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ESC Heart Failure Jun 2024Acute myocarditis, although a rare disease, can be associated with sudden cardiac death or the need for transplantation in both children and young adults. To date, there...
AIMS
Acute myocarditis, although a rare disease, can be associated with sudden cardiac death or the need for transplantation in both children and young adults. To date, there is no definitive evidence to support the routine use of immunosuppressive therapy or treatment targeting inflammation in patients with myocarditis. Animal models of cardiovascular (CV), as well as neurological diseases, have demonstrated that cannabidiol has significant anti-inflammatory properties and may represent a promising therapy in acute myocarditis. This efficacy has been shown in a murine model of autoimmune myocarditis as well as in in vitro and in vivo models of heart failure (HF).
METHODS AND RESULTS
We present the rationale and design of the ARCHER Trial, an international multicentre, double-blind, randomized, placebo-controlled, phase II study examining the safety and efficacy of a pharmaceutically produced cannabidiol formulation, in patients with mild to moderate acute myocarditis. Eligible patients are those with acute myocarditis, randomized within 10 days of the diagnostic cardiac MRI (CMR), which has met defined diagnostic criteria for myocarditis. Oral treatment (cannabidiol or placebo) is titrated from 2.5 mg/kg of body weight up to 10 mg/kg of body weight b.i.d. (or highest tolerated dose) and taken for 12 weeks in addition to standard of care therapy for HF. The primary endpoints are defined as changes in global longitudinal strain (GLS) and extra cellular volume (ECV), measured by CMR at 12 weeks. Assuming 80% power, a 5% alpha risk and 25% missing CMR follow-up data at Week 12, 100 patients are required to demonstrate the desired treatment effect of 18%. The change in left ventricular ejection fraction (LVEF) from baseline to Week 12 was selected as the secondary endpoint. Additional exploratory endpoints include changes in hs-troponin, NT-proBNP, markers of inflammation and endothelial function during the 12-week treatment period. The trial is ongoing but is now more than 50% recruited. As enrolment in the trial continues, no interim data are available for inclusion in this Design paper.
CONCLUSIONS
The ongoing ARCHER Trial is an international, multicentre, double-blind, randomized, placebo-controlled phase II study, designed to determine the effect of a pharmaceutically produced cannabidiol formulation on CMR parameters in patients presenting with acute myocarditis. Enrolment of 100 patients is expected to conclude in Q3 2024. Study results will be available in early 2025.
PubMed: 38937900
DOI: 10.1002/ehf2.14889 -
BMC Cardiovascular Disorders Jun 2024The cardiac toxicity of radiotherapy (RT) can affect cancer survival rates over the long term. This has been confirmed in patients with breast cancer and lymphoma....
Application of two-dimensional speckle-tracking echocardiography in radiotherapy-related cardiac systolic dysfunction and analysis of its risk factors: a prospective cohort study.
BACKGROUND
The cardiac toxicity of radiotherapy (RT) can affect cancer survival rates over the long term. This has been confirmed in patients with breast cancer and lymphoma. However, there are few studies utilizing the two-dimensional speckle-tracking echocardiography (2D-STE) to evaluate the risk factors affecting radiation induced heart disease (RIHD), and there is a lack of quantitative data. Therefore, we intend to explore the risk factors for RIHD and quantify them using 2D-STE technology.
METHODS
We ultimately enrolled 40 patients who received RT for thoracic tumors. For each patient, 2D-STE was completed before, during, and after RT and in the follow up. We analyzed the sensitivity of 2D-STE in predicting RIHD and the relationship between RT parameters and cardiac systolic function decline.
RESULTS
Left ventricle global longitudinal strain (LVGLS), LVGLS of the endocardium (LVGLS-Endo), LVGLS of the epicardium (LVGLS-Epi), and right ventricle free-wall longitudinal strain (RVFWLS) decreased mid- and post-treatment compared with pre-treatment, whereas traditional parameters such as left ventricular ejection fraction (LVEF), cardiac Tei index (Tei), and peak systolic velocity of the free wall of the tricuspid annulus (s') did not show any changes. The decreases in the LVGLS and LVGLS-Endo values between post- and pre-treatment and the ratios of the decreases to the baseline values were linearly correlated with mean heart dose (MHD) (all P values < 0.05). The decreases in the LVGLS-Epi values between post- and pre-treatment and the ratios of the decreases to the baseline values were linearly correlated with the percentage of heart volume exposed to 5 Gy or more (V5) (P values < 0.05). The decrease in RVFWLS and the ratio of the decrease to the baseline value were linearly related to MHD and patient age (all P values < 0.05). Endpoint events occurred more frequently in the right side of the heart than in the left side. Patients over 56.5 years of age had a greater probability of developing right-heart endpoint events. The same was true for patients with MHD over 20.2 Gy in both the left and right sides of the heart.
CONCLUSIONS
2D-STE could detect damages to the heart earlier and more sensitively than conventional echocardiography. MHD is an important prognostic parameter for LV systolic function, and V5 may also be an important prognostic parameter. MHD and age are important prognostic parameters for right ventricle systolic function.
Topics: Humans; Female; Male; Middle Aged; Prospective Studies; Predictive Value of Tests; Aged; Ventricular Function, Left; Radiation Injuries; Risk Assessment; Systole; Cardiotoxicity; Risk Factors; Adult; Time Factors; Thoracic Neoplasms; Radiotherapy; Ventricular Function, Right; Echocardiography; Heart Disease Risk Factors; Stroke Volume
PubMed: 38937716
DOI: 10.1186/s12872-024-03981-1 -
Scientific Reports Jun 2024Circulating proteins may provide insights into the varying biological mechanisms involved in heart failure (HF) with preserved ejection fraction (HFpEF) and reduced...
Circulating proteins may provide insights into the varying biological mechanisms involved in heart failure (HF) with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF). We aimed to identify specific proteomic patterns for HF, by comparing proteomic profiles across the ejection fraction spectrum. We investigated 4210 circulating proteins in 739 patients with normal (Stage A/Healthy) or elevated (Stage B) filling pressures, HFpEF, or ischemic HFrEF (iHFrEF). We found 2122 differentially expressed proteins between iHFrEF-Stage A/Healthy, 1462 between iHFrEF-HFpEF and 52 between HFpEF-Stage A/Healthy. Of these 52 proteins, 50 were also found in iHFrEF vs. Stage A/Healthy, leaving SLITRK6 and NELL2 expressed in lower levels only in HFpEF. Moreover, 108 proteins, linked to regulation of cell fate commitment, differed only between iHFrEF-HFpEF. Proteomics across the HF spectrum reveals overlap in differentially expressed proteins compared to stage A/Healthy. Multiple proteins are unique for distinguishing iHFrEF from HFpEF, supporting the capacity of proteomics to discern between these conditions.
Topics: Humans; Heart Failure; Stroke Volume; Female; Proteomics; Male; Aged; Middle Aged; Proteome; Biomarkers; Blood Proteins
PubMed: 38937570
DOI: 10.1038/s41598-024-65667-0 -
Scientific Reports Jun 2024Experiments on ultrasound propagation through a gel doped with resonant encapsulated microbubbles provided evidence for a discontinuous transition between wave...
Experiments on ultrasound propagation through a gel doped with resonant encapsulated microbubbles provided evidence for a discontinuous transition between wave propagation regimes at a critical excitation frequency. Such behavior is unlike that observed for soft materials doped with non-resonant air or through liquid foams, and disagrees with a simple mixture model for the effective sound speed. Here, we study the discontinuous transition by measuring the transition as a function of encapsulated microbubble volume fraction. The results show the transition always occurs in the strong-scattering limit (l/λ < 1, l and λ are the mean free path and wavelength, respectively), that at the critical frequency the effective phase velocity changes discontinuously to a constant value with increasing microbubble volume fraction, and the measured critical frequency shows a power law dependence on microbubble volume fraction. The results cannot be explained by multiple scattering theory, viscous effects, mode decoupling, or a critical density of states. It is hypothesized the transition depends upon the microbubble on-resonance effective properties, and we discuss the results within the context of percolation theory. The results shed light on the discontinuous transition's physics, and suggest soft materials can be engineered in this manner to achieve a broad range of physical properties with potential application in ultrasonic actuators and switches.
PubMed: 38937552
DOI: 10.1038/s41598-024-63910-2 -
Journal of the American Heart... Jul 2024This study assesses the diagnostic utility of strain parameters from cardiovascular magnetic resonance feature tracking across all cardiac chambers in patients with...
Unveiling the Diagnostic Value of Strain Parameters Across All 4 Cardiac Chambers in Patients With Acute Myocarditis With Varied Ejection Fraction: A Cardiovascular Magnetic Resonance Feature-Tracking Approach.
BACKGROUND
This study assesses the diagnostic utility of strain parameters from cardiovascular magnetic resonance feature tracking across all cardiac chambers in patients with acute myocarditis, stratified by ejection fraction.
METHODS AND RESULTS
Our cohort included 65 patients with acute myocarditis and 25 healthy controls; all underwent cardiac magnetic resonance imaging. Patients were divided into 2 groups based on left ventricular ejection fraction (EF)with a 55% cutoff: acute myocarditis with preserved EF, EF ≥55%, n=48; and acute myocarditis with reduced EF, EF <55%, n=17. The control group matched for age and sex. Cardiovascular magnetic resonance feature tracking evaluated strain parameters across all cardiac chambers. Both acute myocarditis with preserved EF and acute myocarditis with reduced EF groups showed significant decreases in left atrial peak early negative strain rate compared with controls. The acute myocarditis with reduced EF group had significantly reduced left ventricular circumferential strain relative to acute myocarditis with preserved EF and controls. Receiver operating characteristic curve analysis confirmed the diagnostic accuracy in distinguishing patients with acute myocarditis with preserved EF from controls, with left atrial peak early negative strain rate achieving 92.9% specificity, left ventricular circumferential strain demonstrating an area under the curve of 0.832, and similarly effective results for left ventricular longitudinal strain and right ventricular longitudinal strain. Additionally, left atrial peak early negative strain rate and left ventricular circumferential strain showed significant correlations with troponin I levels, indicating myocardial injury.
CONCLUSIONS
Cardiovascular magnetic resonance feature-tracking-derived strain parameters, particularly left atrial peak early negative strain rate and left ventricular circumferential strain, effectively diagnose acute myocarditis across different EFs, enhancing diagnostic accuracy and facilitating early detection, notably in patients with preserved EF.
Topics: Humans; Myocarditis; Male; Female; Stroke Volume; Adult; Acute Disease; Ventricular Function, Left; Magnetic Resonance Imaging, Cine; Middle Aged; Predictive Value of Tests; Case-Control Studies; Retrospective Studies
PubMed: 38934873
DOI: 10.1161/JAHA.123.032781 -
Journal of Radiation Research Jun 2024The aim of this study was to investigate planning target volume (PTV) margin in online adaptive radiation therapy (oART) for gastric mucosa-associated lymphoid tissue...
The aim of this study was to investigate planning target volume (PTV) margin in online adaptive radiation therapy (oART) for gastric mucosa-associated lymphoid tissue (MALT) lymphomas. Four consecutive patients with gastric MALT lymphoma who received oART (30 Gy in 15 fractions) on the oART system were included in this study. One hundred and twenty cone-beam computed tomography (CBCT) scans acquired pre- and post-treatment of 60 fractions for all patients were used to evaluate intra- and interfractional motions. Patients were instructed on breath-holding at exhalation during image acquisition. To assess the intrafraction gastric motion, different PTVs were created by isotropically extending the CTV contoured on a pre-CBCT image (CTVpre) at1 mm intervals. Intrafraction motion was defined as the amount of expansion covering the contoured CTV on post-CBCT images (CTVpost). Interfractional motion was defined as the amount of reference CTV expansion that could cover each CTVpre, as well as the evaluation of the intrafractional motion. PTV margins were estimated from the cumulative proportion of fraction covering the intra- and interfractional motions. The extent of expansion covering the CTVs in 90% of fractions was adopted as the PTV margin. The PTV margin for intrafractional gastric motion using the oART system with breath-holding was 14 mm. In contrast, the PTV margin for interfractional gastric organ motion without the oART system was 25 mm. These results indicated that the oART system can reduce the PTV margin by >10 mm. Our results could be valuable data for oART cases.
PubMed: 38934659
DOI: 10.1093/jrr/rrae052 -
Heliyon Jun 2024Modeling of proton exchange membrane (PEM) fuel cells is attracting more attention as fuel cell technology continues to develop. In this study, we considered a hybrid...
Using a three-dimensional computational fluid dynamics model and an agglomerate model to investigate the effect of varying agglomerate parameters and output voltages on proton exchange membrane fuel cell performance.
Modeling of proton exchange membrane (PEM) fuel cells is attracting more attention as fuel cell technology continues to develop. In this study, we considered a hybrid model that combines an agglomerate model based on the agglomeration of catalyst particles and the coverage-dependent kinetic equation of platinum oxide for ORR, and another 3D numerical model of a PEM fuel cell based on computational fluid dynamics (CFD). The obtained results from our developed models were validated with experimental results from literature. In fact, we investigated the effects of changing the agglomerate radius , the ionomer volume fraction within the agglomerate the effective agglomerate surface area , the distribution of the gases and the temperature on the cell performances. The results revealed that the cell performances are strongly influenced by changing and for medium and high current densities: The activation loss increases with increasing and decreasing . Also, increases with decreasing and increasing . In addition, the PEM fuel cell's power output is significantly enhanced when is decreased and is increased, the optimal power being obtained for values of and = 0.6. The numerical results also showed that decreasing the output voltage from 0.95V to 0.35V can accelerate the electrochemical reaction process.
PubMed: 38933966
DOI: 10.1016/j.heliyon.2024.e32277 -
Journal of Molecular and Cellular... Jun 2024Heart failure remains one of the largest clinical burdens globally, with little to no improvement in the development of disease-eradicating therapeutics. Integrin...
Heart failure remains one of the largest clinical burdens globally, with little to no improvement in the development of disease-eradicating therapeutics. Integrin targeting has been used in the treatment of ocular disease and cancer, but little is known about its utility in the treatment of heart failure. Here we sought to determine whether the second generation orally available, αvβ3-specific RGD-mimetic, , was cardioprotective. Male mice were subjected to transverse aortic constriction (TAC) and treated with 50 μg/kg or volume-matched saline as Vehicle control. At 3 weeks post-TAC, echocardiography showed that treatment significantly restored cardiac function and structure indicating the protective effect of treatment in this model of heart failure. Importantly, treatment improved cardiac function giving improved fractional shortening, ejection fraction, heart weight and lung weight to tibia length fractions, together with partial restoration of Ace and Mme levels, as markers of the TAC insult. At a tissue level, reduced cardiomyocyte hypertrophy and interstitial fibrosis, both of which are major clinical features of heart failure. RNA sequencing identified that, mechanistically, this occurred with concomitant alterations to genes involved molecular pathways associated with these processes such as metabolism, hypertrophy and basement membrane formation. Overall, targeting αvβ3 with provides a novel strategy to attenuate pressure-overload induced cardiac hypertrophy and fibrosis, providing a possible new approach to heart failure treatment.
PubMed: 38933087
DOI: 10.1016/j.jmccpl.2024.100069 -
Annals of Pediatric Cardiology 2024Echocardiographic quantification of left ventricular (LV) volume and ejection fraction (EF) is widely used in the pediatric population. However, there is no consensus on...
BACKGROUND
Echocardiographic quantification of left ventricular (LV) volume and ejection fraction (EF) is widely used in the pediatric population. However, there is no consensus on the most accurate method of quantifying ventricular volumes and systolic function.
PURPOSE
The purpose of this study is to compare two commonly used echocardiographic methods for the evaluation of LV volume and quantification of EF, the five-sixth area-length (5/6 AL) and the modified biplane Simpson (BS), to cardiac magnetic resonance (CMR) imaging in children.
METHODS
CMR studies were paired with echocardiograms and retrospectively analyzed in children 18 years of age and younger. Studies performed more than 3 months between modalities, patients with congenital heart disease, and patients who had changes in medication regimen between corresponding CMR and echocardiograms were excluded. LV volumes and EF were calculated using the 5/6 AL and BS methods and compared to volumes and EF measured on corresponding CMR studies. Subgroup analyses were conducted based on LV function, pathology, and weight.
RESULTS
We retrospectively analyzed 53 CMR and corresponding echocardiogram studies (23 studies for myocarditis and 30 studies for cardiomyopathy) in 46 patients. LVEF derived by both echocardiographic methods showed a good correlation to CMR (5/6 AL = 0.85 and BS = 0.82). However, both echocardiographic methods overestimated LVEF and underestimated LV volumes when compared to CMR.
CONCLUSION
Left ventricular volumes and EF, as measured by echocardiography, correlate well with CMR measurements. Echocardiography underestimates LV systolic and diastolic volumes and overestimates LVEF. While echocardiography is a good surrogate for estimating LVEF, CMR should be considered in patients for whom accurate measurements are needed for critical clinical decision-making.
PubMed: 38933052
DOI: 10.4103/apc.apc_199_23 -
Polymers Jun 2024Pultrusion is a highly efficient continuous process to manufacture advanced fiber-reinforced composites. The injection pultrusion variant permits a higher control of the...
Pultrusion is a highly efficient continuous process to manufacture advanced fiber-reinforced composites. The injection pultrusion variant permits a higher control of the resin flow, enabling the manufacturing of a high reinforcement volume fraction. Moreover, it reduces the emission of volatile compounds that are dangerous for the operators and for the working environment. The present study proposes an experimental analysis of injection pultrusion in three different operative conditions. In particular, the activity focused on the effects of the temperature setup on the thermochemical and rheological behaviors of the resin system and on the interaction between the processed materials and the pultrusion die wall. The setup of the parameters was selected to evidence the behavior of the viscous interaction during the thermoset transition to the solid state, which is particularly challenging due to the localization of high adhesive forces related to the sharp increase in resin viscosity. Microscope observations of the cross-sections were performed to discuss the effects of the process parameters.
PubMed: 38931992
DOI: 10.3390/polym16121642