Echocardiography Imaging Research Articles

Cardiac amyloidosis: a texture issue. a proof of concept study on quantification of granular sparkling in patients with transthyretin-related cardiac amyloidosis using radiomics and granulometry

Abstract Background Granular sparkling is a well-known echocardiographic feature found in patients with transthyretin-related cardiac amyloidosis (ATTR-CA). However, there is no objective technique for quantifying this feature, which therefore remains a qualitative, elusive and ultimately unreliable imaging characteristic. Recent evidence suggests that radiomics and, in particular, ultrasonomics could play an important role in the non-invasive tissue characterization of cardiomyopathies through the study of specific myocardial texture features. Purpose The aim of this study is to statistically and geometrically characterize granular sparkling as a volume-independent texture property of the myocardium in patients with ATTR-CA. Methods We retrospectively collected echocardiogram video-clips in parasternal long axis (PLAX) and 4-chamber (4CH) views of 229 patients with ATTR-CA, and 224 age- and gender-matched hypertensive patients without any known cardiac disease. From each video-clip, one end-diastole frame was extracted and annotated by an expert to identify a region-of-interest (ROI) within the interventricular septum. Left ventricle chamber masks were also extracted, and used as a brightness reference to enforce invariance w.r.t. the settings of the specific ultrasound system (Fig. 1). Because many established radiomic textural features are heavily volume-confounded, we analyzed the ROI texture by extracting a subset of volume-invariant radiomic features (i.e. ROI-independent), as well as morphological granulometry features. We then fitted a logistic regression classifier to discriminate between ATTR-CA and controls based on the computed textural features. Results 94 radiomic features were identified, of which 73 were volume-invariant. The texture-based classifier predicted the diagnosis with a cross-validated accuracy of 91%, a specificity of 90% and a sensitivity of 92% by utilizing 73 volume-invariant radiomic features on both PLAX and 4CH views (Fig. 2). The addition of granulometry and the further addition of 11 volume-confounded features and 9 shape features to the model did not significantly enhance its discriminative performance (Fig. 2). The top 10 volume-invariant discriminative features were largely consistent in PLAX and 4CH views (Fig. 2), with variables descriptive of greater heterogeneity (such as glszm_ZoneEntropy and glszm_RunEnNtropy) and a higher spatial rate of change (such as ngtdm_Complexity) in the texture of ATTR-CA frames as compared to control frames. Conclusions Our results confirm the ability of radiomics in detecting subtle differences in the myocardial texture of echocardiographic images between patients with ATTR-CA and hypertensive controls. High levels of accuracy are obtained with a purely texture-based, volume-independent set of features. These findings suggest that the diagnosis of ATTR-CA could be simplified and made earlier using a statistical model based on the extraction of radiomic features.Figure 1Figure 2

Automated selection of echocardiographic views using a novel artificial intelligence software

Abstract Background/Introduction Evaluation of a single echocardiographic study involves sorting, selecting, measuring and interpreting a large number of images. As these steps are currently performed manually, this can turn into a repetitive, time-consuming and tedious task. Although the use of artificial intelligence (AI) software could potentially improve this entire workflow, most of the efforts have been focused on measurement automatization. Incorporation of automated selection of echocardiographic views could further optimize this process. Purpose We investigated whether an AI-derived measurements software can be supplemented by automated view selection using an AI model. We hypothesized that automated selection of echocardiographic views yields similar results compared to manually selected views when using the same tool for automated measurements in both groups (Figure 1, top). Methods We trained an AI model (convolutional neural network) to recognize the main standard 2D echocardiographic views. This model was trained on individual frames from 20,000 DICOM clips to predict a specific cardiac view, based on the view annotation provided by an echocardiography expert (ground-truth). We then selected a test set of 5,000 DICOMs where we applied the AI model to all images in the study. We selected the highest-ranking apical 2 chamber (A2C) and apical 4 chamber (A4C) images, based on the model’s output probability (Figure 1, bottom). For the same 21 studies, an expert selected the best A2C and A4C image for left ventricular volumes and ejection fraction measurements. Then, we ran Philips AutoMeasure both on manually and automatically selected images. We then compared the measurement values for statistical significance using a pair-wise t-test, see Figure 2. Results The AI model achieved an accuracy of 96% and AUC of 0.99 on the test set. The results obtained when comparing the automatic and manually selected images in the 21 studies are shown in Figure 2. For all the measured parameters, there was no statistically significant difference in mean values between both selection methods. Conclusions Manual and AI-derived selection of standard echocardiographic images do not lead to a statistically significant difference in automated measurements, suggesting that incorporation of automated view selection may contribute to improve daily echocardiographic workflow. Future research could aim in extending these findings to more cardiac views, parameters, and populations.Comparison of the approachesResults

Safety and quality of life assessment at 6 months follow-up of the valvosoft pivotal study

Abstract Background Calcific Aortic stenosis (CAS) is currently the most common heart valve disease. Patients suffering from severe CAS are treated with invasive surgeries based on valve replacement. Symptoms heavily impact quality of life, including chest pain, shortness of breath, dizziness, fatigue, and major risks as heart failure or sudden death, and daily activities might also be strongly impacted. Purpose A prospective, multi-centre, single-arm, pivotal study (NCT05235568) was initiated in 2021 to treat severe CAS patients with Valvosoft, a medical device based on Non-Invasive Ultrasound Therapy (NIUT) intended to treat CAS in patients not eligible for immediate aortic valve replacement (SAVR/TAVR) or refusing such a treatment, to confirm safety and performance at 1-, 3-, 6- and 12 months. We present here the safety and quality of life results at 6M follow-up. Methods Valvosoft NIUT procedure is based on a trans-thoracic delivery of focused, high intensity short therapeutic ultrasound pulses, to precisely generate a cavitation bubble cloud on the aortic valve. Echocardiographic imaging enables to monitor the valve in real-time while cavitation causes both non-thermal tissue softening and calcification fractionation of the diseased valve. 60 planned subjects, suffering from severe calcific aortic stenosis, not recommended for aortic valve replacement or refusing such a procedure, were enrolled in 11 centres in Europe. Patients were awake or lightly sedated, NIUT was delivered during up to 70 minutes per patient per procedure. DSMB and CEC were installed to monitor safety, performance and effectiveness of Valvosoft device, and safety related to participation in the clinical investigation. Results Sixty high-risk patients advanced in age (85.2 ± 9.1) with multiple severe comorbidities were included. Primary safety endpoint (less than 25% MACE) was met at 30D (p=0.002). Furthermore patients experienced an overall quality of life improved. 6 minutes’ walk test increases from baseline towards 6 months with 10 %. At 6M follow-up, no stroke was reported, an average KCCQ score improvement of 17% was noticed, and NYHA class improved or stabilized for 78% of patients. The calcium score or volume on the aortic did not change pre- and post-procedure. Conclusion Valvosoft NIUT safety and quality of life improvement are proven at 6MFU, and the technology is presented as potentially disruptive, in the treatment of severe calcific aortic stenosis.

Prognostic implication of right ventricular - pulmonary arterial coupling in patients with non-valvular atrial fibrillation

Abstract Background The clinical importance of right ventricular (RV) - pulmonary arterial (PA) coupling has been reported in various cardiac diseases such as right heart failure, pulmonary hypertension, and valvular dysfunction. However, there is limited data on patients with non-valvular atrial fibrillation (AF). We aim to investigate whether RV-PA uncoupling affects the clinical outcome in patients with non-valvular AF. Methods A total of 807 consecutive patients with non-valvular AF who underwent echocardiography (mean age 70 ± 12 years, 39% female) were included. We excluded patients with significant (at least moderate degree) valvular diseases, left ventricular ejection fraction (LVEF) <50%, cardiac implantable electronic devices, previous cardiac surgery, and poor echocardiographic image for RV analysis. RV-PA coupling was assessed by the ratio of RV global longitudinal strain (GLS) to PA systolic pressure (PASP), and decreased RV-PA coupling was defined as less than 0.52 %/mmHg based on on the receiver operating characteristic analysis. The primary outcome was the composite of all-cause death and hospitalization for heart failure. Results Over a mean of 4.7 ± 3.5 years of follow-up, 178 (22%) patients had experienced primary outcomes. Among them, 107 (13%) patients were hospitalized for HF and 90 (11%) patients died. Patients with decreased RV-PA coupling were older (73 ± 11 vs. 68 ± 12 years, p<0.001), had a higher prevalence of females (51 vs. 33%, p<0.001) and diabetes (33 vs. 23%, p=0.003), lower left ventricular ejection fraction (60 ± 5 vs. 61 ± 5%, p=0.011), higher E/e’ (14 ± 5 vs. 11 ± 4, p<0.001), larger left atrial volume index (78 ± 37 vs. 62 ± 22 ml/m2, p<0.001) and larger RV end-systolic area (11 ± 4 vs. 10 ± 3 cm2/m2, p=0.001) compared to those with preserved RV-PA coupling. In multivariate Cox regression analysis, decreased RV-PA coupling was associated with worse clinical outcomes even after adjusting for age, diabetes, E/e’, and RV end-systolic area (Hazard ratio [HR] 1.50, 95% Confidence interval [CI] 1.09 – 2.07, p=0.014) (Figure 1). Conclusions In patients with non-valvular AF, RV-PA coupling was associated with clinical outcome, suggesting that it may provide additional information for predicting future cardiovascular risk in this population.

Evaluating the performance of automatic wave speed estimators of natural shear waves to assess myocardial stiffness

Abstract Introduction Cardiac Shear Wave Elastography is an emerging non-invasive technique using ultrafast echocardiographic imaging. Natural shear waves (SW) occur after mitral valve closure (MVC) and aortic valve closure (AVC), and their propagation velocities are directly related to myocardial stiffness. However, the current assessment of SW velocities lacks a gold standard method, and relies on manual measurements with their inherent variability. Purpose To explore new automated methods for shear wave velocity estimates, aiming to achieve greater accuracy, less variability, and high feasibility. Methods To visualize shear waves, anatomical M-modes were drawn (4±1 cm) along ventricular septum in parasternal long axis views (PLAX), acquired with high-frame-rate echocardiography (1055±159 Hz). M-modes were colour coded for tissue acceleration. SWs appear as tilted green bands after MVC & AVC, the slope of which represents the SW propagation velocity. One hundred-twenty different slopes from healthy volunteers (n=67) and patients (n=53) were measured manually and with 9 different automatic methods. All automatic methods were initiated by indicating the approximate position of the shear wave in the M-mode with a mouse click of the user. Measurements were repeated three times to assess measurement reproducibility. (figure 1, A). In order to determine the influence of display settings, three different acceleration colour scales were tested (0.5, 1, 2 m/s²). (Figure 1, B). Failure of correctly identifying shear waves was counted to assess feasibility. Due to the lack of a gold standard, manual measurements of an experienced reader served as reference. Results Three of nine automatic methods: Radon Transformation (RT), Regression Segmentation Maximum value (RM), Regression Segmentation Weighted Maximum (RMW), revealed the least variability with repeated measurements (0.0±0.0 m/s for all) and colour scales (0.0±0.0, 0.1±0.2 and 0.1±0.2 m/s, resp.). Those three methods showed moderate to good agreement (r=0.66, ICC 0.77 [CI 0.64- 0.85]; r= 0.67, ICC 0.75 [CI 0.50 -0.86]; and r= 0.77, ICC 0.85 [CI 0.73-0.90], resp.) with manual measurements (r=0.96, ICC 0.98 [CI 0.97- 0.99] (figure 2). Conclusion RT, RM, and RMW showed a good reproducibility while RMW showed the best agreement with manual measurements. Our data suggest, that the RMW method could offer an objective alternative for SW velocity estimations. Further research is needed to explore their applicability in clinical scenarios.

Long term follow up in pulmonary embolism: can right ventricular strain echocardiographic imaging contribute to refine risk stratification?

Abstract Background In pulmonary embolism (PE), the usual evaluation of early risk of death includes clinical, biological and two-dimensional right ventricular (RV) echocardiographic (TTE) parameters. Purpose We hypothesized that myocardial strain analysis could contribute to risk of death prediction at long term follow up. Methods We retrospectively analyzed 477 patients hospitalized for acute EP. Usual parameters used to define RV dysfunction were evaluated using TTE (RV dilatation, systolic pulmonary arterial pressure, TAPSE, S’, Fractionnal Area Change (FAC), end diastolic RV diameter and right atrial, RA, area). In addition, we evaluated, left ventricle (LV) longitudinal, left atrial (LA), RA and RV free wall strains. Patients without history of cancer (n=419) were analyzed on the primary outcome of death at long term follow up. Results Mean of age was 63.7 ± 17.2 years and 227 (47.6) patients were male. The main clinical and echocardiographic characteristics are displayed in the Table 1. During a mean follow-up was 45.0 ± 16.6 months, the primary outcome occurred in 56 patients. In multivariable analysis, systolic pulmonary arterial pressure, indexed right atrial and left atrial volumes, right ventricle free wall strain, right ventricle global longitudinal strain were the only predictors of death (Table 2). Conclusion Atrial volumes and RV strain appeared as strong predictors of death in PE at long term follow up. Right ventricle myocardial strain analysis should be evaluated in each patient hospitalized for PE.

Early detection of cardiac dysfunction using shear wave imaging: insights into reduced cardiorespiratory fitness in childhood cancer survivors

Abstract Background Diastolic dysfunction is thought to be the earliest cardiotoxic sequel after cancer therapy among childhood cancer survivors. Despite many survivors do exhibit reduced cardiorespiratory fitness (CRF) potentially due to cardiotoxicity, current echocardiographic parameters fail to detect hidden diastolic dysfunction early after therapy (1). High frame rate (HFR) shear wave imaging (SWI) is a novel tool that could give insights about myocardial stiffness, which is a key determining factor of diastolic function. Purpose We aimed at testing the ability of SWI to detect early alterations in myocardial stiffness among childhood cancer survivors and its relation with the reduced CRF. Methods Fifty childhood cancer survivors (mean 20 ±3 years) who received chemo-and/or- radiotherapy (mean time after treatment: 4 ±3 years) and thirty-two matched healthy volunteers (HV) were recruited. Conventional as well as HFR echocardiographic images (ca. 1200 frames/second) were acquired at rest using a modified commercial echocardiography machine. All participants underwent an incremental, symptom-limited cardiopulmonary exercise test on a treadmill measuring peak oxygen consumption (VO2 peak). HFR data were analysed offline. An anatomical M mode was drawn along the ventricular septum, and tissue Doppler acceleration maps were extracted to measure SW velocities after mitral valve closure (MVC) (Figure 1). Results Among cancer survivors, left ventricular ejection fraction (LVEF) and global longitudinal strain were significantly lower compared to HV (56 % ±4 vs 59 % ±4, and 17.6 % ±1.6 vs 19.1 % ±1.2, respectively; p <0.001). However, both LVEF and GLS were within the normal range and none of them correlated with the peak VO2 (Figure 2A&B). None of the echocardiographic diastolic parameters (e.g. mitral E, E/e’, left atrial volume or TR jet velocity) showed significant difference between both groups (P > 0.05). The mean SW velocities were significantly higher in cancer survivors compared to HV (3.9 ±0.6 m/s vs 3.2 ±0.3 m/s respectively; p <0.001). Interestingly, SW velocities among cancer survivors showed moderate significant negative correlation with the VO2 peak (r= -0.590, p <0.001) indicating increasing myocardial stiffness as the cardiorespiratory fitness declined (Figure 2C). Conclusions Our data indicate that myocardial stiffness in cancer survivors is significantly increased. We hypothesize that this increased stiffness may at least in part explain the significantly reduced cardiorespiratory fitness in this population. Echocardiographic shear wave elastography appears as a promising non-invasive tool for early detection of diastolic dysfunction in follow-up of childhood cancer survivors.Figure 1.Figure 2.

Mitral Annular Disjunction in Heritable Thoracic Aortic Disease: Insights From the Montalcino Aortic Consortium.

Mitral annular disjunction (MAD), posterior displacement of the mitral valve leaflet hinge point, predisposes to arrhythmias or sudden cardiac death. We evaluated the burden of MAD, mitral valve prolapse (MVP), and mitral regurgitation (MR) by heritable thoracic aortic disease gene in a cross-sectional analysis of 2014-2023 data in the Montalcino Aortic Consortium registry. MAD was determined by direct measurement of echocardiographic images. MR and MVP were defined according to current clinical guidelines. Associations were evaluated using χ2 or Fisher exact tests. MR and MVP were enriched in Montalcino Aortic Consortium participants (672) with pathogenic variants (PV) in transforming growth factor-β pathway genes. The combination of MR and MVP was associated with mitral surgery and arrhythmias. In the subgroup with available images, MAD was enriched in SMAD3 PV compared with other transforming growth factor-β PV (prevalence ratio 1.8 [1.1-2.8], P <0.02). Severe disjunction (>10 mm) was only observed in the transforming growth factor-β subgroup and was further enriched in participants with SMAD3 PV (prevalence ratio 3.1 [1.1-8.6]). MVP (prevalence ratio 5.2 [3.0-9.0]) and MR (PR 2.7 [1.8-3.9]) were increased in participants with MAD, but MAD was not independently associated with adverse cardiac or aortic events. Pathological mitral valve phenotypes are more prevalent in individuals with PV in transforming growth factor-β pathway genes, particularly SMAD3. MR and MVP but not MAD are associated with adverse aortic and cardiac events. Because congenital mitral disease may be the primary presenting feature of SMAD3 PV, genetic testing for heritable thoracic aortic disease should be considered for such individuals, especially if they also have a family history of heritable thoracic aortic disease.

Deep learning of echocardiography distinguishes between presence and absence of late gadolinium enhancement on cardiac magnetic resonance in patients with hypertrophic cardiomyopathy

BackgroundHypertrophic cardiomyopathy (HCM) can cause myocardial fibrosis, which can be a substrate for fatal ventricular arrhythmias and subsequent sudden cardiac death. Although late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) represents myocardial fibrosis and is associated with sudden cardiac death in patients with HCM, CMR is resource-intensive, can carry an economic burden, and is sometimes contraindicated. In this study for patients with HCM, we aimed to distinguish between patients with positive and negative LGE on CMR using deep learning of echocardiographic images.MethodsIn the cross-sectional study of patients with HCM, we enrolled patients who underwent both echocardiography and CMR. The outcome was positive LGE on CMR. Among the 323 samples, we randomly selected 273 samples (training set) and employed deep convolutional neural network (DCNN) of echocardiographic 5-chamber view to discriminate positive LGE on CMR. We also developed a reference model using clinical parameters with significant differences between patients with positive and negative LGE. In the remaining 50 samples (test set), we compared the area under the receiver-operating-characteristic curve (AUC) between a combined model using the reference model plus the DCNN-derived probability and the reference model.ResultsAmong the 323 CMR studies, positive LGE was detected in 160 (50%). The reference model was constructed using the following 7 clinical parameters: family history of HCM, maximum left ventricular (LV) wall thickness, LV end-diastolic diameter, LV end-systolic volume, LV ejection fraction < 50%, left atrial diameter, and LV outflow tract pressure gradient at rest. The discriminant model combining the reference model with DCNN-derived probability significantly outperformed the reference model in the test set (AUC 0.86 [95% confidence interval 0.76–0.96] vs. 0.72 [0.57–0.86], P = 0.04). The sensitivity, specificity, positive predictive value, and negative predictive value of the combined model were 0.84, 0.76, 0.78, and 0.83, respectively.ConclusionCompared to the reference model solely based on clinical parameters, our new model integrating the reference model and deep learning-based analysis of echocardiographic images demonstrated superiority in distinguishing LGE on CMR in patients with HCM. The novel deep learning-based method can be used as an assistive technology to facilitate the decision-making process of performing CMR with gadolinium enhancement.

Safety and feasibility of transcatheter closure of atrial septal defects in small children weighing less than 10 kg.

When young patients with an oval fossa defect present early with symptoms of heart failure and pulmonary hypertension, surgical treatment is recommended in small bodyweight rather than transcatheter closure. Outcomes of device closure in consecutive symptomatic children weighing under 10 kg were compared with young children aged below 4 years but weighing above 10 kg. Transthoracic echocardiography under conscious sedation guided the procedure in all without need for balloon sizing, transesophageal echocardiogram, and intubation anaesthesia. Symptoms, anthropometry, shunt ratio, pulmonary pressures, defect and device size, percentage oversizing, device/body weight ratio, complications, and post-procedural growth spurt were compared. Ninety-six patients weighing under 10 kg were compared with 160 patients weighing above 10 kg. In total, 83.3% of patients in the study group and 25% of controls were severely malnourished. The median indexed defect size was 35.2 mm/sq.m and 27.4 mm/sq.m, and the device was oversized by 8.7% and 14.2% in the study group and controls, respectively. The device/body weight ratio was 1.93 in study group and 1.4 in controls. Procedure was successful in all except one patient weighing under 10 kg who had a device embolisation. Both groups showed significant growth spurts and proportion, with severe malnutrition reduced to 42% and 11% in the two groups. Device closure was feasible and safe in patients under 10 kg. Transthoracic echocardiographic imaging on conscious sedation provided adequate guidance. Symptoms and growth significantly improved after intervention. Despite a larger defect size, smaller patients had comparable outcomes. In symptomatic children under 10 kg needing early closure, transcatheter intervention should not be deferred.

Sudden cardiac death after myocardial infarction: individual participant data from pooled cohorts.

Risk stratification of sudden cardiac death after myocardial infarction and prevention by defibrillator rely on left ventricular ejection fraction (LVEF). Improved risk stratification across the whole LVEF range is required for decision-making on defibrillator implantation. The analysis pooled 20 data sets with 140 204 post-myocardial infarction patients containing information on demographics, medical history, clinical characteristics, biomarkers, electrocardiography, echocardiography, and cardiac magnetic resonance imaging. Separate analyses were performed in patients (i) carrying a primary prevention cardioverter-defibrillator with LVEF ≤ 35% [implantable cardioverter-defibrillator (ICD) patients], (ii) without cardioverter-defibrillator with LVEF ≤ 35% (non-ICD patients ≤ 35%), and (iii) without cardioverter-defibrillator with LVEF > 35% (non-ICD patients >35%). Primary outcome was sudden cardiac death or, in defibrillator carriers, appropriate defibrillator therapy. Using a competing risk framework and systematic internal-external cross-validation, a model using LVEF only, a multivariable flexible parametric survival model, and a multivariable random forest survival model were developed and externally validated. Predictive performance was assessed by random effect meta-analysis. There were 1326 primary outcomes in 7543 ICD patients, 1193 in 25 058 non-ICD patients ≤35%, and 1567 in 107 603 non-ICD patients >35% during mean follow-up of 30.0, 46.5, and 57.6 months, respectively. In these three subgroups, LVEF poorly predicted sudden cardiac death (c-statistics between 0.50 and 0.56). Considering additional parameters did not improve calibration and discrimination, and model generalizability was poor. More accurate risk stratification for sudden cardiac death and identification of low-risk individuals with severely reduced LVEF or of high-risk individuals with preserved LVEF was not feasible, neither using LVEF nor using other predictors.

A Novel Preclinical Murine Model of Systemic Lupus Erythematosus-Like Cardiovascular Disease.

Systemic lupus erythematosus (SLE) affects nine women to every man worldwide, and these patients are at greater risk for cardiovascular disease (CVD) morbidity and mortality. Clinical studies have demonstrated that patients with SLE are more likely to develop CVD, including cardiac and vascular dysfunction. Although many preclinical models of SLE are available, including treatment with Toll-like receptor (TLR) 7/8 agonists, a consistent preclinical model of SLE-like CVD with systemic, cardiac, renal, and cerebral endothelial activation and cardiac dysfunction has yet to be described. Here, we hypothesize that acceleration of SLE with the TLR7/8 agonist resiquimod (R848) will promote cardiac and endothelial activation with subsequent end-stage organ damage in the SLE-prone B6.Nba2 mouse model. Female and male SLE-prone B6.Nba2 mice were treated with R848 or acetone, administered topically twice weekly over a four-week period, to accelerate the development of SLE-like pathophysiology. Echocardiography was performed at baseline, 4 weeks, and 16 weeks. At 16 weeks, tissues were harvested, weighed, and analyzed by histology, immunofluorescence, real-time quantitative polymerase chain reaction, and enzyme-linked immunosorbent assays. We found that female R848-treated mice had increased serum anti-Smith and immunoglobulin G complex deposition in the kidney, heart, and brain consistent with SLE-like etiology. Tissue analysis revealed significant enlargement of the spleen in both female and male R848-treated mice, with only cardiac and renal enlargement in females compared to their respective controls. Echocardiographic imaging revealed left ventricular wall thickening by 4 weeks that was followed by a progressive increase in left ventricular internal diameters and subsequent decrease in ejection fraction over the 16-week time course in female mice. We found that circulating levels of soluble vascular adhesion molecule-1 and soluble intracellular adhesion molecule-1 were increased in both female and male R848-treated mice, whereas cardiac and renal fibrosis were significantly increased in only female R848-treated mice. Our data demonstrate that R848 treatment of SLE-prone B6.Nba2 mice is a novel preclinical model to study the sex-dependent pathophysiologic mechanisms of SLE-like CVD.

A-019 Unexpectedly High Cardiac Troponin Values in Healthy Athletes after SARS-CoV-2 Infection

Abstract Background Elevated levels of cardiac troponin I or T (cTnI, cTnT) in general have immediate clinical consequences including invasive cardiac imaging and rhythm monitoring. Macro-troponin is a complex of antitroponin autoantibodies and cTnI or cTnT and may result in falsely elevated values. In athletes, a reliable exclusion of cardiac disease is crucial to allow for intensive exercise. The prevalence and causes of falsely elevated cTn in professional athletes after SARS-CoV-2 infection are unknown. Methods These are preliminary results of an observational study including 35 professional athletes (16 -75 years old, median 24 years; 19 females, 16 males) who had post-Covid-19 check-ups at their practicing sports physician mostly in the year 2022 (6 athletes in 2023). One female athlete did not have a proven SARS-CoV-2 infection but vaccination. Divergences in high sensitivity (hs) cTn concentrations were investigated according to the sex-specific cut-off values of 4 different assays (hs-cTnI: Alinity/Abbott Diagnostics, Atellica/Siemens Healthineers, Access/Beckman Coulter and hs-cTnT: Cobas/Roche Diagnostics). All athletes were advised to stop training 48h before routine blood drawing and if required underwent electrocardiography (ECG), echocardiography and magnetic resonance imaging to exclude myocardial involvement, particularly when suspicious symptoms were present. Athletes with divergent hs-cTn assay results were further analyzed for the presence of macro-troponin using the reference method sucrose gradient ultracentrifugation. Results The two main professional sports were cycling (mountain biking or road biking) and soccer, further sports comprised curling, swimming, running including marathon, floorball, cross-country skiing or rhythmic gymnastics. Athletes mostly suffered from postviral exhaustion, mild infectious symptoms like headache, sore throat, dry cough, subfebrile temperature, or sniffles or had atypical thoracic pain. There were two males with known secondary diagnoses, one 25 years old with diabetes mellitus type 1 and one 75 years old with atherosclerosis and hypercholesterolemia. Eighteen (18/35) athletes had hs-cTn concentrations within the sex-specific cut-off values in all assays and did not undergo further investigation for macro-troponin by sucrose gradient ultracentrifugation. However, in 17 athletes (17/35) hs-cTn was increased in at least one assay method which was mostly a hs-cTnI method (for 2/17 all assays elevated). The sucrose-gradient ultracentrifugation method proved macro-troponin in 15/17 with original hs-cTn values for Abbott Alinity: 5 - 170 ng/L; Siemens Atellica: 9.6 - 376 ng/L; Beckman Access: 0.5 - 55 ng/L and Roche Cobas 4 - 77 ng/L. However, 2/17 had the free troponin form, one with only a minor hs-cTnT increase above the sex-specific cut-off and the other with increased values in all hs-cTn assays but normal values in a 2- and 4-days control follow-up measurement. Notably, there were no ECG or cardiac imaging findings including echocardiography or cardiac magnetic resonance imaging suggestive of myocarditis in the investigated athletes. Conclusions After SARS-CoV-2 infection, cTn might be increased in athletes without a correlate in ECG or imaging reports. This should prompt physicians to consider an assay interference by macro-troponin, particularly if a second troponin method such as hs-cTnT remains normal. AHL &amp; CK share first and OH &amp; CM share last authorship

Assessing Left Atrial Appendage Functions by Transesophageal Echocardiography and Speckle Tracking Imaging to Predict Recurring Atrial Fibrillation Post-Radiofrequency Catheter Ablation.

To predict recurring atrial fibrillation (AF) following radiofrequency catheter ablation by assessing the attributes of the left atrium and the left atrial (LA) appendage (LAA) using transesophageal echocardiography (TEE) and speckle tracking imaging. The structural and functional indices of the LA and LAA of 80 patients with AF who underwent preoperative transthoracic echocardiography and TEE were measured. Recurrence was recorded postoperatively at 3, 6, and 12 months. The independent determinants of recurring AF were identified by logistic regression, and their optimum cutoff values, sensitivity, and specificity were estimated from the receiver operating characteristic (ROC) curves. The recurrent and nonrecurrent groups comprised 17 and 63 patients, respectively. The LA internal diameter, LA end-diastolic and end-systolic volumes, LAA length, diameter and area of the opening of the LAA, and LAA end-diastolic volume were higher in the recurrent group. The LA strain in the reservoir phase, the ejection fraction and filling velocity of the LAA, the LAA emptying velocity (LAAeV), and the LAA strain (LAAS) reduced considerably. Multifactorial regression analyses demonstrated that the LAAeV and LAAS were independent determinants of recurring AF. ROC curve analysis revealed that the LAAeV and LAAS predicted postoperative recurrence at 34.5cm/s (area under the curve [AUC]: 0.954, sensitivity: 94.1%, and specificity: 92.1%) and 11.61% (AUC: 0.925, sensitivity: 82.4%, and specificity: 95.2%), respectively, while the AUC, sensitivity, and specificity of the combined predictors (LAAeV+LAAS) were 0.978, 94.1%, and 93.7%, respectively. The LAAeV and LAAS independently influenced the postoperative recurrence of AF.

Echocardiography in Endocarditis.

Infective endocarditis (IE) continues to have high rates of adverse outcomes, despite recent advances in diagnosis and management. Although the use of computer tomography and nuclear imaging appears to be increasing, echocardiography, widely available in most centers, is the recommended initial modality of choice to diagnose and consequently guide the management of IE in a timely-dependent fashion. Echocardiographic imaging should be performed as soon as the IE diagnosis is suspected. Several factors may delay diagnosis, for example, echocardiography findings may be negative early in the disease course. Thus, repeated echocardiography is recommended in patients with negative initial echocardiography if high suspicion for IE persists in patients at high risk. However, systematic echocardiographic screening should not be utilized as a common tool for fever, but only in the presence of a reasonable clinical suspicion of IE. It may increase the risk of false-positive rates of patients requiring IE therapy or may exacerbate diagnostic uncertainty about subtle findings. Considering the complexity of the disease, the echocardiographic use should be increasingly time-efficient and should focus on the correct identification of IE lesions and associated complications. The path to identify patients who need surgery passes through an echocardiographic skill ensuring the identification of the cardiac anatomical structures and their involvement in the destructive infective extension. We pointed out the role of echocardiography focused on the correct identification of IE distinctive lesions and the associated complications, as part of a diagnostic strategy, within an integrated multimodality imaging, managed by an "endocarditis team".

Percutaneous Left Atrial Appendage Closure using a Modified Single-Operator-Technician Approach Under Deep Sedation: A Single-Center Experience

BackgroundHistorically, percutaneous transcatheter left atrial appendage closure (LAAC) has been performed under general anesthesia (GA) with transesophageal echocardiographic (TEE) images obtained by a noninvasive cardiologist and usually requires an overnight stay. Alternatively, we present our single-center experience performing LAACs under deep sedation (DS), implementing an echocardiographic technician instead of a noninvasive cardiologist, and expedited same-day discharge. Middle to long-term outcomes were also evaluated with follow-up imaging at a 45-day visit. ObjectiveTo demonstrate the safety, feasibility, and outcomes of our single-operator-technician LAAC approach MethodsA total of 150 patients, with a mean age of 78 years and an elevated CHA2DS2-VASc score (mean of 4 points), underwent TEE guided LAAC using the WATCHMAN FLX (Marlborough, MA: Boston Scientific) under DS. ResultsThe mean age of the patients was 78 years. 76 (51%) were males. 147 (98%) of patients had the LAAC device successfully implanted, and 145 (97%) were discharged on the same day. Nine patients (6%) required conversion from DS to GA. Only five (4%) patients had complications during the procedure. None of the patients died or had complications from DS. During the 45-day follow-up, a single patient had a significant peridevice leak (maximal diameter ≥5 mm), and another patient had device-related thrombosis. ConclusionsOur novel single-operator-technician approach under DS is safe and feasible. Implementing protocols to simplify the traditional two-operator approach under GA by utilizing DS and an echocardiogram technician and incorporating same-day discharge could make LAACs more widely available and potentially reduce procedural costs.

Comparing Echocardiographic Strain Imaging in Cardiac Amyloid and End-Stage Renal Disease Patients.

Diagnosing cardiac amyloidosis (CA) is difficult due to nonspecific clinical symptoms and echocardiographic findings. Prior studies have suggested that apical sparing strain patterns may be diagnostically useful. With increasing strain usage, it remains unclear how specific this pattern is to diagnose CA. We analyzed strain patterns between CA and end-stage renal disease (ESRD) patient populations. Patients with ESRD proven negative for CA (n=19) were compared to CA patients with CKD stage 3 or less (n=25). The ESRD cohort was stratified based on time on dialysis. Echocardiographic longitudinal strain (LS) parameters were collected, including regional and global LS, echocardiographic, and demographic parameters. Relative apical LS was calculated using the following equation: average apical LS/(average mid LS+average basal LS). No significant differences were found regarding regional strain or relative apical strain. Our study showed a sensitivity of 80% and specificity of 42% when using a relative apical strain ratio of >1. All groups demonstrated an apical sparing strain pattern visually on the bulls-eye plot. ESRD demonstrates significant overlapping findings across various imaging modalities compared to CA. We demonstrated that relative apical sparing strain is nonspecific for CA among patients with ESRD. Our study calls into question the clinical value of relative apical-sparing stain patterns in identifying CA in an ESRD population and suggests that diagnostic evaluation should be driven by strong clinical suspicion and other imaging and demographic variables.

Non-invasive surrogates for right Ventricular-Pulmonary arterial coupling: a systematic review and Meta-Analysis.

Right ventricle-pulmonary artery (RV-PA) coupling describes the energetic relationship between RV contractility and its afterload. The gold standard for assessment of this relationship requires invasive pressure-volume (PV) loop measurements. Non-invasive surrogates of RV-PA coupling have been developed, such as the echocardiographic tricuspid annular plane systolic excursion to pulmonary artery systolic pressure ratio (TAPSE/PASP), but their performance has not been systematically assessed. We sought to assess performance of TAPSE/PASP ratio compared to PV loop-defined RV-PA coupling. A systematic search was conducted. Studies were included if PV loop derived RV-PA coupling metrics were compared to echocardiographic or magnetic resonance imaging surrogates. We conducted a meta-analysis of TAPSE/PASP correlation to PV loop-defined RV-PA coupling. 1452 studies were identified in the initial search, of which ten met inclusion criteria. Five studies allowed for pooled analysis of TAPSE/PASP to Ees/Ea correlation (r = 0.52, 95% confidence interval 0.36-0.65). There was moderate heterogeneity across the pooled studies. Despite the common use of Non-invasive surrogates of RV-PA coupling, there is only moderate correlation with gold standard measurements. These metrics do not inform on the individual components of RV-PA coupling, limiting their use in the management of patients with RV dysfunction.

QRS prolongation is associated with associated with adverse cardiac remodeling in hypertrophic cardiomyopathy

BackgroundSignal-averaged electrocardiogram (SAECG) records myocardial depolarization, and can detect inhomogeneous/slow conduction in fibrotic myocardium, which promotes reentrant ventricular arrhythmias (VAs). Hypertrophic cardiomyopathy (HCM) is associated with a high prevalence of cardiac fibrosis and VAs, but abnormal SAECG has low predictive power for VAs. We hypothesized that HCM-specific structural/electrical remodeling underlies this result. MethodsWe tested our hypothesis by retrospectively studying HCM patients (n = 73) who underwent transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR) imaging within 12 months of SAECG and 12‑lead ECG. Patients were divided into 2 groups (normal-SAECG, abnormal-SAECG) based on filtered-QRS duration (fQRSd), root-mean-square-voltage (RMS40) and low-amplitude (<40 μV) signal of terminal 40 ms of filtered-QRS (late potentials). Abnormal SAECG was defined as fQRSd > 114 ms, RMS40 < 20 μV or LAS40 > 38 ms. ResultsAbnormal SAECG was seen in ~50 % of HCM patients (37/73). In the abnormal-SAECG group, 78 % (n = 29) only had prolonged fQRSd, and 22 % (n = 8) had prolonged fQRSd plus late potentials (RMS40 < 20 μV or LAS40 > 38 ms). Mean fQRSd and LAS40 were significantly higher in the abnormal-SAECG group. The abnormal-SAECG group had significantly larger LA size, lower global-LV longitudinal systolic strain/strain rate and early-diastolic strain rate by TTE; higher LV-mass index (LVMI) and LV-scar burden by CMR; higher prevalence of repolarization abnormalities on 12‑lead ECG. LVEF and adverse outcomes (VT/VF, heart failure, death) were similar in the 2 groups. Univariate analysis showed that fQRSd is positively correlated with LVMI, LV-scar mass, and negatively correlated with global-LV early diastolic strain rate. ConclusionsIn HCM, abnormal SAECG is associated with greater structural/electrical LV-remodeling, reflecting a severe global myopathy.

TCT-82 Prospective Quantification of Tricuspid Regurgitation With Transthoracic Echocardiography vs 4D Flow Cardiac Magnetic Resonance Imaging

TCT-82 Prospective Quantification of Tricuspid Regurgitation With Transthoracic Echocardiography vs 4D Flow Cardiac Magnetic Resonance Imaging