Non-invasive myocardial work as an independent predictor of postprocedural NT-proBNP in elderly patients undergoing transcatheter aortic valve replacement.

Aortic stenosis has become the most prevalent valvular disease with increasing life expectancy and the ageing of the population, representing a significant clinical burden for health care providers. Its treatment has been revolutionized by transcatheter aortic valve replacement (TAVR) as a safe and minimally invasive option for elderly patients. Left ventricular (LV) functional measurement is of particular importance before TAVR, however, increased afterload significantly influences the conventional echocardiographic parameters. Non-invasive myocardial work examines myocardial deformation in the context of instantaneous LV pressure, thus, it might be a more reliable measure of LV function. Accordingly, we aimed to study non-invasive myocardial work and its relationship with functional outcome following TAVR.We enrolled 90 TAVR candidates (80 [75-84] years; 44% female). Using echocardiography, we quantified ejection fraction (EF), global longitudinal strain (GLS), global myocardial work index (GWI) and global constructive work (GCW) before and 12 months after the procedure. Serum NT-proBNP levels were also measured. EF did not change (52.6 ± 13.1 vs. 54.2 ± 10.5%; p = 0.199), while GLS increased (-13.5 ± 4.6 vs. -15.2 ± 3.8%; p < 0.001). GWI decreased (1913 ± 799 vs. 1654 ± 613 mmHg%; p < 0.001) and so did GCW (2365 ± 851 vs. 2177 ± 652 mmHg%; p = 0.018). History of atrial fibrillation (AF) (ß = 0.349) and preprocedural GCW (ß = -0.238) were independent predictors of postprocedural NT-proBNP (p < 0.001).GLS, GWI and GCW changed after TAVR while there was no alteration in EF. The preprocedural GCW and history of AF were independent predictors of postprocedural NT-proBNP. Accordingly, myocardial work indices may help patient selection and the prediction of the functional outcome in this population.

Advanced approach combines integrated weight water quality index and potential toxic elements for environmental and health risk assessment supported by simulation technique in Oued Souf, Algeria.

The current research study evaluated the health and environmental risks issues associated with potentially toxic elements (PTEs) in the complex terminal aquifer located in the Algerian desert. The methods used included principal component and cluster (dendrogram) analysis to estimate source of ions and contamination. Various indices such as the Heavy Metal Pollution Index (HPI), Metal Index, hazard quotient, hazard index (HI), and cancer risk (CR) were applied to assess both environmental and human health risks. Furthermore, the Monte Carlo method was applied for probabilistic assessment of carcinogenic and non-carcinogenic risks through oral and dermal exposure routes in both adults and children. The results revealed that approximately 16% of the samples fell within the low pollution category (HPI < 100), indicating relatively lower levels of heavy metal contamination. However, the remaining 84% of the samples exhibited high pollution levels, indicating a significant presence of heavy metal pollutants in the northeastern part of the investigated area. The calculated average risk index (RI) for the collected samples was 18.99, with a range from 0.03 to 103.21. This indicates that a large portion, 82% of the samples, could cause low ecological risk (RI < 30), whereas the remaining 18% indicate a significant environmental pollution risk. The HI for oral ingestion showed that adults had HI values ranging from 0.231 to 1.54, while children exhibited higher values, ranging from 0.884 to 5.9 (Fig. 5a). For dermal exposure, HI values in adults ranged from 2.71E-07 to 8.74E-06 and in children, from 2.18E-06 to 7.03E-05. These findings highlight the potential non-carcinogenic risks associated with oral exposure to PTEs and underscore the increased vulnerability of children to metals such as Fe, Mn, Pb, and Cr. Most samples showed CR exceeding 1 × 10-4 for chromium (Cr) and lead (Pb), indicating a significant vulnerability to carcinogenic effects in both children and adults.

Impact of Bariatric Surgery on Asthma Severity and Medication Use.

INTRODUCTION: Bariatric surgery improves many obesity-related comorbidities, yet the literature remains inconclusive on the impact of bariatric surgery on asthma. Our primary objective was to identify the long-term impact of bariatric surgery on asthma severity and medication use. METHODS: A retrospective review was completed of all patients with a diagnosis of asthma who underwent bariatric surgery over 10 years at a single institution. Primary outcomes were the number of asthma medications prescribed at five time points (preoperative, postoperative < 18 months, 19-36 months, 37-60 months, 60 + months) after bariatric surgery. Secondary outcomes were spirometry results and BMI. RESULTS: There were 260 patients with 84.6% female predominance. There were 168 sleeve gastrectomy patients and 92 Roux-en-Y gastric bypass patients. Mean age was 47.6 ± 10.7 years, mean BMI was 46.0 ± 6.8 kg/m2, and 54.2% were previous tobacco users. The total number of patients on two or more asthma medications decreased from 46% preoperatively to 41% at 18 months, to 36% at 36 months, and to 32% at 60 months after surgery. The total number of patients free from asthma medication increased from 25% preoperatively to 33% at 60 months postoperatively. Asthma medication use decreased in both surgery groups, and neither operation demonstrated superiority. No significant improvement nor differences were found between groups at any time point regarding FEV1/FVC ratio spirometry measures. CONCLUSION: Bariatric surgery reduces the use of medications taken for management of asthma. The amount of asthma medication usage decreases with time and is sustained at 60 months after bariatric surgery.

Benefits of upgrading right ventricular to biventricular pacing in heart failure patients with atrial fibrillation.

AIMS: Recommendations on cardiac resynchronization therapy (CRT) in patients with atrial fibrillation or flutter (AF) are based on less robust evidence than those in sinus rhythm (SR). We aimed to assess the efficacy of CRT upgrade in the BUDAPEST-CRT Upgrade trial population by their baseline rhythm. METHODS AND RESULTS: Heart failure patients with reduced ejection fraction (HFrEF) and previously implanted pacemaker (PM) or implantable cardioverter defibrillator (ICD) and ≥20% right ventricular (RV) pacing burden were randomized to CRT with defibrillator (CRT-D) upgrade (n = 215) or ICD (n = 145). Primary [HF hospitalization (HFH), all-cause mortality, or <15% reduction of left ventricular end-systolic volume] and secondary outcomes were investigated. At enrolment, 131 (36%) patients had AF, who had an increased risk for HFH as compared with those with SR [adjusted hazard ratio (aHR) 2.99; 95% confidence interval (CI) 1.26-7.13; P = 0.013]. The effect of CRT-D upgrade was similar in patients with AF as in those with SR [AF adjusted odds ratio (aOR) 0.06; 95% CI 0.02-0.17; P < 0.001; SR aOR 0.13; 95% CI 0.07-0.27; P < 0.001; interaction P = 0.29] during the mean follow-up time of 12.4 months. Also, it decreased the risk of HFH or all-cause mortality (aHR 0.33; 95% CI 0.16-0.70; P = 0.003; interaction P = 0.17) and improved the echocardiographic response (left ventricular end-diastolic volume difference -49.21 mL; 95% CI -69.10 to -29.32; P < 0.001; interaction P = 0.21). CONCLUSION: In HFrEF patients with AF and PM/ICD with high RV pacing burden, CRT-D upgrade decreased the risk of HFH and improved reverse remodelling when compared with ICD, similar to that seen in patients in SR.

Comprehensive approach integrating remote sensing, machine learning, and physicochemical parameters to detect hydrodynamic conditions and groundwater quality deterioration in non-rechargeable aquifer systems.

The current study integrates remote sensing, machine learning, and physicochemical parameters to detect hydrodynamic conditions and groundwater quality deterioration in non-rechargeable aquifer systems. Fifty-two water samples were collected from all water resources in Siwa Oasis and analyzed for physical (pH, T°C, EC, and TDS) chemical (SO4 2-, HCO3 -, NO3 -, Cl-, CO3 2-, SiO2, Mg2+, Na+, Ca2+, and K+), and trace metals (AL, Fe, Sr, Ba, B, and Mn). A digital elevation model supported by machine learning was used to predict the change in the land cover (surface lake area, soil salinity, and water logging) and its effect on water quality deterioration. The groundwater circulation and interaction between the deep aquifer (NSSA) and shallow aquifer (TCA) were detected from the pressure-depth profile of 27 production wells penetrating NSSA. The chemical facies evolution in the aquifer systems were (Ca-Mg-HCO3) in the first stage (freshwater of NSSA) and changed to (Na-Cl) type in the last stage (brackish water of TCA and springs). Support vector machine successfully predicted the rapid increase of the hypersaline lake area from 22.6 km2 to 60.6 km2 within 30 years, which deteriorated a large part of the cultivated land, reflecting the environmental risk of over-extraction of water for irrigation of agricultural land by flooding technique and lack of suitable drainage network. The waterlogging in the study was due to a reduction in the infiltration rate (low permeability) of the soil and quaternary aquifer. The cause of this issue could be a complete saturation of agricultural water with chrysotile, calcite, talc, dolomite, gibbsite, chlorite, Ca-montmorillonite, illite, hematite, kaolinite and K-mica (saturation index >1), giving the chance of these minerals to precipitate in the pore spaces of the soil and decrease the infiltration rate. The NSSA is appropriate for irrigation, whereas TCA is inappropriate due to potential salinity and magnesium risks. The best way to manage water resources in Siwa Oasis could be to use underground drip irrigation and combine water with TCA and NSSA.

The effects of mitral stenosis on right ventricular mechanics assessed by three-dimensional echocardiography.

Mitral stenosis (MS) is a complex valvular pathology with significant clinical burden even today. Its effect on the right heart is often overlooked, despite it playing a considerable part in the symptomatic status. We enrolled 39 mitral valve stenosis patients and 39 age- and gender-matched healthy controls. They underwent conventional, speckle-tracking and 3D echocardiographic examinations. The 3D data was analyzed using the ReVISION software to calculate RV functional parameters. In the MS group, 3D RV ejection fraction (EF) (49 ± 7% vs. 61 ± 4%; p < 0.001), global circumferential (GCS) (- 21.08 ± 5.64% vs. - 25.07 ± 4.72%; p = 0.001) and longitudinal strain (GLS) (- 16.60% ± 4.07% vs. - 23.32 ± 2.82%; p < 0.001) were reduced. When comparing RV contraction patterns between controls, MS patients in sinus rhythm and those with atrial fibrillation, radial (REF) (32.06 ± 5.33% vs. 23.62 ± 7.95% vs. 20.89 ± 6.92%; p < 0.001) and longitudinal ejection fraction (LEF) (24.85 ± 4.06%; 17.82 ± 6.16% vs. 15.91 ± 4.09%; p < 0.001) were decreased in both MS groups compared to controls; however, they were comparable between the two MS subgroups. Anteroposterior ejection fraction (AEF) (29.16 ± 4.60% vs. 30.87 ± 7.71% vs. 21.48 ± 6.15%; p < 0.001) showed no difference between controls and MS patients in sinus rhythm, while it was lower in the MS group with atrial fibrillation. Therefore, utilizing 3D echocardiography, we found distinct morphological and functional alterations of the RV in MS patients.

Non-invasive assessment of left ventricular contractility by myocardial work index in veno-arterial membrane oxygenation patients: rationale and design of the MIX-ECMO multicentre observational study.

Introduction and aims: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is an increasingly utilized therapeutic choice in patients with cardiogenic shock, however, high complication rate often counteracts with its beneficial cardiopulmonary effects. The assessment of left ventricular (LV) function in key in the management of this population, however, the most commonly used measures of LV performance are substantially load-dependent. Non-invasive myocardial work is a novel LV functional measure which may overcome this limitation and estimate LV function independent of the significantly altered loading conditions of VA-ECMO therapy. The Usefulness of Myocardial Work IndeX in ExtraCorporeal Membrane Oxygenation Patients (MIX-ECMO) study aims to examine the prognostic role of non-invasive myocardial work in VA-ECMO-supported patients. Methods: The MIX-ECMO is a multicentric, prospective, observational study. We aim to enroll 110 patients 48-72 h after the initiation of VA-ECMO support. The patients will undergo a detailed echocardiographic examination and a central echocardiography core laboratory will quantify conventional LV functional measures and non-invasive myocardial work parameters. The primary endpoint will be failure to wean at 30 days as a composite of cardiovascular mortality, need for long-term mechanical circulatory support or heart transplantation at 30 days, and besides that other secondary objectives will also be investigated. Detailed clinical data will also be collected to compare LV functional measures to parameters with established prognostic role and also to the Survival After Veno-arterial-ECMO (SAVE) score. Conclusions: The MIX-ECMO study will be the first to determine if non-invasive myocardial work has added prognostic value in patients receiving VA-ECMO support.

Trajectory of Diastolic Function after Heart Transplantation as Assessed by Left Atrial Deformation Analysis.

Diastolic dysfunction (DD) is a prevalent and clinically significant complication after heart transplantation (HTX). We aimed to characterize the diastolic function of HTX recipients with both short-term and long-term follow-ups by applying left atrial (LA) deformation analysis. We consecutively enrolled and followed up with 33 HTX patients. Three assessments were performed one month, 3-5 months, and 3-5 years after surgery. Beyond conventional echocardiographic measurements, apical four-chamber views optimized for speckle tracking analysis were acquired and post-processed by dedicated software solutions (TomTec AutoStrain LA and LV). Left atrial phasic functions were characterized by reservoir, conduit, and contraction strains. We categorized diastolic function according to current guidelines (normal diastolic function, indeterminate, DD). At the first assessment, nine (27%) patients were in the DD category, and eleven (33%) were indeterminate. At the second assessment, only one patient (3%) remained in the DD category and six (18%) were indeterminate. At the third assessment, 100% of patients were categorized as having normal diastolic function. LA reservoir strain gradually increased over time. LA contraction strain significantly improved from the second to the third assessment. We found a correlation between the LA reservoir strain and NT-proBNP (r = 0.40, p < 0.05). DD is prevalent immediately after HTX but rare until the end of the first postoperative quarter. Speckle tracking analysis enables the characterization of LA phasic functions that may reflect both short- and long-term changes in diastolic function and correlate with NT-proBNP.

Two-hit mouse model of heart failure with preserved ejection fraction combining diet-induced obesity and renin-mediated hypertension.

Heart failure with preserved ejection fraction (HFpEF) is increasingly common but its pathogenesis is poorly understood. The ability to assess genetic and pharmacologic interventions is hampered by the lack of robust preclinical mouse models of HFpEF. We have developed a novel "2-hit" model, which combines obesity and insulin resistance with chronic pressure overload to recapitulate clinical features of HFpEF. C57BL6/NJ mice fed a high fat diet for >10 weeks were administered an AAV8-driven vector resulting in constitutive overexpression of mouse Renin1d . Control mice, HFD only, Renin only and HFD-Renin (aka "HFpEF") littermates underwent a battery of cardiac and extracardiac phenotyping. HFD-Renin mice demonstrated obesity and insulin resistance, a 2-3-fold increase in circulating renin levels that resulted in 30-40% increase in left ventricular hypertrophy, preserved systolic function, and diastolic dysfunction indicated by altered E/e', IVRT, and strain measurements; increased left atrial mass; elevated natriuretic peptides; and exercise intolerance. Transcriptomic and metabolomic profiling of HFD-Renin myocardium demonstrated upregulation of pro-fibrotic pathways and downregulation of metabolic pathways, in particular branched chain amino acid catabolism, similar to findings in human HFpEF. Treatment of these mice with the sodium-glucose cotransporter 2 inhibitor empagliflozin, an effective but incompletely understood HFpEF therapy, improved exercise tolerance, left heart enlargement, and insulin homeostasis. The HFD-Renin mouse model recapitulates key features of human HFpEF and will enable studies dissecting the contribution of individual pathogenic drivers to this complex syndrome. Addition of HFD-Renin mice to the preclinical HFpEF model platform allows for orthogonal studies to increase validity in assessment of interventions. NEW & NOTEWORTHY: Heart failure with preserved ejection fraction (HFpEF) is a complex disease to study due to limited preclinical models. We rigorously characterize a new two-hit HFpEF mouse model, which allows for dissecting individual contributions and synergy of major pathogenic drivers, hypertension and diet-induced obesity. The results are consistent and reproducible in two independent laboratories. This high-fidelity pre-clinical model increases the available, orthogonal models needed to improve our understanding of the causes and assessment treatments for HFpEF.

Regression of all untreated lesions in multifocal low-grade meningioma following fractionated stereotactic radiotherapy-abscopal effect or spontaneous regression? : Case report and review of the literature.

PURPOSE: Abscopal effects have been reported predominantly in metastatic cancers, indicating a radiographic response in a lesion that has not been included in the radiotherapy target volume. The response is interpreted as a humoral immune response to radiotherapy-generated tumour-specific antigens. In this case study, we present the first histologically confirmed multifocal low-grade meningioma with spontaneous regression of all other lesions after conventionally fractionated stereotactic radiotherapy (RT). CASE REPORT: Two localisations, right frontal and right spheno-orbital, were resected at the time of the initial diagnosis in a 66-year-old woman. RT was performed 1 year later to a progressive occipital lesion at the cerebral falx. RESULTS: Regular magnetic resonance imaging (MRI) showed slightly decreasing tumour volume in untreated lesions 1 year after RT and continued during further follow-up. Up to > 7 years after treatment, MRI demonstrated an almost complete response of all initial lesions. Two prior reports with meningioma were published in one patient with an atypical meningioma after conventionally fractionated RT and another patient with an intracranial meningiomatosis after radiosurgery. CONCLUSION: This case study supports the concepts of treating only progressive or symptomatic meningioma lesions locally and careful regular MRI surveillance for further assessment. Potential active interventions to trigger an abscopal effect are currently not known. Further research of this beneficial effect for our patients should be supported.

Significant Disagreement Between Conventional Parameters and 3D Echocardiography-Derived Ejection Fraction in the Detection of Right Ventricular Systolic Dysfunction and Its Association With Outcomes.

AIMS: Conventional echocardiographic parameters such as tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), and free-wall longitudinal strain (FWLS) offer limited insights into the complexity of right ventricular (RV) systolic function, while 3D echocardiography-derived RV ejection fraction (RVEF) enables a comprehensive assessment. We investigated the discordance between TAPSE, FAC, FWLS, and RVEF in RV systolic function grading and associated outcomes. METHODS: We analyzed two- and three-dimensional echocardiography data from 2 centers including 750 patients followed up for all-cause mortality. Right ventricular dysfunction was defined as RVEF <45%, with guideline-recommended thresholds (TAPSE <17 mm, FAC <35%, FWLS >-20%) considered. RESULTS: Among patients with normal RVEF, significant proportions exhibited impaired TAPSE (21%), FAC (33%), or FWLS (8%). Conversely, numerous patients with reduced RVEF had normal TAPSE (46%), FAC (26%), or FWLS (41%). Using receiver-operating characteristic analysis, FWLS exhibited the highest area under the curve of discrimination for RV dysfunction (RVEF <45%) with 59% sensitivity and 92% specificity. Over a median 3.7-year follow-up, 15% of patients died. Univariable Cox regression identified TAPSE, FAC, FWLS, and RVEF as significant mortality predictors. Combining impaired conventional parameters showed that outcomes are the worst if at least 2 parameters are impaired and gradually better if only one or none of them are impaired (log-rank P < .005). CONCLUSION: Guideline-recommended cutoff values of conventional echocardiographic parameters of RV systolic function are only modestly associated with RVEF-based assessment. Impaired values of FWLS showed the closest association with the RVEF cutoff. Our results emphasize a multiparametric approach in the assessment of RV function, especially if 3D echocardiography is not available.

NASH triggers cardiometabolic HFpEF in aging mice.

Both heart failure with preserved ejection fraction (HFpEF) and non-alcoholic fatty liver disease (NAFLD) develop due to metabolic dysregulation, has similar risk factors (e.g., insulin resistance, systemic inflammation) and are unresolved clinical challenges. Therefore, the potential link between the two disease is important to study. We aimed to evaluate whether NASH is an independent factor of cardiac dysfunction and to investigate the age dependent effects of NASH on cardiac function. C57Bl/6 J middle aged (10 months old) and aged mice (24 months old) were fed either control or choline deficient (CDAA) diet for 8 weeks. Before termination, echocardiography was performed. Upon termination, organ samples were isolated for histological and molecular analysis. CDAA diet led to the development of NASH in both age groups, without inducing weight gain, allowing to study the direct effect of NASH on cardiac function. Mice with NASH developed hepatomegaly, fibrosis, and inflammation. Aged animals had increased heart weight. Conventional echocardiography revealed normal systolic function in all cohorts, while increased left ventricular volumes in aged mice. Two-dimensional speckle tracking echocardiography showed subtle systolic and diastolic deterioration in aged mice with NASH. Histologic analyses of cardiac samples showed increased cross-sectional area, pronounced fibrosis and Col1a1 gene expression, and elevated intracardiac CD68+ macrophage count with increased Il1b expression. Conventional echocardiography failed to reveal subtle change in myocardial function; however, 2D speckle tracking echocardiography was able to identify diastolic deterioration. NASH had greater impact on aged animals resulting in cardiac hypertrophy, fibrosis, and inflammation.

Regime shift in microalgal dynamics: Impact of water level changes on planktonic and benthic algal biomass.

Whole-lake microalgal biomass surveys were carried out in Lake Balaton to investigate the seasonal, spatial, and temporal changes of benthic algae, as well as to identify the drivers of the phytobenthos. Phytobenthos was controlled mainly by light: the highest benthic algal biomass was in the shallow littoral region characterized by large grain size (sand) with good light availability but lower nutrient content in the sediment. During the investigated period, phytoplankton biomass showed a significant decrease in almost the entire lake. At the same time, the biomass of benthic algae increased significantly in the eastern areas, increasing the contribution of total lake microalgae biomass (from 20 % to 27 %). Benthic algal biomass increase can be explained by the better light supply, owing to the artificially maintained high water level which greatly mitigates water mixing. The decrease in planktonic algal biomass could be attributed to increased zooplankton grazing, which is otherwise negatively affected by mixing. As a result of the high water level, the trophic structure of the lake has been rearranged in recent decades with a shift from the planktonic life form to the benthic one while the nutrient supply has largely remained unchanged.

Right ventricular pressure-strain relationship-derived myocardial work reflects contractility: Validation with invasive pressure-volume analysis.

Three-dimensional (3D) echocardiography-derived right ventricular (RV) ejection fraction (EF) and global longitudinal strain (GLS) are valuable RV functional markers; nevertheless, they are substantially load-dependent. Global myocardial work index (GMWI) is a novel parameter calculated by the area of the RV pressure-strain loop. By adjusting myocardial deformation to instantaneous pressure, it may reflect contractility. To test this hypothesis, we enrolled 60 patients who underwent RV pressure-conductance catheterization to determine load-independent markers of RV contractility and ventriculo-arterial coupling. Detailed 3D echocardiography was also performed, and we calculated RV EF, RV GLS, and using the RV pressure trace curve, RV GWMI. While neither RV EF nor GLS correlated with Ees, GMWI strongly correlated with Ees. In contrast, RV EF and GLS showed a relationship with Ees/Ea. By dividing the population based on their Reveal Lite 2 risk classification, different characteristics were seen among the subgroups. RV GMWI may emerge as a useful clinical tool for risk stratification and follow-up in patients with RV dysfunction.

Myocardial work of the systemic right ventricle and its association with outcomes.

We aimed to evaluate clinical and prognostic significance of myocardial work parameters of the systemic right ventricle (SRV). Thirty-eight patients with the SRV underwent echocardiographic assessment of the SRV systolic function including 3D-echocardiography derived ejection fraction, 2D longitudinal strain and myocardial work analysis. The study endpoint was the combination of all-cause mortality and heart transplantation. Global constructive work (GCW) and global work index (GWI) demonstrated moderate correlation with the 3DE-derived SRV ejection fraction (EF) (Rho 0.64, p < 0.0001 and Rho 0.63, p < 0.0001, respectively). GCW showed the strongest correlation with the BNP level (Rho - 0.77, p < 0.0001), closely followed by GWI, 4-chamber longitudinal strain and 3DE EF (all Rho - 0.73, p < 0.0001). GCW and GWI were significantly lower in patients with moderate or severe tricuspid regurgitation compared with less than moderate regurgitation (1226 ± 439 vs 1509 ± 264 mmHg%, p = 0.02, and 984 ± 348 vs 1259 ± 278 mmHg%, p = 0.01, respectively). During a follow-up of 3.5 (2.8-3.9) years, seven patients (18%) died and one received transplantation (3%). They had significantly lower GCW and GWI compared with patients who did not reach the study endpoint (908 ± 255 vs 1433 ± %, p < 0.001 and 721 ± 210 vs 1173 ± 315 mmHg%, p < 0.001, respectively). In Cox regression analysis, GCW, GWI, 3DE SRV volumes and EF were the best-fit models based on the Akaike Information Criterion, outperforming longitudinal strain parameters. GWI and GCW, novel echocardiographic parameters of myocardial work, provided reliable quantification of the SRV systolic function. GWI, GCW and 3DE-derived SRV parameters were closely associated with all-cause mortality and heart transplantation in patients with the SRV.

Deep Learning-Derived Myocardial Strain.

BACKGROUND: Echocardiographic strain measurements require extensive operator experience and have significant intervendor variability. Creating an automated, open-source, vendor-agnostic method to retrospectively measure global longitudinal strain (GLS) from standard echocardiography B-mode images would greatly improve post hoc research applications and may streamline patient analyses. OBJECTIVES: This study was seeking to develop an automated deep learning strain (DLS) analysis pipeline and validate its performance across multiple applications and populations. METHODS: Interobserver/-vendor variation of traditional GLS, and simulated effects of variation in contour on speckle-tracking measurements were assessed. The DLS pipeline was designed to take semantic segmentation results from EchoNet-Dynamic and derive longitudinal strain by calculating change in the length of the left ventricular endocardial contour. DLS was evaluated for agreement with GLS on a large external dataset and applied across a range of conditions that result in cardiac hypertrophy. RESULTS: In patients scanned by 2 sonographers using 2 vendors, GLS had an intraclass correlation of 0.29 (95% CI: -0.01 to 0.53, P = 0.03) between vendor measurements and 0.63 (95% CI: 0.48-0.74, P < 0.001) between sonographers. With minor changes in initial input contour, step-wise pixel shifts resulted in a mean absolute error of 3.48% and proportional strain difference of 13.52% by a 6-pixel shift. In external validation, DLS maintained moderate agreement with 2-dimensional GLS (intraclass correlation coefficient [ICC]: 0.56, P = 0.002) with a bias of -3.31% (limits of agreement: -11.65% to 5.02%). The DLS method showed differences (P < 0.0001) between populations with cardiac hypertrophy and had moderate agreement in a patient population of advanced cardiac amyloidosis: ICC was 0.64 (95% CI: 0.53-0.72), P < 0.001, with a bias of 0.57%, limits of agreement of -4.87% to 6.01% vs 2-dimensional GLS. CONCLUSIONS: The open-source DLS provides lower variation than human measurements and similar quantitative results. The method is rapid, consistent, vendor-agnostic, publicly released, and applicable across a wide range of imaging qualities.

Optimization of assay conditions to quantify ECOD activity in vivo in individual Daphnia magna. Assay performance evaluation with model CYP 450 inducers/inhibitors.

Screening the activity of the cytochrome P450 (CYP450) mixed function oxidase system in aquatic invertebrates received seldom applications in ecotoxicology due to low baseline enzymatic activities characteristic for these organisms. In this study, an existing in vivo spectrofluorometric assay method based on quantifying the cytochrome P450 mediated conversion of 7-ethocycoumarin (EtC) used as substrate to the product 7-hydroxycoumarin (HCm) called: ethoxycoumarin-O-deethylase (ECOD) activity, initially applicable on pooled samples of Daphnia magna, was optimized for use on individual organisms. Optimal assay conditions have been established for as small as 3- and 6 days old individuals, and the limits of spectrofluorometric detection of HCm excreted by daphnids in the incubation media were defined. The modified assay was tested by screening the modulation of ECOD activity in daphnids following 24 h exposure to ß-naphthoflavone (ß-NF, reference CYP450 inducer) and to prochloraz (PCZ), a potent CYP450 inhibitor. Maximal ECOD activity levels in daphnids were recorded following 2 hours of incubation to 200 nM EtC. The limit of spectrofluorometric detection of HCm in the incubation media was 6.25 nM, achieved by more than 80% of three days old daphnids and all six days old individuals. Exposure of daphnids to ß-NF demonstrated a bell-shaped ECOD activity induction potential, while PCZ elicited partial (60%) inhibition of ECOD activity. This optimized in vivo ECOD activity assay may serve as a cost-effective tool to study the responsiveness of Phase-I metabolism in D. magna to toxic pressure and its applicability to other aquatic invertebrates is also worth for consideration.

In chronic kidney disease altered cardiac metabolism precedes cardiac hypertrophy.

Conduit arterial disease in chronic kidney disease (CKD) is an important cause of cardiac complications. Cardiac function in CKD has not been studied in the absence of arterial disease. In an Alport syndrome model bred not to have conduit arterial disease, mice at 225 days of life (dol) had CKD equivalent to humans with CKD stage 4-5. Parathyroid hormone (PTH) and FGF23 levels were one log order elevated, circulating sclerostin was elevated, and renal activin A was strongly induced. Aortic Ca levels were not increased, and vascular smooth muscle cell (VSMC) transdifferentiation was absent. The CKD mice were not hypertensive, and cardiac hypertrophy was absent. Freshly excised cardiac tissue respirometry (Oroboros) showed that ADP-stimulated O2 flux was diminished from 52 to 22 pmol/mg (P = 0.022). RNA-Seq of cardiac tissue from CKD mice revealed significantly decreased levels of cardiac mitochondrial oxidative phosphorylation genes. To examine the effect of activin A signaling, some Alport mice were treated with a monoclonal Ab to activin A or an isotype-matched IgG beginning at 75 days of life until euthanasia. Treatment with the activin A antibody (Ab) did not affect cardiac oxidative phosphorylation. However, the activin A antibody was active in the skeleton, disrupting the effect of CKD to stimulate osteoclast number, eroded surfaces, and the stimulation of osteoclast-driven remodeling. The data reported here show that cardiac mitochondrial respiration is impaired in CKD in the absence of conduit arterial disease. This is the first report of the direct effect of CKD on cardiac respiration.NEW & NOTEWORTHY Heart disease is an important morbidity of chronic kidney disease (CKD). Hypertension, vascular stiffness, and vascular calcification all contribute to cardiac pathophysiology. However, cardiac function in CKD devoid of vascular disease has not been studied. Here, in an animal model of human CKD without conduit arterial disease, we analyze cardiac respiration and discover that CKD directly impairs cardiac mitochondrial function by decreasing oxidative phosphorylation. Protection of cardiac oxidative phosphorylation may be a therapeutic target in CKD.

Right Ventricular Structure and Function in Adolescent Athletes: A 3D Echocardiographic Study.

The aim of this study was to characterize the right ventricular (RV) contraction pattern and its associations with exercise capacity in a large cohort of adolescent athletes using resting three-dimensional echocardiography (3DE). We enrolled 215 adolescent athletes (16±1 years, 169 males, 12±6 hours of training/week) and compared them to 38 age and sex-matched healthy, sedentary adolescents. We measured the 3DE-derived biventricular ejection fractions (EF). We also determined the relative contributions of longitudinal EF (LEF/RVEF) and radial EF (REF/RVEF) to the RVEF. Same-day cardiopulmonary exercise testing was performed to calculate VO2/kg. Both LV and RVEFs were significantly lower (athletes vs. controls; LVEF: 57±4 vs 61±3, RVEF: 55±5 vs 60±5%, p<0.001). Interestingly, while the relative contribution of radial shortening to the global RV EF was also reduced (REF/RVEF: 0.40±0.10 vs 0.49±0.06, p<0.001), the contribution of the longitudinal contraction was significantly higher in athletes (LEF/RVEF: 0.45±0.08 vs 0.40±0.07, p<0.01). The supernormal longitudinal shortening correlated weakly with a higher VO2/kg (r=0.138, P=0.044). Similarly to the adult athlete's heart, the cardiac adaptation of adolescent athletes comprises higher biventricular volumes and lower resting functional measures with supernormal RV longitudinal shortening. Characteristic exercise-induced structural and functional cardiac changes are already present in adolescence.

Long-Term Durability of High- and Very High-Power Short-Duration PVI by Invasive Remapping: The HPSD Remap Study.

BACKGROUND: High-power short-duration ablation has shown impressive efficacy and safety for pulmonary vein isolation (PVI); however, initial efficacy results with very high power short-duration ablation were discouraging. This study compared the long-term durability of PVI performed with a 90- versus 50-W power setting. METHODS: Patients were randomized 1:1 to undergo PVI with the QDOT catheter using a power setting of 90 or 50 W. Three months after the index procedure, patients underwent a repeat electrophysiology study to identify pulmonary vein reconnections. Patients were followed for 12 months to detect AF recurrences. RESULTS: We included 46 patients (mean age, 64 years; women, 48%). Procedure (76 versus 84 minutes; P =0.02), left atrial dwell (63 versus 71 minutes; P =0.01), and radiofrequency (303 versus 1040 seconds; P <0.0001) times were shorter with 90- versus 50-W procedures, while the number of radiofrequency applications was higher with 90 versus 50 W (77 versus 67; P =0.01). There was no difference in first-pass isolation (83% versus 82%; P =1.0) or acute reconnection (4% versus 14%; P =0.3) rates between 90 and 50 W. Forty patients underwent a repeat electrophysiology study. Durable PVI on a per PV basis was present in 72/78 (92%) versus 68/77 (88%) PVs in the 90- and 50-W energy setting groups, respectively; effect size: 72/78-68/77=0.040, lower 95% CI=-0.051 (noninferiority limit=-0.1, ie, noninferiority is met). No complications occurred. There was no difference in 12-month atrial fibrillation-free survival between the 90- and 50-W groups (P =0.2). CONCLUSIONS: Similarly high rates of durable PVI and arrhythmia-free survival were achieved with 90 and 50 W. Procedure, left atrial dwell, and radiofrequency times were shorter with 90 W compared with 50 W. The sample size is too small to conclude the safety and long-term efficacy of the high and very high-power short-duration PVI; further studies are needed to address this topic. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05459831.