Cardiac Echocardiography Research Articles

Body Iron Status and Its Complications in Patients With Beta Thalassemia Major: A Cross-Sectional Study

Introduction: Thalassemia is a genetic condition and is one of the commonest single-gene hereditary disorders. As it is among a group of hemoglobinopathies, it consists of a decrease in either alpha or beta globin chain synthesis. This eventually leads to the inappropriate ratio of alpha or beta globin chains causing ineffective erythropoiesis. Ineffective erythropoiesis thus causes chronic anemia and haemopoietic expansion to compensate for it.
 Aims & Objectives: This study aimed to investigate the serum ferritin levels of patients with beta thalassemia major presenting in a tertiary care hospital in Lahore, Pakistan and study the complications that occur with an abnormal iron load.
 Place and Duration of Study: It was conducted at CMH Hospital, Lahore, and completed over a period of one and a half year, from June 2021 to January 2023.
 Material & Methods: It was a descriptive cross-sectional study. The sample size of 32 was calculated using Raosoft calculator, with 90% Confidence Interval, 9% margin of error and 10.5% response distribution.Data was collected using an interviewer-administered questionnaire that compromised of 4 parts, demographics and socio-economic background of patient and caretakers; medical history and anthropometric measurement of the patient; details regarding serum ferritin levels and chelation; and lastly, laboratory (for example, TSH, T4, HbA1c and ALT for all patients, as well as FSH and LH for only those patients greater than 10 years of age), ultrasound, and cardiac echocardiography findings.Collected data was entered and analyzed in SPSS version 24. P value of <0.05 was taken as significant.
 Results: In this study, thirty-two patients with beta thalassemia major were included with mean age of 7.79 ± 4.57 years. Mean serum ferritin was 3410±2629µg/l and lack of compliance to chelation had significant association with serum ferritin values (p=0.05). Serum ALT levels showed that hepatic dysfunction was the most common endocrine complication in 17 (53.1%) patients. There was a significant association between compliance and echocardiography findings (p=0.04). No significant association of compliance was found with ultrasound findings, serum TSH and T4 levels, serum ALT levels and serum FSH and LH levels.
 Conclusion: This study concluded that high ferritin levels ultimately lead to significant complications.

Evaluation of cardiac diagnostic tests findings based on pro-BNP levels in COVID-19 pregnant patients.

Pro-b-type natriuretic peptide (Pro-BNP) is an inflammatory marker that indicates cardiac damage and inflammation. The elevation of this marker in COVID-19 patients can be used as a predictive factor in the prognosis of these patients. Our cross-sectional study investigated the evaluation of cardiac diagnostic test findings based on pro-BNP levels in pregnant COVID-19 patients in Sayyad Shirazi Hospital, Gorgan, Iran, in 2020-2022. A hundred and ten pregnant patients diagnosed with COVID-19 infection were evaluated for cardiac diagnostic tests (electrocardiogram (ECG) and echocardiography (Echo)) and pro-BNP levels. Data were analyzed using SPSS 25 software. Chi-square and Student's t-test will be used to test and compare the relationship between variables and compare them. A P-value less than 0.05 is considered statistically significant. The chi-square test was used to compare the ratio of qualitative variables among the groups if the presuppositions of chi-square distribution were established. Otherwise, Fisher's exact test was used. The mean age of participants were 31.06 ± 5.533 years and 49.1% of patients had pro-BNP levels above the cut-off value for predicting an adverse outcome of COVID-19. The mean ± standard deviation of pro-BNP levels in the low group was 46.125 ± 17.523 pg/mL and in the high group was 878.814 ± 1038.060 pg/mL. This study revealed that patients with higher pro-BNP plasma levels had a significant relation between, myocardial infarction (MI), pericardial effusion (PE), urgent Caesarean section (C/S), and mortality. In addition, no significant relation between gravid, trimester, vaccination, arrhythmia, heart block, and valves diseases with high pro-BNP levels was found. The current research showed that pro-BNP levels can be used as a diagnostic and valuable prognostic tool in pregnant women to diagnose cardiac complications by using ECG and Echo.

Improvement in Cardiac Morphology Demonstrated by Cardiac Magnetic Resonance Imaging and Echocardiography after Haploidentical Hematopoietic Cell Transplantation in Adults with Sickle Cell Disease

Cardiopulmonary complications account for approximately 40% of deaths in patients with sickle cell disease (SCD). Diffuse myocardial fibrosis, elevated tricuspid regurgitant jet velocity (TRV) and iron overload are all associated with early mortality. While HLA-matched sibling hematopoietic cell transplant (HCT) offers a potential cure, fewer than 20% of patients have a suitable donor. Haploidentical HCT allows for an increased donor pool and has recently demonstrated improved safety and efficacy. Our group has reported improved cardiac morphology via echocardiography at one year after HCT. Herein, we describe the first use of cardiac magnetic resonance imaging (CMR), the gold standard for measuring volume, mass, and ventricular function, to evaluate changes in cardiac morphology post-HCT in adults with SCD. We analyzed baseline and 1-year data from 12 adults with SCD who received nonmyeloablative haploidentical peripheral blood HCT at the NIH. Patients underwent non-contrast CMR at 3T, echocardiography, and laboratory studies. One year after HCT, patients showed marked improvement in cardiac chamber morphology by CMR, including left ventricular (LV) mass and volume (70.2 to 60.1 g/m2, p = 0.02; 114.5 to 90.6 mL/m2, p = 0.001). Furthermore, mean TRV normalized by 1 year, suggesting that HCT may offer a survival benefit. Fewer patients had pathologically prolonged native myocardial T1 times, an indirect marker of myocardial fibrosis at 1 year; these data showed a trend toward significance. In this small sample, CMR was very sensitive in detecting cardiac mass and volume changes after HCT and provided complementary information to echocardiography. Notably, post-HCT improvement in cardiac parameters can be attributed only in part to the resolution of anemia; further studies are required to determine the role of myocardial fibrosis reversal, improved blood flow, and survival impact after HCT for SCD.

Protective role of CXCR7 activation in neonatal hyperoxia-induced systemic vascular remodeling and cardiovascular dysfunction in juvenile rats

Neonatal hyperoxia induces long-term systemic vascular stiffness and cardiovascular remodeling, but the mechanisms are unclear. Chemokine receptor 7 (CXCR7) represents a key regulator of vascular homeostasis and repair by modulating TGF-β1 signaling. This study investigated whether pharmacological CXCR7 agonism prevents neonatal hyperoxia-induced systemic vascular stiffness and cardiac dysfunction in juvenile rats. Newborn Sprague Dawley rat pups assigned to room air or hyperoxia (85% oxygen), received CXCR7 agonist, TC14012 or placebo for 3 weeks. These rat pups were maintained in room air until 6 weeks when aortic pulse wave velocity doppler, cardiac echocardiography, aortic and left ventricular (LV) fibrosis were assessed. Neonatal hyperoxia induced systemic vascular stiffness and cardiac dysfunction in 6-week-old rats. This was associated with decreased aortic and LV CXCR7 expression. Early treatment with TC14012, partially protected against neonatal hyperoxia-induced systemic vascular stiffness and improved LV dysfunction and fibrosis in juvenile rats by decreasing TGF-β1 expression. In vitro, hyperoxia-exposed human umbilical arterial endothelial cells and coronary artery endothelial cells had increased TGF-β1 levels. However, treatment with TC14012 significantly reduced the TGF-β1 levels. These results suggest that dysregulation of endothelial CXCR7 signaling may contribute to neonatal hyperoxia-induced systemic vascular stiffness and cardiac dysfunction.

Cardiac scintigraphy and echocardiography assessment in the diagnosis of transthyretin cardiac amyloidosis.

The aim is to evaluate the diagnostic yield of echocardiography and [99mTc]Tc-DPD scintigraphy in the detection of amyloid cardiomyopathy (CM) and define potential prognostic echocardiographic parameters. 133 patients were retrospectively studied, from 2016 to 2021, with a mean age of 80.2 ± 7.5years. The final diagnosis was established according to international consensus. Patients had a transthoracic echocardiogram (TTE) and [99mTc]Tc-DPD scintigraphy; RWT, E/e, LS, TAPSE, SAB, and IWT scores were calculated. All patients with ATTR-CM were classified into 3 prognostic stages and were compared with Perugini grades and echocardiographic parameters. CM was confirmed in 85 cases (63.9%), 76 (57.1%) ATTR-CM, and 9 (6.8%) AL-CM. The diagnostic yield of [99mTc]Tc-DPD scintigraphy and echocardiography were calculated, with a sensitivity of 90.7%, specificity of 100%, PPV of 100%, and NPV of 87.2% in myocardial scintigraphy, versus 74.6%, 62.5%, 75.6%, 61.2% in the echocardiogram. According to the IWT score, most patients were classified in the intermediate group; 33 presented with grade 2-3 uptakes. Significant results were obtained when comparing Perugini score with IWT (p: 0.02) and SAB (p: 0.03); and between biomarkers stages and LVEF (p: 0.028), E/e´ (p: 0.001), and GLS% (p: 0.022). [99mTc]Tc-DPD scintigraphy is superior in diagnosing CA. SAB could be the most reliable parameter in an early diagnostic phase, showing a strong correlation with Perugini grades 2 and 3.

Prognostic value of modified ADMIIRE-HF risk score in patients with implantable cardioverter defibrillator: a prospective comparative study with 6-minute walk distance

Abstract Background ADIMIRE-HF risk score is a novel risk score that combines clinical characteristics and MIBG imaging variables to predict serious arrhythmic risk in patients with chronic heart failure (CHF) and recent studies showed that highest occurrence of severe arrhythmic events (SAE) was seen in patients with an intermediate decrease in MIBG uptake rather than the lowest values. Six-minute walk distance (6MWD) has also been shown to detect high risk patients with CHF. However, there is no information available on the long-term prognostic value of these indices for the prediction of ventricular tachyarrhythmias in patients with implantable cardioverter defibrillator (ICD). Methods and Results We prospectively enrolled 231 consecutive outpatients with ICD (age: 65±14 years, male: 81%, NYHA class: 1.7±0.7, LVEF: 47±17%). At entry, cardiac MIBG imaging, echocardiography and 6-minute walk test were performed. Modified ADMIRE-HF risk score was derived from the sum of the point values of the following parameters: LVEF (<25%:5 points), MIBG heart-to-mediastinum ratio on delayed planar image (HMR 1.4-1.9: 12 points) and systolic blood pressure (<120: 3 points, 120-139: 0 point, >140: -3 points). During a follow-up period of 4.4±2.8 years, 72 patients had appropriate ICD therapy (ATx). At multivariate Cox analysis, modified ADMIRE-HF risk score and 6MWD were significantly and independently associated with ATx after adjustment of age, sex, non-sustained ventricular tachycardia and NYHA functional class. ATx was significantly more frequently observed in patients with both higher modified ADMIRE HF risk score (>9: median value) and shorter 6MWD (<300m) and with either, than with none of them (54% vs 34% vs 18%, respectively p<0.0001). Conclusion Combination of modified ADMIRE-HF risk score and 6MWD would be strongly associated with an increased risk for ventricular tachyarrhythmias in ICD patients.

Abstract 18817: Dysregulation of Key Calcium Cycling Genes Does Not Drive Right Heart Maladaptation in a Porcine PH Model

Introduction: Pulmonary hypertension (PH), a complex disease characterized by an elevated pulmonary artery pressure, causes maladaptation in patients. Maladaptation, or the hemodynamic and functional changes involved in RV/PA uncoupling, leads to poorer outcomes in patients. Dysregulation of calcium cycling controlled by SERCA2a and modulators, PLN and SUMO1, has been shown to cause left heart failure (HF), however its role in right heart maladaptation is unclear. Hypothesis: The dysregulation of the key calcium cycling genes, SERCA2a, PLN, and SUMO1 contributes to the maladaptation in PH. Methods: In this retrospective study, tissues of a porcine Yorkshire model of post-capillary PH were analyzed to understand molecular differences in right ventricular (RV) remodeling resulting in refractory symptom presentation (maladaptive group, n =6) or symptom absence (adaptive group, n =5). Pulmonary and cardiac hemodynamics, functional assessment, echocardiography, and pressure-volume relationship data were collected. Sham control group, ( n =5) received left thoracotomy only. Results: Calcium cycling genes known to be dysregulated in left HF did not display significant differences in group or spatial expression across RV, septal, and LV tissues (Figure). Other significant findings include increases in RV hypertrophy (p<0.001) and stroke work (p=0.0036) when comparing maladaptive and sham group ( n =5) with RV dilation only in maladaptive group (p=0.0004). Conclusions: Dysregulation of calcium cycling genes in the RV does not explain symptom presentation in the maladaptive group and suggests different processes underlie left and right HF. RV dilation is likely a key driver of maladaptive symptom presentation in a porcine model of PH.

Abstract 13286: Co-Morbidities Clustering According to Imaging Diagnostic Criteria in Cardiac Sarcoidosis

Background: Cardiac sarcoidosis (CS) diagnostic guidelines updated in 2006 and in 2017 now include imaging findings of left ventricular (LV) dysfunction (LV EF < 50%) on cardiac MRI and echocardiography as major diagnostic criterion. Limited data is available with regards to co-morbidities clustering in sarcoidosis and CS according to the 2017 updated guideline diagnostic criteria. Methods: A case control, single tertiary medical center study included 558 sarcoidosis patients with documented extracardiac sarcoidosis and completed electrocardiogram and/or cardiac MRI imaging. CS 2006 and 2017 diagnostic criteria and co-morbidity data were extracted from electronic charts and were available for comparison in 540 patients. Results: The total study population was composed of 52.7% (281/540) females, aged 58.9+/-12.6 years old, with diabetes mellitus (DM) present in 29.6% (160/540), HTN in 51.7% (279/540), CAD in 13.3% (72/540), moderate to severe aortic, mitral, or tricuspid valvular disease in 14.8% (80/540), ESRD in 2.4% (13/540), and COPD or asthma in 21.9% (118/540). There was a significant clustering of co-morbidities according to the imaging CS diagnostic criteria. Patients meeting the 2017 CS imaging criteria were found to be older (61.4+/-11.3 vs 58.8+/-12.8 years old in patients not meeting criteria, p=0.085), predominantly male (69.2%, (54/78) vs. 44.4%, (205/462), p<0.001), and demonstrated significantly increased prevalence of DM (39.7%, (31/78) vs. 27.9%, (129/462), p=0.034), and valvular disease (33.3%, (26/78) vs. 11.7%, (54/462), respectively, p<0.001). However, there were no statistically significant difference in the prevalence of HTN (60.3%, (47/78) vs. 50.2%, (232/462), p=0.101), ESRD (3.9%, (3/76) vs. 2.2%, (10/456), p=0.361), and COPD or asthma (19.2%, (15/78) vs. 22.3%, (103/462), p=0.544) in patients meeting 2017 CS criteria compared to those that did not. Conclusion: CS patients meeting 2017 imaging diagnostic criteria were found to have statistically significant clustering of the following co-morbidities: male gender, DM, and valvular disease. These findings underscore importance of comprehensive care in CS patients and warrant caution in assigning LV abnormalities observed on imaging solely to CS etiology.

The Influence of Food Intake and Preload Augmentation on Cardiac Functional Parameters: A Study Using Both Cardiac Magnetic Resonance and Echocardiography.

(1) Background: To investigate how food intake and preload augmentation affect the cardiac output (CO) and volumes of the left ventricle (LV) and right ventricle (RV) assessed using cardiac magnetic resonance (CMR) and trans-thoracic echocardiography (TTE). (2) Methods: Eighty-two subjects with (n = 40) and without (n = 42) cardiac disease were assessed using both CMR and TTE immediately before and after a fast infusion of 2 L isotonic saline. Half of the population had a meal during saline infusion (food/fluid), and the other half were kept fasting (fasting/fluid). We analyzed end-diastolic (EDV) and end-systolic (ESV) volumes and feature tracking (FT) using CMR, LV global longitudinal strain (GLS), and RV longitudinal strain (LS) using TTE. (3) Results: CO assessed using CMR increased significantly in both groups, and the increase was significantly higher in the food/fluid group: LV-CO (ΔLV-CO: +2.6 ± 1.3 vs. +0.7 ± 1.0 p < 0.001), followed by increased heart rate (HR) (ΔHR: +12 ± 8 vs. +1 ± 6 p < 0.001). LV and RV achieved increased stroke volume (SV) through different mechanisms. For the LV, through increased contractility, increased LV-EDV, decreased LV-ESV, increased LV-FT, and GLS were observed. For the RV, increased volumes, increased RV-EDV, increased RV-ESV, and at least for the fasting/fluid group, unchanged RV-FT and RV-LS were reported. (4) Conclusions: Preload augmentation and food intake have a significant impact on hemodynamic and cardiac functional parameters. This advocates for standardized recommendations regarding oral intake of fluid and food before cardiac assessment, for example, TTE, CMR, and right heart catheterization. We also demonstrate different approaches for the LV and RV to increase SV: for the LV by increased contractility, and for the RV by volume expansion.

ET-1 receptor type B (ETBR) overexpression associated with ICAM-1 downregulation leads to inflammatory attenuation in experimental autoimmune myocarditis.

An experimental autoimmune myocarditis rat model was established by subcutaneous injection of porcine myocardial myosin (PCM). The effect of ET-1 receptor type B (ETBR) overexpression on autoimmune myocarditis was observed via tail vein injection of ETBR overexpression lentivirus in rats. We further investigated the mechanisms involved in the regulation of autoimmune myocarditis by ETBR overexpression. Six rats were randomly selected from 24 male Lewis rats as the NC group, and the remaining 18 rats were injected with PCM on Day 0 and Day 7, to establish the experimental autoimmune myocarditis (EAM) rat model. The 18 rats initially immunized were randomly divided into three groups: the EAM group, ETBR-oe group, and GFP group. On Day 21 after the initial immunization of rats, cardiac echocardiography and serum brain natriuretic peptide (BNP) analysis were performed to evaluate cardiac function, myocardial tissue HE staining was performed to assess myocardial tissue inflammatory infiltration and the myocarditis score, and mRNA expression of IFN-γ, IL-12, and IL-17 was detected by qRT-PCR. Subsequently, immunohistochemical analysis was performed to detect the localization and expression of the ETBR and ICAM-1 proteins, and the expression of ETBR and ICAM-1 was verified by qRT-PCR and western blotting methods. On Day 21 after initial immunization, left ventricular end-diastolic diameter (LVEDd), left ventricular end-systolic diameter (LVEDs), and serum BNP concentrations increased in the hearts of rats in the EAM group compared with the NC group (P < 0.01), and ejection fraction (EF) and fractional shortening (FS) decreased compared with those of the normal control (NC) group (P < 0.01). LVEDd, LVEDs, and serum BNP concentrations decreased in the ETBR-oe group compared with the EAM group, while EF and FS increased significantly (P < 0.01). HE staining showed that a large number of inflammatory cell infiltrates, mainly lymphocytes, were observed in the EAM group, and the myocarditis score was significantly higher than that of the NC group (P < 0.01). Compared with that of the EAM group, myocardial tissue inflammatory cell infiltration was significantly reduced in the ETBR-oe group, and the myocarditis scores were significantly lower (P < 0.01). The mRNAs of the inflammatory factors IFN-γ, IL-12 and IL-17 in myocardial tissue of rats in the EAM group exhibited elevated levels compared with those of the NC group (P < 0.01) while the mRNAs of IFN-γ, IL-12 and IL-17 were significantly decreased in the ETBR-oe group compared with the EAM group (P < 0.01). Immunohistochemistry showed that the staining depth of ETBR protein in myocardial tissue was greater in the EAM group than in the NC group, and significantly greater in the ETBR-oe group than in the EAM group, while the staining depth of ICAM-1 was significantly greater in the EAM group than in the NC group, and significantly lower in the ETBR-oe group than in the EAM group. The ICAM-1 expression level was significantly higher in the EAM group than in the NC group (P < 0.01), and was significantly lower in the ETBR-oe groupthan in the EAM group (P < 0.01).

The relationship between insulin resistance, serum alkaline phosphatase, and left ventricular dysfunction following myocardial infarction

The occurrence of heart failure following acute myocardial infarction (AMI) significantly increases the risk of post-infarction mortality. Alkaline phosphatase (AP) is considered to be an independent predictor of cardiovascular disease (CVD) and adverse outcomes. Furthermore, in recent years, alkaline phosphatase has been associated with insulin resistance (IR). Our aim was to investigate the correlation between IR substitutes (triglyceride-glucose (TyG) index, triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio), AP, and LV dysfunction in patients admitted after AMI. The retrospective study included 810 patients who underwent coronary angiography for myocardial infarction at the First Hospital of Hebei Medical University from August 2018 to December 2021. Patients were categorized into three groups based on their serum AP levels. Clinical characteristics at admission, cardiac echocardiography findings, coronary angiography results, and biochemical markers such as serum AP levels and triglycerides (TG) were recorded during hospitalization. Left ventricular ejection fraction (LVEF) was assessed using cardiac echocardiography conducted from the time of admission until the coronary angiography procedure. A total of 774 patients with AMI were included in this study. The TyG index is significantly correlated with the TG/HDL-C ratio. (R = 0.739, P < 0.001). Binary logistic regression analysis revealed that elevated serum AP (OR 2.598, 95% CI 1.331–5.071, P = 0.005), presence of the left anterior descending (LAD) artery as the infarct-related artery (IRA) (OR 2.452, 95% CI 1.352–4.449, P = 0.003), and triglyceride (TG) levels (OR 0.652, 95% CI 0.429–0.992, P = 0.046) were protective risk factor for an admission LVEF < 40% following AMI. The serum alkaline phosphatase and LAD as IRA are independent risk factors for severe reduction in LVEF during hospitalization for AMI. Conversely, triglyceride are independent protective factor for severe reduction in LVEF during AMI hospitalization.

Abbreviated cardiac magnetic resonance imaging versus echocardiography for interval assessment of systolic function in Duchenne muscular dystrophy: patient satisfaction, clinical utility, and image quality.

Poor acoustic windows make interval assessment of systolic function in patients with (Duchenne Muscular Dystrophy) DMD by echocardiography (echo) difficult. Cardiac magnetic resonance imaging (CMR) can be challenging in DMD patients due to study duration and patient discomfort. We developed an abbreviated CMR (aCMR) protocol and hypothesized that aCMR would compare favorably to echo in image quality and clinical utility without significant differences in exam duration, patient satisfaction, and functional measurements. DMD patients were recruited prospectively to undergo echo and aCMR. Modalities were compared with a global quality assessment score (GQAS), clinical utility score (CUS), and patient satisfaction score (PSS). Results were compared using Wilcoxon signed-rank tests, Spearman correlations, intraclass correlations, and Bland-Altman analyses. Nineteen DMD patients were included. PSS scores and exam duration were equivalent between modalities, while CUS and GQAS scores favored aCMR. ACMR scored markedly higher than echo in RV visualization and assessment of atrial size. Older age was negatively correlated with echo GQAS and CUS scores, as well as aCMR PSS scores. Higher BMI was positively correlated with aCMR GQAS scores. Nighttime PPV requirement and non-ambulatory status were correlated with worse echo CUS scores. Poor image quality precluding quantification existed in five (26%) echo and zero (0%) aCMR studies. There was moderate correlation between aCMR and echo for global circumferential strain and left ventricular four chamber global longitudinal strain. The aCMR protocol resulted in improved clinical relevance and quality scores relative to echo, without significant detriment to patient satisfaction or exam duration.

OR29-04 Vitamin D Signaling Prevents Glucocorticoid-Induced Musculoskeletal Tissue Loss And Cardiac Dysfunction By Targeting The Atrogene Pathway

Abstract Disclosure: A. Sato: None. M. Cregor: None. B. Adhikari: None. M. Boerma: None. T. Bellido: None. Glucocorticoid excess increases the risk of bone fractures and induces cardiovascular events. Earlier studies demonstrated that glucocorticoids upregulate the expression of E3 ubiquitin ligases (atrogenes) in bone and skeletal/cardiac muscles, suggesting a common targetable pathway to prevent harmful glucocorticoid actions. Atrogenes stimulate proteasomal degradation of proteins, which promotes musculoskeletal tissue loss and cardiac dysfunction, known hallmarks of glucocorticoid disease. Here, we investigated whether Vitamin D receptor activation, which has beneficial musculoskeletal effects and may prevent falls, blocks glucocorticoid-induced activation of the atrogene pathway. Skeletally mature female 4-month-old C57Bl6 mice (N=12) were implanted with placebo or 2.1mg/kg/d prednisolone pellets for 8wks and received vehicle or 50ng/kg/d of 1,25D3 (calcitriol), 5x/wk, starting 3d before pellet implantation. In bone, 1,25D3 fully prevented decreases in spinal bone mineral density (BMD) and cancellous bone microarchitectural deterioration (low BV/TV and Tb.Th) induced by glucocorticoids. 1,25D3 prevented glucocorticoid-induced resorption, as quantified by circulating CTX and osteoclast number/surface. In contrast, 1,25D3 did not prevent glucocorticoid-induced suppression of bone formation, as quantified by circulating markers (P1NP and osteocalcin) and histomorphometric indexes (MS/BS and BFR). In skeletal muscle, 1,25D3 fully prevented glucocorticoid-induced loss of lean body mass, a muscle mass index measured by DEXA, and decreases in muscle strength, as determined by in vivo plantarflexion torque testing of the posterior hindlimb muscular compartment. Consistent with clinical evidence, cardiac echocardiography detected glucocorticoid dysfunction as exhibited by left ventricular (LV) wall thinning (anterior and posterior LVs at diastole and systole) and inefficient heart contraction (increased LV systolic volume, reduced ejection fraction and fractional shortening). Remarkably, 1,25D3 prevented the cardiac LV thinning and dysfunction induced by glucocorticoids. Neither glucocorticoid nor 1,25D3 altered heart mass, LV mass, or heart rate. 1,25D3 also prevented glucocorticoid increases in atrogene MuRF1 expression in cardiac and skeletal tissues. Additionally, 1,25D3 prevented glucocorticoid-induced increases in atrogene expression in separate ex vivo organ cultures of bone, skeletal muscle, and left ventricles of the heart, demonstrating direct Vitamin D actions. In conclusion, 1) atrogene upregulation is a central mechanistic hub underlying the damaging actions of glucocorticoid excess in bone, skeletal muscle, and the heart and 2) activation of Vitamin D receptor signaling preserves tissue structure and function by interfering with the atrogene pathway in musculoskeletal and cardiac systems. Presentation: Sunday, June 18, 2023

Role of right heart catheterization in diagnosis of pulmonary arterial hypertension

Abstract Background Pulmonary hypertension (PH) presumably has an impact on 1% or less of the world’s population. Right Heart Catheterization (RHC) is essential for determining PH problems. RHC determines prognosis and offers helpful information on the degree of hemodynamic impairment. Therefore, this comparative study was carried out to determine the diagnostic role, pitfalls associated, and complications encountered during RHC in suspected cases of PAH and chronic thromboembolic pulmonary hypertension (CTEPH). Methods The observational cohort study was conducted on 75 patients with clinical suspicion of PH and CTEPH. All patients were subjected to full history taking, ECG, Echocardiography, and radiological investigations including Chest radiography (CXR), high-resolution computed tomography (HRCT), and computed tomography (CT) pulmonary angiography. Results The mean pulmonary artery mean pressure (PAMP) was 46.05 ± 9.631 mmHg, the mean Pulmonary artery dilatation (PAD) was 30.04 ± 1.082 mm the mean ejection fraction (EF%) was 63.87%, the mean right ventricular diameter was 45.83 ± 0.444 mm. The mean pulmonary artery wedge pressure (PAWP) was 10.91 ± 2.303 mmHg, and the mean cardiac output (CO) was 4.00 ± 0.773 L/min mean cardiac index (CI) was 1.94 ± 0.416 L/min/m2. Doppler echocardiographic estimated pulmonary artery systolic pressure (DE-ePASP) and estimated pulmonary, artery, end-diastolic pressure (ePADP) significantly positively correlated with RHC-PASP (P &lt; 0.001) and mean DE-ePAP significantly positively Correlated with mean RHC-PAP (P &lt; 0.001). Conclusions RHC is still the only method that can completely and accurately diagnose PAH. however, the combination between right cardiac catheterization and echocardiography provides a more accurate diagnosis of the diseases and their complications.

Evaluation of cardiac biomarkers, electrocardiogram changes and echocardiography findings before and after exercise in paediatric athletes

Purpose: The aim of this study was to investigate the structural and electrical changes in the heart associated with exercise in young athletes under 18 years of age and to examine the relationship between these changes and biochemical markers.&#x0D; Materials and Methods: In this study, 32 male paediatric athletes (five rowers, five kayakers and 22 footballers) were prospectively evaluated. Dynamic exercise training for 75 minutes was applied to all athletes. An echocardiographic evaluation was performed on the athletes at rest. An electrocardiogram (ECG) was taken before and after the exercise. Blood samples were taken from all athletes before the exercise, during the first hour of exercise and after the fourth hour of the training session to analyse the serum levels of creatine kinase myocardial band, troponin T(cTnT) and pro-brain natriuretic peptide.&#x0D; Results: The mean age of all athletes was 15.3±0.9 years. In the echocardiography examination, end-diastolic thickness, left ventricular end-diastolic diameter, posterior wall end-diastolic diameter, left ventricular end-systolic diameter, left ventricular mass measurements (LVM) and left ventricular mass indices (LVMI) were higher among the rowers than in the remaining groups. In the post-exercise ECG, T-wave peaks were observed in 16 individuals, including all rowers, all kayakers, and six footballers. The cTnT values in the first hour and after the fourth were 0.31–0.71 ng/ml in football players, 0.10–0.27 ng/ml in rowers, and 0.04–0.15 ng/ml kayakers. An increase in cTnT levels was detected after the fourth hour of exercise in all groups. There was a correlation between T-wave peaks in the ECG taken after exercise and age, cTnT serum level and increased LVM. &#x0D; Conclusion: In this study, we found T-wave peaks in half of the athletes after exercise. The serum cTnT levels of young athletes may be elevated by exercise and that LVM and LVMI may be higher in athletes. Echocardiography and ECG evaluations should be performed in paediatric athletes.

Multimodal Imaging of Cancer Therapy-Related Cardiac Dysfunction in Breast Cancer-A State-of-the-Art Review.

This review focuses on multimodality imaging of cardiotoxicity in cancer patients, with the aim of evaluating the effectiveness of different techniques in detecting and monitoring cardiac changes associated with cancer therapy. Eight studies were included in the review, covering various imaging modalities such as cardiac magnetic resonance imaging, echocardiography, and multigated acquisition scanning. Cardiac magnetic resonance imaging emerged as the most definitive modality, offering real-time detection, comprehensive assessment of cardiac function, the ability to detect early myocardial changes, and superior detection of cardiotoxicity when compared to the other imaging modalities. The studies also emphasize the importance of parameters such as left ventricular ejection fraction and global longitudinal strain in assessing cardiac function and predicting cardiotoxicity. Due to the common use of HER2 agents and anthracyclines within the breast cancer population, the LVEF as a critical prognostic measurement for assessing heart health and estimating the severity of left-sided cardiac malfunction is a commonly used endpoint. CTRCD rates differed between imaging modalities, with cardiac MRI the most sensitive. The use of multimodal cardiac imaging remains a nuanced area, influenced by local availability, the clinical question at hand, body habits, and medical comorbidities. All of the imaging modalities listed have a role to play in current care; however, focus should be given to increasing the provision of cardiac MRI for breast cancer patients in the future to optimize the detection of CTRCD and patient outcomes thereafter.

Effect of trimetazidine on ventricular remodeling, serum Cys C and ET-1 levels in patients with chronic heart failure

Purpose: To evaluate the effect of trimetazidine on ventricular remodeling and serum levels of cystatin C and endothelin-1 in patients with chronic heart failure (CHF).Methods: A total of 96 patients with CHF were randomly divided into two groups, given either conventional treatment (control group) or conventional treatment plus trimetazidine (study group) for 6 months. Clinical efficacy was compared between the two groups. Left ventricular ejection fraction (LVEF), left ventricular end-systolic diameter (LVESD) and left ventricular end-diastolic diameter (LVEDD) were measured using cardiac echocardiography before and after treatment. Patients wererecorded at 6 MVT before and after treatment. An automatic biochemical analyzer was used to assay serum Cys C levels before and after treatment. Serum levels of ET-1, galactose agglutinin-3 (GAL-3), brain natriuretic peptide (BNP) and heart natriuretic peptide (ANP) were determined by enzyme-linked immunosorbent assay (ELISA) before and after treatment. Incidence of adverse events in CHF patients was compared between groups.Results: Study group had a significantly higher level of treatment effectiveness (91.67 %) and better improvement in left ventricular ejection fraction, left ventricular end-systolic diameter and left ventricular end-diastolic diameter than control group (p &lt; 0.05). Serum levels of serum cystatin C, endothelin-1 and other biomarkers were also significantly lower (p &lt; 0.05) in study group. Re-hospitalization rate was also lower in study group.Conclusion: Trimetazidine exerts a therapeutic effect on CHF patients, effectively improves cardiac function and reduces the rate of re-hospitalization.

Preservation of Circumferential and Radial Left Ventricular Function as a Mitigating Mechanism for Impaired Longitudinal Strain in Early Cardiac Amyloidosis

In patients with cardiac amyloidosis (CA), left ventricular ejection fraction (LVEF) is frequently preserved, despite commonly reduced global longitudinal strain (GLS). We hypothesized that nonlongitudinal contraction may initially serve as a mitigating mechanism to maintain cardiac output and studied the relationship between global circumferential (GCS) and radial (GRS) strain with LVEF and extracellular volume (ECV), a marker of amyloid burden. Patients with CA who underwent cardiac magnetic resonance (CMR; n=140, 70.7±11.5years, 66% male) or echocardiography (n=67, 71±13years, 66% male) and normal controls (CMR, n=20; echocardiography, n=45) were retrospectively identified, and GCS, GLS, and GRS were quantified using feature-tracking CMR or speckle-tracking echocardiography and compared between CA patients with preserved and reduced LVEF (CAHFpEF, CAHFrEF) and controls. The prevalence of impaired strain (magnitudes <2.5th percentile of the controls) was compared between CAHFpEF and CAHFrEF and between ECV quartiles. While echocardiography-derived GLS was impaired in both CAHFpEF (-13.4%±3.1%, P<.003) and CAHFrEF (-9.1%±3.2%, P<.003), compared with controls (-20.8%±2.4%), GCS was more impaired in CAHFrEF compared with both controls (-15.6%±5.0% vs -32.3%±3.3%, P<.003) and CAHFpEF (-30.4%±5.7%, P<.003) and did not differ between CAHFpEF and controls (P=.24). The prevalence of abnormal CMR-derived GCS (P<.0001) and GRS (P<.0001) but not GLS (P=.054) varied significantly across ECV quartiles. Among CA patients with preserved LVEF, preserved GCS and GRS, despite near-universally impaired GLS, may be explained by an initial predominantly subendocardial involvement, where mostly longitudinal fibers are located. If confirmed in future studies, these findings may facilitate identification of patients with early stages of CA, when treatments may be most effective.

Remodeling in early myocardial infarction: alteration of extracellular matrix; Collagen-1, Collagen-3, α-SMA, and α-Actinin in Porcine heart model

Link of Video Abstract: https://youtu.be/lThOW40upEc Background: Myocardial infarction (MI) leads to remodeling due to altered cardiac structure and function. The study of MI histopathology in humans or large animals mimicking the human heart is limited. Using the porcine heart model, our study investigated the composition of myocardial extracellular matrix (ECM) in collagen-1, collagen-3, α-smooth muscle actin (α-SMA), and α-actinin before and after myocardial infarction. Methods: This study used two groups of domestic pigs: the Infarct group (n=4) and the Sham group (n=4). MI was induced by permanent ligation of the proximal branch of the posterior left ventricular artery. Cardiac enzymes, electrocardiography, and echocardiography data were collected before and after ligation. Cardiac tissue was harvested from the infarcted area after 60 minutes of ligation and stained with hematoxylin-eosin and Movat's Pentachrome. Collagen-1, collagen-3, and α-SMA were identified with immunohistochemical labeling, and the labeled area was measured using ImageJ. Meanwhile, α-actinin was visualized using immunofluorescence. Results: Expression of collagen-1, collagen-3, and α-SMA in the infarct group were significantly decreased after 60 minutes of infarction compared with those in the sham group (p&lt;0.01). The α-actinin was fragmented and diminished in the infarct group. Conclusion: Myocardial remodeling was detected 60 minutes after infarction with mild alteration in myocardial histoarchitecture and significant deterioration of ECM composition of collagen-1, collagen-3, α-SMA, and fragmented α-actinin fibers in the porcine heart model.

Effect of vinpocetine alone and in combination with enalapril in experimental model of diabetic cardiomyopathy in rats: possible involvement of PDE-1/TGF-β/ Smad 2/3 signalling pathways.

Diabetic cardiomyopathy (DC) is one of the severe secondary complications of diabetes mellitus in humans. Vinpocetine is an alkaloid having pleiotropic pharmacological effects. The present study is designed to investigate the effect of vinpocetine in DC in rats. Rats were fed a high-fat diet for nine weeks along with single dose of streptozotocin after the second week to induce DC. The haemodynamic evaluation was performed to assess the functional status of rats using the Biopac system. Cardiac echocardiography, biochemical, oxidative stress parameters and inflammatory cytokine level were analysed in addition to haematoxylin-eosin and Masson's trichome staining to study histological changes, cardiomyocyte diameter and fibrosis, respectively. Phosphodiesterase-1 (PDE-1), transforming growth factor-β (TGF-β) and p-Smad 2/3 expression in cardiac tissues were quantified using western blot/RT-PCR. Vinpocetine treatment and its combination with enalapril decreased the glucose levels compared to diabetic rats. Vinpocetine improved the echocardiographic parameters and cardiac functional status of rats. Vinpocetine decreased the cardiac biochemical parameters, oxidative stress, inflammatory cytokine levels, cardiomyocyte diameter and fibrosis in rats. Interestingly, expressions of PDE-1, TGF-β and p-Smad 2/3 were ameliorated by vinpocetine alone and in combination with enalapril. Vinpocetine is a well-known inhibitor of PDE-1 and the protective effect of vinpocetine in DC is exerted by inhibition of PDE-1 and subsequent inhibition of the expression of TGF-β/Smad 2/3.