR) due to its interactions with insulin levels. Previous studies demonstrated that heart failure prevalence was higher in IR patients. Evaluation of myocardial deformation by multilayer global longitudinal strain (MGLS) might provide more information about IR related left ventricular dysfunction. In this study, we aimed to investigate subclinical LV dysfunction with MGLS in patients with IR. The study was designed as a prospective cross-sectional study. The present study included 64 patients with IR(+), and 54 subjects without IR(−) prospectively. The homeostasis model of insulin resistance (HOMA-IR) was used to quantify insulin resistance. Specific analysis for endocardial, mid-myocardial and epicardial layers were performed by two-dimensional (2D) speckle tracking echocardiography (STE) for multilayer global longitudinal strain. MGLS (Endocard-Mid-myocard-Epicard) values were significantly lower in the IR(+) group compared to IR(−) group ((GLS-endocard; −15.1±1.5 vs. −18.7±1.3, p&amp;lt;0.001), (GLS-mid-myocard; −16.0±2.0 vs. −18.0±2.0, p&amp;lt;0.001), (GLS-epicard; −17.0±1.7 vs. −18.01±1.94, p=0.004)). GLS-endocard levels were significantly and positively correlated with HOMA-IR levels (r=0.643, p&amp;lt;0.001). HOMA-IR and age were found to be independent factors in detecting a decrease in GLS-endocard level in regression analysis. In conclusion, our data reveal that IR(+) patients had significantly lower strain values compared to IR(−) group. Besides, we presented that the HOMAIR value was an independent predictor of subclinical left ventricular dysfunction. Funding Acknowledgement Type of funding sources: None.

Differences in left ventricular twisting and different strains in patients with heart failure with preserved ejection fraction versus patients with arterial hypertension

Abstract Patients with advanced arterial hypertension (HPT) without heart failure often have left ventricular (LV) changes similar to hypertensive patients with heart failure with preserved ejection fraction (HFpEF). We assumed that cardiac mechanics may be different in both groups. Methods We study 58 patients (23 female) with HPT and with left ventricular concentric hypertrophy (LVH) as well as negative diastolic stress test and 52 HPT patients (29 female) with HFpEF NYHA II-III 72±5 years. All patients where in sinus rhythm. HPT and HFpEF patients has comparable degree of LV mass index (LVMI 85.3±8.6 g/m2 vs 86.2±8.9 g/m2, P=NS). Incidence of diabetes mellitus, chronic kidney disease or chronic obstructive lung disease was comparable between groups. 43 sex and age matched healthy subjects served as control (C). Comprehensive 2D/3D echocardiography (EchoCG) with offline measurements of longitudinal (LS), circumferential (CS) and radial strain (RS) global values of entire walls and 3 myocardial layers, LV twist (LVT)was performed before and after symptom limited or heart rate of 120 bpm limited diastolic stress test. Results HPT and HFpEF patients had significantly lower absolute values LS, CS, AS, as well as lower values of RS, and LVT compared with controls at rest and after stress test. The values of LS, RS and LVT did not significantly differ at rest in HPT patients and HFpEF patients, but HFpEF patients had lower values of global CS (GCS) due to reduction only in endocardial layer CS (ECS) (LS: 16.4±5.2% vs 16,8±5.9, p=0.07; ECS: 10.9±2,3% vs 17.3±4.1%, p&amp;lt;0.01; GCS: 12.8±3.5% vs 15.1±2.1%, p&amp;lt;0.03; RS: 29.7±10.2% vs 31.1±12.4%, p=0.06; LVT: 2.3±1.4deg vs 2.6±1.7deg, p=0.06). After diastolic stress test patients with HFpEF had significantly lower values of LVT and GCS compared with HPT patients (LVT: 1.8±0.9deg vs 3.4±1.8deg, p&amp;lt;0.001; GCS: 10.4±2.7% vs 17.1±3.4%, p&amp;lt;0.01). We also found greater relative increase (RI) in endocardial LS and LVT in patients with HPT after stress test compared with HFpEF patients, RI of other parameters did not differ between these two groups (RI ELS: 16±2.1% vs 10.5±1,7%, p&amp;lt;0.03; RI LVT 33.3±6,4% vs −21.7±4.1%, p&amp;lt;0.0001). ECS had the diagnostic value to predict HFpEF (area under curve 0.874), RI LVT was the best predictor of HFpEF symptoms (area under curve 0.912) with cut off value 22.3%. Conclusion ECS is reduced in HFpEF patients compared with HPT patients with the same degree of structural abnormalities on conventional EchoCG and is a predictor of HFpEF. HPT patients have more relative improvement in ELS during stress test compared with HFpEF patients. RI LVT was the best predictor of HFpEF symptoms. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): City Hall resources

Value of layer-specific speckle tracking echocardiography for early detection of myocardial injury caused by chemotherapy in breast cancer patients with cardiovascular risk.

The probability of toxicity-related myocardial injury event with anthracyclines is controversial, which could be related to the underlying cardiac status before chemotherapy. Our study sought to investigate the influence of cardiovascular risk factors on myocardial motion and cardiac function using layer-specific speckle tracking echocardiography (STE) during chemotherapy with epirubicin. Female patients with first-diagnosed breast cancer were prospectively enrolled in our study and received 4 chemotherapeutic cycles with epirubicin in each cycle of 21days. All patients underwent echocardiography for layer-specific STE analysis before and after all chemotherapy. Clinical data including cardiovascular risk factors were collected. According to the Framingham score, patients with cardiovascular risk factors were divided into groups with low, medium, and high risk. 134 patients existed in the final analysis. The accumulated dose of epirubicin for were 560.0 ± 103.8mg. 97 (72.4%) patients had cardiovascular risk factors. According to the Framingham score, 57 (42.5%) patients categorized in high risk. Endocardial layer strain after chemotherapy were lower than those at baseline (p < 0.05, all), especially for patients with high risk. The changes of endocardial longitudinal strain during chemotherapy were associated with cardiovascular risks at baseline with correlation coefficient of 0.627. Our study found that layer-specific STE is valuable for early detection of toxicity-related myocardial injury for patients with breast cancer after epirubicin chemotherapy and cardiovascular risk factors have greatly influenced on cardiac function during chemotherapy. The endocardial layer strain is sensitive to evaluate early-stage toxicity-related myocardial injury after epirubicin chemotherapy.

B-PO05-076 REPRODUCIBILITY OF LEFT ATRIAL ENDO AND EPICARDIAL WALL EXTRACTION FROM CTA

LA wall thickness (LAWT) is a major determinant of lesion transmurality in AF ablation. Computed tomography angiography (CTA) provides sub-millimetric resolution allowing reliable 3D LAWT segmentation. To analyze the intra and inter-user reproducibility of 3D CTA LAWT segmentations. Three observers with different levels of expertise performed, using ADAS 3D, complete LAWT segmentation of CTA (0.5x0.5x0.6mm) once for thirty patients and twice for ten. The endocardial layer was generated by a semi-automatic threshold-based segmentation. The epicardial, by manual contouring of key transverse slices followed by automatic interpolation. Finally, the user adjusted the 3D reconstructions. LAWT, presented as a discretized color map, was generated assigning at each point of the endocardium the distance to the epicardium. Reproducibility was calculated as the point to surface distance between different analyses of the same patient. Pulmonary veins, LAA and mitral annulus were excluded from analysis. Endocardial segmentations were closer than 1mm in 99.38%±0.86 of the vertices for intra and 95.12%±5.07 for inter-user variability, with a mean distance between meshes of 0.17mm±0.08 and 0.30mm±0.18, respectively. For the epicardium, mean distances between meshes were 0.54mm±0.17 for intra and 0.72mm±0.16 for inter-observer, and closer than 1 mm in 82.38%±9.89 of points for intra and 77.68%±7.16 for inter-user analyses. Reproducibility improved significantly (p<0.05) with user expertise. Obtaining reliable CTA-derived 3D LAWT maps by means of endo and epicardial segmentation of the LA wall is feasible with high reproducibility.