Ventricular Contractility Research Articles

Abstract 17096: Immune Modulation to Treat Ischemic Heart Failure

Introduction: Clinical use of induced pluripotent derived cardiomyocytes (iPSC-CMs) has been slow because their mechanism is not well defined. Our lab developed a cardiac patch composed of iPSC-CMs and human neonatal dermal fibroblast (NDF) seeded on a bioresorbable matrix. Implantation on the epicardium of the infarcted heart in immune competent animal models of ischemic CHF (mice, rats, swine) repaired the damaged heart, improved cardiac function/structure with increased viable myocardium, increased myocardial blood flow, improved left ventricular (LV) contractility, and reversal of maladaptive LV remodeling. Preliminary analysis indicates that the patch created a novel host derived immune response not observed in untreated animals. Hypothesis: The iPSC-CMs and NDFs coordinate an immunomodulatory response that results in reduction of inflammatory cytokine producing M1 macrophages with concomitant polarization to the M2 state. Methods: Spatial transcriptomics and histological analysis was utilized for investigation of patch driven immunomodulatory responses in WT BL6 mice. All animals underwent two procedures; 1) Infarct via left coronary ligation 2) Left lateral sternotomy with patch placement (N=5) (no patch for controls, N=3) 3 weeks post MI. Patch secretions underwent quantitative mass spectroscopy to identify drivers of immunomodulation. Results: Histology demonstrated reduction of left chamber dimension and presence of viable cardiomyocytes in the LV wall. IF demonstrated a novel immune response in the treated group absent in the controls. This response is isolated to the epicardial infarct-patch interface. Cellular deconvolution of the infarct region revealed macrophages and dendritic cells compose this response. Macrophage phenotype was assessed via expression of classical M1(CD68, NOS2, AXL) as well as M2 markers (RETNLA, MRC1, ADGRE1) which were found to be significantly elevated in treated groups. Proteomic analysis of the patch secretome indicates the patch has a role in coordinating this response by upregulation of Il-4/Il-13 signaling and wound healing that stimulates enrichment of pathways associated with reorganization of the ECM.

Abstract 13550: Prognostic Value of the Global Left Ventricular Contractility Index in Patients With Severe Mitral Regurgitation and Preserved Left Ventricular Ejection Fraction

Introduction: Global left ventricular (LV) contractility index, dσ*/dt max , defined as the maximal rate of change of pressure-normalized LV wall stress, is given by the formula 3(dV/dt) max /2V m where dV/dt max is the product of left ventricular outflow tract (LVOT) velocity and area; and V m , left ventricular mass index (LVMI). In published reports, prediction of clinical outcomes in aortic stenosis were observed. It is unknown if dσ*/dt max would predict clinical outcomes in patients with severe mitral regurgitation (MR). Aim: We studied the association of dσ*/dt max with clinical outcomes in severe MR with preserved LV ejection fraction (EF). Methods: Consecutive patients with severe MR and LVEF ≥50% diagnosed on index echocardiogram at a single centre were retrospectively analyzed. Patients with other valvular lesions of moderate severity or more, or valvular interventions, were excluded. Clinical outcomes were ascertained by review of medical records. The primary outcome was a composite of heart failure hospitalizations and all-cause mortality. Results: 176 patients were included in the analysis. Table 1 depicts the characteristics of the study population. Patients with composite outcomes were older, more likely to be female, had higher LVMI, lower regurgitation volume and dσ*/dt max (2.2 +/- 0.7 vs 2.7 +/- 0.9, p = 0.02). On multivariable Cox regression (Table 2), only age and dσ*/dt max (adjusted HR 0.42, 95% CI: 0.220 - 0.806, p = 0.01) remained independently associated with occurrence of the primary outcome. Conclusions: In patients with isolated severe mitral regurgitation and preserved LVEF, low dσ*/dt max was an independent predictor of adverse clinical outcomes.

Abstract 15649: Human Induced Pluripotent Stem Cell-Derived Cardiac Fibroblast Assembled Extracellular Matrix Rescues Cardiac Function in an Acute Myocardial Infarction Mouse Model

Background: Acute myocardial infarction (AMI) is the leading cause of heart failure (HF). Therapies to curb post-AMI pathological left ventricular remodeling could reduce the burden of HF. Human iPSC derived cardiac fibroblast assembled extracellular matrix (iCFX) is a novel acellular biomaterial that consists of a unique blend of extracellular matrix proteins with tissue reparative potential. We hypothesize that direct cardiac injection of iCFX into the peri-infarct border in a mouse AMI model will restore cardiac function and reduce pathological remodeling. Methods: Acute MI was induced by permanent ligation of the left anterior descending coronary artery in 10-week immunocompetent C57BL/6 mice. iCFX was supplied by Cellular Logistics Inc, Madison, WI. One day post-AMI, mice were randomly treated with a 50 microliter epicardial injection of either PBS control, 1 mg iCFX or 10 mg iCFX. Baseline and 28-day echo were performed. Results: At baseline, there were no differences in any echo parameter between treatment groups. By 28 days post treatment, mice treated with 10 mg iCFX had increased ejection fraction ((25.8+/-3.1% (n=8) vs. (13.9+/-1.8% (n=11) p=0.001), fractional shortening ((15.5+/-2.0% (n=8) vs. 6.9+/-1.3%) (n=11) p=0.003), and cardiac output (16.0+/-2.3 ml/min (n=8) vs. 9.7+/-1.2 ml/min (n=11) p=0.002) compared to placebo treated animals. The 1 mg dosing group showed non-significant improvements in contractility parameters. Reduced end systolic and end diastolic volumes in the 10 mg group was observed, but these were not statistically significant. Conclusions: Therapeutic administration of human iCFX was associated with significant improvements in left ventricular contractility following AMI in an immunocompetent mouse model. Furthermore, a clear dose response pattern was observed.

Abstract 15449: Cardiopulmonary Best Abstract Award : Pausing Reveals Exercise-Induced Uncoupling: Exploring the Dynamics of RV-PA Coupling in the Six-Minute Walking Test

Background: The six-minute walking test (6MWT) is a commonly used test for assessing the functional capacity of patients with pulmonary hypertension (PH), providing functional and prognostic information. Functional capacity depends on RV-PA coupling, the matching of right ventricular contractility to afterload. However, the dynamics of RV-PA coupling during the 6MWT have never been studied. Methods: We used a wireless hemodynamic monitoring system (CorLog, emka-medical, Germany) to continuously measure right ventricular pressure in 10 patients with PH (8 = group I, 1 = III, 1 = IV) during a 6MWT. We calculated right ventricular ejection fraction (RVEF) and Ees/Ea based on the pressure signal as shown in the figure (panel a). Dyspnea was evaluated using the Borg scale. Results: By analyzing the hemodynamic response during the 6MWT, we identified two patterns: 1) Improved/preserved coupling: Five patients exhibited an initial improvement in Ees/Ea and maintained coupling at least at the baseline level throughout the test, without requiring pauses. 2) Uncoupling associated with pauses: Five patients experienced a slight increase in Ees/Ea at the beginning, followed by a progressive loss of coupling and ejection fraction, necessitating pauses. During pauses, Ees/Ea values restored, enabling patients to resume walking. Patients of the second phenotype reported higher levels of dyspnea. The highest reported Borg score was 8 ± 0.9 vs. 4.6 ± 1.2 in the first group. Also, the covered distance was shorter in the second group (159 ± 64m vs. 288 ± 88m, p=0.03). Both groups showed differences in Ees/Ea (0.47 [0.46 - 0.57] vs. 0.34 [0.30 - 0.43], P=0.05) and RVEF (34 ± 4.1% vs. 28.5 ± 2.6%, P=0.03) at baseline, with Group One exhibiting superior values. Conclusion: This is the first investigation into the significance of RV-PA coupling in real-life exercise limitation and dyspnea during the 6MWT. Pauses observed during the 6MWT can serve as indicators of exercise-induced uncoupling.

Abstract 14278: 14 Days of Severe, Sustained Normobaric Hypoxic Enhances Left Ventricular Contractility in Patients After Myocardial Infarction

Studies in mice with experimental myocardial infarction revealed, that sustained severe normobaric hypoxia (FiO2=0.07) reactivates cardiomyocyte proliferation and improves left ventricular ejection fraction. Our study aimed to test safety and feasibility in humans and to assess whether hypoxia improves left ventricular contractility in selected patients with myocardial scars following myocardial infarction.Three males, who suffered myocardial infarction 49-126 months prior to study entry, whose capability for hypoxia acclimatization was validated previously and one healthy male control participated in this proof-of-concept study. After preacclimatization we induced severe hypoxia by adding nitrogen until alveolar oxygen partial pressure reached about 35 mmHg. Hypoxia was maintained for 14 consecutive days (FiO2=0.095) and nights (FiO2=0.105). We assessed ventricular function by echocardiographic-derived global longitudinal strain (LVGLS), serum NTproBNP, high-sensitive Troponin I levels, and marker of myocardial repair. Cardiac 18F-FDG-PET-MRI was done at baseline, end of hypoxia exposure, and at 30 days follow-up. LVGLS increased in prior viable myocardium, but also in areas adjacent to the myocardial scar (baseline: -12.57±2.4 %, end of hypoxia: -14.37±2.62% recovery day 3: -14.33±2.72%, 30 days follow-up: -15.2±3.11%, p=0.0182). NTproBNP tended to decrease (baseline: 189±134 pg/ml, end of hypoxia: 127±28 pg/ml, recovery day 3: 114±18 pg/ml, 30 days follow-up: 108±65 pg/ml). These parameters were not affected in the control. MRI-derived left ventricular enddiastolic volume remained unchanged, but end-systolic left ventricular volume decreased in patients (baseline: 108±49 ml, recovery day 3: 92±50 ml, 30 days follow-up: 101±47 ml, p=0.0068). Troponin I remained in the reference range in all participants. The patient with the most pronounced increase in LVGLS revealed a relevant increase in FDG-uptake at the follow-up, which was also observed in areas adjacent to the myocardial scar.Given the small sample size and the selection of patients, our results have to be interpreted with caution. However, the data indicate potentially beneficial hypoxia-mediated effects in selected patients with ischemic heart disease.

When too much closeness harms: circumflex artery injury during mitral valve surgery.

Occlusion of the left coronary circumflex artery (LCX) during surgical procedures of the mitral valve is an infrequent but potentially life-threatening complication (1-3). Due to its close anatomical relationship to the posterior mitral valve annulus, there is a relevant risk of causing a stenosis or an occlusion of the left circumflex artery, especially by surgical annular sutures. The perioperative clinical course is heterogeneous, ranging from-initially-asymptomatic or solely electrocardiographic abnormalities to cardiogenic shock. Both severely impaired ventricular contractility or malignant arrhythmia may potentially lead to a weaning failure from cardiopulmonary bypass (CPB) and eventually result in chronic heart failure with persistently reduced ejection fraction. Possible therapeutic strategies include the immediate reopening of causal sutures, aortocoronary bypass grafting or percutaneous coronary intervention (PCI), yet PCI seems to be the preferred method at present.

Differences in Mechanical, Electrical and Calcium Transient Performance of the Isolated Right Atrial and Ventricular Myocardium of Guinea Pigs at Different Preloads (Lengths)

There are only a few studies devoted to the comparative and simultaneous study of the mechanisms of the length-dependent regulation of atrial and ventricular contractility. Therefore, an isometric force-length protocol was applied to isolated guinea pig right atrial (RA) strips and ventricular (RV) trabeculae, with a simultaneous measurement of force (Frank–Starling mechanism) and Ca2+ transients (CaT) or transmembrane action potentials (AP). Over the entire length-range studied, the duration of isometric contraction, CaT and AP, were shorter in the RA myocardium than in the RV myocardium. The RA myocardium was stiffer than the RV myocardium. With the increasing length of the RA and RV myocardium, the amplitude and duration of isometric contraction and CaT increased, as well as the amplitude and area of the “CaT difference curves” (shown for the first time). However, the rates of the tension development and relaxation decreased. No contribution of AP duration to the heterometric regulation of isometric tension was found in either the RA or RV myocardium of the guinea pig. Changes in the degree of overlap of the contractile proteins of the guinea pig RA and RV myocardium mainly affect CaT kinetics but not AP duration.

Right Ventricular Contractility and Pulmonary Arterial Coupling After Less Invasive Left Ventricular Assist Device Implantation.

Right ventricular failure contributes significantly to morbidity and mortality after left ventricular assist device implantation. Recent data suggest a less invasive strategy (LIS) via thoracotomy may be associated with less right ventricular failure than conventional median sternotomy (CMS). However, the impact of these approaches on load-independent right ventricular (RV) contractility and RV-pulmonary arterial (RV-PA) coupling remains uncertain. We hypothesized that the LIS approach would be associated with preserved RV contractility and improved RV-PA coupling compared with CMS. We performed a retrospective study of patients who underwent durable, centrifugal left ventricular assist device implantation and had paired hemodynamic assessments before and after implantation. RV contractility (end-systolic elastance [Ees]), RV afterload (pulmonary effective arterial elastance [Ea]), and RV-PA coupling (Ees/Ea) were determined using digitized RV pressure waveforms. Forty-two CMS and 21 LIS patients were identified. Preimplant measures of Ees, Ea, and Ees/Ea were similar between groups. After implantation, Ees declined significantly in the CMS group (0.60-0.40, p = 0.008) but not in the LIS group (0.67-0.58, p = 0.28). Coupling (Ees/Ea) was unchanged in CMS group (0.54-0.59, p = 0.80) but improved significantly in the LIS group (0.58-0.71, p = 0.008). LIS implantation techniques may better preserve RV contractility and improve RV-PA coupling compared with CMS.

Cardiovascular sex-differences: insights via physiology-based modeling and potential for noninvasive sensing via ballistocardiography.

In this study, anatomical and functional differences between men and women in their cardiovascular systems and how these differences manifest in blood circulation are theoretically and experimentally investigated. A validated mathematical model of the cardiovascular system is used as a virtual laboratory to simulate and compare multiple scenarios where parameters associated with sex differences are varied. Cardiovascular model parameters related with women's faster heart rate, stronger ventricular contractility, and smaller blood vessels are used as inputs to quantify the impact (i) on the distribution of blood volume through the cardiovascular system, (ii) on the cardiovascular indexes describing the coupling between ventricles and arteries, and (iii) on the ballistocardiogram (BCG) signal. The model-predicted outputs are found to be consistent with published clinical data. Model simulations suggest that the balance between the contractile function of the left ventricle and the load opposed by the arterial circulation attains similar levels in females and males, but is achieved through different combinations of factors. Additionally, we examine the potential of using the BCG waveform, which is directly related to cardiovascular volumes, as a noninvasive method for monitoring cardiovascular function. Our findings provide valuable insights into the underlying mechanisms of cardiovascular sex differences and may help facilitate the development of effective noninvasive cardiovascular monitoring methods for early diagnosis and prevention of cardiovascular disease in both women and men.

Development and validation of risk prediction and neural network models for dilated cardiomyopathy based on WGCNA.

Dilated cardiomyopathy (DCM) is a progressive heart condition characterized by ventricular dilatation and impaired myocardial contractility with a high mortality rate. The molecular characterization of DCM has not been determined yet. Therefore, it is crucial to discover potential biomarkers and therapeutic options for DCM. The hub genes for the DCM were screened using Weighted Gene Co-expression Network Analysis (WGCNA) and three different algorithms in Cytoscape. These genes were then validated in a mouse model of doxorubicin (DOX)-induced DCM. Based on the validated hub genes, a prediction model and a neural network model were constructed and validated in a separate dataset. Finally, we assessed the diagnostic efficiency of hub genes and their relationship with immune cells. A total of eight hub genes were identified. Using RT-qPCR, we validated that the expression levels of five key genes (ASPN, MFAP4, PODN, HTRA1, and FAP) were considerably higher in DCM mice compared to normal mice, and this was consistent with the microarray results. Additionally, the risk prediction and neural network models constructed from these genes showed good accuracy and sensitivity in both the combined and validation datasets. These genes also demonstrated better diagnostic power, with AUC greater than 0.7 in both the combined and validation datasets. Immune cell infiltration analysis revealed differences in the abundance of most immune cells between DCM and normal samples. The current findings indicate an underlying association between DCM and these key genes, which could serve as potential biomarkers for diagnosing and treating DCM.

FRI500 Atypical Case Of Undifferentiated Shock

Abstract Disclosure: V. Vadini: None. P. Vasistha: None. Introduction: Shock is encountered frequently in the ICU. Undifferentiated shock, however, poses a diagnostic challenge. The differentials and work up are broad and time sensitive. Endocrinopathies are a known etiology but thyroid cardiomyopathy causing cardiogenic shock is rare. Clinical case: A 78 y old man presented to the ER with hypotension that did not improve after administration of 2.5 L IV fluids. Vasopressors were initiated and he was admitted to the ICU. Patient reported 2-month history of generalized weakness, nausea, vomiting, falls and poor oral intake. Review of systems was notable for 20-pound weight loss in 6 months, dyspnea with exertion, loss of appetite and occasional diarrhea. On exam, patient was afebrile, hypotensive 80/40, PR 87, O2 saturation > 90% on room air. He appeared pale with JVP measured at 11 cm of water. Pulse was irregular, heart sounds normal without murmurs. Bilateral lower extremities were mildly edematous. Strength in lower extremities was 4/5 proximal and distally. Labs were notable for normocytic anemia, troponin 1.05, elevated anion gap 18, lactate 1.8, creatinine 3.3 from a baseline of 1 and BNP 1425. ECG showed sinus rhythm with frequent premature atrial contractions. Chest Xray on admission was unremarkable. Additional labs were negative drug screen, normal cortisol, urinalysis. Blood cultures were sent. Overnight, the patient developed tachycardia and atrial fibrillation with rapid ventricular rate. Cardiology was consulted, bedside echo was suspicious for low left ventricular ejection fraction. The patient was anticoagulated with heparin. TSH was sent. He was requiring 2 vasopressors to maintain MAP>65. CT chest abdomen pelvis was unremarkable except stable pulmonary nodule. Patient became hypoxic on Day 2 of admission, CXR now showed features of pulmonary edema. TSH returned less than 0.01, free T4 4.69 Endocrinology was consulted, methimazole was started for thyrotoxicosis. Formal TTE showed LVEF 20-25% with global reduction in left ventricular contractility, dilated left atrium and mild MR. He was given furosemide for pulmonary edema. TSI and TRAB were positive indicating Grave’s disease. He was successfully transferred out of the ICU. Patient gradually became euvolemic with significant improvement in energy, appetite and functional capacity. He was able to participate in physical therapy and was eventually discharged to rehab. Conclusion: This case addresses an uncommon but potentially life-threatening cause of undifferentiated shock. Physical exam, history and high degree of suspicion are key in early identification and treatment. Although thyroid cardiomyopathy is rare, Grave’s disease is common and ruling our thyrotoxicosis should be included in preliminary work up of undifferentiated shock. Presentation: Friday, June 16, 2023

Concordancia de la evaluación ecocardiográfica básica funcional del ventrículo izquierdo entre médicos no expertos y cardiólogos especialistas en ecocardiografía

IntroductionThe clinical decisions of patients in the intensive care unit are based on the integration of the clinical history and complementary tests. The echocardiographic evaluation can reveal decisive information in the interventions and in the prognosis of the patients. ObjectiveTo determine the concordance in the analysis of left ventricular systolic function performed by physicians with basic training in echocardiography compared with the assessment by expert cardiologists. MethodologyCross-sectional study of diagnostic concordance with prospective recruitment. Patients hospitalized in the intensive care unit during 2023 in a university clinic with a high level of complexity were included. The concordance between the trained physician and the expert was analyzed using the Kappa index (κ) for the qualitative variables, and the intraclass correlation coefficient for the quantitative ones. Results131 patients were included, with a mean age of 62 years. The concordance of the echocardiographic assessment was determined, finding very good concordance for left ventricular contractility (κ: 0.97), pericardial effusion (κ: 0.82) and its location (κ: 0.85), contractility disorders (κ: 0.84) and in the quantitative measurement of the ejection fraction (intraclass correlation coefficient: 0.91). ConclusionsThere is agreement in the evaluation of left ventricular systolic function in patients hospitalized in the intensive care unit by non-expert medical personnel with training and expert cardiologists. The results should be interpreted as part of a comprehensive assessment at the patient's bedside and not as an isolated diagnosis, always under quality standards and with the necessary verification.

The Anti-Inflammatory Mediator 17(R)-Resolvin D1 Attenuates Pressure Overload-Induced Cardiac Hypertrophy and Fibrosis.

Increased inflammation contributes to pressure overload-induced myocardial remodeling. 17(R)-Resolvin D1 (17(R)-RvD1), a potent lipid mediator derived from docosahexaenoic acid, possesses anti-inflammatory and pro-resolving properties. However, the association between 17(R)-RvD1 and pressure overload-induced cardiac hypertrophy remains unclear. Transverse aortic constriction (TAC) surgery was performed to establish a cardiac hypertrophy model. C57BL/6J mice were randomly assigned to the Sham, TAC and TAC+17(R)-RvD1 groups. 17(R)-RvD1 was injected (2 μg/kg, i.p.) before TAC surgery and once every other day after surgery for 4 weeks. The same volume of saline was injected into the mice in both Sham group and TAC group. Then, cardiac function was evaluated and heart tissues were collected for biological analysis. 17(R)-RvD1 treatment attenuated TAC-induced increase in left ventricular diameter and decrease in left ventricular contractility, mitigated increased cardiomyocyte cross-sectional area, and downregulated the expression of hypertrophic genes. Besides, 17(R)-RvD1 attenuated myocardial fibrosis, as indicated by the decreased LV collagen volume and expression of fibrotic genes. In addition, 17(R)-RvD1 ameliorated the inflammatory response in cardiac tissue, as illustrated by the decreased infiltration of CD68+ macrophages and reduced production of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6. 17(R)-RvD1 treatment significantly suppressed the activation of NLRP3 inflammasome after TAC surgery, which might be responsible for the attenuation of inflammation in cardiac tissue. 17(R)-RvD1 attenuated pressure overload-induced cardiac hypertrophy and fibrosis, and the possible mechanism may be associated with the inhibition of NLRP3 inflammasome. 17(R)-RvD1 may serve as a potential drug for the treatment of cardiac hypertrophy.

Diagnostic value of exercise stress echocardiography on a horizontal cycle ergometer in patients with low-risk non-ST elevation acute coronary syndrome

Aim. To evaluate the diagnostic accuracy of exercise stress echocardiography on a horizontal cycle ergometer for the detection of obstructive coronary artery disease (CAD) in patients with low-risk non-ST-elevation acute coronary syndrome (NSTE-ACS).Material and methods. The study included 95 patients aged 53 (46;63) years (men, 58%), hospitalized in the regional vascular center with low-risk NSTE-ACS. Patients with known CAD, impaired resting left ventricular contractility were not included. During hospitalization, standard stress echocardiography on a horizontal cycle ergometer and invasive or non-invasive coronary angiography (CAG) were performed. All values of coronary obstruction ≥70% were verified by invasive CAG. The assessment of myocardial revascularization was observational.Results. All patients had normal structural and functional cardiac parameters at rest. No adverse events were recorded during the tests. The result of stress echocardiography according to impaired local contractility (ILC) criterion was positive in 9 (16%), negative in 28 (49%), incomplete symptom-limited in 20 (35%) patients. Coronary artery stenosis ≥50%/≥70% was detected in 78/78% of cases in the subgroup with a positive result, in 29/11% — with a negative result, 30/10% — with a non-diagnostic result. The association of ILC with stenosis ≥70% was higher, with an odds ratio of 30,1 (4,9; 186,5) vs 8,5 (1,6; 46,1) for stenosis ≥50%. There were following diagnostic accuracy for stenosis ≥70%: sensitivity — 70%, specificity — 93%, positive predictive value — 78%, negative predictive value — 89%, overall accuracy — 86%.Conclusion. Exercise stress echocardiography on a horizontal cycle ergometer in patients with low-risk NSTE-ACS patients is safe and feasible. The method has moderate sensitivity and positive predictive value and high specificity, negative predictive value and overall accuracy for the detection of anatomically significant coronary artery stenosis. In the structure of results, there is a significant proportion (35%) of symptom-limited tests incomplete due to heart rate, characterized by the lowest incidence of obstructive atherosclerosis.

Comparison of hemodynamic effects of chest compression delivered via machine or human in asphyxiated piglets

BackgroundHigh-quality chest compressions (CC) are an important factor of neonatal resuscitation. Mechanical CC devices may provide superior CC delivery and improve resuscitation outcomes. We aimed to compare the hemodynamic effects of CC delivered by machine and human using a neonatal piglet model.MethodsTwelve asphyxiated piglets were randomized to receive CC during resuscitation using an automated mechanical CC device (“machine”) or the two-thumb encircling technique (“human”). CC was superimposed with sustained inflations.ResultsTwelve newborn piglets (age 0–3 days, weight 2.12 ± 0.17 kg) were included in the study. Machine-delivered CC resulted in an increase in stroke volume, and minimum and maximum rate of left ventricle pressure change (dp/dtmin and dp/dtmax) compared to human-delivered CC.ConclusionsDuring machine-delivered CC, stroke volume and left ventricular contractility were significantly improved. Mechanical CC devices may provide improved cardiopulmonary resuscitation outcomes in neonatal cardiac arrest induced by asphyxia.ImpactMachine chest compression leads to changes in hemodynamic parameters during resuscitation of asphyxiated neonatal piglets, namely greater stroke volume and left ventricular contractility, compared with standard two-thumb compression technique. Mechanical chest compression devices may provide improved cardiopulmonary resuscitation outcomes in neonatal and pediatric asphyxia-induced cardiac arrest.

Acausal Modelling of Advanced-Stage Heart Failure and the Istanbul Heart Ventricular Assist Device Support with Patient Data.

In object-oriented or acausal modelling, components of the model can be connected topologically, following the inherent structure of the physical system, and system equations can be formulated automatically. This technique allows individuals without a mathematics background to develop knowledge-based models and facilitates collaboration in multidisciplinary fields like biomedical engineering. This study conducts a preclinical evaluation of a ventricular assist device (VAD) in assisting advanced-stage heart failure patients in an acausal modelling environment. A comprehensive object-oriented model of the cardiovascular system with a VAD is developed in MATLAB/SIMSCAPE, and its hemodynamic behaviour is studied. An analytically derived pump model is calibrated for the experimental prototype of the Istanbul Heart VAD. Hemodynamics are produced under healthy, diseased, and assisted conditions. The study features a comprehensive collection of advanced-stage heart failure patients' data from the literature to identify parameters for disease modelling and tovalidate the resulting hemodynamics. Regurgitation, suction, and optimal speeds are identified, and trends in different hemodynamic parameters are observed for the simulated pathophysiological conditions. Using pertinent parameters in disease modelling allows for more accurate results compared to the traditional approach of arbitrary reduction in left ventricular contractility to model dilated cardiomyopathy. The current research provides a comprehensive and validated framework for the preclinical evaluation of cardiac assist devices. Due to its object-oriented nature, the featured model is readily modifiable for other cardiovascular diseases for studying the effect of pump operating conditions on hemodynamics and vice versa in silico and hybrid mock circulatory loops. The work also provides a potential teaching tool for understanding the pathophysiology of heart failure, diagnosis rationale, and degree of assist requirements.

Cardiovascular disorders in children with COVID-19

Background. The purpose of the work is to study the prevalence of cardiac disorders in hospitalized children with coronavirus disease (COVID-19). Materials and methods. A retrospective, cohort, monocenter study of the medical records of children who underwent inpatient treatment between September and December 2021 at the Kyiv City Children’s Clinical Infectious Disease Hospital was conducted. For our study, we selected the medical records of patients with polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the presence of at least one result of cardiac activity examination by electrocardiography (ECG) and/or echocardiography. The first study of cardiac activity by ECG and/or echocardiography was carried out in the first three days of inpatient treatment. Standard methods of descriptive statistics were used for data processing. Non-parametric statistical methods (Mann-Whitney test, chi-square, Pearson’s exact test) were used for mathematical analysis. The research was carried out in accordance with the Declaration of Helsinki principles. The study was approved by the bioethics committee of the hospital. Results. Among 305 children hospitalized with a diagnosis of U07.1 (2019-nCoV acute respiratory disease), there were selected 195 medical histories of patients aged 15 days to 18 years (median of 5.37 years), who were examined for cardiac activity by ECG and/or echocardiography. The most common changes were rhythm disturbances in the form of sinus tachycardia (20.8 %), bradycardia (11.9 %) and sinus arrhythmia (7.9 %), ventricular conduction disorders (25.7 %), deviation of the electrical axis of the heart (10.9 %) and repolarization disorders (31.7 %). During echocardiographic examination, structural abnormalities in the form of myocardial hypertrophy were detected in 3.1 % of patients, dilated heart chambers in 2 %, and pericardial effusion in 9.2 %. Among the functional changes, we observed: a decrease in left ventricular contractility in 4.1 % of cases, in cardiac output in 28.6 %, and an increase in total peripheral resistance in 41.8 %. Heart rhythm disturbances in the form of sinus tachycardia, deviation of the electrical axis of the heart, a decrease in the amplitude of the ECG waves, repolarization disorders, and pericardial effusion were associated with an increased risk of death in children with COVID-19. Clinical cases of cardiovascular complications in the form of jugular vein thrombosis and infectious endocarditis illustrate the role of the cardiovascular system in the pathogenesis of coronavirus disease. Conclusions. SARS-CoV-2 infection is often associated with damage to the cardiovascular system. In most pediatric patients, this occurs in the form of subclinical changes registered during laboratory or instrumental studies, but the development of manifest forms such as myocarditis, endocarditis, pericarditis, heart attack, coronary disease, thrombotic complications, and heart failure is possible. Using simple non-invasive methods (ECG and echocardiography) during screening, it is possible to diagnose damage to the cardiovascular system, as well as to detect changes in the cardiovascular system, which are subclinical, but can have an important prognostic value regarding the adverse course of the disease in children, which are hospitalized with SARS-CoV-2 infection.

Safety confirmation of induced pluripotent stem cell-derived cardiomyocyte patch transplantation for ischemic cardiomyopathy: first three case reports.

With the expected increase in patients with heart failure and ischemic 15 cardiomyopathy, the development of myocardial regenerative medicine using cell transplantation as a novel treatment method is progressing. This first-in-human clinical trial aimed to confirm the safety of cardiomyocyte patch transplantation derived from allogeneic induced pluripotent stem (iPS) cells based on the results of several preclinical studies. The inclusion criteria were left ventricular ejection fraction of 35% or less; heart failure symptoms of New York Heart Association class III or higher despite existing therapies such as revascularization; and a 1-year observation period that included a 3-month immunosuppressive drug administration period after transplantation of iPS cell-derived cardiomyocyte patches to evaluate adverse events, cardiac function, myocardial blood flow, heart failure symptoms, and immune response. In the first three cases of this trial, no transplanted cell-related adverse events were observed during the 1-year observation period, and improvement in heart failure symptoms was observed. In addition, improvements in left ventricular contractility and myocardial blood flow were observed in two of the three patients. Regarding immune response, an increase in transplant cell-specific antibody titer was observed in all three patients after immunosuppressive drug administration. In one patient with poor improvement in cardiac function and myocardial blood flow, an increase in antibody titer against HLA-DQ was observed even before cell transplantation. Our case findings demonstrate that the transplantation of iPS cell-derived cardiomyocyte patches for ischemic cardiomyopathy can be safely performed; however, further investigation of the therapeutic effect and its relationship with an immune response is needed by accumulating the number of patients through continued clinical trials.

Autonomic neuro-cardiac profile of electrical, structural and neuronal remodeling in myocardial infarction-induced heart failure.

Heart failure is a clinical syndrome typified by abnormal autonomic tone, impaired ventricular function, and increased arrhythmic vulnerability. This study aims to examine electrophysiological, structural and neuronal remodeling following myocardial infarction in a rabbit heart failure model to establish its neuro-cardiac profile. Weight-matched adult male New Zealand White rabbits (3.2±0.1kg, n=25) were randomized to have coronary ligation surgeries (HF group, n=13) or sham procedures (SHM group, n=12). Transthoracic echocardiography was performed six weeks post-operatively. On week 8, dual-innervated Langendorff-perfused heart preparations were set up for terminal experiments. Seventeen hearts (HF group, n=10) underwent ex-vivo cardiac MRI. Twenty-two hearts (HF group, n=7) were examined histologically. Electrical remodeling and abnormal autonomic profile were evident in HF rabbits with exaggerated sympathetic and attenuated vagal effect on ventricular fibrillation threshold, ventricular refractoriness and restitution curves, in addition to increased spatial restitution dispersion. Histologically, there was significant neuronal enlargement at the heart hila and conus arteriosus in HF. Structural remodeling was characterized by quantifiable myocardial scarring, enlarged left ventricles, altered ventricular geometry and impaired contractility. In an infarct-induced rabbit heart failure model, extensive structural, neuronal and electrophysiological remodeling in conjunction with abnormal autonomic profile provide substrates for ventricular arrhythmias.

Cardiac magnetic resonance imaging in mortality risk stratification of patients with pulmonary hypertension

Aim. To compare cardiac magnetic resonance imaging (MRI) parameters with known prognosis determinants in patients with pulmonary hypertension (PH).Material and methods. This prospective single-center study included 60 patients with PH aged 21-72 years. Cardiac MRI, right heart catheterization, echocardiography, N-terminal pro-brain natriuretic peptide (NT-proBNP) and 6-minute walk test (6MWT) were assessed at baseline.Results. Significant correlations between invasive hemodynamic parameters, NTproBNP and cardiac MRI parameters were confirmed. There were no significant correlations between the right ventricular (RV) contractility, RV volume and 6MWT distance, the functional class of PH. Cardiac MRI values allowed us to reliably separate patients at low risk from those at intermediate and high risk according to the 2015 ESC/ERS score. According to multivariate regression analysis, the right ventricular end systolic volume index >54 ml/m2 (hazard ratio, 0,2; 95% confidence interval, 0,05-0,9; p=0,004) and class 3-4 PH (hazard ratio, 0,2; 95% confidence interval, 0,07-0,8; p=0,026) remained independent predictors of mortality.Conclusion. The use of cardiac MRI in low-risk patients can significantly improve the early detection of right ventricular myocardial dysfunction and contribute to the timely optimization of PH-specific therapy. During monitoring patients with PH, cardiac MRI has the potential to reduce the need for repeated invasive investigations.