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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]

Background: Type 2 diabetes mellitus (T2DM) intensifies the clinical symptoms of heart diseases and leads to a worse prognosis in heart failure patients. Although hypertrophic cardiomyopathy (HCM) and DM rarely co‐occur, particularly in older individuals, the impact of DM on cardiac function and outcomes in individuals with HCM remains insufficiently understood. Methods: A total of 421 HCM patients were included and followed up in a prospective cohort study (mean 68.7 months). In the diabetic HCM group (n = 47), patients had a mean age of 47 ± 17 years, and 31 (66%) were male, while the non‐diabetic HCM group (n = 374) had a mean age of 44 ± 14 years, and 246 (65%) were male. At study entry, all patients underwent echocardiographic evaluation, encompassing left ventricular (LV) regional and global longitudinal strain (GLS), as well as strain rate (SR) analysis. Results: In diabetic HCM, there was a greater prevalence of hypertension (p < 0.0001), while the ratio of septal to posterior wall thickness (PWT) (p < 0.003) and E' value were lower (p < 0.009) compared to non‐diabetic HCM. No significant difference between groups in NYHA class or cardiac phenotype. Diabetic HCM exhibited notable reductions in GLS (p < 0.02), systolic SR (SRsys) (p < 0.04), and early diastolic SR (SRe) p < 0.006. Additionally, there was a significant inverse correlation between LVGLS and HbA1c levels (r = −0.58, p < 0.0001), and the duration of diabetes (r = −0.39, p < 0.006). Hospitalization rates were greater in the diabetic HCM than in the non‐diabetic group (44.7% vs.19.5%, p < 0.001). Among all demographic characteristics, phenotypic data, conventional echocardiographic measurements, and LV mechanics, diabetes emerged as the sole determinant of hospitalization among HCM patients. The presence of diabetes nearly tripled the odds of hospitalization (odds ratio: 2.813 [1.448–5.465], p < 0.002). However, diabetes did not negatively affect long‐term survival, and age remained the only independent predictor of all‐cause mortality. Conclusions: In HCM, T2DM is linked to more deterioration of cardiac mechanics and contributes to unfavorable consequences by frequent hospitalization on its own, independent of age, comorbidities, or phenotype. [ABSTRACT FROM AUTHOR]

Many cases of total anomalous pulmonary venous return (TAPVR) present with life‐threatening pulmonary venous obstruction within hours following delivery. As a result, prenatal detection represents an important approach to optimizing outcome. Unfortunately, TAPVR remains one of the most challenging major forms of congenital heart disease to detect prenatally; most cases elude diagnosis until postnatal life, despite the widespread recognition of multiple fetal two‐dimensional (2D) and color Doppler sonographic markers. This commentary demonstrates that even the 2D and color Doppler appearance of pulmonary venous drainage to the left atrium may be seen in cases of TAPVR. Accordingly, we describe, for the first time, a novel color Doppler fetal sonographic marker to rule out TAPVR. [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]

Aim: Fontan surgery is a palliative procedure commonly performed for functional single‐ventricle heart diseases. Fontan circulation is characterized by elevated central venous pressure and low cardiac output. It causes placental hypoxia, which could lead to poor obstetric outcomes. During post‐Fontan pregnancies, ultrasonography may detect abnormal appearance of the placenta. We have focused on higher incidences of unexpected onset of labor when this ultrasonographic finding is present. In this study, we aimed to investigate whether this finding could be an indicator of premature delivery before pre‐scheduled dates in post‐Fontan pregnancies. Methods: During post‐Fontan pregnancies, the placenta exhibits a mosaic pattern with areas of low and high echogenicity and unusually thick on ultrasonography. We refer to these changes as "ultrasonographic placental edematous changes." We retrospectively analyzed clinical charts and ultrasonograms for post‐Fontan pregnancies between 2015 and 2022. Results: Fifteen patients were included in this study. Ultrasonographic placental edematous changes in the placenta during pregnancy were detected in eight cases (53%). Six (75%) of these patients experienced unexpected premature labor. Two patients underwent vaginal delivery because of sudden onset of labor. Four patients underwent emergency cesarean sections. Two patients underwent planned preterm cesarean sections. In the seven pregnancies without placental edematous changes, all deliveries occurred on the pre‐scheduled dates determined based on the maternal heart condition. Conclusions: Pregnancies with ultrasonographic placental edematous changes have a higher risk of unexpected preterm delivery than those without these changes. Ultrasonographic placental edematous changes may serve as predictive markers for unplanned preterm births in post‐Fontan pregnancies. [ABSTRACT FROM AUTHOR]

Percutaneous ventricular assist devices (pVADs) incorporated with admittance electrodes have been validated in animal studies for accurate instantaneous volumetric measurements. Since miniaturization of the pVAD profile is a priority to reduce vascular complications in patients, our study aimed to validate admittance measurements using three electrodes instead of the standard four. Complex admittance was measured between an electrode pair and a pVAD metallic blood-intake tip, both with finite element analysis and on the benchtop. The catheter and electrode arrays were first simulated inside prolate ellipsoid models of the left ventricle (LV) demonstrating current flow throughout all parts of the LV as well as minimal influence of off-center catheter placement in the recorded signal. Admittance measurements were validated in 3D-printed models of healthy and dilated hearts (100–400 mL end-diastolic volumes). Minimal interference between a pVAD motor and the current signal of our admittance system was demonstrated. A modified Wei's equation focused on three electrodes was developed to be compatible with reduced profile pVADs occurring clinically, incorporated with admittance electrodes and wires. The modified equation was compared against Wei's original equation showing improved accuracy of calculated volumes. Reducing electrode footprint can simplify the incorporation of Admittance technology on any pVAD, allowing for instantaneous recognition of native heart recovery and assistance with pVAD weaning. [ABSTRACT FROM AUTHOR]

The article focuses on the effectiveness of transcatheter aortic valve replacement (TAVR) in patients with moderate aortic stenosis (AS) and systolic dysfunction compared to medical surveillance. Topics include the clinical outcomes of early TAVR, the trial's methodology and safety findings, and its implications for current treatment guidelines.

Measurements of fetal atrial size, shape, and contractility have been previously reported using the TomTec fetal heart speckle tracking analysis software, which currently is no longer available in the marketplace. At the present time, the only software available for speckle‐tracking analysis of the fetal heart is fetalHQ, which analyzes the fetal heart ventricles using the same algorithms as the TomTec software used for speckle‐tracking analysis. This communication will review how to use the fetalHQ software to measure the size, shape, and contractility of the atrial chambers. [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]

The author comments on calculating a corrected QT interval (QTc) in acute care settings and the significant role of pharmacists in QTc interpretation. Topics discussed include standards for pharmacists in assessing the risk of QTc prolongation, the methods used to correct QT values, and factors to be considered in assessing the risk of torsades de pointes.

Introduction Methods Results Conclusion The purpose of this study was to address the gap in knowledge in the incidence, presentation and imaging features of PPGL in Fontan patients. It has been hypothesised in the literature that Fontan circulation patients have an increased incidence of these tumours. This study is the largest cohort of adult Fontan patients in North America. The Fontan procedure is a palliative procedure for single ventricle congenital heart disease where the systemic venous return is directed into the pulmonary circulation. Fontan patients are at increased risk of developing several extracardiac complications including phaeochromocytoma and paraganglioma (PPGL).This retrospective single‐centre study includes all adult patients who were treated between 1 September 2015 and 1 September 2022 in a tertiary referral centre for adult congenital heart disease. Imaging and electronic medical records were retrospectively searched for the presence of PPGL.Five hundred and forty‐seven Fontan patients were included in the study. Three patients had PPGL with an incidence of 0.5%. Two patients were diagnosed with paraganglioma and one with phaeochromocytoma. All patients were female. Median age of Fontan procedure was 1.8 years (range: 1.75–27 years). Median age of PPGL diagnosis was 19 years (range: 12–39 years). Median time from Fontan operation to diagnosis of PPGL was 12 years (range: 10.3–17.2 years).Fontan patients are at increased risk of PPGL. Clinically, the diagnosis of PPGL is challenging as symptoms and serum markers can be confounding in this population; however, the imaging features of PPGL remain typical making the role of the radiologist crucial. [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]

The article focuses on a case involving a 6-year-old girl with complex genetic anomalies, including a caudal limb-like appendage and spinal dysraphism. Topics include the identification of a likely pathogenic variant in Actin Beta (ACTB), its connection to Baraitser-Winter syndrome, and the patient's development of a limb-like appendage due to spinal dysraphism.

OBJECTIVES To assess the incremental prognostic value of right ventricular free wall longitudinal strain over conventional risk scores in predicting the peri-operative mortality in patients with severe tricuspid regurgitation (TR) undergoing isolated tricuspid valve (TV) surgery. METHODS We retrospectively enrolled 110 consecutive patients with severe TR who underwent isolated TV surgery between November 2016 and July 2022 at San Raffaele Hospital, Milan, Italy. Exclusion criteria were previous TV surgery, urgent surgery, complex congenital heart disease, active endocarditis and inadequate acoustic window. Baseline clinical data were included, as well as laboratory tests and clinical risk score, as TRI-SCORE and MELD-XI. The clinical outcome was peri-operative mortality, defined as all-cause mortality within 30 days. RESULTS The final cohort included 79 patients. The end-point occurred in 7 patients (9%), who died within 30 days after isolated TV surgery. Receiver operator characteristic curves analysis showed that, among parameters of right ventricular function, right ventricular free wall longitudinal strain was the best parameter to predict peri-operative mortality (AUC: 0.854, 95% CI 0.74–0.96, P  = 0.005, sensitivity 68%, specificity 100%). At univariable analysis, left ventricular ejection fraction, diabetes mellitus, creatinine, estimated glomerular filtration rate, serum sodium, MELD-XI, TRI-SCORE, right ventricular areas, right ventricular global longitudinal strain, right ventricular free wall longitudinal strain, fractional area change and the ratio between right ventricular free wall longitudinal strain/pulmonary arterial systolic pressure were significantly associated with the end-point. The combination of TRI-SCORE and right ventricular Strain, evaluating right ventricular systolic function with speckle-tracking echocardiography, outperformed classic TRI-SCORE in outcome prediction (AUC 0.874 vs 0.787, P  = 0.05). CONCLUSIONS Right ventricular free wall longitudinal strain has an incremental prognostic value over conventional parameters and significantly improves the ability of clinical scores to predict peri-operative mortality in patients undergoing isolated TV surgery. [ABSTRACT FROM AUTHOR]

OBJECTIVES The impact of residual pulmonary stenosis (rPS) or right ventricular (RV) outflow tract obstruction on prognosis after surgical pulmonary valve insertion) in repaired tetralogy of Fallot patients with pulmonary regurgitation (PR) remains controversial. rPS assessment is partially dependent on RV contractility. We investigated the impact of rPS according to RV ejection fraction (RVEF). METHODS In this multicentre, retrospective study, 117 repaired tetralogy of Fallot patients who underwent surgical pulmonary valve insertion for more than moderate PR between 2003 and 2021 were examined. Regarding rPS, the threshold for PR with rPS (PSR) and PR was 25 mmHg. For RVEF, the threshold for preserved RVEF (pEF) and reduced RVEF (rEF) was 40%. The patients were divided into 4 groups: patients with PR and pEF (PR-pEF) (n  = 48), those with PR and rEF (PR-rEF) (n  = 44), those with PSR and pEF (PSR-pEF) (n  = 16), and those with PSR and rEF (PSR-rEF) (n  = 9). Clinical parameters, postoperative adverse event rates and their associations were studied. RESULTS The 5-year freedom from adverse cardiovascular events was the highest in the PSR-pEF and the lowest in the PSR-rEF groups. The PSR-rEF group had the highest RV end-diastolic pressure (RVEDP) (12 ± 2.2 mmHg) (P = 0.006). From multivariable analysis, RVEDP was associated with postoperative adverse events (P = 0.016). RVEDP > 8 mmHg was associated with a lower freedom from adverse events. CONCLUSIONS The freedom from adverse events was the lowest in the PSR-rEF group, with the highest RVEDP, suggesting RV systolic and diastolic dysfunction. Reduced RVEF may mask the intrinsic degree of residual stenosis, delay surgical pulmonary valve insertion timing and increase adverse events. [ABSTRACT FROM AUTHOR]

Introduction: Recently, a subcostal en‐face view of the tricuspid valve (TV) was described which can determine right ventricular (RV) lead position on the TV level. We sought to (1) prospectively evaluate the feasibility of this novel view in patients with cardiac implantable electronic devices (CIED) to visualize the position of the device lead relative to the TV leaflets and (2) study the association between lead position and degree of tricuspid regurgitation (TR). Methods: Consecutive patients with a history of CIED implantation with at least one RV lead who underwent echocardiography for any cause at our tertiary center were included in this prospective observational study. A subcostal 2D en‐face view of the TV was obtained and the position of the RV lead in the TV plane was determined whenever feasible. Results: A total of 176 patients were included, 70% were male, the median age was 74 years. The exact RV lead position in respect to the TV plane could be determined in 112/176 patients (64%) via the proposed view. In 37 patients (21%) moderate TR could be found, while 10 patients (6%) presented with severe TR. The lead position was not associated with the degree of TR. Conclusion: A novel 2D en‐face view of the TV can accurately identify the RV lead position in the TV plane. At least moderate TR was present in 27% of patients with CIED. There was no association of lead position with the occurrence of moderate or more TR. [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]

Introduction: Initial data suggest that His Bundle Pacing (HBP) could preserve long‐term cardiac structure and function better than Right Ventricular Pacing (RVP), but evidence is limited. Methods: We studied consecutive patients with baseline ejection fraction (EF) ≥ 50% who underwent HBP attempt, either successful (HBP group) or failed (RVP group). Two‐dimensional (2D) and three‐dimensional (3D) echocardiography were carried out at baseline and after 6 months of ventricular pacing burden > 20%. Results: Among 68 patients, 40 underwent successful HBP, and 28 RVP. The HBP and RVP groups did not differ for age, sex and pacing indication. At baseline, the HBP and RVP groups did not differ for 2D EF (62% vs. 62%), 3D EF (60% vs. 63%), 2D (−19% vs. −19%) and 3D global longitudinal strain (GLS) (−15% vs. −16%). After 6 months, 2D EF (−3.86%) and 3D EF (−5.71%) significantly decreased in the RVP group and did not change in the HBP group (p for interaction.006 and <.001, respectively). 2D GLS (3.08%) and 3D GLS (2.22%) significantly increased in the RVP group, but did not change in the HBP group (p for interaction.013 and <.016, respectively). Pacing induced cardiomyopathy (PICM) (EF drop ≥ 10% and EF < 50%) occurred in 14% (RVP) versus 0% (HBP) of patients (p =.025). Conclusions: Successful HBP was superior to RVP in preserving LV systolic function despite a high ventricular pacing burden, and was less frequently associated with PICM. [ABSTRACT FROM AUTHOR]

Objective Fetal diagnosis of coarctation of the aorta (CoA) is currently associated with a high false-positive rate. Many predictive markers may be gestational age (GA)-specific. We sought to establish GA-specific traditional and speckle-tracking fetal echocardiography (STE) markers predictive of true CoA in neonates with prenatal suspicion. Study Design This is a retrospective case–control study. We compared the fetal ventricular and arch dimensions, as well as the deformation parameters by STE, of infants who required a postnatal intervention for their CoA with those who did not. Cohort was stratified based on GA before or after 30 weeks. Data extractors were masked to the outcome. The first fetal echocardiogram available was used. Results Seventy-five newborns with a fetal echocardiography performed between October 2013 and May 2022 for an antenatal suspicion of CoA were included, of which 59 (79%) had an aortic arch with nonsignificant obstruction upon ductal closure, and 16 (21%) underwent a neonatal intervention for a confirmed CoA. Before 30 weeks' GA, the right ventricular to left ventricular (RV/LV) end-diastolic width and end-diastolic area (EDA) ratios were most associated with postnatal CoA confirmation (area under the curve [AUCs] = 0.96 and 0.92). After 30 weeks' GA, the RV/LV end-diastolic width ratio (AUC = 0.95), the Z-score for the ascending aorta (AUC = 0.93), and the LV end-diastolic width Z-score (AUC = 0.91) performed the best. A decreased RV peak longitudinal strain was observed in those who developed true CoA and performed well by receiver operating characteristic analysis after 30 weeks (AUC = 0.85). In the overall cohort, the RV/LV EDA ratio was the most sensitive predictor of CoA and identified all cases with CoA. Indeed, a cutoff > 1.24 had a specificity of 69.5% and a sensitivity of 100% (receiver operating characteristic curve with an AUC of 0.88). Conclusion We outlined sensitive and specific fetal markers associated with postnatal CoA based on GA at suspicion. Key Points Fetal ventricular disproportion predicts postnatal coarctation. A decreased right ventircular contraction was observed in those with coarctation. Fetal markers differ based on gestational age at fetal evaluation. [ABSTRACT FROM AUTHOR]

Exposure to temperatures outside of a fish's optimal range results in suppression of the immune system, ultimately leaving aquaculture stocks susceptible to disease outbreaks. This effect is exacerbated in triploid fishes, which demonstrate greater susceptibility to stress than their diploid counterparts. This study investigates the impacts of acute heat stress on the abundance of immune transcripts and proteins in diploid and triploid Chinook salmon (Oncorhynchus tshawytscha), an important finfish crop. This study also demonstrates that acute heat stress induces significant increases in the abundance hsp70, hsp90 and il1b transcripts in the head kidneys, gills and heart ventricles of both diploid and triploid Chinook salmon. Widespread dysregulation of antigen‐presentation transcripts was also observed in fish of both ploidies. These results suggest that acute heat stress activates acute‐phase responses in Chinook salmon and dysregulates antigen presentation, potentially leaving fish more susceptible to infection. At the protein level, IL‐1β was differentially expressed in the head kidney and ventricles of diploid and triploid salmon following heat shock. Differential expression of two tapasin‐like proteins in diploid and triploid salmon subjected to heat shock was also observed. Altogether, these data indicate that diploid and triploid Chinook salmon respond differently to acute thermal stressors. [ABSTRACT FROM AUTHOR]

The article explains the importance of assessing cardiac output for optimal vessel opacification in computed tomography for proper diagnoses. Topics discussed include different classifications of heart failure based on the sidedness and pumping abilities of the heart, determinants of cardiac output such as heartbeat, heart rate, preload, contractility and afterload, as well as Laplace's law of physiological wall stress and its effects on cardiac output.

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.

Purpose: Vascular Ehlers-Danlos syndrome (vEDS) is a rare and aggressive heritable aortic disease caused by pathogenic variants in COL3A1 gene, characterized by spontaneous arterial dissection and organ rupture. The purpose of this study is to evaluate ventricular size and function and to explore their associations with complications in vEDS. Methods: Adults with genetically confirmed vEDS who underwent clinical cardiac MRI were retrospectively compared with controls matched for age and sex. Cardiac MRI analysis included assessment of ventricular volumetry and arterial vasculature. vEDS-related complications were evaluated including dissection, aneurysm, and pneumothorax. Multivariable logistic regression was performed. Results: We studied 26 individuals with vEDS (38.6 ± 15.6 years, 50.0% female) and 26 healthy controls. Median clinical follow-up was 2.4 (1.1-3.6) years. Left and right ventricular ejection fractions were lower in vEDS compared with controls (LVEF 58 ± 6% vs 61 ± 4%, P =.03; RVEF 54 ± 5% vs 58 ± 4%, P =.03). After controlling for age, sex, and antihypertensive medication, LV end-diastolic volume indexed to body surface area (LVEDVi) predicted dissections (OR 1.1, 95% CI 1.01-1.2, P =.04) and aneurysms (OR 1.1, 95% CI 1.01-1.3, P =.03). Indexed LV end systolic volume (LVESVi) also predicted aneurysms (OR 1.2, 95% CI 1.03-1.5, P =.02). LVEF predicted the presence of any complication (OR 0.71, 95% CI 0.52-0.99, P =.04). Pneumothorax occurred exclusively in vEDS group among those with LVEF <58% (below the mean), 50.0% versus 0.0%, P =.02. Those with LVEF <58% had more frequent dissection and/or aneurysm (75.0% vs 12.5%, P =.04). Conclusion: Lower LVEF and larger cardiac size are associated with complications in vEDS. [ABSTRACT FROM AUTHOR]

Purpose: Peripartum cardiomyopathy (PPCM) affects women in late pregnancy and postpartum. Cardiovascular magnetic resonance (CMR) can contribute to PPCM diagnosis and management. We explored CMR findings in PPCM, including myocardial strain and late gadolinium enhancement (LGE) patterns. Materials and Methods: This retrospective single-centre study included patients with PPCM who underwent CMR from 2010 to 2018. Exclusions were other cardiomyopathy causes. CMR parameters, including ventricular function, LGE, and myocardial strain, were compared between the PPCM group and healthy controls. Transthoracic echocardiographic data were reviewed to assess functional improvement in PPCM patients. Results: Thirty-two women with PPCM (mean age 42 ± 6 years) and 26 controls (mean age 43 ± 14 years) were included. PPCM patients had significantly lower left ventricular (LV) ejection fractions (median 37.5% vs 60.5%, P <.001), higher LV end-diastolic volumes (median 108 ml/m² vs 76 ml/m², P <.001), and reduced global LV strain compared to controls. Eighteen PPCM patients (58%) had non-ischaemic pattern LGE, with no LGE in controls besides hingepoint LGE (23%). LGE was most prevalent in the basal and mid anteroseptum. LGE patterns included linear mid-wall, subepicardial, and right ventricular side of the septum. Twenty-four patients (92%) showed improvement in LVEF at follow-up echocardiogram (mean LVEF 28% ± 1.9% at diagnosis and 45% ± 3% at follow-up, P <.001). Conclusion: We identified a non-ischaemic pattern LGE that is nonspecific in isolation but could suggest PPCM in the correct clinical context along with abnormal CMR strain values. Future studies should evaluate the clinical application of these findings to facilitate earlier diagnosis and enhance management. [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.

Background: Patients with chronic kidney disease (CKD) possess a pronounced risk for cardiovascular events. A noninvasive left ventricular pressure‐strain loop (LV‐PSL) has recently been introduced to detect subtler changes in cardiac function. This study aims to investigate the value of LV‐PSL for quantitative assessment of myocardial work (MW) in patients with CKD. Methods: Seventy‐five patients with CKD were enrolled retrospectively (37 patients with CKD Stages 2–3, and 38 patients with CKD Stages 4–5), and 35 healthy volunteers were included as controls. All subjects underwent transthoracic echocardiography. LV‐PSL analysis was performed to estimate LV MW and efficiency. Global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) were obtained by echocardiography, and the differences among the groups were compared. Results: There was a significant increase in GWW and reduction in GWE in patients with CKD compared to normal controls (p < 0.05). No significant difference in GWI and GCW was observed among the three groups. Multiple linear regression revealed that increased GWW was significantly associated with age, serum creatinine, and systolic pressure, and decreased GWE was associated with age, serum creatinine, and GLS. Conclusion: LV‐PSL can be used for noninvasive quantitative assessment of MW in patients with CKD, providing a new sensitive approach for the clinical assessment of myocardial function. [ABSTRACT FROM AUTHOR]

Tricuspid regurgitation (TR) is an increasingly prevalent condition, especially in older populations, and presents significant challenges due to its association with right heart failure, hospital admissions, and high mortality rates. The management of TR has evolved, with new percutaneous valve repair and replacement techniques emerging alongside traditional surgical approaches. However, accurately assessing right ventricular (RV) function–a key prognostic factor in TR–remains difficult due to the RV's unique anatomy and sensitivity to loading conditions. Current echocardiographic methods, such as Tricuspid Annular Plane Systolic Excursion (TAPSE), S' wave analysis, and RV fractional area change (FAC), offer valuable insights but have limitations, particularly regarding load dependence and incomplete assessment of RV function. Advances in 3D echocardiography and myocardial strain imaging provide more comprehensive evaluations, yet challenges persist in integrating these measures in routine clinical practice. The review highlights the importance of a multimodal approach to RV assessment in TR patients, considering both the right atrium and pulmonary artery interactions, and explores potential future tools such as myocardial work and dynamic testing to improve prognostic accuracy and patient outcomes. [ABSTRACT FROM AUTHOR]

Immunohistochemistry (IHC) and immunofluorescence (IF) are crucial techniques for studying cardiac physiology and disease. The accuracy of these techniques is dependent on various aspects of sample preparation and processing. However, standardised protocols for sample preparation of tissues, particularly for fresh‐frozen human left ventricle (LV) tissue, have yet to be established and could potentially lead to differences in staining and interpretation. Thus, this study aimed to optimise the reproducibility and quality of IF staining in fresh‐frozen human LV tissue by systematically investigating crucial aspects of the sample preparation process. To achieve this, we subjected fresh‐frozen human LV tissue to different fixation protocols, primary antibody incubation temperatures, antibody penetration reagents, and fluorescent probes. We found that neutral buffered formalin fixation reduced image artefacts and improved antibody specificity compared to both methanol and acetone fixation. Additionally, incubating primary antibodies at 37°C for 3 h improved fluorescence intensity compared to the commonly practised 4°C overnight incubation. Furthermore, we found that DeepLabel, an antibody penetration reagent, and smaller probes, such as fragmented antibodies and Affimers, improved the visualisation depth of cardiac structures. DeepLabel also improved antibody penetration in CUBIC cleared thick LV tissue fragments. Thus, our data underscores the importance of standardised protocols in IF staining and provides various means of improving staining quality. In addition to contributing to cardiac research by providing methodologies for IF, the findings and processes presented herein also establish a framework by which staining of other tissues may be optimised. LAY DESCRIPTION: Every cell in your body contains proteins that enable them to perform their functions, keeping you healthy. In the human heart, a complex array of such proteins is crucial for pumping blood throughout the body. One way to observe proteins is through techniques called immunofluorescence and immunohistochemistry. These techniques involve labelling proteins with fluorescent dyes and probes, allowing us to see their location when illuminated with a fluorescent light and viewed on a microscope. Researchers utilise these powerful tools for studying health and disease. However, to obtain high‐quality microscopy images, we need to identify the best choice of probes and laboratory conditions for these techniques. In our study, we compared different fluorescent probes and different conditions in thin slices of heart tissue, the essential organ that pumps blood around the body. By identifying better ways of viewing proteins, our study will enable other researchers to improve the quality of their microscopy, and enhance the understanding of how cells function. [ABSTRACT FROM AUTHOR]

To assess the hemodynamics of twin-to-twin transfusion syndrome (TTTS), we measured the intraventricular pressure difference (IVPD), a sensitive marker of myocardial diastolic function, using fetal echocardiography. We included 28 monochorionic diamniotic (MD) twins diagnosed with TTTS who underwent fetoscopic laser photocoagulation (FLP) between 2018 and 2022. Color M-mode Doppler images of both cardiac ventricles were obtained before and after FLP. According to this evaluation, the IVPDs were divided into three groups; those with total, basal, and mid-apical IVPD. Of the 28 twins, 21 were available for analysis (including eight, eight, three, and two cases in stages Quintero Ⅰ, Ⅱ, Ⅲd, and Ⅲr, respectively). Comparing the pre and postFLP results, significant increases in total and mid-apical IVPD in the left ventricle (LV) of recipient twins were noted (total and mid-apical IVPD: p=0.026 and 0.013, respectively). In the LV of the donor twins, all IVPDs were significantly increased after FLP (total, basal, and mid-apical IVPD: p=0.003, 0.001, and 0.022, respectively). In addition, comparisons between the donor and recipient groups did not show significant differences in either ventricle before FLP. IVPD detected subtle hemodynamics changes, such as volume overload and diastolic dysfunction in TTTS before and after FLP. Therefore, IVPD may be a useful marker for monitoring myocardial diastolic function in TTTS. [ABSTRACT FROM AUTHOR]

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]

Biomechanics-based patient-specific modeling is a promising approach that has proved invaluable for its clinical potential to assess the adversities caused by ischemic heart disease (IHD). In the present study, we propose a framework to find the passive material properties of the myocardium and the unloaded shape of cardiac ventricles simultaneously in patients diagnosed with ischemic cardiomyopathy (ICM). This was achieved by minimizing the difference between the simulated and the target end-diastolic pressure–volume relationships (EDPVRs) using black-box Bayesian optimization, based on the finite element analysis (FEA). End-diastolic (ED) biventricular geometry and the location of the ischemia were determined from cardiac magnetic resonance (CMR) imaging. We employed our pipeline to model the cardiac ventricles of three patients aged between 57 and 66 years, with and without the inclusion of valves. An excellent agreement between the simulated and the target EDPVRs has been reached. Our results revealed that the incorporation of valvular springs typically leads to lower hyperelastic parameters for both healthy and ischemic myocardium, as well as a higher fiber Green strain in the viable regions compared to models without valvular stiffness. Furthermore, the addition of valve-related effects did not result in significant changes in myofiber stress after optimization. We concluded that more accurate results could be obtained when cardiac valves were considered in modeling ventricles. The present novel and practical methodology paves the way for developing digital twins of ischemic cardiac ventricles, providing a non-invasive assessment for designing optimal personalized therapies in precision medicine. [ABSTRACT FROM AUTHOR]

Objectives: Observational studies have suggested an association between age at natural menopause (ANM) and ventricular structure and function. Nevertheless, the causal relationship remains unclear. This study aimed to evaluate the causal effects of ANM on ventricular structure and function by Mendelian randomization (MR) analysis. Methods: Genome-wide association summary statistics for ANM and 16 ventricular structures and functions were obtained. The inverse variance weighted (IVW) method was the primary MR approach for assessing causal associations. In addition, three additional MR methods (MR-Egger, weighted median and weighted mode) were performed to complement the IVW method. Furthermore, various sensitivity tests were conducted to evaluate the reliability of the MR results. Results: The IVW method identified no causal association between ANM and all 16 ventricular structures or functions (p > 0.05). Three additional MR methods yielded parallel results to the IVW approach (p > 0.05). Various sensitivity tests revealed stability of the MR results, indicating no heterogeneity or horizontal pleiotropy. Conclusion: The present MR study indicated that ANM would not causally affect ventricular structure or function. Therefore, the correlation between ANM and ventricular characteristics in previous observational studies might be attributed to shared upstream cardiovascular risk factors or unidentified genetic mutations that simultaneously affect both ANM and ventricular structure and function. [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]

Background: Endless loop tachycardia (ELT) is the commonest pacemaker mediated tachycardia (PMT) encountered among patients with cardiac implantable electronic devices (CIEDs). Despite being enabled with various preventive algorithms, we encountered several cases having recurrent, long, and symptomatic ELT. Materials and Methods: We retrospectively analyzed consecutive device checkups at device clinic at a single center of eastern India between January 2019 to March 2023. Results: There were 20 cases of confirmed and sustained ELT among 4520 device checks. Although mostly benign, in two cases ELT led to clinical worsening in patients having left ventricular (LV) systolic dysfunction. Even with good ventricular function, ELT resulted in improper atrioventricular (AV) synchrony leading to disabling symptom in one case. The differentiation of ELT from sinus tachycardia and atrial tachycardia (AT) was not always easy. Magnet application is certainly useful to differentiate. The situations that provoked ELT in this study were—long AV delays, VIP (ventricular intrinsic preferences)/MVP (managed ventricular pacing), atrial non‐capture, atrial under/over sensing, premature ventricular contractions (PVCs)/couplets, premature atrial contractions (PAC) and slower ventriculo‐atrial (VA) conduction. Rate responsive shortening of post‐ventricular atrial refractory period (PVARP) also promoted its occurrence and hindered troubleshooting. When ELT occurred despite post‐PVC extension of PVARP, lowering the atrial sensitivity, switching to bipolar sensing and manual setting of longer PVARP after measuring VA conduction time were useful. "Rate responsive PVARP" had to be turned off in a few cases to prevent ELT. On the contrary, an over aggressive prolongation of PVARP led to repetitive non‐reentrant ventriculo‐atrial synchrony (RNRVAS) in two cases. Checking VA conduction during implantation and noninvasive program stimulation (NIPS) during follow up were useful to check the tendency for ELT. Conclusion: Clinically significant ELT is rare but not uncommon among devices having in‐built preventive algorithms. Manual adjustments are often useful to troubleshoot the same. [ABSTRACT FROM AUTHOR]