Assessment Of Cardiac Function Research Articles

Abstract 4139191: ETX-258 - A GalOmic™ siRNA for the Treatment of Heart Failure Following Myocardial Infarction

Introduction: Heart failure with reduced ejection fraction (HFrEF) remains a significant clinical challenge, evidenced by high hospitalization rates and five-year mortality. Current treatments are limited by side effects, poor patient compliance, and the necessity for gradual drug titration. These challenges highlight the need for new therapies that are both safe and effective in targeting the structural remodeling pivotal to disease progression post-myocardial infarction (MI). e-therapeutics (ETX) uniquely combines computation and RNAi to discover life-transforming medicines. ETX’s RNAi platform, GalOmic™, enables generation of specific, potent, and long-acting siRNA therapies that effectively silence novel gene targets in hepatocytes. This highly specific mechanism of action limits unwanted side effects, positioning it as a promising approach to HFrEF treatment. Methods: Potent siRNAs against a hepatic target with cardioprotective potential were designed in silico. Candidate siRNAs were screened in vitro in HEK293 cells and in vivo in C57BL/6J mice to select the lead GalOmic™ siRNA, ETX-258. MI was induced by ligation of the left anterior descending artery in C57BL/6J mice after which ETX-258 was injected subcutaneously weekly for 6 weeks. Eplerenone, a mineralocorticoid receptor antagonist which is part of the current treatment regimen for HFrEF, was used as a comparator. Cardiac function was assessed by echocardiography at 2-, 4- and 6-weeks post-MI. Cardiac damage and structural remodeling were evaluated using circulating biomarkers of cardiac function and histological assessment. Results: ETX-258 was selected as a highly active siRNA for the treatment of heart failure with a long duration of action. Post-MI treatment with ETX-258 significantly improved key echocardiographic parameters of cardiac function, including ejection fraction and total cardiac output, achieving results comparable to eplerenone. Additionally, both structural cardiac parameters and markers of damage and remodeling showed significant improvements, reaching similar levels in both ETX-258 and eplerenone-treated mice. Conclusions: High unmet need remains for HFrEF patients despite existing therapies. These results highlight the potential of ETX-258 to improve cardiac function and pathogenic structural remodeling post-MI. This, paired with the long duration of action and favorable safety profile of GalOmic™ siRNAs, makes ETX-258 a promising candidate for further clinical development.

Assessment of Cardiac Autonomic Function by Short-Term Sensor-Based and Long-Term Heart Rate Variability Analyses in Individuals with Spinal Cord Injury After Long-Term Table Tennis Training

This study aimed to examine the acute and chronic effects of an exercising table tennis program on cardiac Autonomic Nervous System (ANS) and functional capacity in people with tetraplegia. Twenty males with tetraplegia (C6–C7), with a mean age of 38.50 ± 4.04 years old, were randomly assigned into two equal groups: A, who followed a 6-month exercise training program with table tennis 3 times per week, and B, who remained untrained. Additionally, 11 healthy sedentary men (group C) with a mean age of 39.71 ± 5.87 years old participated in the study as healthy controls. At baseline, all participants underwent a short-term (5 min) and a long-term (24 h ambulatory) ECG monitoring to evaluate the heart rate variability (HRV) indices and a maximal arm ergometric and dynamometric testing of the upper limbs. Moreover, the acute cardiac autonomic responses to maximal arm cycle exercise test were evaluated by Polar S810i sensor chest strap. At the end of the 6-month study, all parameters were revaluated only in groups A and B. At baseline, there was no statistically significant difference between the two patient groups. However, intra-group changes at the end of the 6-month study regarding the 24-h HRV monitoring indicated that group A statistically increased the standard deviation of R-R intervals (SDNN) by 13.9% (p = 0.007), the standard deviation of R-R intervals calculated every 5 min (SDANN) by 8.4% (p = 0.007), the very low frequency (VLF) by 7.1% (p = 0.042), and the low frequency [LF (ms2)] by 10.5% (p = 0.009), which almost reached the levels of group C. Favorable improvements were also noticed at the end of the study for group A in maximal exercise time of the upper limbs by 80.4% (p < 0.001) and maximal strength of the right hand by 27.8% (p < 0.001). Linear regression analysis after training showed that maximal exercise time was positively correlated with SDNN (r = 0.663, p = 0.036) and with LF (ms2) (r = 0.623, p = 0.045). Our results indicate that a 6-month table tennis training program is efficient and can improve cardiac ANS activity mainly by increasing sympathovagal balance.

Clinical utility of echocardiography in internal medicine: a narrative review

Echocardiography has emerged as an invaluable tool in internal medicine, providing real-time, non-invasive evaluation of cardiac structure and function. Its clinical utility spans a wide range of applications, including the diagnosis and management of heart failure, valvular heart diseases, and cardiomyopathies, as well as systemic conditions like sepsis and chronic kidney disease. The ability to perform bedside echocardiography has made it particularly useful in critical care settings, allowing for rapid assessment of cardiac function in hemodynamically unstable patients. Echocardiography also plays a key role in guiding therapeutic interventions, from fluid management to valvular repair and replacement procedures. Despite its many advantages, echocardiography is not without limitations. Image quality may be compromised in patients with obesity, lung disease, or prior thoracic surgery, necessitating alternative imaging modalities like cardiac magnetic resonance imaging or computed tomography. Operator expertise is another critical factor influencing diagnostic accuracy, underscoring the importance of proper training. Recent advancements, including artificial intelligence integration and portable devices, are expected to further expand the role of echocardiography, making it more accessible in diverse clinical settings. This narrative review highlights the broad clinical utility of echocardiography in internal medicine, its challenges, and the future directions that promise to enhance its role in patient care.

Acute echocardiographic assessment of patients with ST-elevation myocardial infarction in detecting clinically hidden hemodynamic deterioration

Abstract Background Transthoracic echocardiography (TTE) offers an immediate non-invasive assessment of cardiac morphology and function that can be performed bedside. Acute TTE in the catheterization laboratory (cath.lab.) may be helpful to identify markers of subsequent development of cardiogenic shock (CS) in patients with ST-elevation myocardial infarction (STEMI) in addition to the previously validated ORBI risk score. This relationship has not been investigated thoroughly previously. Purpose To investigate the association between acute TTE estimates of left ventricular (LV) function prior to primary percutaneous coronary intervention (pPCI) in STEMI patients and pro-B-type natriuretic peptide (proBNP) as a proxy associated with of CS development. Method From September 2023 all non-CS STEMI patients at one tertiary heart center underwent acute bedside TTE in the cath.lab. and ORBI risk score assessing the risk of CS development aiming for inclusion of 500 patients. The 5 minutes TTE-protocol consisted of LV ejection fraction (EF), LV outflow tract velocity time integral (LVOT VTI), mitral inflow (E and E/A), mitral deceleration time, and mitral annular early diastolic velocity é lateral. The primary endpoint was proBNP measured 24 hours (h) after pPCI (12-36h) stratified in quartiles (Q4 vs. Q1-3). The correlation between proBNP and TTE measurements and proBNP and ORBI risk score was examined using univariate linear regression models. Results Until now 153 STEMI patients (mean age 64 years, 25% female) were studied. Anterior STEMI was present in 36%, and median time from cath. lab. arrival to first wire over the culprit lesion was 28 minutes (IQR 24; 37). Patients with high proBNP level (Q4 vs. Q1-3) had significantly higher heart rate (median 84 bpm vs. 72 bpm) and Killip Class>1 (16% vs. 0%) at admission, but similar lactate levels (1.8mM vs. 1.5mM), systolic blood pressure (130 mmHg vs. 137 mmHg), and out-of-hospital cardiac arrest (11% vs. 12%). Patients with high proBNP levels (Q4 vs. Q1-3) had significantly lower LVEF (35% vs. 50%), higher E/é lateral (median 11.4 vs. 7.9), and higher ORBI risk score (median 8 vs. 4). LVEF, LVOT VTI, E/é lateral, and ORBI risk score were significantly associated with proBNP (Figure 1). Two patients developed CS after the pPCI; one with high proBNP level Q4, and one deceased prior to proBNP measurement. Conclusion Acute TTE is an easy tool for assessment of the acute hemodynamic status in STEMI patients bedside in the cath.lab., and it can be without delaying time to revascularization. LVEF, LVOT VTI, E/é lateral, and ORBI were all parameters associated with increased levels of the hemodynamic biomarker proBNP, and may together with the ORBI risk score improve the assessment and risk stratification of STEMI-patients at risk of CS-development.Figure 1.

Echo triaging works. How to use international guidelines

Abstract Introduction Transthoracic echocardiography (TTE) is the first-choice non-invasive imaging modality for the assessment of cardiac structure and function due to its wide availability, speed, cost-effectiveness and reproducibility. Therefore, there is exponential increase in demand in TTE across all specialties in medicine and surgery. Hence, it is important to carefully triage patients according to current international guidelines. Purpose To reduce inappropriate TTE scans by using guideline driven indications in triaging echo scans in the UK tertiary hospital. Methods Strict list of guidelines driven indications adapted to local practice was used for triaging echo requests which included both inpatient and outpatient TTEs. The 4 objectives: appropriateness, completeness of requests as well as impact of performed studies on the follow-up and patient management plan were assessed before and after implementation of new triaging tool. To ensure similar working and staff environment was sustained we studied the pattern of referrals in the same month of the year- September. The triage process was conducted by accredited physiologists. The same month was chosen to reflect true change of practice. Change in patient management and follow up were evaluated for a minimum duration of 6-months. Results Overall there were 1112 TTEs performed in September 2022 and 1081 - in September 2023. Prospective TTE referral triaging began in March 2023. We have studied and analyzed above criteria retrospectively. In 2022 there were 18% inappropriate requests; 37% of requests lacked sufficient clinical information and 10% of studies did not lead to change in management plan according to clinical letters. There was also high proportion of inappropriate requests for inpatients (9%). Within 6 months of implementation there was a significant improvement in the appropriateness (82% vs. 99%, p<0.001), with increase in supply of adequate clinical information (63.4% vs. 86.1%, p<0.001). However, there was no significant change using TTE study results in changing patient management (10%). All inpatients had 100% appropriate requests. Conclusion The implementation of triage criteria resulted in a significant improvement in TTE referrals: both in appropriateness and completeness of requests. However, some clinicians did not use echo in patient management plan. Future research on lack of use of TTE results in clinical practice might help to utilize the limited echo capacity to full.

Ferroptosis contributes to the development of cardiac dysfunction in iron overload cardiomyopathy

Abstract Background Ferroptosis is a novel form of cell death, and its role in iron overload cardiomyopathy (IOC) has not been elucidated. Purpose To explore whether ferroptosis of cardiomyocytes contributes to cardiac dysfunction in IOC by cardiac MR (CMR) and molecular biology techniques in vivo. Methods A total of 14 Sprague-Dawley (SD) rats were randomly divided into two groups: the control group (n=6) and the IOC group (n=8). The latter was induced by intraperitoneal injection of iron dextran on alternate days for 9 weeks and underwent a 7T CMR for assessment of cardiac function, including left ventricular ejection fraction (LVEF) and global longitude strain (GLS), along with the assessment of iron overload severity and fibrosis using Cine, T2 mapping, and late gadolinium enhancement (LGE), respectively. Circulating iron overload was determined via blood biochemistry analysis, measuring serum iron, ferritin, and transferrin levels. Furthermore, Prussian blue and Masson staining were employed to identify iron and fibrosis deposition within the myocardium, respectively. Cardiac ultrastructure, especially mitochondria, was examined via transmission electron microscopy (TEM). A sensitive fluorescent probe, dihydroethidium (DHE), was employed for the detection of reactive oxygen species (ROS) levels. Malondialdehyde (MDA), prostaglandin-endoperoxide synthase 2 (PTGS2), and glutathione peroxidase 4 (GPX4) were utilized to identify and quantify levels of lipid peroxidation, thereby providing comprehensive insights into cardiac cellular ferroptosis. Results 6 rats survived in the control group and 5 in the IOC group. Compared with the control group, the IOC rats had reduced T2 values of the cardiac septum (P<0.001), with normal LVEF (P>0.05) but decreased GLS (P<0.01), seen in Fig 1A. Based on blood biochemistry and Prussian blue staining, they were evident that IOC rats exhibited both circulating and cardiac iron overload, as seen in Figure 1B, C. Masson staining showed no obvious myocardial fibrosis, which was consistent with negative CMR LGE results, seen in Fig 1A, B. TEM further elucidated cardiac mitochondrial injuries in IOC rats, including focal vacuolization, swelling, crest disruption, and even disappearance, seen in Fig 2A. The fluorescent probe results revealed a striking increase in red fluorescence within the myocardium of IOC rats, seen in Fig 2B. Additionally, IOC rats exhibited significantly elevated levels of MDA and PTGS2mRNA (P<0.001), accompanied by notable downregulation of GPX4mRNA expression (P<0.001), seen in Fig 2C. These findings suggested the occurrence of ferroptosis in the myocardium of IOC rats. Conclusions In IOC, ferroptosis rather than necrosis is the primary driver of cardiac dysfunction, which is characterized by maintaining normal LVEF but experiencing a reduction in GLS without accompanying myocardial fibrosis. Our study sheds light on the potential involvement of ferroptosis in the pathogenesis of IOC.

Scan-rescan variability of AI-enabled cardiac functional assessment from cine CMR

Abstract Background/Introduction Cine cardiovascular magnetic resonance (CMR) is the gold-standard technique for the assessment of cardiac function and structure. Manual analysis of cine CMR to estimate structural and functional biomarkers is costly and time-consuming, motivating the use of artificial intelligence (AI) for automation. However, the scan-rescan repeatability of AI derived biomarkers remains unknown. Purpose Measure the repeatability of AI-based cine CMR biomarkers in scan-rescan data. Methods 92 scan-rescan short-axis cine CMR were acquired from volunteers on the same day (i.e. 184 in total) and annotated with ground truth (GT) manual segmentations of the left and right ventricle (LV, RV) blood pools, and LV myocardium at end-diastole (ED) and end-systole (ES). AI segmentations and subsequent biomarker estimates were produced using the AI-CMR-QC tool described in [1]. Segmentation performance was assessed with Dice score, pixelwise sensitivity and specificity, and Hausdorff distance. Scan-rescan differences in cardiac biomarkers for each subject were used to assess repeatability. Repeatability of LV ejection fraction (EF) based classification (LVEF<40 = abnormal, 40>LVEF>50 = mildly reduced, LVEF>50 = normal) [2] was also estimated from scan-rescan data. Results The segmentation model obtained high Dice scores (> 88% for LV and RV blood pools, >83% for LV myocardium). The summary of scan-rescan biomarker differences in Fig. 1(a) highlights that biomarker repeatability is generally better in GT segmentations, with lower differences between the two scans. While performance is satisfactory, a more in-depth analysis reveals that in some pairs of scans there are inconsistencies in the segmentations, leading to fluctuations in the calculation of blood pool volumes, which affects the repeatability of the computed biomarkers, as seen in Fig. 2(b). For instance, significant changes in LVEF between pairs of scans can arise from inconsistencies in the segmentation of the LV in basal slices, as shown in Fig. 2(a). This has consequences in the classification of subjects based on LVEF, as shown in Fig. 1(b). Only two subjects belonged to the mildly reduced LVEF class, however, when comparing predicted scan and rescan LVEF, both sensitivity and specificity decrease, suggesting inconsistency in the biomarker estimation. Conclusion(s) While we have demonstrated successful AI cardiac segmentation and biomarker estimation based on conventional performance metrics, additional refinement is necessary to enhance reliability and consistency. Further work is needed to obtain a better delineation of the valve plane, which would help addressing the inconsistencies at the LV basal slice. An automated segmentation and analysis pipeline for cine CMR is vital to support overworked clinicians, however, demonstrably repeatable performance, particularly when looking at therapy response, will have a significant impact on patient care and clinical outcomes.Repeatability of GT and AI biomarkersRepeatability of GT and AI segmentations

The importance of heart rate on left ventricular global longitudinal strain in echocardiography: novel insights facilitated by automated deep learning methods

Abstract Background Heart rate (HR) is assumed to influence echocardiographic measurements. Consequently, HR needs to be considered for accurate assessment of cardiac function. Despite left ventricular global longitudinal strain (LV GLS) being recognised as a valuable measure of cardiac function, its normal reference ranges remain confined to patients within a limited range of resting HR. So far, time-consuming manual analyses and high measurement variability have precluded comprehensive assessment of the interplay between HR and LV GLS. Using fully automated GLS measurements provided by novel deep learning (DL) methods, it is now possible to evaluate changes in LV GLS across a wide range of HR. Purpose To improve echocardiographic assessments across a wide range of HR intervals, we aimed to study the influence of controlled HR variations on LV GLS using programmable pacemakers and fully automated DL measurements. Methods Participants with sinus node dysfunction and implanted programmable pacemakers were enrolled. Echocardiographic acquisitions were obtained at baseline HR and during stepwise increments by 10 beats/min, targeting a range from 50 to 140 beats/min. Recordings of cine-loops including 10 cardiac cycles were obtained for the four-chamber, two-chamber, and apical long axis view. LV GLS was measured for all cycles using a fully automated DL method developed by our group, and presented as mean of the three standard apical views for all patients at each HR level. A linear mixed model was used for construction of an overall trendline based on the estimated fixed effects across all 50 patients, stating patient number as the random effect. The correlation between HR and LV GLS was evaluated by a likelihood ratio test. Results Fifty patients were included, 52% females, mean age 68 years (27 to 88 years). All patients had preserved atrioventricular conduction. Resting HR ranged from 50 to 87 beats/min (mean 64 beats/min). At baseline echocardiographic acquisition, most participants were within normal ranges for LV volumes, systolic and diastolic function. A total of about 13,000 cardiac cycles were automatically analysed by the DL method. The overall trend demonstrated a linear relation between increasing HR and decreasing absolute LV GLS (Figure 1). Across HR increments from 50 to 140 beats/min, there was a 32% (22%–42%) reduction in absolute LV GLS, declining from -17.1% to -11.7%. The strong correlation between changes in HR and LV GLS was further supported by a highly significant likelihood ratio test (p-value <0.001). Conclusions There was a reduction of absolute LV GLS with increasing HR. These findings emphasize the importance of integrating HR considerations into clinical echocardiography practice. Moreover, the results highlight that DL methods can unlock substantially richer insights from individual patient data, offering a new pathway towards more personalized and precise cardiac diagnostics.Figure 1

Prediction of cancer therapy related cardiac dysfunction by using a machine learning approach with cardiac magnetic resonance images

Abstract Background There is inconsistent data on the value of baseline and early cardiac function assessment on identifying patients at risk of cancer therapy related cardiac dysfunction (CTRCD). Whether machine learning (ML) approaches applied to cardiac MRI (CMR) images may help risk stratify patients is unclear. Purpose In women with HER2+ breast cancer receiving sequential anthracyclines and trastuzumab we sought to (i) assess if a ML approach applied to pre-cancer therapy and early post anthracycline CMR short axis (SAX) cines can help identify patients at risk for future CTRCD and (ii) whether this approach is superior to using clinical and manual quantitative CMR data. Methods Women with HER2+ breast cancer from the EMBRACE-MRI study underwent 5 CMR studies (pre-cancer therapy, post anthracyclines, 3, 6 and 12 months during trastuzumab). CTRCD was defined using the CREC criteria by end of treatment. Three models were created: 1) clinical data (demographics, cardiovascular risk factors and medications); 2) clinical and manual quantitative CMR data (right and left ventricular volumes and LVEF); and 3) ML model based on SAX cine CMR images only. We focused on the pre-cancer therapy CMR and 1st visit post-anthracycline CMR. All images underwent standardised formatting. A 3D convolutional neural networks model architecture was used. The model consisted of multiple convolutional layers followed by max pooling and global average pooling layers. The output of the convolutional layers were then fed into a dense layer of 128 nodes incorporating an L2 activity regularizer and a subsequent dropout layer. To train and tune the model, the process was iterated 50 times. In each iteration, the patient participant dataset was shuffled, and a random 80% of patients were selected for training and tuning. The tuned model was then applied to the remaining 20% of patients in each iteration, and this entire cycle of shuffling, training, and testing was repeated 50 times with replacement. Area Under the Curve (AUC), accuracy, sensitivity, and specificity were calculated on the test set and averaged across folds to determine each model’s performance. Results 135 women were included (mean age 51.1±9.2 years) mean doxorubicin equivalent was dose 204.9±12.5mg/m2. Cardiovascular risk factors were prevalent: 33 (24%) had a smoking history; 21 (15%) had hypertension. 37 (27%) developed CTRCD. The ML model using baseline CMR cine data only had a higher AUC (0.84 95% CI [0.83-0.86]) for the detection of CTRCD compared to clinical data (0.62 95% CI [0.59-0.65]) and clinical and CMR data (0.62 95% CI [0.60-0.65]). This further improved with the addition of post-anthracycline CMR data (Table 1). Conclusion A ML model examining early cardiac MRI data with short axis cine CMR images performed better than those using clinical or manual quantitative CMR data for the prediction of CTRCD. Further studies including external validation are needed.Table 1 Mean and 95% CIs

Assessing boundary conditions in CFD for transvalvular pressure gradient calculation in cardiac hemodynamics

Abstract Background Computational fluid dynamics (CFD), which has the advantages of providing detailed pressure distribution, has been widely used for cardiac function assessment and heart disease diagnosis. However, the results are usually influenced by the boundary conditions. Particularly, the transvalvular pressure gradient, which serves as a crucial indicator for mitral stenosis and the efficacy of mitral valve surgery, can easily be miscalculated. Here, we assess the effects of widely used boundary conditions on the transvalvular pressure gradient computed based on the Bernoulli equation and the line probe, respectively. Purpose This study aims to determine the effects of boundary conditions on the transvalvular pressure gradient in CFD. Methods We constructed cardiac models including left atrium, left ventricle, aorta from CT and mitral valve from transesophageal echocardiography data (Figure 1). The intraventricular flow fields were computed using CFD tool with four different boundary conditions (BC) at the same cardiac output. BC1 involved specifying the total flow rate of the aorta, with zero pressure at the entrance of the pulmonary veins. BC2 maintained equal flow rates at the entrances of the pulmonary veins. BC3 followed Murray's law, where the flow rate ratio in the pulmonary veins is proportional to the 1.5 power of the area ratio. BC4 followed Poiseuille's law, where the flow rate ratio is proportional to the square of the area ratio. The results encompassed the mean transvalvular pressure gradient and peak transvalvular pressure gradient obtained through the Bernoulli equation and the line probe methods, respectively. Results Figures 2(A-D) present the contours of transvalvular pressure under peak flow velocity conditions and the isosurfaces of vorticity within the ventricle. The results show that the pressure within the atrium is notably lower in the BC2, leading to a 63% underestimation in the mean transvalvular pressure gradient and a 22.9% deviation in the peak transvalvular pressure gradient (Figure 2 F). The transvalvular pressure gradient for BC1, BC3, and BC4 do not exceed 10%. The results reveal that the pressure distribution and vorticity within the ventricle are consistent, primarily due to the influence of the mitral valve. Conclusion When evaluating transvalvular pressure gradient using CFD, it is crucial to specify appropriate boundary conditions. Using inappropriate boundary conditions may lead to underestimation of the transvalvular pressure gradient, thereby affecting further diagnostic decisions. In research studies, it is recommended to allocate flow in different branch vessels according to Murray's law, where the flow in different branch vessels is proportional to the 1.5 power of the vessel cross-sectional area.Modelling flow chartTransvalvular pressure gradient

Short-Term Proteasome Inhibition: Assessment of the Effects of Carfilzomib and Bortezomib on Cardiac Function, Arterial Stiffness, and Vascular Reactivity.

Proteasome inhibitors such as bortezomib and carfilzomib induce apoptosis and are a cornerstone in the treatment of relapsed or refractory multiple myeloma. However, concerns have emerged concerning their link to cancer therapy-related cardiovascular dysfunction (CTRCD). Bortezomib, a reversible first-generation inhibitor, and carfilzomib, a second-generation irreversible inhibitor, are associated with hypertension, heart failure, and cardiac arrhythmias. The current study investigated the effects of bortezomib and carfilzomib on cardiac (left ventricular ejection fraction, LVEF) and vascular (arterial stiffness, vascular reactivity) function. Cardiac function assessment aimed to build upon existing evidence of proteasome inhibitors CTRCD, while arterial stiffness served as an early indicator of potential vascular remodeling. Groups of 12-week-old C57BL/6J male mice (n = 8 per group) were randomly assigned to receive vehicle, carfilzomib (8 mg/kg I.P.), or bortezomib (0.5 mg/kg I.P.). Additionally, proteasome inhibition was assessed in mice treated with L-NAME (0.5 mg/kg) to induce hypertension. Cardiac and vascular parameters were evaluated via echocardiography on days 0 and 3. On day 6, mice were sacrificed for ex vivo analysis of arterial stiffness and vascular reactivity. Overall, no changes in arterial stiffness were detected either in vivo or ex vivo at basal pressures. However, a steeper pressure-stiffness curve was observed for carfilzomib in normotensive (p < 0.01) and hypertensive (p < 0.0001) mice ex vivo. Additionally, in hypertensive mice, carfilzomib decreased LVEF (p = 0.06), with bortezomib exhibiting similar trends. Vascular reactivity remained largely unchanged, but proteasome inhibition tended to enhance endothelial-independent relaxations in both control and hypertensive mice. In conclusion, short-term treatment with carfilzomib and bortezomib is considered relatively safe for the protocols assessed in the study.

The overview of imaging protocols for chest CT

Computed Tomography (CT) is a common method of choice in the diagnosis of thoracic diseases. Since CT operates on the principle of ionizing radiation and frequently involves the use of contrast agents, it is crucial to standardize CT protocols to reduce the need for repeat imaging and, consequently, minimize patient exposure to radiation. The selection of a CT protocol primarily depends on the patient’s clinical indications and needs. The main classification of CT protocols distinguishes between the use of contrast agents (CECT) and non-contrast protocols (NCCT). The LDCT protocol is characterized by a low radiation dose and high sensitivity for detecting pulmonary nodules, making it suitable for lung cancer screening. Ultra-LDCT yields satisfactory results in diagnosing pneumonia and pneumothorax. Cine CT enables the assessment of cardiac function throughout the entire cardiac cycle, though it involves a high radiation dose and low temporal resolution. The use of contrast agents is particularly beneficial for differentiating adjacent non-vascular structures, more accurately identifying vascular anatomy, and improving the detection and characterization of pathological lesions. For diagnosing vascular pathologies, CTA is used, while CTPA is essential for diagnosing pulmonary embolism (PE) with high sensitivity and specificity. TRO CT is useful in cases of acute chest pain to rule out emergencies. Dynamic changes in tissue perfusion are monitored with DCE-CT, which is also valuable in tumor diagnostics. In pediatric applications of CT for the chest, it is essential to emphasize the use of the lowest possible radiation dose and contrast agent to minimize risks.

Assessment of Respiratory Muscles, Lung Parenchyma, and Cardiac Function by Ultrasound for Predicting Weaning Failure in Critically Ill Adults: A Prospective Observational Study.

The parasternal intercostal muscle activity, a marker of accessory muscle usage, is found to correlate inversely with the pressure-generating capacity of the diaphragm and level of support of mechanical ventilation. The primary objective of our study was to determine whether the parasternal intercostal muscle thickening fraction (PMTF) measured by ultrasonography can predict weaning. We also evaluated whether addition of lung ultrasound score and echocardiographic assessment can add on to predicting weaning failure. This prospective observational study conducted in a mixed medical-surgical intensive care unit, included 60 adult patients who were eligible for a spontaneous breathing trial (SBT) after being invasively mechanically ventilated for more than 48 hours. Ultrasound of respiratory muscles, lung parenchyma, and echocardiographic assessment were performed before and after 120 minutes of SBT. Parasternal intercostal muscles were imaged with a high frequency linear probe on the right second intercostal space 5 cm lateral to the sternal margin. PMTF was calculated as (maximum-minimum thickness)/minimum thickness. Among 60 patients, SBT failure was seen in 11 patients and extubation failed in 8 patients. PMTF (%) was significantly higher in the weaning failure group (13.33 [8.33-19.05]) as compared to patients with successful weaning (6.67 [6.06-11.54]). Diaphragmatic thickening fraction (DTF) correlated inversely to PMTF in patients with weaning failure. A pre-SBT PMTF cut-off of ≥7.7% and post-SBT cut-off of ≥15.38% were good predictors of weaning failure and extubation failure, respectively. PMTF has good discriminatory power to predict weaning outcomes (area under the receiver operating characteristic curve: 0.74 [0.59-0.88]). Pre-SBT PMTF had similar power as DTF to predict weaning failure.

Assessment of fetal cardiac function in pregnant women with anemia: prospective case-control study.

To compare fetal cardiac function in pregnant women with iron deficiency anemia (IDA) vs healthy pregnant controls. This was a single-center, prospective, case-control study conducted in a tertiary hospital between November 2022 and September 2023. Women diagnosed with IDA who attended as outpatients at the pregnancy follow-up clinic at 30-34 weeks' gestation or who were hospitalized for intravenous iron treatment owing to profound anemia were included. The control group consisted of randomly selected gestational-age-matched pregnant women with no obstetric complications or comorbidities and who did not have anemia. Patients underwent two-dimensional imaging, followed by pulsed-wave Doppler and M-mode and tissue Doppler imaging (TDI) to evaluate fetal cardiac function. A fetal cardiac score was calculated using systolic, diastolic and global hemodynamic function parameters, and was compared between patients with IDA and those without. The fetal cardiac score was also assessed according to the severity of anemia in the IDA group. A total of 150 patients, comprising 50 patients with IDA and 100 healthy pregnant women at 30-34 weeks' gestation, were included in the study. Of the patients with IDA, 20 had mild, 18 had moderate and 12 had severe anemia. The fetal myocardial performance index and isovolumetric relaxation time were significantly higher in the IDA group compared with the control group (P < 0.0001 for both), while isovolumetric contraction time was similar. Among the fetal tricuspid and mitral valve diastolic parameters, the E, A and E/A values were significantly lower in the IDA group (P < 0.05 for all). Mitral (MAPSE) and tricuspid (TAPSE) annular plane systolic excursions were significantly lower in the IDA group (P < 0.05 for both). The IDA group also had significantly lower values for the TDI parameters mitral and tricuspid E', A', S' and E'/A' ratio and a significantly higher E/E' ratio (P < 0.05 for all). Among the IDA subgroups, a significant decrease was observed in the tricuspid and mitral A, E and E/A ratio in fetuses whose mothers had severe anemia (P = 0.001). M-mode Doppler analysis revealed significantly lower fetal TAPSE and MAPSE in the patient group with severe maternal anemia (P = 0.001 for both). According to the subgroup comparison of TDI findings, the fetuses of mothers with severe anemia had significantly lower tricuspid and mitral E', A', S' and E'/A' ratio values and a significantly higher E/E' ratio (P < 0.05 for all). The fetal cardiac score was significantly higher in the maternal IDA group compared with the control group (P < 0.001). A significant negative correlation was found between maternal hemoglobin level and fetal cardiac score (P < 0.001). We observed differences in fetal systolic and diastolic cardiac function in pregnancies with maternal IDA. Fetal cardiac function was affected more among patients with severe anemia. This study found an increased E/E' ratio in the fetuses of pregnant women with IDA, suggesting decreased fetal heart maturation. Prenatal fetal cardiac evaluation, especially in women with severe anemia, can facilitate a more seamless transition to the postnatal period for these newborns. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Phonocardiogram (PCG) Murmur Detection Based on the Mean Teacher Method.

Cardiovascular diseases (CVDs) are among the primary causes of mortality globally, highlighting the critical need for early detection to mitigate their impact. Phonocardiograms (PCGs), which record heart sounds, are essential for the non-invasive assessment of cardiac function, enabling the early identification of abnormalities such as murmurs. Particularly in underprivileged regions with high birth rates, the absence of early diagnosis poses a significant public health challenge. In pediatric populations, the analysis of PCG signals is invaluable for detecting abnormal sound waves indicative of congenital and acquired heart diseases, such as septal defects and defective cardiac valves. In the PhysioNet 2022 challenge, the murmur score is a weighted accuracy metric that reflects detection accuracy based on clinical significance. In our research, we proposed a mean teacher method tailored for murmur detection, making full use of the Phyionet2022 and Phyionet2016 PCG datasets, achieving the SOTA (State of Art) performance with a murmur score of 0.82 and an AUC score of 0.90, providing an accessible and high accuracy non-invasive early stage CVD assessment tool, especially for low and middle-income countries (LMICs).

Clinical Findings, Laboratory Results, Electrocardiography and Echocardiography Findings in Dairy Buffaloes with Theileriosis.

Tropical theileriosis is a tick-borne haemoprotozoan disease, and cardiac function assessment in buffaloes with theileriosis was poorly documented. The Present study was carried out from April 2022 to December 2022. Theileriosis was confirmed by microscopic examination of stained blood smears and lymphnode smearsfurther confirmed by PCR assay. Electrocardiography was performed byusing the base apex lead system, and echocardiography was performed byusing the right parasternal view. The incidence of theileriosis was 16.25% by examination of stained blood smears, and 30.42% by PCR examination in 240 buffaloes. Repeatedly noted clinical signs were the absence of rumination, anorexia, loss of milk yield, depressed demeanour, emaciation, hyperthermia, lymphadenopathy, tick infestation, tachycardia, cardiac arrhythmia, and increased intensity of heartbeat. Haematological findings disclosed decreased haemoglobin, packed cell volume, total erythrocyte count, and neutrophils; increased eosinophils and monocytes. Serum biochemical findings revealed decreased albumin, albumin/globulin ratio, glucose, calcium, phosphorous, sodium, potassium, and chloride; increased globulin, aspartate aminotransferase, bilirubin, blood urea nitrogen, creatinine, cholesterol, lactate dehydrogenase, gamma-glutamyl transferase, and creatine kinase myocardial band isoenzymes. Electrocardiography explorations were sinus tachycardia, broad T wave, and sinus arrhythmia. Echocardiography examination showed ventricular wall thickening, cardiac chamber dilatation, valvular defects/valvular regurgitation, and pericarditis/cardiac tamponade. The present research proposes the changes in the electrocardiography and echocardiography findings in buffaloes with theileriosis, which are essential in clinics to identify the secondary complications during theileriosis and formulate therapeutics.

Ultrasound assessment of embryo cardiac function as a predictive criterion of adverse pregnancy outcome

Purpose to evaluate the value of the embryo/fetus heart rate (HR) in early pregnancy assessed by ultrasound for the formation of a group at high risk of adverse pregnancy outcomes.Materials and methods. A retrospective analysis of ultrasound examinations of 1073 pregnant women at 5+0–10+6 weeks was carried out. The embryo/fetus heart rate was compared with the gestational age calculated by the crown rump length (CRL) and the date of the last menstruation period (LMP). Retrospectively, all examined pregnant women were divided into two groups: group 1—with intrauterine embryo death before 14 weeks of pregnancy (n = 107); group 2—with prolongation of pregnancy until the second trimester (n = 966). When analyzing the data array using a decision tree, the embryo heart rate was assessed at various stages of pregnancy by LMP, CRL, and regardless of the exact period of pregnancy.Results. Analysis of heart rate values at different stages of pregnancy by LMP showed significant differences in heart rate between groups, the cases of later embryo loss characterized by lover heart rate values. There were no significant differences in heart rate between the groups at different stages of pregnancy by CRL (significant differences were obtained only at 8+0–9+6 weeks). Cut-off values of embryo heart rate for prediction of adverse pregnancy outcomes have been proposed for different stages of pregnancy, as well as a universal cut-off for the entire embryonic period.Conclusion. The proposed cut-off values of embryo heart rate for different stages of pregnancy, calculated by LMP, may be used for timely prediction of adverse pregnancy outcomes. When the exact gestational age is unknown, a universal heart rate cut-off value of &lt;116 bpm may be used. All proposed HR cut-off values were characterized by high specificity, but none of them by high sensitivity. A sensitivity of HR cut-off values can be increased by the use in combination with other ultrasound and clinical signs of adverse pregnancy outcome.

Cardiac Evaluation in Children With Chronic Renal Failure and Effect of Kidney Transplant.

Cardiovascular diseases are an important cause of mortality and morbidity in children with chronic renal failure. Cardiac evaluation and followup are crucial for these patients before and after renal transplant. Echocardiography is a noninvasive imaging modality that allows for the assessment of cardiac structure and function. We retrospectively investigated pretransplant and posttransplant echocardiography findings for 55 pediatric patients who had underwent kidney transplant. We recorded patient characteristics before and after transplant, including age, sex, follow-up period, etiology of renal failure, left ventricular systolic and diastolic diameters and the associated z scores, left ventricular mass indexes and z scores, ejection fraction and fractional shortening, aortic valve and atrioventricular valve insufficiencies, presence of pulmonary hypertension, and pericardial effusion (if any) in echocardiography. All participants underwent echocardiography at baseline and after 6 months following the transplant procedure. Posttransplant echocardiography evaluations showed that the z scores of left ventricular systolic and diastolic diameters decreased significantly, mitral regurgitation decreased, and left ventricular systolic functions and left ventricular mass index increased. Our study revealed that kidney transplant has a beneficial effect on the cardiovascular status of patients with end-stage renal disease, as shown by improvements in both structural and functional echocardiographic features. Cardiac functions must be monitored regularly before and after transplant. Transplantation is the optimal treatment option for preservation and improvement of cardiovascular functions.

Clinical Complications of Beck's Triad in Cardiac Tamponade: Implications for Management and Patient Outcomes

Cardiac tamponade is a critical medical emergency caused by fluid accumulation in the pericardial space, resulting in heart compression. Beck's triad is a key clinical indicator for diagnosing this condition. This integrative review aimed to assess the clinical complications associated with Beck's triad in cardiac tamponade and its implications for patient management and treatment. An electronic search was conducted in the PubMed and BVS (Lilacs &amp; Medline) databases using targeted descriptors. Studies published in the last 10 years that addressed Beck's triad's clinical complications in cardiac tamponade were included, while studies that did not meet the inclusion criteria were excluded. The review identified a range of clinical complications associated with Beck's triad, such as cardiac tamponade, pericardial effusion, hemoptysis, and cardiac arrhythmias, arising from causes including congenital heart disease, viral infections, and invasive procedures. Cardiac tamponade can also lead to systemic complications, raising the risk of thromboembolic events. Management of these complications should be individualized based on the clinical presentation and underlying cause of cardiac tamponade. Echocardiography is essential for diagnosis and ongoing monitoring, allowing accurate assessment of cardiac function and pericardial fluid volume. Timely treatment, including pericardial drainage and hemodynamic support, is critical to lowering morbidity and mortality in cardiac tamponade cases. Early recognition, accurate diagnosis, and prompt management of complications related to Beck's triad are vital for optimizing outcomes. Recognizing early signs and symptoms of severe complications is essential for timely intervention and prevention of further adverse outcomes. A multidisciplinary approach, coupled with continuous education of healthcare professionals, is crucial to implementing best practices and improving patient outcomes in cardiac tamponade.

Cardiovascular Risk Factors Associated with Mitral Annular Calcification in a Non-Rheumatic Population

Mitral Annular Calcification (MAC), cardiovascular disease marker was common in non-rheumatic populations but was frequently disregarded in clinical evaluations. Objective: To MAC and to assess effect of these factors on cardiac function in non-rheumatic adult population. Methods: From September 2022 to August 2023, we conducted this cross-sectional study at Cardiac Center, Pakistan institute of medical sciences Islamabad that included 182 adults aged 50 years and older. We evaluated the patient's clinical history, demographic data and echocardiographic and laboratory results. The association between the presence of MAC and cardiovascular risk factors (age, hypertension, diabetes, dyslipidemia, smoking, obesity and chronic renal disease) was analyzed using logistic regression. Echocardiographic data were used to provide insight into cardiac function. Results: The prevalence of MAC was substantially correlated with hypertension (OR = 2.30), diabetes (OR = 2.00), dyslipidemia (OR = 1.75) and obesity (OR = 1.07). Also, smoking demonstrated a significant correlation with MAC. In comparison to those without MAC, individuals with MAC exhibited substantially lower ejection fractions, increased left atrial diameters and impaired diastolic function, as indicated by cardiac function assessments. Conclusion: In non-rheumatic population, MAC was significantly associated with conventional cardiovascular risk factors, particularly hypertension and diabetes.