Cardiac Chambers Research Articles

Lung ultrasound, echocardiography and fluid loading for the differential diagnosis of pulmonary hypertension

Abstract Background There may be interest in combining echocardiography and lung ultrasound for the differential diagnosis between pulmonary arterial hypertension (PAH) and post-capillary pulmonary hypertension on heart failure with preserved ejection fraction (PH-HFpEF). Methods Patients referred for PH underwent a right heart catheterization, echocardiography and lung ultrasound before and after rapid infusion of 7 ml/kg of saline. A 7-points echocardiographic score based on cardiac chamber dimensions and estimates of filling pressures was implemented for the prediction of pre-capillary PH. Pulmonary congestion was identified by lung ultrasound B-lines. Results The study enrolled 70 patients with PAH and 77 patients with HFpEF. The PAH patients had a higher echocardiographic score (3.5±1.8 v 1.6±1.5, p <0.001). Figure 1 represents the typical baseline echocardiographic components of pre-capillary pulmonary hypertension prediction score and pre- and post-fluid loading lung ultrasound imaging from patients with PAH and HFpEF respectively. The HFpEF patients had more B-lines both before (8.1±4.2 vs 5.1±3.0; p <0.001) and after fluid loading (14.6±5.4 vs 7.6±3.5; p <0.001), and a more important increase (Δ) of B-lines after fluid loading (6.5±2.9 vs 2.5±1.6; p <0.001). The sensitivity and specificity of the echocardiographic score alone for PAH were 0.91 and 0.49 respectively [area under the curve (AUC) 0.78]. The AUC for PAH was improved by addition of smaller ΔB-lines to the echocardiography prediction score after fluid loading, with significant increase in sensitivity [0.94 (95% CI 0.89;1.00)] and specificity [0.91 (95% CI 0.84;0.97)] and a positive predictive value of 0.90 (CI 0.84;0.97) and a negative predictive value of 0.95 (CI 0.89;1.00). Figure 2 represents the bar plot of AUC for echocardiographic score, pre- fluid loading B-lines, delta E/e', delta B-lines, post- fluid loading E/e', post- fluid loading B-lines, in ascending order. Conclusion Lung ultrasound combined with echocardiography at baseline and after fluid loading has an incremental value for the differential diagnosis between PAH and PH-HFpEF.Figure 1Figure 2

Artificial intelligence-assisted examination of cardiac health status through electrocardiogram

Abstract Background Cardiac diseases are the main causes of death. Echocardiogram is the standard testing tool of heart diseases but it is inconvenient and expensive. This study aims at developing an artificial intelligence (AI)-assisted method to interpret electrocardiograms (ECG) for cardiac health status. Method A total of 70757 subjects undergoing concomitant ECG and echocardiography were enrolled. ECG was analyzed by using Philips DXL algorithm to obtain 512 parameters, and a healthy heart is defined by normal cardiac chamber size, myocardial thickness, systolic function, diastolic function, and valvular function. A multi-layer perceptron (MLP) and Long short term memory (LSTM) were developed with hold-out validation (training dataset 80% and testing dataset 20%). Three categories of input data are made based on the percentage of healthy data of 30.6%. Death of the participants were confirmed via linking database to the National Death Registry A Kaplan-Meier survival curve analysis was conducted in the testing dataset stratified by AI-determined cardiac health status. Results The testing results of the proposed methods on an independent dataset are shown in Table 1. It is interesting that using MLP has similar performance as the LSTM model. Furthermore, the 30-layer MLP model has a F1 value of 83.8% and the 50-layer MLP model has a F1 value of 83.8, while the F1 value of 2-layer LSTM_0.2 is 85.2% and 2-layer LSTM_0.2 is 84.6%. In addition, AI-determined healthy hearts were associated with better long-term survival. Conclusion An AI-assisted analysis on ECG can act as a preliminary examination of cardiac diseases to facilitate the arrangement of echocardiograms for early detections.

Abstract 19109: AI-Enabled Automated Cardiac Chambers Volumetry in ECG-Gated Coronary Calcium Scans vs. Non-Gated Lung Cancer Screening Scans

Introduction: We have developed an AI-enabled automated volume measurement of cardiac chambers (AutoChamber) that works on ECG-gated non-contrast coronary artery calcium scans and correlates well with contrast enhanced coronary CT angiography scans. Automated LA and LV volumes have shown to predict atrial fibrillation (Afib) and congestive heart failure. Hypothesis: In this study, we hypothesize that AutoChamber volumetry results in ECG-gated CAC scans correlated well with those of non-gated full-chest lung cancer screening scans in the same individuals. Methods: We have studied 169 cases of paired ECG-gated cardiac CT scans and non-gated lung scans. Mean±SD for age was 62±10 with 52% female. All caseswere asymptomatic and were scanned for preventive health assessment. AutoChamber was run on all cases by an independent operator who was not involvedin data analysis. P value was calculated using a two-tailed test of significance with α=0.05. Results: AutoChamber in cardiac scans vs lung scans reported volume (Mean±SD) for left atrium (LA) as 67.2 and 70.1, left ventricle (LV) 102.8 and 105.5 right atrium (RA) 81.9 and 85.7 right ventricle (RV) 140.7 and 134.2 left ventricle wall (LVW) 113.0 and 109.7 respectively (P < 0.0001). Correlations between cardiac and lung scans for each cardiac chamber: LA (R2= 0.85), LV (R 2= 0.93), RA (R2= 0.91), RV (R2= 0.92), and left ventricular wall (LVW) R2= 0.95. (P <0.0001 for all). Conclusions: AutoChamber volumetry results are similar in ECG-gated cardiac scans vs non-gated full-chest lung scans. This AI-enabled automated tool is promising as it can provide added value to patients undergoing coronary calcium and lung cancer screening scans flagging enlarged cardiac chambers at risk of future Afib and heart failure.

Abstract 16599: Deep Learning Prediction of Cardiac Chamber Enlargement on Chest Radiographs

Background: Chest radiographs (CXRs) are the most commonly performed radiographic exam. The heart is routinely assessed on frontal CXRs using the cardiothoracic ratio (CTR) to identify cardiomegaly, but the predictive performance of CTR is limited by variability in patient position, lung volumes, and radiographic technique. Thus, CXR may miss a substantial proportion of patients with cardiac disease. Hypothesis: A deep learning (DL) algorithm can accurately identify cardiac chamber enlargement on CXRs and exceed the predictive performance of cardiothoracic ratio. Methods: Frontal CXRs (n=6,228 cases from unique patients, single-site, dated 2014-2022), obtained on the same day as transthoracic echocardiography (reference standard for cardiac chamber enlargement), were randomly grouped for DL model training (n=4,969), validation (n=627), and testing (n=634). A pre-trained EfficientNet-B6 convolutional neural network was modified to predict the presence of one or more enlarged cardiac chambers. The DL model's performance was benchmarked against manual CTR measurements by two radiologists on a random subset of 150 anteroposterior CXRs from the test set. Results: The DL model demonstrated an AUROC (Area under the Receiver Operating Characteristic curve) of 0.78 in the validation set and an AUROC of 0.79 in the unseen test set. The model achieved 73% accuracy, 77% sensitivity, and 67% specificity on the validation set and showed similar results on the test set with 72% accuracy, 77% sensitivity, and 64% specificity. The model outperformed manual CTR measurements for identification of chamber enlargement on the random subset of test set CXRs (AUROC of 0.85 vs. 0.75; p < 0.006, Figure 1). Conclusion: The DL model significantly outperformed traditional CTR assessment for cardiac chamber enlargement on CXR. DL models may improve radiologist identification of cardiac disease on CXR and prompt formal cardiac evaluation.

Abstract 15371: Mice Lacking S-Nitrosoglutathione Reductase (GSNOR -/- ), a Mouse Model of Preeclampsia, Exhibited Nitroso-Redox Imbalance and Deterioration of Cardiovascular Structure and Function in Postpartum Mothers

Introduction: Preeclampsia (PE), a leading cause of maternal mortality, is linked to persistent pathological changes in the heart, predisposing the mother to increased risk of chronic cardiovascular (CV) disease later in life. PE is characterized by increased S-nitrosylated (SNO) proteins and nitroso-redox imbalance. We recently showed that mice lacking S-nitrosoglutathione reductase (GSNOR -/- mice), a denitrosylase that regulates protein S-nitrosylation, exhibit the clinical features of PE including maternal hypertension, blunted increase in cardiac output, abnormal remodeling of left ventricular (LV) cardiac structure, dysregulation in nitrosylation and nitroso-redox imbalance. Hypothesis: The nitroso-redox imbalance seen during pregnancy in GSNOR -/- mice persists in postpartum (PP), leading to increased maternal susceptibility to CV injury. Methods: Pregnant control (WT [C57Bl/6J]) and GSNOR -/- mice (N=5) were examined at baseline, late-stage pregnancy (17.5 dpc) and 6 weeks PP. LV structure, cardiac output and stroke volume were determined using echocardiography (Vevo 2100). Cardiomyocytes (CM) were isolated at 6 weeks PP and ROS and peroxynitrite levels determined using fluorescent dyes. Results: In WT mice, all normal maternal CV adaptions to pregnancy, reverted to pre-pregnant levels 6 weeks PP. In contrast, GSNOR -/- mice exhibited increased cardiac output (+21% vs. -19% in WT), stroke volume (+21% vs. -41% in WT), and LV chamber dimension (+13% vs. -4% in WT) at 6 weeks PP, indicating high cardiac output LV cardiomyopathy. CM isolated from GSNOR -/- hearts showed ~5-fold more ROS generation (9.9x10 -4 ±9x10 -5 vs. 2.1x10 -4 ±1.5 x10 -4 ΔF/F max .min -1 ) and elevated peroxynitrite levels (0.318±0.011 vs. 0.243±0.012 ΔF/F 0 ) compared to WT at 6 weeks PP, suggesting the presence of nitroso-redox imbalance. All changes P<0.05. Conclusion: Postpartum GSNOR -/- (preeclamptic) mothers exhibited cardiac dysfunction which was accompanied by the presence of of nitroso-redox imbalance. These changes may predispose the mother to higher risk for future CV injury.

Abstract 13987: RBX1-CRLs Are Essential for Perinatal Heart Development by Regulating Hippo-YAP Signaling

Defects in cardiac development can lead to congenital heart diseases (CHD) or predispose the heart to cardiomyopathies in adult life. The molecular mechanisms that regulate this process remain elusive. Cullin-RING E3 ligases (CRLs) are multi-subunit complexes that are critical to maintain protein homeostasis by targeting a variety of protein substrates for proteasomal degradation. In the CRLs, RBX1 serves as the catalytic subunit that promotes the transfer of ubiquitin to the target protein. Previous animal studies uncovered a crucial role for RBX1 in development. However, its importance in the developing heart has not been explored. Here, we report for the first time the indispensable role of RBX1 in perinatal cardiac development. We created mice with cardiac-specific deletion of RBX1 driven by αMHC Cre . Compared with littermate control mice, RBX1-deficient mouse embryos exhibited no gross morphological abnormalities at E12.5 and E14.5, displayed peripheral edema at E16.5 indicative of heart failure, and eventually died around E18.5. Histological analysis revealed myocardial hypoplasia and a substantially thinner compact layer in E16.5 mutant hearts. This event was preceded by a remarkable decrease in cardiomyocyte proliferation and diminished nuclear localization of YAP, a powerful regulator of cardiomyocyte proliferation, at E14.5. In cultured cardiomyocytes, depletion of RBX1 inhibited proliferation and induced profound transcriptomic changes like the upregulation of cardiomyopathy-related genes. Mechanistically, RBX1 deficiency destabilized multiple CRLs and resulted in the accumulation of Hippo kinases and adaptor proteins such as SAV1, LATS1/2, and MOB1 leading to the inactivation of YAP by phosphorylation. We further demonstrated that RBX1 degrades the Hippo adaptors SAV1 and MOB1. Collectively, we propose that the fine-tuned, RBX1-mediated removal of Hippo components serves as a critical checkpoint to activate YAP signaling ensuring cardiac ventricular chamber development and morphogenesis.

Abstract 12143: Hearing is Believing: A Case of a Ruptured Sinus of Valsalva Aneurysm

A 36-year-old previously active and healthy male was referred to our Adult Congenital Heart Disease clinic with worsening exertional dyspnea and intermittent palpitations over the past 6 months. He had recently been diagnosed with a membranous ventricular septal defect (VSD) and membranous septal aneurysm at another hospital, although images were not available for review.On physical exam, a continuous cardiac murmur was noted which prompted reconsideration of the diagnosis, with highest suspicion of ruptured sinus of Valsalva aneurysm (SVA). An urgent cardiac CT was obtained, which showed a large, mobile right SVA protruding into and partially obstructing the right ventricular outflow tract (RVOT), with pulmonic regurgitation and dynamic closure of a supracristal VSD (Figure 1A). A margin of the SVA was ill-defined and suspicious for rupture, although no definite communication was seen. An expedited TTE showed findings consistent with SVA rupture (Figure 1B), and he was admitted for surgery soon thereafter. Intra-operatively (Figure 1C), SVA rupture into the RVOT was confirmed by direct inspection; the SVA tissue was resected, the defect closed with a fresh autologous pericardial patch, and the VSD was closed with pledgeted sutures. Post-operatively, there was no leakage around the patch margin and only trace aortic regurgitation.A ruptured SVA causes continuous shunting from the aorta into an adjacent cardiac chamber and if left unrecognized, can lead to right heart failure, arrhythmia, and potentially sudden death, emphasizing the need for early identification. Echocardiography may show an aneurysmal sinus of Valsalva with a continuous (with accentuation in diastole) high-velocity, turbulent flow-jet into an adjacent cardiac chamber, and holodiastolic aortic flow reversal; a VSD is often present. Cross-sectional imaging is also important for diagnosis and surgical planning. A comprehensive physical exam is crucial to mitigate the risk of misdiagnosis.

Abstract 17216: Limited Concordance of Core Lab Left Ventricular Ejection Fraction With Automated Assessments: A Sub-Study From VALOR-HCM

Introduction: The performance of automated left ventricular ejection fraction (LVEF) assessment in patients with altered cardiac chamber geometry, such as those with obstructive hypertrophic cardiomyopathy (HCM), is not well described. Aims: Accurate assessment of LVEF is required for dose titration and continuation of myosin inhibitors in obstructive HCM. From the VALOR-HCM trial (NCT04349072), the agreement of two commercially available software packages was compared with blinded core lab assessment of LVEF. Methods: From baseline and week 16, among 112 patients randomized to either mavacamten or placebo, 178 echocardiograms were analyzed. Representative clips were manually selected, and automated LVEFs were calculated. Comparisons of LVEFs were made using Pearson’s correlation coefficients and Bland-Altman analysis. Results: With core lab assessment, the overall median LVEF was 68% (Q1 66%, Q3 70%). The correlation with vendor 1 was moderate (r = 0.47, 95% CI 0.35-0.58, p <0.001) and weak with vendor 2 (r =0.21, 95% CI 0.07-0.35, p =0.004). Correlation was also weak between vendor 1 and 2 (r = 0.14, 95% CI 0.00-0.28, p = 0.06). Vendors 1 and 2 had an underestimation bias of LVEF of 8% (95% CI 6-9%) and 8% (95% CI 7-9%), respectively, compared to core lab LVEF (Figure 1). Conclusions: In VALOR-HCM, the concordance of LVEF between different commercially available software packages with each other and with a core lab assessment was limited. Further study is needed to evaluate and improve the performance of automated LVEF tools in obstructive HCM patients who have altered cardiac chamber geometry.

Abstract 13245: Neural Network-Derived Electrocardiographic Features Predict Future Cardiovascular Disease and All-Cause Mortality

Background Subtle prognostically-important ECG features may not be apparent to physicians. In the course of supervised machine learning (ML), many thousands of ECG features are identified. These are not limited to conventional ECG parameters and morphology. Hypothesis: Novel neural network (NN)-derived ECG features can predict future cardiovascular disease and mortality Methods and Results: We extracted 5120 NN-derived ECG features from an AI-ECG model trained for six simple diagnoses and applied unsupervised machine learning to identify three phenogroups. In the derivation cohort (CODE, 1,558,421 subjects), the three phenogroups had significantly different mortality profiles. After adjusting for known covariates, phenogroup B had a 20% increase in long-term mortality compared to phenogroup A (HR 1.20, 95% CI 1.17-1.23, p < 0.0001). The predictive ability of the phenogroups was retained in a group with physician confirmed normal ECGs. We externally validated our findings in five diverse cohorts (Figure) and found phenogroup B had a significantly greater risk of mortality in all cohorts. Phenome-wide association study (PheWAS) showed phenogroup B had a higher rate of future AF, ischaemic heart disease, AV block, heart failure, VT and cardiac arrest. Phenogroup B had increased cardiac chamber volumes and decreased cardiac output. A single-trait GWAS yielded four loci. SCN10A, SCN5A and CAV1 have roles in cardiac conduction and arrhythmia. ARHGAP24 does not have a clear cardiac role and may be a novel target. Gradient-weighted Class Activation Mapping (Grad-CAM) identified the terminal QRS and terminal T wave as important regions of the ECG for identification of phenogroup B. Conclusion: NN-derived ECG features can be used to predict all-cause mortality and future cardiovascular diseases. We have identified biologically plausible and novel phenotypic and genotypic associations that describe mechanisms for the increased risk identified.

Abstract 13419: Transient Coronary Artery to Left Ventricular Fistula With Diastolic Mitral Regurgitation

Introduction: A fistula from a coronary artery to the cardiac chamber is incidentally found in 0.08% to 0.3% of patients undergoing coronary angiography. Case Presentation: A 73-year-old woman with hypertension, diabetes mellitus, chronic renal failure, and nephrosis visited our department due to dyspnea. The patient’s physical examination revealed a blood pressure of 191/109 mmHg and a pulse rate of 77 beats per min. The blood sampling results revealed a plasma brain natriuretic peptide level of 2,001 pg/mL. A 12-lead electrocardiogram showed poor R wave progression in leads V1 to V4. Chest radiography revealed left pleural effusion. Parasternal transthoracic echocardiography showed left ventricular hypertrophy. Left ventricular (LV) ejection fraction was 41%. A pulsed-wave Doppler echocardiography at the mitral inflow showed diastolic mitral regurgitation and a fusion of E and A waves. An unusual myocardial flow was noted in the apical myocardium. It was directed toward the apical surface during systole (Fig. 1a), and directed toward the LV lumen during diastole (Fig. 1b), suggesting coronary artery to LV fistula through sinusoid. Global strain obtained from apical long axis imaging showed myocardial shortening continued to diastole, suggesting post-systolic shortening (PSS). After treatment for hypertension, both of myocardial flow and diastolic MR disappeared. A longitudinal global strain imaging revealed disappearance of PSS. Conclusion: This is a rare case of diastolic MR due to PSS at the fistula from the coronary artery to the left ventricle.

Abstract 16809: Deep-Learning-Based Assessment of Left Atrial Volume in Coronary Calcium CT: Association With NT-proBNP and Clinical Outcomes

Introduction: Artificial Intelligence (AI) promises to extract imaging biomarkers for cardio-cerebrovascular (CV) risk prediction, though validation is still lacking. Recognizing the importance of left atrial pathology on CV events, we developed an AI algorithm to measure left atrial volume (LAvol) from CAC-CT. Its correlation with MRI, biomarkers, and CV incidents was then tested in the Dallas Heart Study 2 (DHS). Hypothesis: LAvol will be associated with elevations in baseline NT-proBNP levels and incident CV events. Methods: We trained a 3D U-Net model for cardiac chamber segmentation on CAC-CT, assessing congruity with manual segmentation via the Dice score. Normalized left atrial volume (LAvol/BSA) from 3D segmentations was compared to MRI using ICC, and its associations with baseline NT-proBNP and incident Afib, TIA, and stroke were evaluated with logistic regression and Cox models. Results: Cardiac segmentation showed an excellent Dice score of 0.93 ± 0.01. Moderate correlation was observed between CAC-CT estimates of LAvol/BSA and MRI (ICC 0.57, 95% CI 0.52-0.62). Our study, excluding those with prior events, comprised 1852 participants (mean age 50, 41% male, 46% black, 15% Hispanic). Upon multivariable adjustment (detailed in the table), LAvol/BSA was linked with elevated NT-proBNP (≥ 100 pg/mL) (OR 1.9, 95% CI 1.6-2.2 per 1SD LAvol/BSA). Over a 12.5-year follow-up, CAC-CT-derived LAvol/BSA showed association with a composite of Afib, TIA, and stroke (55 events) (HR 1.4, 95% CI 1.1 - 1.8), and Afib (HR 1.7, 95% CI 1.2 - 2.3), post-adjustment. No significant association was found with TIA (HR 1.2, 95% CI 0.6 - 2.1) or stroke (HR 1.3, 95% CI 0.9 - 1.8). Among 749 subjects, MRI-derived LAvol/BSA correlated with NT-proBNP (OR 1.7, 95% CI 1.44 - 2.10) but not with other clinical outcomes. Conclusions: Given associations with NT-proBNP levels and incident CV events, AI-measured LAvol from CAC-CT promises to improve risk prediction.

Heart Chamber Segmentation in Cardiomegaly Conditions Using the CNN Method with U-Net Architecture

Cardiomegaly is a disease in which sufferers show no symptoms and have symptoms such as shortness of breath, abnormal heartbeat and edema. Cardiomegaly will cause the sufferer's heart to pump harder than usual. Early diagnosis of cardiomegaly can help make decisions about whether the heart is abnormal or normal. In addition, due to the problem that manual examination takes time and requires human interpretation and experience, tools are needed to automatically develop and identify normal and abnormal hearts. Therefore, this study proposes cardiac chamber segmentation using 2D (two-dimensional) ultrasound convolutional neural networks for rapid cardiomegaly screening in clinical applications based on heart ultrasound examination. The proposed approach uses a CNN with a U-Net architecture model with abnormal and normal heart data. The research results obtained used the pixel matrix evaluation Avg_accuracy of 99.50%, Val_accuracy of 97.98% and Mean_IoU of 90.01%.

Abstract 16178: A Deep Learning Algorithm to Estimate Left Ventricular Mass From Coronary Calcium CT Scans: Association With Incident Heart Failure Events From the Dallas Heart Study

Introduction: Coronary artery calcium CT (CAC-CT) scans used for ASCVD risk prediction may contain additional clinical information that is currently underexploited. We developed a novel deep-learning algorithm to estimate LV mass from CAC-CT (CT-LVM) and analyzed associations with cardiac biomarkers and incident CV outcomes in the Dallas Heart Study (DHS). Hypothesis: Higher CT-LVM will be associated with baseline cardiac biomarker elevations (hsTnT and NT-proBNP) and a higher risk of incident CVD (heart failure, MI, stroke, and all-cause death). Methods: We included 1841 DHS phase 2 participants (mean age 50, 59% female, 46% Black race) who were free of baseline CVD and underwent CAC-CT and cardiac MRI. Our novel deep-learning algorithm features automatic cardiac chamber segmentation via a 3D U-Net architecture on CAC-CT, followed by a 3D DenseNet model to predict LV mass, using concurrent cardiac MRI as gold standard. LV mass was indexed to BSA. Statistical analysis included multivariable logistic regression models for baseline biomarker elevation assessment (hs-cTnT > 5ng/L or NT-proBNP > 100pg/mL) and Cox proportional hazards models for clinical outcomes. Models were adjusted for age, sex, ethnicity, BMI, hypertension, blood pressure, diabetes, smoking, creatinine, and CAC score. Results: CT-LVM correlated strongly with MRI defined LV mass (R = 0.87). CT-LVM/BSA was associated with elevated hsTnT (adjusted OR 1.3, 95% CI 1.1-1.6) and NT-proBNP (adjusted OR 1.8, 95% CI 1.5-2.2). There were 172 CVD events over a median follow up of 12.5 years. Higher CT-LVM was associated with higher CVD risk (adjusted HR 1.4, 95% CI 1.2-1.6) and higher risk of incident heart failure (adjusted HR 2.1, 95% CI 1.5-2.9). Conclusions: A novel deep-learning method for estimating LV mass from CAC-CT provided independent risk information from traditional risk factors and CAC score. This represents a novel low-cost approach to improving the risk assessment opportunities from a CAC-CT.

Sex-Specific Limitation of Cardiac Capacity During the Adult Life Span: Return to Fundamental Structure and Function.

Physiology underlying reduced cardiac pumping capacity in women compared with men and its interaction with aging remains unresolved. Herein, the pressure gradient (PG) driving venous return was manipulated to evidence whether cardiac structure and/or function explain sex differences in cardiac capacity. Healthy women/men matched by age and physical activity were included within young (n = 40, age = 25 ± 4 years) and older (n = 55, age = 60 ± 8 years) groups. Cardiac volumes/output (Q) were assessed up-to-peak exercise under 2 hemodynamic conditions ("low"/"high" PG between lower/upper body). Main outcomes included sex differences in delta ("high" - "low" PG) left ventricular (LV) end-diastolic volume (∆LVEDV), stroke volume (∆SV), and Q (∆Q). In young individuals, "high"-PG increased exercise LVEDV and SV in men (p ≤ .002), but not in women (p ≥ .562), relative to "low"-PG (control condition). Accordingly, peak ∆LVEDV, ∆SV, and ∆Q were enhanced in young men versus young women (p ≤ .019). Notwithstanding, right/left atrial volumes during exercise were similarly increased by "high"-PG in both young sexes (p ≤ .007). "High"-PG exclusively prolonged moderate exercise LV filling time in young men (p ≤ .036). In older individuals, "high"-PG did not modify exercise cardiac volumes and reduced LV diastolic function (p ≤ .049). In conclusion, the female young heart is unrestrained by venous return or structural factors external to the myocardium. As determined during moderate exercise, impaired LV filling time lengthening limits female-specific cardiac capacity. With older age, cardiac chambers are not distended and LV relaxation is impaired with increased PG in both sexes. During early but not late adulthood, a functional LV limitation may explain sex differences in cardiac capacity.

Echocardiographic Reference Ranges of Global Longitudinal Strain for All Cardiac Chambers Using Guideline-Directed Dedicated Views

BackgroundMyocardial deformation by echocardiographic strain imaging is a key measurement in cardiology, providing valuable diagnostic and prognostic information. Reference ranges for strain should be established from large healthy populations with minimal methodologic biases and variability. ObjectivesThe aim of this study was to establish echocardiographic reference ranges, including lower normal limits of global strains for all 4 cardiac chambers, by guideline-directed dedicated views from a large healthy population and to evaluate the influence of subject-specific characteristics on strain. MethodsIn total, 1,329 healthy participants from HUNT4Echo, the echocardiographic substudy of the 4th wave of the Trøndelag Health Study, were included. Echocardiographic recordings specific for each chamber were optimized according to current recommendations. Two experienced sonographers recorded all echocardiograms using GE HealthCare Vivid E95 scanners. Analyses were performed by experts using GE HealthCare EchoPAC. ResultsThe reference ranges for left ventricular (LV) global longitudinal strain and right ventricular free-wall strain were −24% to −16% and −35% to −17%, respectively. Correspondingly, left atrial (LA) and right atrial (RA) reservoir strains were 17% to 49% and 17% to 59%. All strains showed lower absolute values with higher age, except for LA and RA contractile strains, which were higher. The feasibility for strain was overall good (LV 96%, right ventricular 83%, LA 94%, and RA 87%). All chamber-specific strains were associated with age, and LV strain was associated with sex. ConclusionsReference ranges of strain for all cardiac chambers were established based on guideline-directed chamber-specific recordings. Age and sex were the most important factors influencing reference ranges and should be considered when using strain echocardiography.

Surgical experience in cardiac myxomas at a tertiary hospital

IntroductionCardiac myxomas account for 50% of all benign cardiac tumors. Their clinical presentation varies from embolisms to fever. Our objective was to describe the surgical experience in the resection of cardiac myxomas during an 8-year period. MethodsThis is a retrospective, descriptive study of a series of cases with cardiac myxomas diagnosed from 2014 to 2022 at a tertiary care center. Descriptive statistics were used to define the populational and surgical characteristics. We used Pearson’s correlation to study the relationship between postoperative complications and age, tumor size and affected cardiac chamber. Results31 patients were included, with a predominance of females (1:2 ratio). The prevalence was 0.44%, which was calculated based on the number of cardiac surgeries performed in our unit over the 8-year period. The main clinical manifestation was dyspnea (85%, n = 23), followed by cerebrovascular event (CVE) (18%, n = 5). Atriotomy and resection of the pedicle were performed with preservation of the interatrial septum. Mortality was 3.2%. The postoperative evolution was uneventful in 77%. Tumor recurrence occurred in 2 patients (7%), both debuting with embolic phenomena. No association was observed between postoperative complications or recurrence and tumor size, nor aortic clamping and extracorporeal circulation times with regard to age. ConclusionsFour atrial myxoma resections are performed in our unit per year, with an estimated prevalence of 0.44%. The tumor characteristics described coincide with the previous literature. A relationship between embolisms and recurrences cannot be ruled out. Wide surgical resection of the pedicle and base of tumor implantation may influence tumor recurrence, although further studies are needed.

The Tbx20-TLE interaction is essential for the maintenance of the second heart field.

T-box transcription factor 20 (Tbx20) plays a multifaceted role in cardiac morphogenesis and controls a broad gene regulatory network. However, the mechanism by which Tbx20 activates and represses target genes in a tissue-specific and temporal manner remains unclear. Studies show that Tbx20 directly interacts with the Transducin-like Enhancer of Split (TLE) family of proteins to mediate transcriptional repression. However, a function for the Tbx20-TLE transcriptional repression complex during heart development has yet to be established. We created a mouse model with a two amino acid substitution in the Tbx20 EH1 domain, thereby disrupting the Tbx20-TLE interaction. Disruption of this interaction impaired crucial morphogenic events, including cardiac looping and chamber formation. Transcriptional profiling of Tbx20EH1Mut hearts and analysis of putative direct targets revealed misexpression of the retinoic acid pathway and cardiac progenitor genes. Further, we show that altered cardiac progenitor development and function contribute to the severe cardiac defects in our model. Our studies indicate that TLE-mediated repression is a primary mechanism by which Tbx20 controls gene expression.

Association of right atrial strain and long-term outcome in severe secondary tricuspid regurgitation

ObjectiveSevere secondary tricuspid regurgitation (STR) causes significant right atrial (RA) volume overload, resulting in structural and functional RA-remodelling. This study evaluated whether patients with severe STR and reduced RA function,...

Efficient multi-fidelity computation of blood coagulation under flow.

Clot formation is a crucial process that prevents bleeding, but can lead to severe disorders when imbalanced. This process is regulated by the coagulation cascade, a biochemical network that controls the enzyme thrombin, which converts soluble fibrinogen into the fibrin fibers that constitute clots. Coagulation cascade models are typically complex and involve dozens of partial differential equations (PDEs) representing various chemical species' transport, reaction kinetics, and diffusion. Solving these PDE systems computationally is challenging, due to their large size and multi-scale nature. We propose a multi-fidelity strategy to increase the efficiency of coagulation cascade simulations. Leveraging the slower dynamics of molecular diffusion, we transform the governing PDEs into ordinary differential equations (ODEs) representing the evolution of species concentrations versus blood residence time. We then Taylor-expand the ODE solution around the zero-diffusivity limit to obtain spatiotemporal maps of species concentrations in terms of the statistical moments of residence time, [Formula: see text], and provide the governing PDEs for [Formula: see text]. This strategy replaces a high-fidelity system of N PDEs representing the coagulation cascade of N chemical species by N ODEs and p PDEs governing the residence time statistical moments. The multi-fidelity order (p) allows balancing accuracy and computational cost providing a speedup of over N/p compared to high-fidelity models. Moreover, this cost becomes independent of the number of chemical species in the large computational meshes typical of the arterial and cardiac chamber simulations. Using a coagulation network with N = 9 and an idealized aneurysm geometry with a pulsatile flow as a benchmark, we demonstrate favorable accuracy for low-order models of p = 1 and p = 2. The thrombin concentration in these models departs from the high-fidelity solution by under 20% (p = 1) and 2% (p = 2) after 20 cardiac cycles. These multi-fidelity models could enable new coagulation analyses in complex flow scenarios and extensive reaction networks. Furthermore, it could be generalized to advance our understanding of other reacting systems affected by flow.

Coronary air embolism during transcatheter patent foramen ovale closure for platypnea-orthodeoxia syndrome in a patient with severe respiratory disorder: a case report

Abstract Background Coronary air embolism (CAE) is a rare and life-threatening complication of endovascular procedures, mostly due to procedure-related causes. Case summary A 70-year-old man with severe respiratory disorder presented with patent foramen ovale (PFO)-related platypnea-orthodeoxia syndrome (POS). Transcatheter PFO closure was performed under local anaesthesia and intracardiac echocardiographic guidance. After a 5-Fr catheter was passed through the PFO via a 7-Fr femoral vein sheath, the patient suddenly coughed and breathed deeply. Thereafter, intracardiac echocardiography showed massive microbubbles in all cardiac chambers and the ascending aorta, and an electrocardiogram showed ST-segment elevations in the anterior and inferior leads. Emergency coronary angiography confirmed occlusion of the mid-left anterior descending artery, suggesting CAE. As the intracoronary infusion of saline, nitroglycerine, and nicorandil was ineffective, we performed air aspiration using a thrombectomy device, achieving coronary blood flow improvement and ST-segment resolution. Thereafter, positive pressure support using manual bag-valve-mask ventilation under intravenous sedation supported successful transcatheter PFO closure without further air embolization. Discussion In this case with severe respiratory dysfunction, spontaneous deep breathing (spontaneous Valsalva manoeuvre) caused negative intrathoracic pressure and large drops in intravascular pressure. This phenomenon might have induced air contamination during device advancement, either by entrapping or leaving residual air in the gaps between the catheter and the sheath. Additionally, PFO with right-to-left shunts is more likely to cause paradoxical air embolization. Thus, the spontaneous Valsalva manoeuvre should be avoided with appropriate respiratory management to prevent paradoxical air embolization, including CAE, during transcatheter PFO closure under local anaesthesia in severe respiratory dysfunction patients.