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BACKGROUNDLeft ventricular hypertrophy (LVH) and dyslipidemia are strong, independent predictors for cardiovascular disease, but their relationship is less well studied. A longitudinal lipidomic profiling of left ventricular mass (LVM) and LVH is still lacking.METHODSUsing liquid chromatography-mass spectrometry (LC-MS), we repeatedly measured 1,542 lipids from 1,755 unique American Indians attending 2 exams (mean, 5 years apart). Cross-sectional associations of individual lipid species with LVM index (LVMI) were examined by generalized estimating equation (GEE), followed by replication in an independent biracial cohort (65% White, 35% Black). Baseline plasma lipids associated with LVH risk beyond traditional risk factors were identified by logistic GEE model in American Indians. Longitudinal associations between changes in lipids and changes in LVMI were examined by GEE, adjusting for baseline lipids, baseline LVMI, and covariates.RESULTSMultiple lipid species were significantly associated with LVMI or the risk of LVH in American Indians. Some lipids were confirmed in Black and White individuals. Moreover, some LVH-related lipids were inversely associated with risk of coronary heart disease (CHD). Longitudinal changes in several lipid species were significantly associated with changes in LVMI.CONCLUSIONAltered fasting plasma lipidome and its longitudinal change over time were significantly associated with LVMI and risk for LVH in American Indians. Our results offer insight into the role of individual lipid species in LV remodeling and risk of LVH, independent of known risk factors.FUNDINGThis study was supported by the NIH grant (R01DK107532). The Strong Heart Study has been funded in whole or in part with federal funds from the National Heart, Lung, and Blood Institute, NIH, Department of Health and Human Services, under contract nos. 75N92019D00027, 75N92019D00028, 75N92019D00029, and 75N92019D00030.

INTRODUCTION: Reducing cardiopulmonary bypass (CPB) induced inflammatory injury is a potentially important strategy for children undergoing multiple operations for single ventricle palliation. We sought to characterize the soluble receptor for advanced glycation end products (sRAGE), a protein involved in acute lung injury and inflammation, in pediatric patients with congenital heart disease and hypothesized that patients undergoing single ventricle palliation would have higher levels of sRAGE following bypass than those with biventricular physiologies. METHODS: This was a prospective, observational study of children undergoing CPB. Plasma samples were obtained before and after bypass. sRAGE levels were measured and compared between those with biventricular and single ventricle heart disease using descriptive statistics and multivariate analysis for risk factors for lung injury. RESULTS: sRAGE levels were measured in 40 patients: 19 with biventricular and 21 with single ventricle heart disease. Children undergoing single ventricle palliation had a higher factor and percent increase in sRAGE levels when compared to patients with biventricular circulations (4.6 vs. 2.4, p = 0.002) and (364% vs. 181%, p = 0.014). The factor increase in sRAGE inversely correlated with the patients preoperative oxygen saturation (Pearson correlation (r) = -0.43, p = 0.005) and was positively associated with red blood cell transfusion (coefficient = 0.011; 95% CI: 0.004, 0.017; p = 0.001). CONCLUSIONS: Children with single ventricle physiology have greater increase in sRAGE following CPB as compared to children undergoing biventricular repair. Larger studies delineating the role of sRAGE in children undergoing single ventricle palliation may be beneficial in understanding how to prevent complications in this high-risk population.

The heart beats approximately 100,000 times per day in humans, imposing substantial energetic demands on cardiac muscle. Adenosine triphosphate (ATP) is an essential energy source for normal function of cardiac muscle during each beat, as it powers ion transport, intracellular Ca2+ handling, and actin-myosin cross-bridge cycling. Despite this, the impact of excitation-contraction coupling on the intracellular ATP concentration ([ATP]i) in myocytes is poorly understood. Here, we conducted real-time measurements of [ATP]i in ventricular myocytes using a genetically encoded ATP fluorescent reporter. Our data reveal rapid beat-to-beat variations in [ATP]i. Notably, diastolic [ATP]i was

BACKGROUND: The effect of contact force (CF) on lesion formation is not clear during pulsed field ablation (PFA). The aim of this study was to evaluate the impact of CF, PFA, and their interplay through the PFA index (PF index) formula on the ventricular lesion size in swine. METHODS: PFA was delivered through the CF-sensing OMNYPULSE catheter. Predefined PFA applications (×3, ×6, ×9, and ×12) were delivered maintaining low (5-25 g), high (26-50 g), and very high (51-80 g) CFs. First, PFA lesions were evaluated on necropsy in 11 swine to investigate the impact of CF/PFA-and their integration in the PF index equation-on lesion size (study characterization). Then, 3 different PF index thresholds-300, 450, and 600-were tested in 6 swine to appraise the PF index accuracy to predict the ventricular lesion depth (study validation). RESULTS: In the study characterization data set, 111 PFA lesions were analyzed. CF was 32±17 g. The average lesion depth and width were 3.5±1.2 and 12.0±3.5 mm, respectively. More than CF and PFA dose alone, it was their combined effect to impact lesion depth through an asymptotically increasing relationship. Likewise, not only was the PF index related to lesion depth in the study validation data set (r2=0.66; P

The heart, which is the first organ to develop, is highly dependent on its form to function1,2. However, how diverse cardiac cell types spatially coordinate to create the complex morphological structures that are crucial for heart function remains unclear. Here we integrated single-cell RNA-sequencing with high-resolution multiplexed error-robust fluorescence in situ hybridization to resolve the identity of the cardiac cell types that develop the human heart. This approach also provided a spatial mapping of individual cells that enables illumination of their organization into cellular communities that form distinct cardiac structures. We discovered that many of these cardiac cell types further specified into subpopulations exclusive to specific communities, which support their specialization according to the cellular ecosystem and anatomical region. In particular, ventricular cardiomyocyte subpopulations displayed an unexpected complex laminar organization across the ventricular wall and formed, with other cell subpopulations, several cellular communities. Interrogating cell-cell interactions within these communities using in vivo conditional genetic mouse models and in vitro human pluripotent stem cell systems revealed multicellular signalling pathways that orchestrate the spatial organization of cardiac cell subpopulations during ventricular wall morphogenesis. These detailed findings into the cellular social interactions and specialization of cardiac cell types constructing and remodelling the human heart offer new insights into structural heart diseases and the engineering of complex multicellular tissues for human heart repair.

The left and right ventricles of the human heart are functionally and developmentally distinct such that genetic or acquired insults can cause dysfunction in one or both ventricles resulting in heart failure. To better understand ventricle-specific molecular changes influencing heart failure development, we first performed unbiased quantitative mass spectrometry on pre-mortem non-diseased human myocardium to compare the metabolome and proteome between the normal left and right ventricles. Constituents of gluconeogenesis, glycolysis, lipogenesis, lipolysis, fatty acid catabolism, the citrate cycle and oxidative phosphorylation were down-regulated in the left ventricle, while glycogenesis, pyruvate and ketone metabolism were up-regulated. Inter-ventricular significance of these metabolic pathways was then found to be diminished within end-stage dilated cardiomyopathy and ischaemic cardiomyopathy, while heart failure-associated pathways were increased in the left ventricle relative to the right within ischaemic cardiomyopathy, such as fluid sheer-stress, increased glutamine-glutamate ratio, and down-regulation of contractile proteins, indicating a left ventricular pathological bias. Human myocardial proteomic and metabolomic analyses reveal ventricle-specific metabolic remodelling from normal hearts to heart failure, showing differential regulation in glucose and lipid metabolism, with a left ventricular pathological bias. [ABSTRACT FROM AUTHOR]

Although the heart atria have a lesser functional importance than the ventricles, atria play an important role in the pathophysiology of heart failure and supraventricular arrhythmias, particularly atrial fibrillation. In addition, knowledge of atrial morphology recently became more relevant as cardiac electrophysiology and interventional procedures in the atria gained an increasingly significant role in the clinical management of patients with heart disease. The atrial chambers are thin-walled, and several vessels enter at the level of the atria. The left and right atrium have different structures and shape. In general, both atrial chambers have the venous part, the appendage, and the vestibule; different aspects of each part allow us to distinguish morphologically between the left and right atrium. The human atrial conduction system consists of the sinus node and the atrioventricular node with no histologically specialized conduction pathways in the atrial chamber and an interatrial connection. The data show that the propagation of the impulse depends mainly on the myocardial architecture in the atria and the orientation of the myocytes plays a significant role in conduction. To complete the picture, it is also important to know how the atria develop and what is the embryonic origin of its different structures, as this may play a role in the development of some pathological conditions such as atrial fibrillation or certain types of congenital heart defects. Functional impairment of the atria can in some situations severely compromise heart pumping function, and conversely, can support it if other areas are damaged, balancing the blood flow to the body for some time. [ABSTRACT FROM AUTHOR]

Objectives: Due to poor treatment adherence and lifestyle-based interventions, chronic hypertension is a dominant risk factor predisposing individuals to heart failure and malignant arrhythmias. We investigated the impact of the postnatal acclimation of hairless SHR to ambient temperature that is, for them, below thermoneutrality, on the electrical coupling protein connexin-43 (Cx43) and pro-fibrotic markers in both heart ventricles of male and female hairless SHR rats compared to the wild SHR. Methods: Some 6-month-acclimated male and female hairless SHR as well as age- and sex-matched wild SHR were included and compared with the non-hypertensive Wistar strain. The left and right heart ventricles were examined for Cx43 topology, myocardial structure, and the histochemistry of capillaries. The protein levels of Cx43, relevant protein kinases, and extracellular matrix proteins (ECMs) were determined by immunoblotting. MMP-2 activity was assessed via zymography, and susceptibility to malignant arrhythmias was tested ex vivo. Results: Cx43 and its phosphorylated variant pCx43368 were significantly reduced in the left heart ventricles of wild SHR males, while to a lesser extent in the hairless SHR. In contrast, these proteins were not significantly altered in the right heart ventricles of males or in both heart ventricles in females, regardless of the rat strain. Pro-arrhythmic Cx43 topology was detected in the left heart ventricle of wild SHR and to a lesser extent in hairless SHR males. TGFβ protein was significantly increased only in the left ventricle of the wild SHR males. MMP-2 activity was increased in the right ventricle but not in the left ventricles of both males and females, regardless of the rat strain. Conclusions: The findings indicate that the postnatal acclimation of hairless SHR to ambient temperature hampers the downregulation of Cx43 in the left heart ventricle compared to wild SHR males. The decline of Cx43 was much less pronounced in females and not observed in the right heart ventricles, regardless of the rat strain. It may impact the susceptibility of the heart to malignant arrhythmias. [ABSTRACT FROM AUTHOR]

Background: The current review aims to present the beneficial effects of SGLT2 inhibitors (dapagliflozin and empagliflozin) on several hemodynamic parameters such as blood pressure, filtration pressure at the level of the glomerular capillaries, and the improvement of the preload and afterload of heart muscle. In order to stop chronic kidney disease (CKD) from progressing, SGLT2 inhibitors have become an important disease-modifying treatment. Materials and methods: Recent clinical studies have shown the success of these drugs in treating heart failure, reducing the risk of cardiovascular events, hospitalization, and mortality. Results: The hemodynamic effects of SGLT2 inhibitors include a diuretic effect, due to reduced sodium reabsorption. Also, at this level, numerous studies have confirmed the beneficial effect of dapagliflozin in patients with chronic kidney disease, associated with a 44% reduced risk of progression in this pathology. SGLT2 inhibitors are associated with a reduction in blood pressure and weight loss, because of their diuretic effect, especially empagliflozin, which can explain the beneficial effects in patients with heart failure. In addition, mainly empagliflozin reduces stiffness and arterial resistance. Conclusions: Although the exact mechanism of action is unknown, SGLT2 inhibitors reduce the interstitial volume by blocking the tubular reabsorption of glucose. This leads to reduced blood pressure and enhanced endothelial function. Consequently, there have been improvements in hospitalization and fatality rates. Because of their beneficial effects, these medications have been guidelines for managing heart failure and chronic kidney disease. [ABSTRACT FROM AUTHOR]

Simple Summary: Anthracycline chemotherapy is essential in treating breast cancer, yet it can lead to heart damage, particularly affecting the left ventricle. Less is known about its impact on the right ventricle. This meta-analysis examines how anthracyclines may cause subclinical damage to the right ventricle in breast cancer patients, as shown by both advanced strain parameters and traditional echocardiographic measures. Analyzing data from 15 studies and nearly 1200 patients, we found significant declines in right ventricular function post-treatment. Interestingly, this subclinical dysfunction does not appear linked to left ventricle damage or to higher chemotherapy doses, suggesting a unique mechanism for right ventricular impairment. These insights underscore the potential benefit of monitoring RV function in patients undergoing anthracycline treatment, as early detection may lead to improved patient care. Aim: This meta-analysis aims to evaluate the impact of anthracycline chemotherapy on subclinical right ventricular (RV) dysfunction in breast cancer patients, using traditional echocardiographic parameters and strain-based measures, such as the RV global longitudinal strain (RV GLS) and the RV free-wall longitudinal strain (RV FWLS). Methods and Results: A systematic search was conducted according to PRISMA guidelines, including 15 studies with a total of 1148 breast cancer patients undergoing anthracycline chemotherapy. The primary outcome was the evaluation of changes in RV GLS and RV FWLS pre- and post-chemotherapy. Secondary outcomes included changes in traditional echocardiographic parameters: TAPSE, FAC, and TDI S'. Meta-analysis revealed significant declines in RV function post-chemotherapy across all parameters. RV GLS decreased from 23.99% to 20.35% (SMD: −0.259, p < 0.0001), and RV FWLS from 24.92% to 21.56% (SMD: −0.269, p < 0.0001). Traditional parameters like TAPSE, FAC, and TDI S' also showed reductions, but these were less consistent across studies. A meta-regression analysis showed no significant relationship between post-chemotherapy left ventricular ejection fraction (LVEF) and the changes in RV GLS and RV FWLS, suggesting that RV dysfunction may not be solely a consequence of LV impairment. Conclusions: Anthracycline chemotherapy induces subclinical RV dysfunction in breast cancer patients. RV strain analysis, especially 3D strain, shows greater sensitivity in detecting early dysfunction. However, further research is needed to clarify the clinical significance and prognostic value of these findings, as well as the role of routine RV strain analysis in guiding early interventions. [ABSTRACT FROM AUTHOR]

Preliminary evidence suggests perturbations of the kynurenine pathway (KP) of tryptophan metabolism in infants with single ventricle heart disease (SVHD). In 72 infants with SVHD undergoing stage 2 palliation (S2P) and 41 controls, we quantified serum KP metabolite concentrations via tandem mass spectroscopy pre‐S2P and post‐S2P at 2, 24, and 48 h and assessed metabolite relationships with post‐S2P outcomes (length of stay, hypoxemia burden, and intubation duration). Pre‐S2P, SVHD infants had lower tryptophan and serotonin levels and higher kynurenic acid, 3‐hydroxykynurenine, and picolinic acid levels than controls. Post‐S2P, metabolites peaked at 2 h, with return to baseline by 48 h for all except kynurenic acid, which remained elevated. Metabolite concentrations pre‐S2P were poorly associated with outcomes. A lower serotonin peak 2 h post‐S2P was associated with longer length of stay and intubation duration. Multiple metabolites at 24 and 48 h correlated with outcomes; notably, elevated kynurenic acid was associated with worse results for all three outcomes. Our results confirm that interstage SVHD infants have altered KP activity compared to controls. Further, the link between outcomes and KP metabolites post‐S2P—but not at baseline—demonstrates that acute, perioperative changes in tryptophan catabolism may be more important to tolerating S2P physiology than chronic interstage changes. [ABSTRACT FROM AUTHOR]

Pulmonary arteriovenous malformations (PAVMs) universally develop in patients with single ventricle congenital heart disease. Single ventricle PAVMs have been recognized for over 50 years but remain poorly understood. To improve our understanding, we developed a surgical rat model of Glenn circulation and characterized PAVM physiology over multiple time points. We performed a left thoracotomy and end‐to‐end anastomosis of the left superior vena cava to the left pulmonary artery (unilateral Glenn), or sham surgical control. To assess PAVM physiology, we quantified intrapulmonary shunting using two independent methods (bubble echocardiography and fluorescent microsphere injection). Additionally, we performed arterial blood gas measurements to assess oxygenation and plethysmography to assess ventilation. We identified pathologic intrapulmonary shunting by bubble echocardiography as early as 2 weeks post‐Glenn, and shunting continued at 2‐ and 6‐months post‐Glenn. Shunting also progressed over time, demonstrated by increased shunting of 10 μm microspheres at 6 months. Shunting was accompanied by mildly decreased oxygenation but no differences in ventilation. Our surgical animal model of unilateral Glenn circulation recreates the clinical condition of single ventricle PAVMs with early and progressive intrapulmonary shunting. This model is poised to characterize single ventricle PAVM pathophysiology and lead to mechanistic and therapeutic discovery. [ABSTRACT FROM AUTHOR]

Objective: B-type natriuretic peptide (BNP) is a neurohormone primarily secreted from cardiac ventricles in reaction to increased volume and pressure. The plasma level of BNP is used to measure the mechanical function of the heart and the risk of developing chronic obstructive pulmonary disease (COPD). Alpha-1 antitrypsin (AAT) is a glycoprotein that acts as an inhibitor of serine proteases and plays a crucial role in protecting the lungs against potential harm. AAT deficiency also causes COPD. The data on the prevalence of BNP and AAT in African Americans (AA) are limited and inconsistent. No previous studies have investigated whether any association exists between BNP and AAT. We collected fasting blood samples from 114 AA subjects who provided informed consent. The plasma levels of the biomarkers were measured using ELISA. Results: Our findings revealed a significant negative correlation between AAT and BNP (r=-0.266, p = 0.01) as well as between AAT and TNF-α (r=-0.242, p = 0.01). Sex hormones (estrogen and testosterone) have a significant relationship with the levels of AAT and BNP. Increasing the AAT and reducing the levels of inflammation can lower the levels of BNP, which in turn could help lower the risk of heart disease in the AA population. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to evaluate the prognosis of idiopathic premature ventricular beats (PVBs) in children. Materials and Methods: We retrospectively evaluated 73 children (<18 years old) with idiopathic PVBs and structurally normal hearts. All patients were evaluated by 24-hour Holter electrocardiography (ECG) and echocardiography at the first admission and followed with a mean of 27 ± 7.6 months after diagnosis. Baseline Holter ECG and echocardiographic findings were compared to the last visit. Results: The mean age of the patients was 11.1 ± 4.8 years, and half were symptomatic at initial examination. Baseline Holter showed complex beats in 35 cases, non-sustained ventricular tachycardia in 7 cases, and frequent PVBs in 19 cases. Complete recovery (CR) of PVBs was observed in 37 cases (50.7%) at a median of 15 (minimum: 5, maximum: 33) months after diagnosis. There were no significant differences in CR rates between patient groups with left bundle branch block (LBBB) vs. right bundle branch block (RBBB) morphology of PVBs, simple vs. complex PVBs, and daytime vs. nighttime dominance of PVBs (P > .05 for all parameters). The CR rate of PVBs was different among patients with infrequent, moderate, and frequent PVBs (62.8%, 36.4%, and 31.6%, respectively). Premature ventricular beats disappeared more often during follow-up in patients with infrequent PVBs (P = .045). However, the absolute decrease and disappearance rates of PVBs were similar across all groups (72.1%, 81.8%, and 89.5%, respectively; P = .319). The resolution rates of PVBs were not statistically different between the patient group who received pharmacological treatment and the group who followed up without treatment (P = .070). No myocardial dysfunction was observed in any patient during follow-up. No cases experienced major cardiac events. Conclusion: Idiopathic PVBs usually regress in childhood regardless of frequency and complexity or receiving antiarrhythmic medication. The risk of ventricular dysfunction is low during childhood; however, they require careful evaluation and follow-up. [ABSTRACT FROM AUTHOR]

Cardiac remodelling is often most profound in male athletes and in athletes with the greatest volumes of endurance training and is characterized by chamber enlargement and a mild-to-modest hypertrophy. The diastolic filling of the left ventricle (LV) is a complex process including the early recoil of the contracted LV, the active relaxation of the myocardium, the compliance of the myocardium, the filling pressures, and heart rate. Echocardiography is the cornerstone for the clinical assessment of LV diastolic function. LV diastolic function is usually enhanced in elite endurance athletes characterized by improved early filling of the ventricle, while it is preserved or enhanced in other athletes associated with the type of training being performed. This allows for the high performance of any endurance athlete. Typical findings when using resting echocardiography for the assessment of LV diastolic function in endurance athletes include a dilated LV with normal or mildly reduced LV ejection fraction (EF), significantly enlarged left atrium (LA) beyond the commonly used cut-off of 34 mL/m2, and a significantly elevated E/A ratio. The early-diastolic mitral annular velocity and the E-wave peak velocity are usually normal. Importantly, interpretation of the echocardiographic indices of LV diastolic function should always consider the clinical context and other parameters of systolic and diastolic functions. In the absence of an underlying pathology, single measurements outside the expected range for similar athletes will often not represent the pathology. [ABSTRACT FROM AUTHOR]

Clinical data: A nine-month-old female infant diagnosed with transposition of the great arteries with symptoms of heart failure associated with cyanosis and difficulty in gaining weight was referred to our center with late diagnosis (at nine months of age). Chest radiography: Cardiomegaly; attenuated peripheral vascular markings. Electrocardiography: Sinus rhythm with biventricular overload and aberrantly conducted supraventricular extra systoles. Echocardiography: Wide atrial septal defect, ventricular axis torsion with concordant atrioventricular connection and discordant ventriculoarterial connection. Computed tomography angiography: Concordant atrioventricular connection, right ventricle positioned superiorly and left ventricle positioned inferiorly; discordant ventriculoarterial connection with right ventricle connected to the aorta and left ventricle connected to pulmonary artery. Diagnosis: Crisscross heart is a rare congenital heart defect, accounting for 0.1% of congenital heart diseases. It consists of the 90° rotation of ventricles' axis in relation to their normal position; therefore, ventricles are positioned in the superior-inferior direction rather than anterior-posterior. Most cases have associated cardiac anomalies, and in this case, it is associated with transposition of the great arteries. The complexity and rarity of its occurrence make diagnosis and surgical treatment challenging. Operation: Modified Senning procedure using the pericardial sac in the construction of a tunnel from pulmonary veins to the right atrium. Cardiopulmonary bypass time of 147 minutes with nine minutes of total circulatory arrest. [ABSTRACT FROM AUTHOR]

The composite material-like extracellular matrix (ECM) in the sinoatrial node (SAN) supports the native pacemaking cardiomyocytes (PCMs). To test the roles of SAN ECM in the PCM phenotype and function, we engineered reconstructed-SAN heart tissues (rSANHTs) by recellularizing porcine SAN ECMs with hiPSC-derived PCMs. The hiPSC-PCMs in rSANHTs self-organized into clusters resembling the native SAN and displayed higher expression of pacemaker-specific genes and a faster automaticity compared with PCMs in reconstructed-left ventricular heart tissues (rLVHTs). To test the protective nature of SAN ECMs under strain, rSANHTs and rLVHTs were transplanted onto the murine thoracic diaphragm to undergo constant cyclic strain. All strained-rSANHTs preserved automaticity, whereas 66% of strained-rLVHTs lost their automaticity. In contrast to the strained-rLVHTs, PCMs in strained-rSANHTs maintained high expression of key pacemaker genes (HCN4, TBX3, and TBX18). These findings highlight the promotive and protective roles of the composite SAN ECM and provide valuable insights for pacemaking tissue engineering.

The aim was to test the hypothesis that left ventricular (LV) and right ventricular (RV) activation from body surface electrical mapping (CardioInsight 252-electrode vest, Medtronic) identifies optimal cardiac resynchronization therapy (CRT) pacing strategies and outcomes in 30 patients. The LV80, RV80, and BIV80 were defined as the times to 80% LV, RV, or biventricular electrical activation. Smaller differences in the LV80 and RV80 (|LV80-RV80|) with synchronized LV pacing predicted better LV function post-CRT (p = 0.0004) than the LV-paced QRS duration (p = 0.32). Likewise, a lower RV80 was associated with a better pre-CRT RV ejection fraction by CMR (r =  - 0.40, p = 0.04) and predicted post-CRT improvements in myocardial oxygen uptake (p = 0.01) better than the biventricular-paced QRS (p = 0.38), while a lower LV80 with BIV pacing predicted lower post-CRT B-type natriuretic peptide (BNP) (p = 0.02). RV pacing improved LV function with smaller |LV80-RV80| (p = 0.009). In conclusion, 3-D electrical mapping predicted favorable post-CRT outcomes and informed effective pacing strategies.

We report a technique to generate a murine model of lung metastases by selectively injecting tumor cells into the right heart ventricle under ultrasound guidance. First, we describe cell preparation and reference animal preparation as previously described. We then detail the technique using a previously described 3D-printed instrument stabilization device. Finally, we describe tumor growth surveillance using bioluminescent imaging. For complete details on the use and execution of this protocol, please refer to Labora et al.1.

Computational models provide an efficient paradigm for integrating and linking multiple spatial and temporal scales. However, these models are difficult to parameterize and match to experimental data. Recent advances in both data collection and model analyses have helped overcome this limitation. Here, we combine a multiscale, biventricular interaction model with mouse data before and after left ventricular (LV) ischemia. Sensitivity analyses are used to identify the most influential parameters on pressure and volume predictions. The subset of influential model parameters are calibrated to biventricular pressure-volume loop data (n = 3) at baseline. Each mouse underwent left anterior descending coronary artery ligation, during which changes in fractional shortening and RV pressure-volume dynamics were recorded. Using the calibrated model, we simulate acute LV ischemia and contrast outputs at baseline and in simulated ischemia. Our baseline simulations align with the LV and RV data, and our predictions during ischemia complement recorded RV data and prior studies on LV function during myocardial infarction. We show that a model with both biventricular mechanical interaction and systems-level cardiovascular dynamics can quantitatively reproduce in-vivo data and qualitatively match prior findings from animal studies on LV ischemia.

Introduction: Previous studies have investigated the potential influence of prior aspirin use on cardiac function in patients with ST-elevation myocardial infarction (STEMI) who undergo primary percutaneous coronary intervention (PPCI). However, the results from these studies have been conflicting. This study aimed to investigate whether prior aspirin use affects left ventricular (LV) function in these patients using echocardiography. Methods: The study included 260 consecutive STEMI patients, who were divided into two groups based on the presence or absence of prior aspirin use. Echocardiographic parameters, such as maximal left atrial (LA) size, LV ejection fraction (LVEF), early diastolic velocity (e’), E/A ratio, and E/e’ ratio, were assessed within 72 hours of admission. Results: Aspirin users had an older age compared to non-users, as well as lower body mass index and renal function. They also had a greater history of hypertension and were more likely to be taking statins, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and calcium channel blockers. There were no significant differences in LVEF, maximal LA size, E/A ratio, E/e’ ratio, and deceleration time between aspirin users and non-users. e’ wave was marginally lower in aspirin users (P=0.054). After controlling for confounding variables, the previous use of aspirin did not show a significant impact. Conclusion: Prior aspirin use in STEMI patients does not have a significant impact on LV echocardiographic parameters. Our conclusions remained consistent even after adjusting for potential confounders.

Objective: Fetuses with single ventricle physiology (SVP) exhibit reductions in fetal cerebral oxygenation, with associated delays in fetal brain growth and neurodevelopmental outcomes. Maternal supplemental oxygen (MSO) has been proposed to improve fetal brain growth, but current evidence on dosing, candidacy and outcomes is limited. In this pilot study, we evaluated the safety and feasibility of continuous low‐dose MSO in the setting of SVP. Methods: This single‐center, open‐label, pilot phase‐1 safety and feasibility clinical trial included 25 pregnant individuals with a diagnosis of fetal SVP. Participants self‐administered continuous MSO using medical‐grade oxygen concentrators for up to 24 h per day from the second half of gestation until delivery. The primary aim was the evaluation of the safety profile and feasibility of MSO. A secondary preliminary analysis was performed to assess the impact of MSO on the fetal circulation using echocardiography and late‐gestation cardiovascular magnetic resonance imaging. Early outcomes were assessed, including perinatal growth and preoperative brain injury, and neurodevelopmental outcomes were assessed at 18 months using the Bayley Scales of Infant and Toddler Development 3rd edition, and compared with those of a contemporary fetal SVP cohort (n = 217) that received the normal standard of care (SOC). Results: Among the 25 participants, the median maternal age at conception was 35 years, and fetal SVP diagnoses included 16 with right ventricle dominant, eight with left ventricle dominant and one with indeterminate ventricular morphology. Participants started the trial at approximately 29 + 2 weeks' gestation and self‐administered MSO for a median of 16.1 h per day for 63 days, accumulating a median of 1029 h of oxygen intake from enrolment until delivery. The only treatment‐associated adverse events were nasal complications that were resolved typically by attaching a humidifier unit to the oxygen concentrator. No premature closure of the ductus arteriosus or unexpected fetal demise was observed. In the secondary analysis, MSO was not associated with any changes in fetal growth, middle cerebral artery pulsatility index, cerebroplacental ratio or head‐circumference‐to‐abdominal‐circumference ratio Z‐scores over gestation compared with SOC. Although MSO was associated with changes in umbilical artery pulsatility index Z‐score over the study period compared with SOC (P = 0.02), this was probably due to initial baseline differences in placental resistance. At late‐gestation cardiovascular magnetic resonance imaging, MSO was not associated with an increase in fetal cerebral oxygen delivery. Similarly, no differences were observed in neonatal outcomes, including preoperative brain weight Z‐score and brain injury, mortality by 18 months of age and neurodevelopmental outcomes at 18 months of age. Conclusions: This pilot phase‐1 clinical trial indicates that low‐dose MSO therapy is safe and well tolerated in pregnancies diagnosed with fetal SVP. However, our protocol was not associated with an increase in fetal cerebral oxygen delivery or improvements in early neurological or neurodevelopmental outcomes. © 2024 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Aims Epicardial fat is a metabolically active adipose tissue depot situated between the myocardium and visceral pericardium that covers ∼80% of the heart surface. While epicardial fat has been associated with the development of atherosclerotic coronary artery disease, less is known about the relationship between epicardial fat and coronary vascular function. Moreover, the relations between excess epicardial fat and cardiac morphology and function remain incompletely understood. Methods and results To address these knowledge gaps, we retrospectively analysed data from 294 individuals from our database of women with suspected ischaemia with no obstructive coronary disease (INOCA) who underwent both invasive coronary function testing and cardiac magnetic resonance imaging. Epicardial fat area, biventricular morphology, and function, as well as left atrial function, were assessed from cine images, per established protocols. The major novel findings were two-fold: first, epicardial fat area was not associated with coronary vascular dysfunction. Secondly, epicardial fat was associated with increased left ventricular concentricity (β = 0.15, P = 0.01), increased septal thickness (β = 0.17, P = 0.002), and reduced left atrial conduit fraction (β = −0.15, P = 0.02), even after accounting for age, BMI, and history of hypertension. Conclusion Taken together, these data do not support a measurable relationship between epicardial fat and coronary vascular dysfunction but do suggest that epicardial fat may be related to concentric remodelling and diastolic dysfunction in women with suspected INOCA. Prospective studies are needed to elucidate the long-term impact of epicardial fat in this patient population. [ABSTRACT FROM AUTHOR]

Aims Standard methods of heart chamber volume estimation in cardiovascular magnetic resonance (CMR) typically utilize simple geometric formulae based on a limited number of slices. We aimed to evaluate whether an automated deep learning neural network prediction of 3D anatomy of all four chambers would show stronger associations with cardiovascular risk factors and disease than standard volume estimation methods in the UK Biobank. Methods and results A deep learning network was adapted to predict 3D segmentations of left and right ventricles (LV, RV) and atria (LA, RA) at ∼1 mm isotropic resolution from CMR short- and long-axis 2D segmentations obtained from a fully automated machine learning pipeline in 4723 individuals with cardiovascular disease (CVD) and 5733 without in the UK Biobank. Relationships between volumes at end-diastole (ED) and end-systole (ES) and risk/disease factors were quantified using univariate, multivariate, and logistic regression analyses. Strength of association between deep learning volumes and standard volumes was compared using the area under the receiving operator characteristic curve (AUC). Univariate and multivariate associations between deep learning volumes and most risk and disease factors were stronger than for standard volumes (higher R 2 and more significant P- values), particularly for sex, age, and body mass index. AUCs for all logistic regressions were higher for deep learning volumes than standard volumes (P < 0.001 for all four chambers at ED and ES). Conclusion Neural network reconstructions of whole heart volumes had significantly stronger associations with CVD and risk factors than standard volume estimation methods in an automatic processing pipeline. [ABSTRACT FROM AUTHOR]

Aims Advanced age is associated with an increased risk of adverse cardiovascular events. The relationship between biological age acceleration (BAA), cardiac size, cardiac function, and heart failure (HF) is not well-defined. Methods and results Utilizing the UK Biobank cohort, we assessed biological age using the Klemera–Doubal and PhenoAge methods. BAA was quantified by residual analysis compared with chronological age. Cardiovascular magnetic resonance (CMR) imaging provided detailed insights into cardiac structure and function. We employed multivariate regression to examine links between BAA and CMR-derived cardiac phenotypes. Cox proportional hazard regression models analysis was applied to explore the causative relationship between BAA and HF. Additionally, Mendelian randomization was used to investigate the genetic underpinnings of these associations. A significant correlation was found between increased BAA and deleterious changes in cardiac structure, such as diminished left ventricular mass, lower overall ventricular volume, and reduced stroke volumes across ventricles and atria. Throughout a median follow-up of 13.8 years, participants with greater biological aging showed a heightened risk of HF [26% per standard deviation (SD) increase in KDM-BA acceleration, 95% confidence intervals (CI): 23–28%; 33% per SD increase in PhenoAge acceleration, 95% CI: 32–35%]. Mendelian randomization analysis suggests a likely causal link between BAA, vital cardiac metrics, and HF risk. Conclusion In this cohort, accelerated biological aging may serve as a risk indicator for altered cardiac dimensions, functionality, and the onset of heart failure among middle-aged and elderly adults. It holds promise as a focal point for evaluating risk and developing targeted interventions. [ABSTRACT FROM AUTHOR]

Cardiomyopathy syndrome (CMS) caused by piscine myocarditis virus (PMCV) has emerged with the rise of the aquaculture of Atlantic salmon (Salmo salar). The lack of cell culture cultivation has hampered the study of this infection. In this study, samples from naturally PMCV-infected Atlantic salmon from different commercial farms were collected and used. In situ hybridization (ISH) revealed intense staining of PMCV RNA in myocardial cells in the spongiform layer of the heart ventricle but almost no staining in the compact layer. In the kidneys, only sporadic staining was seen. Viral RNA was present in all organs, with the highest loads in the heart, kidney, and spleen. The high viral PMCV RNA loads in the heart were due to extensive viral mRNA transcription. The high ratio of viral mRNA to viral genomic dsRNA indicated active transcription but limited production of new viral particles. This suggests that the histopathological changes in the heart are caused by viral mRNA and corresponding viral proteins and not by virus particle formation. The production of full-length transcripts is regulated, with a reduction in the relative number of ORF3-containing transcripts at high transcription rates. Efforts to identify alternative hosts, such as fungi, were inconclusive, as fungal sequences were found inconsistently in the salmon tissue samples. The results of this study reinforce the need for further research to fully understand PMCV's life cycle and potential alternative hosts and its whereabouts when it is not infecting the hearts of the Atlantic salmon. [ABSTRACT FROM AUTHOR]

Accurate analysis of Fluorodeoxyglucose (FDG)-Positron Emission Tomography (PET) images is crucial for the diagnosis, treatment assessment, and monitoring of patients suffering from various cancer types. FDG-PET images provide valuable insights by revealing regions where FDG, a glucose analog, accumulates within the body. While regions of high FDG uptake include suspicious tumor lesions, FDG also accumulates in non-tumor-specific regions and organs. Identifying these regions is crucial for excluding them from certain measurements, or calculating useful parameters, for example, the mean standardized uptake value (SUV) to assess the metabolic activity of the liver. Manual organ delineation from FDG-PET by clinicians demands significant effort and time, which is often not feasible in real clinical workflows with high patient loads. For this reason, this study focuses on automatically identifying key organs with high FDG uptake, namely the brain, left cardiac ventricle, kidneys, liver, and bladder. To this end, an ensemble approach is adopted, where a three-dimensional Attention U-Net (3D AU-Net) is employed for robust three-dimensional analysis, while a two-dimensional U-Net (2D U-Net) is utilized for analysis in the coronal plane. The 3D AU-Net demonstrates highly detailed organ segmentations, but also includes many false positive regions. In contrast, 2D U-Net achieves higher reliability with minimal false positive regions, but lacks the 3D details. Experiments conducted on a subset of the public AutoPET dataset with 60 PET scans demonstrate that the proposed ensemble model achieves high accuracy in segmenting the required organs, surpassing current state-of-the-art techniques, and supporting the potential utilization of the proposed methodology in accelerating and enhancing the clinical workflow of cancer patients. [ABSTRACT FROM AUTHOR]

Introduction: It has been demonstrated that an increase in the diameter of the right ventricle or pulmonary artery in COVID-19 patients could be associated with the severity of lung involvement and may lead to unfavorable outcomes, particularly in the presence of pulmonary vascular diseases. This study investigated the relationship between these right heart strain features, the extent of lung involvement, and their prognostic values in patients without vascular comorbidities. Methods: This study selected 154 consecutive patients with positive chest computed tomography (CT) findings and no evidence of concurrent pulmonary disease. Clinical characteristics and adverse outcomes in in-hospital settings were collected retrospectively. Diameters of cardiac ventricles and arteries, along with lung opacification scores, were obtained using CT pulmonary angiography (CTPA) findings, and the association of these variables was evaluated. Results: An increase in pulmonary artery (PA) to ascending aorta (AO) diameter ratio and lung parenchymal damage were significantly and positively correlated (P =0.017), but increased right ventricle (RV) to left ventricle (LV) diameter ratio showed no association with the extent of chest opacification (P =0.098). Evaluating the prognostic ability of both ratios using logistic regression and receiver operating characteristic (ROC) analysis proved no significant class separation in regards to predicting adverse outcomes (PA/AO: OR:1.081, P Value:0.638, RV/LV: OR:1.098, P Value:0.344). Conclusion: In COVID-19 patients without vascular comorbidities, a higher PA/AO diameter ratio was significantly associated with increased lung involvement severity on CT imaging but not with adverse in-hospital outcomes. Conversely, an increased RV/LV ratio on CTPA did not correlate significantly with adverse outcomes or the severity of parenchymal lung damage. [ABSTRACT FROM AUTHOR]

Introduction: Previous studies have investigated the potential influence of prior aspirin use on cardiac function in patients with ST-elevation myocardial infarction (STEMI) who undergo primary percutaneous coronary intervention (PPCI). However, the results from these studies have been conflicting. This study aimed to investigate whether prior aspirin use affects left ventricular (LV) function in these patients using echocardiography. Methods: The study included 260 consecutive STEMI patients, who were divided into two groups based on the presence or absence of prior aspirin use. Echocardiographic parameters, such as maximal left atrial (LA) size, LV ejection fraction (LVEF), early diastolic velocity (e'), E/A ratio, and E/e' ratio, were assessed within 72 hours of admission. Results: Aspirin users had an older age compared to non-users, as well as lower body mass index and renal function. They also had a greater history of hypertension and were more likely to be taking statins, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and calcium channel blockers. There were no significant differences in LVEF, maximal LA size, E/A ratio, E/e' ratio, and deceleration time between aspirin users and non-users. e' wave was marginally lower in aspirin users (P =0.054). After controlling for confounding variables, the previous use of aspirin did not show a significant impact. Conclusion: Prior aspirin use in STEMI patients does not have a significant impact on LV echocardiographic parameters. Our conclusions remained consistent even after adjusting for potential confounders. [ABSTRACT FROM AUTHOR]

The intracavitary coronary arteries (ICCA) course is a rare phenomenon, where the segments of the coronary artery go through the atria or ventricles of the heart. In the past, these changes were incidentally detected during invasive diagnostic procedures for other reasons, as well as during postmortem examinations. As the use of multidetector computed tomography angiography (CTA) becomes more widespread, it has emerged that the incidence of ICCA has been underestimated. We present images from two coronary computed tomography angiography cases, which document the existence of ICCA in patients with non-specific chest pain. In the first case, in a 66-year-old woman, in addition to confirming coronary artery disease without significant stenosis (CAD-RADS 2-category 2 in the coronary-artery-disease-reporting and data system), the course of the middle section of the right coronary artery (RCA) in the lumen of the right atrium was demonstrated. In the second case, in a 47-year-old man in whom the presence of atherosclerotic lesions in the coronary arteries was excluded (CAD-RADS 0), the course of the distal segment of the left anterior descending (LAD) was found in the lumen of the apical layers of the right ventricle. To sum up, it should be stated that coronary CTA is a non-invasive diagnostic method that allows for visualization of the ICCA. In coronary CTA performed for indications consistent with the guidelines of scientific societies, attention should also be paid to the possible intracavitary course of the coronary arteries. The identification of such a course of the coronary arteries may be useful when preparing the patient for potential future invasive procedures involving the cardiac cavities. [ABSTRACT FROM AUTHOR]

Background: There is lack of evidence regarding safety, effectiveness and applicability of prehabilitation on cardiac surgery population, particularly in patients candidates to cardiac valve replacement. The aim of the study is to assess and compare the effect of a multimodal prehabilitation program on functional capacity in patients with severe aortic stenosis (AoS) and severe mitral regurgitation (MR) proposed for valve replacement surgery. Methods: Secondary analysis from a randomised controlled trial whose main objective was to analyze the efficacy of a 4–6 weeks multimodal prehabilitation program in cardiac surgery on reducing postoperative complications. For this secondary analysis, only candidates for valve replacement surgery were selected. The primary outcome was the change in endurance time (ET) from baseline to preoperative assessment measured by a cycling constant work-rate cardiopulmonary exercise test. Results: 68 patients were included in this secondary analysis, 34 (20 AoS and 14 MR) were allocated to the prehabilitation group and 34 (20 AoS and 14 MR) to control group. At baseline, patients with AoS had better left systolic ventricular function and lower prevalence of atrial fibrillation compared to MR (p = 0.022 and p = 0.035 respectively). After prehabilitation program, patients with MR showed greater improvement in ET than AoS patients (101% vs. 66% increase from baseline). No adverse events related to the prehabilitation program were observed. Conclusions: A 4–6 week exercise training program is safe and overall improves functional capacity in patients with severe AoS and MR. However, exercise response is different according to the cardiac valve type disfunction, and further studies are needed to know the factors that predispose some patients to have better training response. Trial registration: The study has been registered on the Registry of National Institutes of Health ClinicalTrials.gov (NCT03466606) (05/03/2018). [ABSTRACT FROM AUTHOR]

A relevant role of osteopontin (OPN) and gremlin 1 (Grem1) in regulating cardiac tissue remodeling and formation of heart failure (HF) are documented, with the changes of OPN and Grem1 levels in blood plasma due to acute ischemia, ischemic heart disease-induced advanced HF or dilatative cardiomyopathy being the primary focus in most of these studies. However, knowledge on the early OPN and Grem1 proteins expression changes within cardiomyocytes during remodeling due to chronic ischemia remains insufficient. The aim of this study was to determine the OPN and Grem1 proteins expression changes in human cardiomyocytes at different stages of ischemic HF. A semi-quantitative immunohistochemical analysis was performed in 105 myocardial tissue samples obtained from the left cardiac ventricles. Increased OPN immunostaining intensity was already detected in the stage A HF group, compared to the control group (p < 0.001), and continued to increase in the stage B HF (p < 0.001), achieving the peak of immunostaining in the stages C/D HF group (p < 0.001). Similar data of Grem1 immunostaining intensity changes in cardiomyocytes were documented. Significantly positive correlations were detected between OPN, Grem1 expression in cardiomyocytes and their diameter as well as the length, in addition to positive correlation between OPN and Grem1 expression changes within cardiomyocytes. These novel findings suggest that OPN and Grem1 contribute significantly to reorganization of cellular geometry from the earliest stage of cardiomyocyte remodeling, providing new insights into the ischemic HF pathogenesis. [ABSTRACT FROM AUTHOR]

Background: There is limited research on the intra‐individual efficacy of ventricular pacing minimization algorithms developed by Biotronik—the Ventricular Pace Suppression algorithm (VpS) and the Intrinsic Rhythm Support plus algorithm (IRSplus) (BIOTRONIK SE & Co. KG, Berlin, Germany). We performed a randomized pilot trial that evaluated the efficacy of two algorithms in patients with symptomatic sinus node dysfunction (SND) who received a dual‐chamber pacemaker. Methods: The trial was conducted in 11 tertiary hospitals in South Korea. The patients were randomized to either the VpS or IRSplus algorithm group after a 3‐month period of fixed atrioventricular (AV) delay. The primary outcome was the ventricular pacing percentage (Vp%) at each follow‐up visit. The secondary outcomes were the occurrence of heart failure (HF) and atrial fibrillation (AF) during the study period. Results: Data from 131 patients were analyzed. Initially, their average Vp% over 3 months with a fixed AV interval was 14.1 ± 19.4%. Patients were randomly assigned to VpS and IRSplus groups, with 66 and 65 in each. Algorithms reduced average Vp% to 4.0 ± 11.3% at 9 months and 6.7 ± 14.9% at 15 months. These algorithms were more effective for patients with paced AV delay (PAVD) ≤300 ms compared to those with PAVD >300 ms. Both algorithms were equally effective in reducing Vp%. Clinical AF or HF hospitalization was not observed during the study period. Conclusion: The VpS and IRSplus algorithms are effective and safe in minimizing unnecessary ventricular pacing in patients with SND. [ABSTRACT FROM AUTHOR]

Background. The purpose of the present study was to investigate the effect of aerobic)resistance training on the population of cardiac multipotent cells, thickness, and diameter of the ventricular through the C-Kit pathway of male rats during the growth stages. Methods. Overall, 30 male Wistar rats in three age groups of 2 (n = 10), 8 (n = 10), and 96 (n = 10) weeks were accidentally divided into exercise and control groups. Resistance training programs (resistance ladder, 3 days a week) and aerobics (treadmill running, 3 days a week) were performed for 6 weeks. Hematoxylin-Eosin staining was done the heart tissue and histological images were prepared. Afterward, C-Kit gene expression was examined by the real-time polymerase chain reaction method. The statistical method of one-way analysis of variance (P ≥ 0.05) and Tukey’s test were used at a significant level (P ≥ 0.01). Results. The trained neonatal group had higher values in heart weight to body weight index, and the trained neonatal and trained young adult groups had higher values in left ventricular thickness (P ≥ 0.01). The decrease in left ventricular internal diameter in the trained young adult group was significant compared to the control group (P ≥ 0.01). There was a significant increase in C-Kit gene expression in trained young adult and trained old groups (P ≥ 0.01). Conclusion. Aerobic-resistance training can be an effective stimulus for increasing the number of cardiac stem cells and creating structural adaptations of the heart, including increasing thickness and ventricular diameter in neonatal and young adult groups. Practical Implications. Participation in aerobic-resistance training programs leads to the improvement of the cardiac structure and an increase in cardiac stem cells. [ABSTRACT FROM AUTHOR]

This document has been developed to provide a guide for basic and advanced reporting in paediatric echocardiography. Furthermore, it aims to help clinicians in the interpretation of echocardiographic measurements and functional data for estimating the severity of disease in different paediatric age groups. The following topics will be reviewed and discussed in the present document: (i) the general principle in constructing a paediatric echocardiographic report, (ii) the basic elements to be included, and (iii) the potential and limitation of currently employed tools used for disease severity quantification during paediatric reporting. A guide for the interpretation of Z-scores will be provided. Use and interpretation of parameters employed for quantification of ventricular systolic function will be discussed. Difficulties in the adoption of adult parameters for the study of diastolic function and valve defects at different ages and pressure and loading conditions will be outlined, with pitfalls for the assessment listed. A guide for careful use of prediction scores for complex congenital heart disease will be provided. Examples of basic and advanced (disease-specific) formats for reporting in paediatric echocardiography will be provided. This document should serve as a comprehensive guide to (i) structure a comprehensive paediatric echocardiographic report; (ii) identify the basic morphological details, measures, and functional parameters to be included during echocardiographic reporting; and (iii) correctly interpret measurements and functional data for estimating disease severity. [ABSTRACT FROM AUTHOR]

Aims Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by progressive myocardial dysfunction and associated with an increased risk of major cardiovascular (CV) events. To determine right heart strain (ventricular and atrial global longitudinal strain (RVGLS and RAGLS) in patients with definite ARVC and its association with adverse events during follow-up. Methods and results RVGLS and RAGLS were analysed in focused right heart apical views from 70 patients using TomTec ImageArena and association with a composite endpoint was determined (sustained ventricular arrhythmia and cardiovascular death). Over a median follow-up duration of 4.9 years, 26 (37%) patients met the endpoint. RVGLS was significantly impaired in the event group (−11.5 [−13.3 to −10.2] %) vs. the no-event group (−15.8 [−17.1 to −14.5] %, P < 0.001), and so was RAGLS (22.8 [21.4–27.4] % vs. 31.5 [25.1–39.6] %, respectively, P < 0.001). In Cox regression, RVGLS (HR 1.36, P < 0.001) and RAGLS (HR 0.92, P = 0.002) were associated with a higher risk of adverse events. In multivariable Cox regression models, RVGLS and RAGLS remained independent of and were incremental to age, gender, and conventional RV parameters, and model fitness was improved when RVGLS and RAGLS were applied together rather than alone. Conclusion RVGLS and RAGLS are more impaired in patients with adverse events and associated with adverse events independent of age, gender, and conventional RV parameters. When RVGLS and RAGLS are applied together, prediction models are improved suggesting that right heart strain may form part of the echocardiographic routine protocol in patients with ARVC. [ABSTRACT FROM AUTHOR]

ABSTRACT This case report discusses the migration of a foreign body from the breast to the mediastinum, which is rarely reported, and highlights complications associated with Okibari acupuncture. This technique involves the insertion of metal fragments into the skin. A 53-year-old woman underwent mammography showing acupuncture-related metallic fragments in the breast. Cardiac evaluation revealed the presence of metallic fragments in the right ventricle and myocardium. Despite the fragments‘ location in the mediastinum, the patient remained asymptomatic, leading us to take a conservative approach. This case highlights the importance of awareness of the potential complications of foreign bodies and emphasizes the need for careful monitoring.

BackgroundFalse ventricular tachycardia (VT) alarms are common during in-hospital electrocardiographic (ECG) monitoring. Prior research shows that the majority of false VT can be attributed to algorithm deficiencies.PurposeThe purpose of this study was: (1) to describe the creation of a VT database annotated by ECG experts and (2) to determine true vs. false VT using a new VT algorithm created by our group.MethodsThe VT algorithm was processed in 5320 consecutive ICU patients with 572,574 h of ECG and physiologic monitoring. A search algorithm identified potential VT, defined as: heart rate >100 beats/min, QRSs > 120 ms, and change in QRS morphology in >6 consecutive beats compared to the preceding native rhythm. Seven ECG channels, SpO2 , and arterial blood pressure waveforms were processed and loaded into a web-based annotation software program. Five PhD-prepared nurse scientists performed the annotations.ResultsOf the 5320 ICU patients, 858 (16.13%) had 22,325 VTs. After three levels of iterative annotations, a total of 11,970 (53.62%) were adjudicated as true, 6485 (29.05%) as false, and 3870 (17.33%) were unresolved. The unresolved VTs were concentrated in 17 patients (1.98%). Of the 3870 unresolved VTs, 85.7% (n = 3281) were confounded by ventricular paced rhythm, 10.8% (n = 414) by underlying BBB, and 3.5% (n = 133) had a combination of both.ConclusionsThe database described here represents the single largest human-annotated database to date. The database includes consecutive ICU patients, with true, false, and challenging VTs (unresolved) and could serve as a gold standard database to develop and test new VT algorithms.

OBJECTIVE: Biaxial mechanical testing is a common method for elucidation of mechanical properties of excised ventricular myocardium, especially in the context of structural remodeling that accompanies heart disease. Current imaging strategies in biaxial testing are based on optical camera imaging of the tissue surface, thus providing no information about the tissue microstructure and limiting strain measurements to two dimensions. Here, these limitations are overcome by replacing the camera with ultrasound imaging in order to measure both transmural fiber orientation and 3D tissue deformation during biaxial testing. METHODS: Quasi-static biaxial mechanical testing is applied to four samples of excised porcine ventricular myocardium (two left- and two right-ventricular tissues). During testing, a rotational scan of an ultrasound linear array provides data for both backscatter tensor imaging and 3D speckle tracking, from which transmural fiber orientation and tissue deformation are computed, respectively. Ultrasound-derived fiber orientation and tissue strain are validated against histology and camera surface imaging, respectively. DISCUSSION: Ultrasound-derived fiber angle and tissue strain exhibit good accuracy, with root-mean-square errors of 9.9° and 1.2% strain, respectively. Further investigation into the optimization of backscatter tensor imaging is warranted. Replacing the rotational scan of a linear array with volume imaging with a matrix array will improve the technique. CONCLUSION: Ultrasound imaging can replace the optical camera measurement during biaxial mechanical testing of ventricular myocardium in order to accurately provide measurements of transmural fiber orientation and tissue strain. In situ knowledge of transmural fiber structure and tissue deformation can enhance the inverse problem used to determine tissue mechanical properties from biaxial testing.

Sympathetic efferent axons regulate cardiac functions. However, the topographical distribution and morphology of cardiac sympathetic efferent axons remain insufficiently characterized due to the technical challenges involved in immunohistochemical labeling of the thick walls of the whole heart. In this study, flat-mounts of the left and right atria and ventricles of FVB mice were immunolabeled for tyrosine hydroxylase (TH), a marker of sympathetic nerves. Atrial and ventricular flat-mounts were scanned using a confocal microscope to construct montages. We found (1) In the atria: A few large TH-immunoreactive (IR) axon bundles entered both atria, branched into small bundles and then single axons that eventually formed very dense terminal networks in the epicardium, myocardium and inlet regions of great vessels to the atria. Varicose TH-IR axons formed close contact with cardiomyocytes, vessels, and adipocytes. Multiple intrinsic cardiac ganglia (ICG) were identified in the epicardium of both atria, and a subpopulation of the neurons in the ICG were TH-IR. Most TH-IR axons in bundles traveled through ICG before forming dense varicose terminal networks in cardiomyocytes. We did not observe varicose TH-IR terminals encircling ICG neurons. (2) In the left and right ventricles and interventricular septum: TH-IR axons formed dense terminal networks in the epicardium, myocardium, and vasculature. Collectively, TH labeling is achievable in flat-mounts of thick cardiac walls, enabling detailed mapping of catecholaminergic axons and terminal structures in the whole heart at single-cell/axon/varicosity scale. This approach provides a foundation for future quantification of the topographical organization of the cardiac sympathetic innervation in different pathological conditions.

PurposeTo extend the MR MultiTasking-based Multidimensional Assessment of Cardiovascular System (MT-MACS) technique with larger spatial coverage and water-fat separation for comprehensive aortocardiac assessment.MethodsMT-MACS adopts a low-rank tensor image model for 7D imaging, with three spatial dimensions for volumetric imaging, one cardiac motion dimension for cine imaging, one respiratory motion dimension for free-breathing imaging, one T2-prepared inversion recovery time dimension for multi-contrast assessment, and one T2*-decay time dimension for water-fat separation. Nine healthy subjects were recruited for the 3T study. Overall image quality was scored on bright-blood (BB), dark-blood (DB), and gray-blood (GB) contrasts using a 4-point scale (0-poor to 3-excellent) by two independent readers, and their interreader agreement was evaluated. Myocardial wall thickness and left ventricular ejection fraction (LVEF) were quantified on DB and BB contrasts, respectively. The agreement in these metrics between MT-MACS and conventional breath-held, electrocardiography-triggered 2D sequences were evaluated.ResultsMT-MACS provides both water-only and fat-only images with excellent image quality (average score = 3.725/3.780/3.835/3.890 for BB/DB/GB/fat-only images) and moderate to high interreader agreement (weighted Cohen's kappa value = 0.727/0.668/1.000/1.000 for BB/DB/GB/fat-only images). There were good to excellent agreements in myocardial wall thickness measurements (intraclass correlation coefficients [ICC] = 0.781/0.929/0.680/0.878 for left atria/left ventricle/right atria/right ventricle) and LVEF quantification (ICC = 0.716) between MT-MACS and 2D references. All measurements were within the literature range of healthy subjects.ConclusionThe refined MT-MACS technique provides multi-contrast, phase-resolved, and water-fat imaging of the aortocardiac systems and allows evaluation of anatomy and function. Clinical validation is warranted.

AimsCardiac arrhythmia originating from the papillary muscle (PM) can trigger ventricular fibrillation (VF) and cause sudden cardiac death even in the absence of structural heart disease. Most premature ventricular contractions, however, are benign and hitherto difficult to distinguish from a potentially fatal arrhythmia. Altered repolarization characteristics are associated with electrical instability, but electrophysiological changes which precede degeneration into VF are still not fully understood.Methods and resultsVentricular arrhythmia (VA) was induced by aconitine injection into PMs of healthy sheep. To investigate mechanisms of degeneration of stable VA into VF in structurally healthy hearts, endocardial high-density and epicardial mapping was performed during sinus rhythm (SR) and VA. The electrical restitution curve, modelling the relation of diastolic interval and activation recovery interval (a surrogate parameter for action potential duration), is steeper in VA than in non-arrhythmia (ventricular pacing and SR). Steeper restitution curves reflect electrical instability and propensity to degenerate into VF. Importantly, we find the parameter repolarization time in relation to cycle length (RT/CL) to differentiate self-limiting from degenerating arrhythmia with high specificity and sensitivity.ConclusionRT/CL may serve as a simple index to aid differentiation between self-limiting and electrically instable arrhythmia with the propensity to degenerate to VF. RT/CL is independent of cycle length and could easily be measured to identify electrical instability in patients.

Cardiac shape modeling is a useful computational tool that has provided quantitative insights into the mechanisms underlying dysfunction in heart disease. The manual input and time required to make cardiac shape models, however, limits their clinical utility. Here we present an end-to-end pipeline that uses deep learning for automated view classification, slice selection, phase selection, anatomical landmark localization, and myocardial image segmentation for the automated generation of three-dimensional, biventricular shape models. With this approach, we aim to make cardiac shape modeling a more robust and broadly applicable tool that has processing times consistent with clinical workflows. Cardiovascular magnetic resonance (CMR) images from a cohort of 123 patients with repaired tetralogy of Fallot (rTOF) from two internal sites were used to train and validate each step in the automated pipeline. The complete automated pipeline was tested using CMR images from a cohort of 12 rTOF patients from an internal site and 18 rTOF patients from an external site. Manually and automatically generated shape models from the test set were compared using Euclidean projection distances, global ventricular measurements, and atlas-based shape mode scores. The mean absolute error (MAE) between manually and automatically generated shape models in the test set was similar to the voxel resolution of the original CMR images for end-diastolic models (MAE = 1.9 ± 0.5 mm) and end-systolic models (MAE = 2.1 ± 0.7 mm). Global ventricular measurements computed from automated models were in good agreement with those computed from manual models. The average mean absolute difference in shape mode Z-score between manually and automatically generated models was 0.5 standard deviations for the first 20 modes of a reference statistical shape atlas. Using deep learning, accurate three-dimensional, biventricular shape models can be reliably created. This fully automated end-to-end approach dramatically reduces the manual input required to create shape models, thereby enabling the rapid analysis of large-scale datasets and the potential to deploy statistical atlas-based analyses in point-of-care clinical settings. Training data and networks are available from cardiacatlas.org.

Right ventricular (RV) function is an important marker of mortality in chronic left-sided heart failure. Right ventricular function is particularly important for patients receiving left ventricular assist devices as it is a predictor of postoperative RV failure. RV stroke work index (RVSWI), the area enclosed by a pressure-volume (PV) loop, is prognostic of RV failure. However, clinical RVSWI approximates RVSWI as the product of thermodilution-derived stroke volume and the pulmonary pressure gradient. This ignores the energetic contribution of regurgitant flow and does not allow for advanced energetic measures, such as pressure-volume area and efficiency. Estimating RVSWI from forward flow may underestimate the underlying RV function. We created single-beat PV loops by combining data from cine computed tomography (CT) and right heart catheterization in 44 heart failure patients, tested the approximations made by clinical RVSWI and found it to underestimate PV loop RVSWI, primarily due to regurgitant flow in tricuspid regurgitation. The ability of RVSWI to predict post-operative RV failure improved when the single-beat approach was used. Further, RV pressure-volume area and efficiency measures were obtained and show broad agreement with other functional measures. Future work is needed to investigate the utility of these PV metrics in a clinical setting.

During heart development, the embryonic ventricle becomes enveloped by the epicardium, which adheres to the outer apical surface of the heart. This is concomitant with onset of ventricular trabeculation, where a subset of cardiomyocytes lose apicobasal polarity and delaminate basally from the ventricular wall. Llgl1 regulates the formation of apical cell junctions and apicobasal polarity, and we investigated its role in ventricular wall maturation. We found that llgl1 mutant zebrafish embryos exhibit aberrant apical extrusion of ventricular cardiomyocytes. While investigating apical cardiomyocyte extrusion, we identified a basal-to-apical shift in laminin deposition from the internal to the external ventricular wall. We find that epicardial cells express several laminin subunits as they adhere to the ventricle, and that the epicardium is required for laminin deposition on the ventricular surface. In llgl1 mutants, timely establishment of the epicardial layer is disrupted due to delayed emergence of epicardial cells, resulting in delayed apical deposition of laminin on the ventricular surface. Together, our analyses reveal an unexpected role for Llgl1 in correct timing of epicardial development, supporting integrity of the ventricular myocardial wall. [ABSTRACT FROM AUTHOR]

Background: Surgical intervention is the definitive treatment for Ebstein anomaly, offering both biventricular and nonbiventricular repair options. The objective of this study is to identify a specific cutoff value for tricuspid septal leaflet displacement, which will be a crucial factor in determining the selection of a surgical approach with lower mortality risk in biventricular repair. Methods and Results: This is a retrospective cohort study of consecutive patients with Ebstein anomaly undergoing surgical intervention at the National Cardiovascular Center Harapan Kita from January 2010 to December 2023. A total of 83 patients with Ebstein anomaly were treated surgically; 43 of those underwent biventricular repair, whereas the remaining underwent nonbiventricular repair. Echocardiography was performed, and the Great Ormond Street Echocardiography score was calculated. Several risk factors were identified and stratified for patients with biventricular repair (n = 43). Tricuspid septal leaflet displacement was measured for each patient, and there was a statistically significant higher mortality risk directly proportional to higher displacement in patients with biventricular repair (P < 0.05). A cutoff value of 43.5 mm/m² for the tricuspid septal leaflet displacement is the best predictor of mortality risk in biventricular repair with 83.3% sensitivity and 93.3% specificity. Conclusions: In patients with Ebstein anomaly undergoing a biventricular repair, mortality rates are significantly elevated in patients with a higher tricuspid septal leaflet displacement distance. The results of the study indicated that the mortality risk in biventricular repair can be predicted based on the tricuspid septal leaflet displacement distance using a cutoff value of 43.5 mm/m². [ABSTRACT FROM AUTHOR]

Introduction: Mitral Valve Replacement (MVR), an important treatment for rheumatic mitral valve disease, is being widely promoted worldwide. MVR using the total leaflet preservation technique can produce good results; however, patient-specific factors and anatomical considerations must be taken into account when selecting the appropriate surgical approach. Aim: To investigate the benefits of Posterior Leaflet Preservation (PLP) in MVR in individuals with severe mitral stenosis. Materials and Methods: The current prospective interventional study included patients with Rheumatic Heart Disease (RHD) who had severe mitral valve stenosis and/or regurgitation and underwent MVR between December 2019 and December 2021 in the Department of Cardiothoracic and Vascular Surgery at Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India. The study included 50 patients with MVR (PLP) to preserve the posterior leaflets and 50 patients with classic MVR (no PLP). Left Ventricular Ejection Fraction (LVEF), Left Ventricular End-Systolic Diameter (LVESD), and Left Ventricular End-Diastolic Diameter (LVEDD) were measured before surgery, one, three, and six months after surgery. Results: The majority of patients in the present study were between 23 and 46 years old. The PLP group consisted of 17 men and 33 women, while the non-PLP group had 16 men and 34 women. The difference in cross-clamp time between Group-A and B was significant (p=0.0001). Cardiopulmonary Bypass (CPB) time was significantly different between Group-A and B (p=0.001). Only 4 (8%) patients in Group-A had low cardiac output syndrome, compared with 8 (16%) of patients in Group-B. Comparison of LVEF between groups over time revealed no significant difference (p=0.05). The mean change in LVEF from pre-operative to six months in Group-A was significant (p=0.004), but there was no significant change in Group-B (p=0.25). Conclusion: PLP had no improved beneficial outcome on left ventricular performance in cases with rheumatic stenosis during the six-month follow-up. Even after long-term follow-up, haemodynamic valve properties do not alter with adequate PLP. [ABSTRACT FROM AUTHOR]

Implant-supported-screw-retained prostheses are highly popular. Some of the most frequent complications are connected with the mechanical properties of the fixing elements. These include abutment screw loosening or even screw fracture. Using an intermediate abutment can offer several advantages. However, few studies detail how this affects the mechanical behavior of dental restorations. This study focuses on understanding the mechanical behavior of implant-supported restorations with a transepithelial component compared to direct implant-supported restoration. It was carried out using the finite element method (FEM) and was experimentally validated. The results showed that in the case of transepithelial-supported restoration, the prosthetic screw mounted over the transepithelial component suffered higher stress than the one screwed directly into the implant. After applying a cyclic fatigue load, it was experimentally proven that, in the transepithelial-supported restorations, the fuse changed from being the screw that went into the implant to being the upper one. In conclusion, we can state that the use of an intermediate abutment in dental restoration not only provides better protection for the rest of the dental restoration but also allows for easier repair in the event of a fracture. This can potentially lead to more efficient procedures and improved patient outcomes. [ABSTRACT FROM AUTHOR]