Reduction In Fraction Research Articles

Molybdenum, lead and zinc mobility potential in agricultural environments: a case study of the Kočani field, North Macedonia

The research focuses on the assessment of potential toxic elements (PTEs) contamination of the soils of the Kočani field (North Macedonia) due to the surrounding past and current polymetallic mining activities. The Zletovska River drains the untreated wastewater from the Pb-Zn mine in the Zletovo-Kratovo region and is unfortunately used to irrigate the surrounding rice fields. Elevated levels of molybdenum (Mo) and especially lead (Pb) and zinc (Zn) were found in the soil samples from the rice fields near the Zletovska River (in the western part of the Kočani field), which are well above the limit and critical emission values for PTEs content in soils. In addition, Mo was consistently bound to water soluble, exchangeable and oxidizable fractions in all samples, while reducible and residual fractions were predominated by Pb and Zn. According to the sum of the water-soluble and exchangeable fractions, the mobility and environmental bioavailability potential of the investigated PTEs in the soil-plant system decreased in the following order: Mo > Pb > Zn. It is therefore very important to emphasize that when assessing the environmental impact of PTEs on the respective surroundings, not only the commonly considered trace and minor PTEs (such as Pb and Zn) that occur in geological materials should be taken into account, but also in lower contents (such as Mo). The translocation of PTEs within the ecosystem does not depend on their total content in the primary geological materials, but on their individual mobility and binding capacity.

The Diagnosis and Treatment of Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) with or without left ventricular outflow tract (LVOT) obstruction is a common primary myocardial disease, with a prevalence of 1:500. It is characterized by thickening of the myocardium. Its diagnostic evaluation includes history-taking and physical examination, genetic studies, transthoracic echocardiography, and cardiac MRI. When optimally treated, it carries a mortality of less than 1% per year. This review is based on pertinent publications retrieved by a selective literature search, including the current guidelines. In symptomatic patients with high LVOT gradients (≥ 50 mm Hg), the treatment of first choice is pharmacotherapy with non-vasodilating beta-blockers or non-dihydropyridine-type calcium channel antagonists. Common side effects include bradycardia and hypotension, and there is a risk of AV nodal blockade. Both substance classes lower the LVOT gradient. Beta-blockers alleviate dyspnea and improve patients' quality of life. Verapamil can increase physical resilience. A further option is mavacamten, a myosin inhibitor that gained approval in Germany in mid-2023: it, too, lowers the LVOT gradient and improves quality of life. In 7-10% of patients, there is a reversible reduction of the left ventricular ejection fraction to less than 50%. Septal reduction treatments can be considered if drug therapy fails. Attention must also be paid to the management of sequelae such as atrial fibrillation, malignant arrhythmias, and mitral valve insufficiency. Patients with HCM have a near-normal life expectancy if the disease is diagnosed early and treated according to the guidelines. The treatment of HCM and HOCM (hypertrophic obstructive cardiomyopathy) have been studied in no more than a few clinical trials, and randomized studies with clinical endpoints are needed.

Wavy mathematical modeling of dynamically reactive shear thinning materials under the influence of gravity and wavy structures amplitude

PurposeResultant leading equations are formed with non-linear partial differential equations by adopting a low Reynolds theory approximation. For a better and easier understanding of the role of physical features of the main problem, the equations are reduced to non-dimensional ordinary differential equations by incorporating the locally similar and non-similar dimensionless variables. In light of practical importance, all the significant findings are approximated by solving the equations with the assistance of a modified bvp4c built-in package. The effective speed, temperature and volume fraction of the same materials are displayed to address the behaviors of different controlling influences.Design/methodology/approachThis work is inaugurated to investigate thermal cycling, thermal striping and thermal stratification, which cause thermally induced damage during the wavy confined flow domains. Such physical constraints are imposed on the wavy surface while considering the wavy dynamics of shear thinning materials. The impact of gravity is assumed on the vertical wavy surface, which is observed as the main source for the wavy flow occurrence. The surface’s amplitude plays a critical role in generating a high temperature difference. The same phenomenon is further extended with the applications of thermal radiation, mixed convection and dynamical homogeneous/heterogeneous reactions.FindingsFor instance, the higher stratification factor causes a reduction in the liquid wavy speed and temperature, and the rising chemically reactive rate factor declines the volume fraction during the typical wavy motion of the materials. Moreover, the larger amplitude and mixed convective factor reduced and uplifted the speed of the materials, respectively. The surface resistive forces are monitored with the graphical visualization of local similar skin friction and are determined larger by varying the Weissenberg and mixed convective factors. The affective liquid speed, temperature and volume fraction are plotted to address the behaviors of different controlling factors. These impacts are listed, i.e. with higher stratification factors, a reduction is noticed in the liquid velocity and temperature. On the other hand, an opposite depict is noticed for higher heat generation factors. The reduction in volume fraction is reported with variation in the reaction factor and Schmidt number.Originality/valueAfter carefully assessing the previously referenced work, it is evident that the literature has yet to incorporate thermally stratified Williamson fluid. Meanwhile, the motion of the materials is noticed due to the gravitationally affected wavy surface. Such physical phenomenon is further approximated by testing a dynamical reaction during its motion. An effective presentation of all the outcomes is portrayed via graphs and approximated numerical results.

Atypical presentation of Andersen-Tawil syndrome: heart failure with reduced ejection without periodic paralysis or dysmorphic features

Background: Andersen-Tawil syndrome (ATS) is a rare autosomal dominant disorder caused by variants in the KCNJ2 gene. It is associated with periodic paralysis, dysmorphic features and cardiac arrhythmias. The syndrome exhibits incomplete penetrance, leading to a broad spectrum of clinical manifestations, making diagnosis challenging. Case description: A male in his mid-20s with class 3 obesity presented to the emergency department with a week-long history of worsening chest pain, orthopnoea and fatigue. His family history was significant for sudden cardiac death affecting both his mother and brother, with his father having died from complications of Wolff-Parkinson-White syndrome. Cardiovascular examination revealed an S3 heart sound and elevated brain natriuretic peptide levels at 875 pg/ml, with undetectable troponins; potassium level on admission was 3.6 mEq/l. An electrocardiogram showed normal sinus rhythm, first-degree heart block, left atrial enlargement, left bundle branch block and a prolonged QTc of 486 ms. A transthoracic echocardiogram demonstrated a 15-20% reduction in ejection fraction with global left ventricular hypokinesis and left atrial enlargement. Ultimately, he was diagnosed with non-ischaemic dilated cardiomyopathy and referred for genetic testing, which revealed a KCNJ2 variant. Shortly after discharge, he experienced a 55-second run of ventricular tachycardia, necessitating the placement of a single-chamber ICD. Currently, the patient remains on guideline-directed medical therapy and is listed for a heart transplant. Conclusions: Dilated cardiomyopathy, although a rare manifestation in ATS, can profoundly increase the risk of fatal arrythmias, necessitating the need for a low threshold of suspicion, to ensure timely diagnosis and management.

Comparative mineralogical characterization of REEs ore samples from the Mushgai Khudag and Lugiin Gol deposits, Mongolia

Mongolia, situated in the Central Asian orogenic belt, is characterized by geology that is highly conducive to the abundance of mineral resources, including significant rare earth elements (REEs) reserves. However, limited knowledge of the mineralogy of its deposits has hindered the development of efficient REEs extraction methods. This study presents a detailed investigation of the mineralogical characteristics of Mongolian ores and analyzes their compositions, mineral associations, liberation, and REEs concentrations via advanced analytical techniques, including the TESCAN Integrated Mineral Analyzer (TIMA). Additionally, the BCR sequential extraction method was employed to determine the binding and leaching properties of REEs. Our results revealed that the two ore samples were predominantly rich in light rare earth elements (LREEs), with REE-bearing minerals closely associated with gangue minerals such as calcite, albite, and quartz, leading to poor liberation. The extraction data indicated that >85 % of the REEs in the Mushgai Khudag deposit were retained in the residual fraction, whereas in the Lugiin Gol deposit, the majority of the REEs were associated with the reducible fraction. These findings underscore the challenges associated with extracting REEs from Mongolian deposits, which demand stringent conditions for effective recovery. This research contributes valuable insights into the complex mineralogy of Mongolian REEs deposits, offering a foundation for future advancements in REE extraction technologies.

Cadmium distribution and availability in different particle-size aggregates of post-harvest paddy soil amended with bio-based materials

Research on the use of organic materials as soil amendments for the remediation of Cd-contaminated agricultural land exists. However, the mechanisms based on which organic materials affect the distribution and availability of Cd in soil aggregates remain unclear. Here, Cd-contaminated paddy soil and different bio-based materials were used for rice pot experiments. Rhizosphere soils were separated into six particle sizes. Cd fractions were analyzed with BCR sequential extraction and specific functional groups associated with Cd were characterized using XPS. We found that bio-based materials promoted the formation of large aggregates to different extents. Cd tended to be enriched in fine- and coarse-grained soil particles, which is mainly related to the soil organic matter. Bio-based materials reduced the relative content of the weak-acid extractable fraction and increased the relative content of the reducible fraction, resulting in soil Cd immobilization. Soil dissolved organic matter (DOM) was the key factor affecting the distribution and availability of Cd in soil aggregates and different organic matter and Cd-binding functional groups in aggregates altered the Cd availability in soil. The results provide insight and guidance for understanding the cadmium immobilization mechanism and screening appropriate materials in the remediation of agricultural land.

Exercise-induced Reduction in Left Ventricular Ejection Fraction in the Absence of Coronary Artery Disease: Clinical Characteristics and Outcomes

During exercise stress echocardiography (ESE) there are patients with normal left ventricular ejection fraction (LVEF) who paradoxically develop reduced LVEF during exercise despite absence of coronary artery disease (CAD) and a significant hypertensive response. This study sought to describe the clinical features and outcomes of this population. Among ESE performed between 2003 and 2022, patients without CAD by angiogram within 90 days of ESE, resting LVEF ≥50% with a ≥5% LVEF decrease during ESE were included. Outcomes assessed were all-cause mortality, heart failure (HF) hospitalization, and atrial fibrillation (AF). Kaplan-Meier and Cox regression methods were used to analyze time-to-event outcomes. Among 213,643 ESE, 134 patients met eligibility criteria. The mean age of the population was 66±10 years, 76% were women, and 16% had AF at baseline. Mean LVEF was 58±4% at rest and 43±4% at peak stress. Stress ECG met criteria for ischemia in 14% of these patients. The 10-year estimated incidence of HF hospitalization was 17.6% (95% CI 9.0-26.2). Among the subgroup without AF at baseline, the 10-year estimated incidence of developing AF was 23.4% (95% CI 13.4-33.4). The 10-year estimated incidence of all-cause mortality was 12.9% (95% CI 5.5-20.3), with 89% of deaths occurring due to non-cardiovascular causes. Patients with exercise-induced reduction in LVEF in the absence of obstructive CAD have a high incidence of HF hospitalizations and AF. The underlying pathophysiology of this disease process needs to be further investigated.

Impact of single chamber and dual chamber permanent pacemaker implantation on left ventricular function: An observational study.

Permanent pacemaker implantation has the potential to impact left ventricular (LV) function and hence quality of life (QoL) in the long term. To assess the effect of single- and dual-chamber pacing on LV function and QoL. This study included 56 patients who underwent permanent pacing: Dual pacing, dual sensing, dual responsive and rate responsive (DDDR) for the initial 3 months and ventricular pacing, ventricular sensing, inhibited response and rate responsive (VVIR) for the next 3 months, and DDDR mode for the last 3 months. Throughout the study period, various echocardiographic parameters, functional status, and QoL were measured to assess the impact of pacing on LV function compared with baseline and at every 3 months interval. A significant change appeared in cardiac function after VVIR pacing which included diastolic properties of LV as shown by increase in isovolumic relaxation time from (85.28 ± 9.54 ms) to (89.53 ± 9.65 ms). At the 3-, 6-, and 9-month follow-up, reduction in LV ejection fraction was observed to be 62.71 ± 4.66%, 61.07 ± 4.41%, and 58.48 ± 3.89%, respectively. An increase in the QoL scores was noted at every follow-up visit. An apparent depressant effect on LV function due to right ventricular pacing, with a higher incidence of adverse outcomes in the VVIR mode. In addition, an upsurge in QoL scores for the study population was noted, which indicates improvement in the QoL of patients post-pacing, irrespective of the mode. Generally, the DDDR mode is a highly preferable pacing mode.

Novel Pyrroloquinoline Quinone-Modified Cerium Oxide Nanoparticles and Their Selective Cytotoxicity Under X-Ray Irradiation

Ionizing radiation leads to the development of oxidative stress and damage to biologically important macromolecules (DNA, mitochondria, etc.), which in turn lead to cell death. In the case of radiotherapy, both cancer cells and normal cells are damaged. In this regard, the development of new selective antioxidants is relevant. In this study, we first investigated the redox activity of cerium oxide-pyrroloquinoline quinone nanoparticles (CeO2@PQQ NPs) and their cytotoxic effects on normal (mouse fibroblasts, L929) and cancer (mouse adenocarcinoma, EMT6/P) cell cultures. Furthermore, the biological activity of CeO2@PQQ NPs was evaluated in comparison with that of CeO2 NPs and PQQ. The nanoparticles demonstrated pH-dependent reductions in the content of hydrogen peroxide after X-ray exposure. Our findings indicate that viability of EMT6/P cells was more adversely affected by CeO2@PQQ NPs at lower concentrations (0.1 μM) compared to L929. Following X-ray irradiation at a dose of 5 Gy, significant changes in mitochondrial potential (by 29%) and decreased glutathione levels (by 32%) were also observed in EMT6/P culture following irradiation and incubation with CeO2@PQQ NPs. Furthermore, EMT6/P exhibited a 2.5-fold increase in micronuclei and a 2-fold reduction in survival fraction compared to L929. It is hypothesized that CeO2@PQQ NPs may exhibit selective cytotoxicity and radiosensitizing properties against EMT6/P cancer cells. The findings suggest that CeO2@PQQ NPs may have potential as a selective redox-active antioxidant/pro-oxidant in response to X-ray radiation.

Abstract 4118387: Artificial Intelligence-Enhanced Echocardiogram Assessment Helps Distinguish Cardiomyopathy from Beat-to-Beat Variation in Atrial Fibrillation

Background: Atrial fibrillation (AF) can be associated with reductions in left ventricular ejection fraction (LVEF) that improve upon conversion of AF to sinus rhythm. Such LVEF changes during AF may be due to LVEF measurement error from beat-to-beat variations related to AF itself. More precise artificial intelligence (AI)-enhanced LVEF assessment could help distinguish between such LVEF “pseudo-reduction” during AF and true cardiomyopathy, thus potentially preventing unnecessary downstream workup and treatment. Methods: Using a transthoracic echocardiogram database at a large academic medical center, we identified all patients whose LVEF fell below 50% while in AF who had subsequent LVEF recovery to over 50% within 90 days after converting from AF to sinus rhythm. For echocardiograms in AF, we compared the clinically assessed LVEF with AI-enhanced LVEF assessment by EchoNet-Dynamic, a validated deep learning algorithm. Results: In our cohort of 84 patients, the mean age was 74 years old, 36.9% were female, and 26.2% non-White. The mean LVEF recovery was 19.3% (95% CI 17.1-21.5%) after converting from AF to sinus rhythm with a mean duration of 27.4 days between the AF and sinus rhythm echocardiograms (Figure 1). For AF echocardiograms, the LVEF when reassessed by deep learning was 8.4% (6.3-10.5%) higher than the original clinical read, resulting in 30.3% of patients being reclassified as no longer having a reduced LVEF less than 50% while in AF. Among these patients with LVEF reductions during AF, 27.4% and 19.0% were given a new or worsened heart failure with reduced ejection fraction (HFrEF) diagnosis, 15.5% underwent ischemic testing, and 17.9% were started on new HFrEF medications. Discussion: LVEF reductions during AF can lead to new HFrEF diagnosis, workup, and treatment. However, such LVEF reductions may be temporary and partially explained by undermeasurement of LVEF during AF. AI-enhanced LVEF assessment may help reduce such measurement errors during AF and thereby prevent overdiagnosis of HFrEF. Further research is needed to understand the clinical significance of true but temporary LVEF reductions during AF.

Mavacamten: Real-World Experience from 22 Months of the Risk Evaluation and Mitigation Strategy (REMS) Program.

Background: Mavacamten is the only cardiac myosin inhibitor approved by the US FDA for treatment of symptomatic New York Heart Association class II-III obstructive hypertrophic cardiomyopathy (HCM) patients. Under the risk evaluation and mitigation strategy (REMS) program for mavacamten, patients are required to be monitored for development of systolic heart failure, and reduction of left ventricular ejection fraction (LVEF) to <50%. We report results from the mavacamten REMS database (28-Apr-2022 to 27-Feb-2024). Methods: Data on healthcare providers and pharmacy certification, patient monitoring (from Patient Status Forms, based partly on echocardiograms), and screening for drug interactions prior to each dispense were collected. Results: Of 6,299 patients who received ≥1 dose of mavacamten, 60.0% were women; 64.6% were >60 years of age. Of 5,573 patients with submitted Patient Status Forms, 256 (4.6%) developed LVEF <50% and 71 (1.3%) experienced heart failure requiring hospitalization (HFH). On the 29,111 status forms in these patients, each representing an assessment of an echocardiogram, LVEF <50% was reported on 276 (0.9%) and HFH was reported on 86 (0.3%). Of 1,929 patients with ≥1 year of treatment, 78 (4.0%) had an LVEF reduction to <50% and 4 (0.2%) experienced LVEF <50% + HFH but later resumed treatment. Of 3,228 patients initiated on 5 mg/day mavacamten and were treated for at least 6 months, 2,391 (74.1%) remained at 5 or 10 mg/day. At 3- and 6-months following mavacamten treatment initiation, 57.2% and 70.3%, respectively, demonstrated post-Valsalva LV outflow tract gradient <30 mmHg. Conclusions: We describe the feasibility and experience of the first 22 months of the REMS program for prescribing mavacamten in >6,000 symptomatic obstructive HCM patients. The need for temporary interruption for LVEF <50% was low, including for patients on therapy ≥1 year, with even fewer LVEF reductions associated with HFH.

THE EFFECT OF EMPAGLIFLOZIN AND RANOLAZINE ON THE DYNAMICS OF STRUCTURAL AND FUNCTIONAL PARAMETERS OF THE HEART AND LEVELS OF BIOMARKERS NT-proBNP AND SOLUBLE (s)ST-2 IN PATIENTS WITH ATRIAL FIBRILLATION AND HEART FAILURE

Atrial fibrillation (AF) is the most common long-term arrhythmia worldwide and has a strong association with heart failure (HF).Aim. To investigate the effect of empagliflozin and ranolazine in addition to standard therapy on the dynamics of structural and functional parameters of the heart and levels of biomarkers NT-proBNP and soluble (s)ST-2 in patients with atrial fibrillation and heart failure.Materials and Methods. We examined 300 patients aged 45-65 years. All patients were divided into groups: Group I - patients with HF without AF (n=150). Group II - patients with HF and AF (permanent form) (n=150). Group of 136 practically healthy individuals. All patients underwent clinical examination, echocardiography (Echo), determination of NT-proBNP and (s)ST-2 levels by enzyme-linked immunosorbent assay.Results. The dynamics of parameters of the LV in the main group was more significant compared to the control group (p&lt;0.05). After treatment, the concentration of circulating NT-ProBNP in the control group decreased by an average of 26.2% (p&lt;0.05), and in the main group of patients - by 15.9% (p&lt;0.05). As for the blood levels of the (s)ST-2 biomarker, after treatment in the control group there was an average decrease of 13.1% (p&lt;0.05) compared with the dynamics in the main group of patients - by 38.8% (p&lt;0.05).Conclusions. The use of INSKTG-2 empagliflozin against the background of standard therapy of heart failure reduction of myocardial remodelling and increase ejection fraction. Complex treatment with empagliflozin and ranolazine as INZCTG-2 helps to reduce the level of NT-ProBNP and (s)ST-2 in the blood serum.

Nutrition Modulation of Cardiotoxicity in Breast Cancer: A Scoping Review.

Advancements in breast cancer therapeutics, such as anthracyclines, are improving cancer survival rates but can have side effects that limit their use. Cardiotoxicity, defined as damage to the heart caused by cancer therapeutics, is characterised by a significant reduction in left ventricular ejection fraction (LVEF) and symptoms of cardiac dysfunction. Multiple oral supplements exist with antioxidant and anti-inflammatory properties that have the potential to lower cardiotoxicity risk and ameliorate the complications associated with left ventricular dysfunction. In this review, we evaluate the current status of using nutritional interventions to modulate cardiotoxicity. We used specific keywords to search for articles that met our predetermined inclusion and exclusion criteria to review the evidence and provide insights for future research. Seven studies were identified as eligible for this review: six focused on oral supplementation strategies in breast cancer patients undergoing chemotherapy, and one focused on nutritional counselling and adherence to the Mediterranean diet in breast cancer survivors' post-treatment. There was a significantly attenuated reduction in LVEF in five studies that monitored cardiometabolic health, and there were significant improvements in blood serum levels of cardiac biomarkers across all studies. Current evidence suggests that appropriate nutritional interventions, alongside chemotherapy, can modulate the risk of cardiotoxic side effects. This highlights the potential of oral antioxidant supplementation and Mediterranean diet counselling to decrease tertiary cancer therapy costs associated with cardiovascular complications.

Evaluating the role of sex-related structure-function differences on airway aerosol transport and deposition.

Several experimental studies have found that females have higher particle deposition in the airways than males. This has implications for the delivery of aerosolized therapeutics and for understanding sex differences in respiratory system response to environmental exposures. This study evaluates several factors that potentially contribute to sex differences in particle deposition, using scale-specific structure-function models of one-dimensional (1-D) ventilation distribution, particle transport, and deposition. The impact of gravity, inhalation flow rate, and dead space are evaluated in 12 structure-based models (7 females; 5 males). Females were found to have significantly higher total, bronchial, and alveolar deposition than males across a particle size range from 0.01 to 10 μm. Results suggest that higher deposition fraction in females is due to higher alveolar deposition for smaller particle sizes and higher bronchial deposition for larger particles. Females had higher alveolar deposition in the lower lobes and slightly lower particle concentration in the left upper lobe. Males were found to be more sensitive to changes due to gravity, showing greater reduction in bronchial deposition fraction. Males were also more sensitive to change in inhalation flow rate and to scaling of dead space due to the larger male baseline airway size. Predictions of sex differences in particle deposition-that are consistent with the literature-suggest that sex-based characteristics of lung and airway size interacting with particle size gives rise to differences in regional deposition.NEW & NOTEWORTHY Sex differences in airway tract particle deposition are analyzed using computational models that account for scale-specific structure and function. We show that sex-related differences in lung and airway size can explain experimental observations of increased deposition fraction in females, with females tending toward enhanced fine particle deposition in the alveolar airways and enhanced bronchial deposition for larger particles.

Iron-Based Superconductors for High-Field Applications: Realization of High Engineering Critical Current Density.

Iron-based superconductors have strong potential for magnet applications through their very high upper critical field, low anisotropy and manufacturability through the powder-in-tube (PIT) route. The engineering critical current density (Je) is a key parameter for measuring the maximum current density that superconducting materials can withstand in practical applications. It serves as a bridge between theoretical research and practical applications of superconductors and has great significance in promoting the development and application of superconducting technology. In this study, Ag sheathed Ba0.6K0.4Fe2As2 (Ba-122) iron-based superconducting tapes were prepared by using the process of drawing, flat rolling and heat treatment by hot pressing (HP). For the first time, the filling factor of the tapes increased to about 40%, leading to a reduction in the volume fraction of Ag, consequently lowering the overall cost. The optimal parameters for achieving high transport Je were obtained by comparing the effects of different HP pressures on the properties and micro-morphology of the tapes. The prepared mono-filament tapes are capable of carrying the transport Je of 4.1 × 104 A/cm2 (Ic = 350 A) at 4.2 K, 10 T, marking the highest Je reported for Ba-122 wires and tapes to date. Our results show that high transport Je can be obtained in Ba-122 superconducting tapes, and iron-based superconductors have a promising future in practical applications.

Development of machine learning models for prediction of left ventricular systolic dysfunction in patients with isolated left ventricular dilation

Abstract Background/Introduction Isolated left ventricular dilation (ILVD), in the absence of concomitant LV systolic dysfunction, is a risk factor for new reduction in LV ejection fraction (LVEF) and adverse clinical outcomes. We assessed the performance of different machine learning (ML) models in predicting new reduction in LVEF in patients with ILVD. Methods A retrospective analysis of de-identified patient records in the Tempus Database with at least two transthoracic echocardiograms (TTE) conducted between January 2019 and December 2022 were retrospectively analyzed, with the follow up period ending in January 2023. Inclusion/exclusion criteria are shown in Figure 1A. Briefly, patients with ILVD were defined based on echocardiographic parameters as those with LVEF &amp;gt; 50% and LV end diastolic volume indexed (LVEDVi) &amp;gt; 62 mL/m2 for females and &amp;gt; 75 mL/m2 for males, without prior LVEF &amp;lt; 50% and/or grade 2/3 diastolic dysfunction. The endpoint was LVEF &amp;lt; 40% on future (≥90 days) TTE. Five hard voting ML models and one soft voting ensemble model were trained with data parsed from TTE reports (Figure 1B). Feature importance (SHAP) was calculated, and receiver operating characteristic (ROC) and Kaplan Meier curves evaluated the final model (Figure 1C-E). Results A total of 2,962 patients met the inclusion criteria. The median time from index to last TTE was 578 (IQR = 500) days. LVEF &amp;lt; 40% on follow up TTE was noted in 6% of patients (177 patients, median 478 days to endpoint, IQR = 535 days). Of the six models developed, the ensemble model had the highest ROC area under the curve (0.791, Figure 1D), precision (0.163), F1-score (0.266), and specificity (0.773). The ensemble model also had the lowest predicted prevalence (25.5%), although this was higher than the observed prevalence in the test set (5.7%). Patients predicted to develop LVEF &amp;lt; 40% had a 8.2x higher risk of developing LVEF &amp;lt; 40% within five years of index (p&amp;lt;0.001, Figure 1E). Feature importance showed that male gender, higher heart rate, lower LVEF at index TTE, higher LVEDVi, and lower tricuspid annular plane systolic excursion had the highest mean absolute impact on the model’s output probability (Figure 1C). Conclusion Using only data parsed from the index TTE, ensembling a model for the prediction of developing LVEF &amp;lt; 40% in patients with ILVD and without a history of LV diastolic or systolic dysfunction performed the best. Additional analyses including clinical variables such as comorbidities, symptoms, and medications may improve the model’s performance.

Acute changes in right ventricular geometry and function following transcatheter tricuspid valve interventions

Abstract Background Little is known about acute changes in right ventricular (RV) function and geometry following transcatheter tricuspid edge-to-edge repair (T-TEER) or transcatheter tricuspid valve replacement (TTVR). Pressure-strain-volume loop-derived myocardial work metrics showed associations with myocardial energetics and contractility in conditions accompanied by volume overload, suggesting their potential utility in patients with tricuspid regurgitation (TR). Purpose To define acute changes in RV volumes and RV myocardial work following T-TEER and TTVR using conventional and pressure-strain-volume derived RV work metrics. Methods In this multicenter, observational study, 3D echocardiographic datasets and invasively acquired RV pressures were collected before and after transcatheter tricuspid valve procedure. Using dedicated software (ReVISION, Argus Cognitive) 3D RV volumes and strains were quantified and decomposed to longitudinal, radial and anterio-posterior motion. Forward stroke volume (SV) was calculated by subtracting TR volumes from RV 3D end-diastolic volume (EDV) and end-systolic volume (ESV) difference. Three-dimensional pressure-strain-volume loops were constructed and global RV work-index (RV-Wi) was calculated. Changes in RV parameters before and after the intervention were compared using paired-samples t test. Results Of 37 patients included in this study (65% male), 20 underwent T-TEER and 17 underwent TTVR. Compared to T-TEER patients, patients undergoing TTVR had higher prevalence of torrential TR at baseline but also achieved a higher reduction in TR volumes after the intervention (44 ± 11 ml vs 60 ± 16ml; p = 0,001). Following T-TEER there was a significant reduction in RV EDV (240 ± 93 ml vs 200 ± 80 ml; p &amp;lt; 0.001) and increase in SV (55 ± 34 ml vs 68 ± 26 ml; p = 0.036). Following TTVR there was a significant increase in RV ESV (121 ± 46 vs 146 ± 48, p = 0.003) and no significant change in SV (47 ± 24 ml vs 55 ± 20 ml; p = 0.143). There was significant reduction in RV strain and ejection fraction (EF) (all p &amp;lt; 0.001) primarily driven by reduction of radial motion component in both groups. RV-Wi increased in 35% (7/20) of T-TEER patients and in 18% of (3/17) TTVR patients. Conclusion An acute reduction in RV EF was observed in all patients and was mainly caused by decrease in RV EDV in T-TEER patients and increase in RV ESV in TTVR patients. Despite decrease of conventional metrics of RV function in both groups, an increase in RV-Wi was observed in 27% of all patients.Baseline and follow-up characteristicsCentral Figure

Cardioprotective role of statins in breast cancer patients treated with anthracyclines and/or trastuzumab: a systematic review and meta-analysis

Abstract Background Statins may have cardioprotective effects in patients undergoing cardiotoxic chemotherapy regimens. Yet, their role in mitigating anthracycline and/or trastuzumab-induced cardiotoxicity in patients with breast cancer remains unclear. Purpose To perform a systematic review and meta-analysis to evaluate the efficacy of statins in mitigating anthracycline and/or trastuzumab-induced cardiotoxicity among patients with breast cancer. Methods We systematically searched PubMed, Embase, and Cochrane databases until January 2024 for studies comparing the efficacy of statin therapy versus no statin therapy in breast cancer patients receiving either anthracyclines, trastuzumab, or both. Cardiotoxicity was defined as per the definition of each individual study. A random-effects model was used to assess pooled risk ratios (RR) and mean differences (MD) with corresponding 95% confidence intervals. Statistical analyses were performed using Review Manager version 5.4.1. Results We included five studies, of which two were randomised trials. The pooled population comprised 1,839 anthracyclines and/or trastuzumab-treated patients with breast cancer, of whom 864 (47%) received statin therapy. In the pooled analyses, cardiotoxicity was significantly lower in the statin therapy group as compared with the no statin therapy group (RR 0.45; 95% CI 0.27 to 0.72; p=0.001; Figure 1A), additionally statin therapy was associated with a significantly lower reduction in left ventricular ejection fraction as compared with no statin therapy (MD 4.11%; 95% CI 2.68 to 5.53; p&amp;lt;0.00001; Figure 1B). Conclusion In this meta-analysis, statin therapy in anthracyclines and/or trastuzumab-treated patients with breast cancer was associated with lower cardiotoxicity and decline in left ventricular ejection fraction.

New onset of left ventricular dysfunction and diastolic dysfunction are uncommon in patients with her2+ breast cancer after completion of cancer therapy

Abstract Background Cardiotoxicity from anthracyclines and trastuzumab is common among patients with breast cancer during therapy. However, there are limited data on new onset of cardiotoxicity (systolic or diastolic dysfunction) after completion of therapy. This knowledge has implications to guide long-term follow-up. Purpose The aim of this study was to evaluate the incidence of cancer therapy related cardiac systolic dysfunction (CTRCD) and diastolic dysfunction (DD) in women with HER2+ breast cancer after completion of cancer therapy and compare to incidence during cancer therapy. Methods We conducted a prospective cohort study of women with HER2+ breast cancer who were treated with sequential anthracycline and trastuzumab therapy, with or without radiation therapy (The EMBRACE-MRI trial, NCT02306538). Comprehensive surveillance echocardiograms were performed at baseline and every 3 months during treatment, early post-trastuzumab, then at years 1, 2, and 3 post trastuzumab completion. CTRCD was defined as a reduction in 3D-left ventricular ejection fraction (LVEF) by ≥ 10% from baseline to &amp;lt; 55%. Diastolic dysfunction was defined as per the American Society of Echocardiography guidelines. Results A total of 136 female patients, with a mean age of 51.1 ± 9.2 years were recruited. Among them, 15.4% had hypertension, 3.7% had diabetes mellitus, and 10.3% had dyslipidemia. The mean cumulative doxorubicin equivalent dose was 203.9 ± 12.5 mg/m2, 120 patients received radiation therapy with the mean heart dose of 170.8 ± 75.9 cGy. During cancer treatment, 27 out of 136 patients (19.9%) developed CTRCD. In long-term follow-up, due to death or interruption due to the COVID-19 pandemic, follow-up was available in 128 patients at 1 year, 117 at 2 years and 111 at 3 years. 5 of the 27 patients still had persistent LV dysfunction (3 at 1 year, 1 at 2 year and 1 at 3 year), however, there were no new diagnosis of CTRCD post completion of therapy. Of 129 patients with baseline normal or indeterminate diastolic function, new DD was identified in 25/129 patients (19.4%) during cancer treatment (17 grade I, 2 grade II, 6 unable to grade). After completion of cancer therapy, 5 patients had persistent DD. In patients with no DD during therapy and completed 3 year follow-up, 5 patients developed new DD after therapy (2 grade I, 3 unable to grade). Figure 1 illustrates the percentage of patients with new CTRCD or new diastolic dysfunction at each timepoint. None of the patients developed clinical heart failure. Conclusion Although both CTRCD and diastolic dysfunction are common during sequential therapy with anthracyclines and trastuzumab in women with HER2+ breast cancer, new onset after treatment completion is rare during a careful follow-up. These findings have implications for long-term surveillance.

The CNP analogue vosoritide reduces arrhythmia in diabetic cardiomyopathy via cGMP-dependent PDE2 stimulation on cellular and organ level

Abstract Background Detrimental arrhythmia occurs frequently in patients with diabetic cardiomyopathy (DiabCM), but safe and effective therapies are limited. Diabetes-associated neuropathological alterations increase the sympathetic tone, leading to hyperactivation of β-adrenoceptor-mediated cAMP signalling in cardiomyocytes (CM). Increased activity of deleterious cAMP-dependent kinases causes pro-arrhythmic dysregulation of intracellular Ca2+ homeostasis. Phosphodiesterases (PDE) can reduce cAMP levels. Exceptionally, the cAMP-hydrolysing activity of PDE2 can be cGMP-dependently increased by C-type natriuretic peptide (CNP). Thus, the CNP analogue vosoritide (approved for the treatment of achondroplasia) might mediate this cGMP/cAMP crosstalk, reducing arrhythmia. Purpose Here, we aim to study whether the cGMP-dependent activation of PDE2 by vosoritide (VO) is sufficient to reduce arrhythmia and arrhythmogenic triggers in DiabCM. Methods Diabetes was induced by 5 consecutive injections of streptozotocin (50 mg/kg) in control (WT) mice and mice with a CM-specific PDE2 knockout (KO). All experiments were performed 5 weeks later. Cardiac function was characterised by echocardiography. Primary ventricular CM were isolated to assess protein expression and phosphorylation levels by Western blot (WB) and cAMP levels by ELISA. Patch-clamp and Ca2+ imaging experiments were used to investigate pro-arrhythmic triggers. Arrhythmic events were quantified in ex vivo perfused hearts after ischaemia-reperfusion (I/R) injury. Results Compared to healthy controls, diabetic animals showed impaired systolic function with a ~9 % reduction in ejection fraction. The significant increase in E/E’ ratio by ~34 % indicated a diastolic dysfunction. Interestingly, the cardiac function was further worsened in diabetic PDE2 KO. WB analysis revealed upregulation of the CNP receptor NPR-B and PDE2 in diabetic CM and altered regulation of proteins involved in cAMP-dependent Ca2+ cycling such as protein kinase A, Ca2+/calmodulin-dependent kinase II and phospholamban. Interestingly, VO significantly reduced isoprenaline (Iso)-induced cAMP levels in diabetic CM. The effect of VO was prevented by specific PDE2 inhibition with BAY 60-7550 (BAY). Furthermore, VO was able to reduce the Iso-induced increase in L-type Ca2+ current, whereas BAY or genetic PDE2 deletion counteracted this effect. Accordingly, VO significantly decreased the Iso-triggered Ca2+ spark frequency by ~40 %. Concomitant PDE2 inhibition or PDE2 KO prevented this anti-arrhythmic effect. Finally, ECG analysis revealed that VO clearly reduced arrhythmia development after I/R in ex vivo perfused diabetic hearts via PDE2 activation. Conclusion Our data indicate that vosoritide-induced PDE2 stimulation may attenuate abnormal cardiac Ca2+ cycling and thereby reduce arrhythmia in diabetic hearts. Thus, vosoritide may be repurposed as a novel anti-arrhythmic drug in DiabCM.