Left Ventricular Contractility Research Articles

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.

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.

The left ventricle in well newborns versus those with perinatal asphyxia, haemodynamically significant ductus arteriosus or fetal growth restriction.

Hemodynamic changes accompanying the initial breaths at the time of birth are especially important for a smooth transition of fetal to neonatal circulation. Understanding the normal transitional physiology and the clinical impact of adverse adaptation is important for delineating pathology so as to guide physiologically relevant therapies. Disorders such as severe perinatal asphyxia, hemodynamically significant patent ductus arteriosus (and its surgical ligation) and utero-placental insufficiency underlying fetal growth restriction, can adversely affect left ventricular (LV) function. The left ventricle is the predominant chamber involved in systemic perfusion during postnatal life. Cardiac output is closely linked to afterload; the latter is determined by arterial properties such as stiffness and compliance. This article outlines normal transition in term and preterm infants. It also highlights the adverse impact of three not uncommon neonatal disorders on LV function. Perinatal asphyxia leads to a reduced LV output, superior vena cava and coronary artery blood flow and an increase in the troponin level. Multiple haemodynamic changes are observed in the premature infant with a large patent ductus arteriosus. They need careful analysis to determine when ligation should proceed. Ligation itself generally results in a dramatic increase in afterload which may lead to a reduction in LV contractility and the need for ionotropic support. Fetal growth restricted infants have a higher systolic pressure, a somewhat hypertrophied heart arising from an increased arterial wall thickness/stiffness and systemic peripheral resistance. Point of care ultrasound (POCUS) helps differentiate normal transition and that resulting from neonatal disorders. It may be increasingly utilized in guiding management.

Physical model of end-diastolic and end-systolic pressure-volume relationships of a heart.

Left ventricular stiffness and contractility, characterized by the end-diastolic pressure-volume relationship (EDPVR) and the end-systolic pressure-volume relationship (ESPVR), are two important indicators of the performance of the human heart. Although much research has been conducted on EDPVR and ESPVR, no model with physically interpretable parameters combining both relationships has been presented, thereby impairing the understanding of cardiac physiology and pathology. Here, we present a model that evaluates both EDPVR and ESPVR with physical interpretations of the parameters in a unified framework. Our physics-based model fits the available experimental data and in silico results very well and outperforms existing models. With prescribed parameters, the new model is used to predict the pressure-volume relationships of the left ventricle. Our model provides a deeper understanding of cardiac mechanics and thus will have applications in cardiac research and clinical medicine.

Topographical Association Between Left Ventricular Strain and Brain Lesions in Patients With Acute Ischemic Stroke and Normal Cardiac Function.

Background Although it is well known that the disordered brain provokes cardiac autonomic dysfunction, the detailed location of brain lesions related to cardiac function warrants further investigation. We aimed to elucidate the brain lesions topographically associated with left ventricular (LV) systolic function measured by myocardial strain in patients with acute ischemic stroke without preexisting primary cardiac dysfunction by using support vector regression lesion-symptom mapping. Methods and Results Subjects were those with LV ejection fraction of 50% or more among patients with acute ischemic stroke registered in the Samsung Medical Center stroke registry between 2016 and 2017. To evaluate LV systolic performance and contractility, we measured LV ejection fraction and LV global and regional longitudinal strain using 2-dimensional speckle-tracking echocardiography. The association between stroke lesion location and cardiac strain was assessed using support vector regression lesion-symptom mapping. Of a total of 776 patients, 286 subjects (mean age of 67.0 years, 65.4% men) were finally enrolled in this study. The mean global longitudinal strain was -17.0±3.4%, and the mean LV ejection fraction was 64.7±5.7%. The support vector regression lesion-symptom mapping analysis revealed that the right insula and peri-insular regions and left parietal cortex were associated with impaired LV global longitudinal strain in patients with acute ischemic stroke. In addition, impaired regional longitudinal strain showed topographical associations with these regions. Conclusions This study suggests that brain lesions in the right insula and peri-insular regions and left parietal cortex are topographically associated with impaired LV strain in patients with acute ischemic stroke without preexisting cardiac dysfunction.

Yixin Granules Reduce Myocardial Inflammation and Fibrosis in Rats with Heart Failure by Inhibiting the Expression of ADAMTS8.

Yixin granules are medications modified from a Chinese prescription (Sheng Xian Tang) that has been used to alleviate shortness of breath. ADAM metallopeptidase with thrombospondin type 1 motif 8 (ADAMTS8) is upregulated in the myocardium of patients with dilated cardiomyopathy. Its high expression is associated with tumor necrosis factor (TNF) -α and myocardial fibrosis. This study aimed to explore the effect of Yixin granules on heart failure (HF) in rats and whether this effect is correlated with ADAMTS8 to provide new ideas for the treatment of HF.HF rat models were established by ligation of the left anterior descending coronary artery. Model rats were injected with adeno-associated virus vectors for the overexpression of ADAMTS8 and/or treated with Yixin granules for 4 weeks. Hematoxylin-eosin and Masson staining were used to detect myocardial injury and fibrosis, respectively. Reverse transcription polymerase chain reaction, western blotting, and/or enzyme-linked immunosorbent assay were used to detect the expression of ADAMTS8, TNF-α, interleukin (IL) -1β, IL-6, collagen I, collagen III, and α-smooth muscle actin in myocardium. The myocardial infarction area of rats was measured using 2,3,5-triphenyltetrazolium chloride staining.ADAMTS8 was upregulated in the myocardium of HF rats. Yixin granule treatment improved left ventricular contractility and reduced ADAMTS8 expression, myocardial injury, inflammation, and fibrosis in HF rats. ADAMTS8 overexpression aggravated myocardial injury, inflammation, and fibrosis. Moreover, ADAMTS8 overexpression counteracted the cardioprotective effects of Yixin granules.Yixin granules may reduce myocardial inflammation and fibrosis in HF rats by inhibiting the expression of ADAMTS8.

Increased NT-proBNP levels and cardiac ventricular function during aortic valve replacement (pilot study)

The objective was to study the relationship between the increased preoperative N-terminal segment of B-type natriuretic peptide precursor (NT-proBNP) blood levels and the parameters of the heart ventricles function, as well as the conditions for coronary perfusion of their myocardium before and after on-pump aortic valve replacement.Materials and methods. The study involved 27 patients aged 57.7±2.5 years who underwent aortic valve replacement. NT-proBNP blood level was determined before surgery. The level of NT-proBNP > 1000 pg/ml was considered increased. Invasive hemodynamics, including the data of the right ventricle thermodilution volumetry, and transesophageal echocardiography data were analyzed at the stages: the 1st – after anesthesia induction, the 2nd – at the end of surgery. Logistic regression and ROC analysis were used for data processing.Results. Preoperative blood levels of NT-proBNP > 1000 (3163.0[2507.25–7319]) pg/ml were recorded in 55.6% of patients. At the 1st stage, the biomarker increased level was associated with increased index of left ventricular end-systolic volume (OR 1.0955, 95% CI 1.0097–1.1885, p = 0.028, AUC 0.903), decreased left ventricular ejection fraction (OR 0, 9447, 95% CI 0.8949–0.9973, p = 0.040, AUC 0.753) and area contraction fraction (OR 0.8868, 95% CI 0.8086–0.9726, p = 0.011, AUC 0.890), increased mean pulmonary artery pressure (OR 1.1824, 95% CI 1.0020–1.3952, p = 0.047, AUC 0.722), and increased transpulmonary gradient (OR 1.4497, 95% CI 1.0103–2.0802, p = 0.044, AUC 0.810), increased right ventricular stroke work index (OR 1.5151, 95% CI 1.0319–2.2246, p = 0.034, AUC 0.761), and decreased coronary perfusion gradients of the left (OR 0.8961–0.9241, 95% CI 0.8229–0.9459 – 0.8630–0.9896, p = 0.012–0.024, AUC 0.793–0.861) and right (OR 0.9519, 95% CI 0.9136–0.9918, p = 0.019, AUC 0.847) ventricles. At the 2nd stage, NT-proBNP blood values > 1000 pg/ml were associated with impaired left ventricular function, decreased mean arterial pressure (OR 0.9066, 95% CI 0.8264–0.9946, p = 0.038, AUC 0.761), and the vasopressor and inotropic support (OR 8.4000, 95% CI 1.2584–56.0694, p = 0.028, AUC 0.710).Conclusions. Prior to aortic valve replacement, the blood level of NT-proBNP > 1000 pg/ml is associated with a moderate decrease in the left ventricular ejection fraction and area contraction fraction, an increased left ventricular end-systolic volume with a normal end-diastolic volume, an increased index of right ventricular stroke work in combination with moderately increased mean pulmonary artery pressure and increased transpulmonary gradient, as well as a decreased coronary perfusion gradients. At the end of operations, increased NT-proBNP blood level is associated with signs of impaired left ventricular contractility, a tendency to arterial hypotension, and the vasopressor and inotropic support. Increased preoperative NT-proBNP blood level are not associated with right ventricular volumes and ejection fraction both before and after on-pump aortic valve replacement.

Complexity of left ventricular strains in response to elevated volumes in healthy adults – Detailed analysis from the three-dimensional speckle-tracking echocardiographic MAGYAR-Healthy Study

IntroductionCardiac haemodynamics is described by the Frank-Starling law, which states that the strength of the left ventricular (LV) systolic contraction is related to the LV diastolic filling, with other words LV stroke volume increases as LV volume increases due to the stretching of the myocyte. The purpose of the present study was to examine how the increasing LV volumes affect LV contractility represented by three-dimensional (3D) speckle-tracking echocardiography (3DSTE) -derived LV strains in healthy adults. MethodsThis is post-hoc analysis of the MAGYAR-Healthy Study employing a novel method for technical analysis of echocardiographic datasets. The present study consisted of 301 healthy adults. Due to inferior image quality, 127 subjects have been excluded, therefore the remaining population included 174 subjects (mean age: 32.9 ± 12.1 years, 80 males). All cases have undergone complete two-dimensional Doppler echocardiography extended with 3DSTE. ResultsLV global longitudinal (gLS) and area (gAS) strains were lowest in case of the highest LV end-diastolic volume (EDV). LV global radial (gRS) and 3D (g3DS) strains tendentiously increased with increasing LV-EDV. When segmental analysis was performed, increased LV-EDV was associated with increase of basal LV-RS and LV-3DS. Increased LV strains were associated with increased LV ejection fraction (EF) due to higher LV-EDV for LV-gRS (and LV-g3DS), lower LV-ESV for LV-gCS and lower LV-EDV and LV-ESV for LV-gLS (and LV-gAS). With increasing LV-gRS, LV-gCS and LV-g3DS, all LV strains increased except LV-gLS. With increasing LV-gLS, LV-gRS did not show any increase, LV-gCS and LV-g3DS were the highest when LV-gLS was the highest, while LV-gAS increased simultaneously. With increasing LV-gAS, all LV strains increased. ConclusionsThere is a complex contractility pattern of LV segments/regions in response to elevated LV volumes in healthy circumstances.

Predictors of Pacing-Induced Cardiomyopathy in Patients with Permanent Right Ventricular Pacing and Preserved Left Ventricular Systolic Function

Right ventricular pacing may impair left ventricular systolic function in patients with reduced left ventricular ejection fraction (LVEF).
 The aim. To determine the frequency of pacing-induced cardiomyopathy (PICM) in patients with permanent right ventricular pacing (at least 90%) and preserved LVEF (≥50%). To determine the risk factors for the occurrence of PICM.
 Materials and methods. The study included 34 patients with indications for permanent ventricular pacing in whom pacemaker was implanted from 2012 to 2022 (mean follow-up period 44.97 ± 28.45 months). PICM was defined as a decrease in LVEF <45% during follow-up regardless of clinical manifestations. Risk factors for PICM were determined through univariate and multivariate regression analysis.
 Results. The incidence of PICM in this study was 26% during the mean observation period of 44.9 ± 28.4 months. The mean time to the onset of PICM was 29 months in 5 out of 9 patients (55%), the time from implantation to diagnosis of PICM was less than a year. The mean LVEF and end-diastolic volume index at the time of follow-up differed significantly in the groups with and without PICM: 38.6 ± 5.9% vs. 53.5 ± 5.7% (p<0.001) and 97.9 ± 20.75 ml/m2 vs. 60.9 ± 19.32 ml/m2 (p<0.001), respectively. In the PICM group intraventricular asynchrony was 261.1 ± 61 ms vs. 146.1 ± 62.8 ms (p<0.001), interventricular asynchrony 91 ± 36.4 ms vs. 54.2 ± 22.2 ms (p = 0.014), the number of segments with reduced deformation 8.1 ± 2.6 vs. 3.91 ± 2.3 (p<0.001), global longitudinal strain –9.7 ± 2.6 % vs. –14.9 ± 3.4 % (p<0.001). At the time of the follow-up examination, the signal of sensitivity on ventricular lead in the PICM group was significantly reduced compared to patients without PICM (6.26 ± 4.02 mV vs. 11.56 ± 3.86 mV, p = 0.045). Paced QRS width in the PICM group was significantly larger (163 ± 22.7 ms vs. 150.8 ± 14.5 ms) and there were more patients with rate-adapted cardiac pacing in the PICM group: 4 (40%) vs. 2 (8%) (p = 0.0428). In multivariate regression analysis, a wider paced QRS (hazard ratio 1.09 for every 1 ms increment in QRS width, 95% confidence interval 1.01-1.17, p = 0.025) was an independent predictor of PICM. In two patients from PICM group, upgrade of pacemaker system to biventricular pacing was performed with an improvement in the left ventricular contractility: in one patient from 37% to 44%, in another from 34% to 51% in one and two month, respectively.
 Conclusions. Cardiomyopathy due to right ventricular pacing tends to occur instantaneously in the first years after pacemaker implantation, rather than slowly progressing over time. A wider paced QRS complex is an independent predictor of PICM. Biventricular pacing effectively eliminates the consequences of non-physiological right ventricular pacing, improves left ventricular systolic function.

Glucocorticoids ameliorate cardiorenal syndrome through the NPR1/SGK1 pathway in natriuretic peptide receptor A‑heterozygous mice.

Natriuretic peptides, which are produced by the heart, bind to natriuretic peptide receptor A (NPR1 encoded by natriuretic peptide receptor 1 gene) and cause vasodilation and natriuresis. Thus, they serve an important role in regulating blood pressure. In the present study, microinjection of CRISPR associated protein 9/single guide RNA into fertilized C57BL/6N mouse eggs was performed to generate filial generation zero (F0) Npr1 knockout homozygous mice (Npr1-/-). F0 mice mated with wild-type (WT) mice to obtain F1 Npr1 knockout heterozygous mice with stable heredity (Npr1+/-). F1 self-hybridization was used to expand the population of heterozygous mice (Npr1+/-). The present study performed echocardiography to investigate the impact of NPR1 gene knockdown on cardiac function. Compared with those in the WT group (C57BL/6N male mice), the left ventricular ejection fraction, myocardial contractility and renal sodium and potassium excretion and creatinine-clearance rates were decreased, indicating that Npr1 knockdown induced cardiac and renal dysfunction. In addition, expression of serum glucocorticoid-regulated kinase 1 (SGK1) increased significantly compared with that in WT mice. However, glucocorticoids (dexamethasone) upregulated NPR1 and inhibited SGK1 and alleviated cardiac and renal dysfunction caused by Npr1 gene heterozygosity. SGK1 inhibitor GSK650394 ameliorate cardiorenal syndrome by suppressing SGK1. Briefly, glucocorticoids inhibited SGK1 by upregulating NPR1, thereby ameliorating cardiorenal impairment caused by Npr1 gene heterozygosity. The present findings provided novel insight into the understanding of cardiorenal syndrome and suggested that glucocorticoids targeting the NPR1/SGK1 pathway may be a potential therapeutic target to treat cardiorenal syndrome.

Partial Mural Cell Ablation Disrupts Coronary Vasculature Integrity and Induces Systolic Dysfunction.

Background Although the critical role of pericytes in maintaining vascular integrity has been extensively demonstrated in the brain and the retina, little is known about their role in the heart. We aim to investigate structural and functional consequences of partial pericyte depletion (≈60%) in the heart of adult mice. Methods and Results To deplete pericytes in adult mice, we used platelet-derived growth factor receptor β-Cre/ERT2; RosaDTA mice and compared their phenotype with that of control mice (RosaDTA) chosen among their littermates. Cardiac function was assessed via echocardiography and left ventricular catheterization 1 month after the first tamoxifen injection. We found mice depleted with pericytes had a reduced left ventricular ejection fraction and an increased end-diastolic pressure, demonstrating both systolic and diastolic dysfunction. Consistently, mice depleted with pericytes presented a decreased left ventricular contractility and an increased left ventricular relaxation time (dP/dtmin). At the tissue level, mice depleted of pericytes displayed increased coronary endothelium leakage and activation, which was associated with increased CD45+ cell infiltration. Consistent with systolic dysfunction, pericyte depletion was associated with an increased expression of myosin heavy chain 7 and decreased expression of ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 and connexin 43. More important, coculture assays demonstrated, for the first time, that the decreased expression of connexin 43 is likely attributable to a direct effect of pericytes on cardiomyocytes. Besides, this study reveals that cardiac pericytes may undergo strong remodeling on injury. Conclusions Cardiac pericyte depletion induces both systolic and diastolic dysfunction, suggesting that pericyte dysfunction may contribute to the occurrence of cardiac diseases.

Myocardial work as an independent predictor of postoperative NT-proBNP after transcatether aortic valve replacement

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): SUPPORTED BY THE ÚNKP-22-3-I NEW NATIONAL EXCELLENCE PROGRAM OF THE MINISTRY FOR CULTURE AND INNOVATION FROM THE SOURCE OF THE NATIONAL RESEARCH, DEVELOPMENT AND INNOVATION FUND. Introduction Aortic valve stenosis is one of the most prevalent valvular disease with significant clinical burden. Its treatment has been revolutionized by transcatether aortic valve replacement (TAVR). Left ventricular function is key element of preprocedural patient assessment, however, conventional echocardiographic parameters are substantially influenced by the increased afterload associated with the valvular disease. Myocardial work index is a novel echocardiographic parameter that quantifies myocardial deformation in the context of the concomitant left ventricular pressure, therefore, it may be a reliable measure of left ventricular contractility even with increased afterload. Purpose Our aim was to evaluate the left ventricular function of the TAVR patients using conventional echocardiographic parameters and myocardial work index, and examine their association with the clinical characteristics of the patients. Methods 84 TAVR candidates were enrolled (age 79±6 years; 48% female). Conventional and advanced echocardiographic measurements were performed prior to the procedure and at 12 months as a part of a follow-up visit. We measured ejection fraction (EF), and also global longitudinal strain (GLS) by speckle-tracking echocardiography, then using left ventricular volume curves estimated from systolic blood pressure and mean transaortic gradient, we quantified global myocardial work index (GWI). Detailed medical history, symptomatic status and as a marker of congestion, NT-proBNP levels were also obtained. Results EF did not change significantly (53±13 vs. 55±10 %; p = 0.172), while the absolute value of GLS increased substantially (−13.5±4.5 vs. −15.3±3.6 %; p<0.001). GWI significantly decreased (1914±787 vs. 1666±594 mmHg%; p = 0.001) compared to the preprocedural values (Figure 1). TAVR significantly reduced the NT-proBNP levels of the cohort (1057 [586–3037] vs. 627 pg/mL [376–1198]; p<0.001). Using multivariate regression analysis, examining relevant preprocedural clinical and echocardiographic parameters, the presence of atrial fibrillation (β=0.31; p<0.01), and the preprocedural GWI value (β=-0.32; p<0.01) proved to be significant independent predictors of postprocedural NT-proBNP (R²=0.30; p<0.001). Conclusions In our study population global longitudinal strain and myocardial work changed significantly after the procedure. The GWI value and the presence of atrial fibrillation proved to be independent predictors of NT-proBNP measured during the postprocedural follow-up. Accordingly, GWI may help in the improvement of patient selection and the estimation of the clinical prognosis in this complex population.

Cardiac phenotype of propionic acidemia in the Amysh community

Abstract Funding Acknowledgements Type of funding sources: None. Background/Introduction Propionic acidemia (PA) is an organic acid disorder with poorly described cardiac phenotype despite progressive important cardiac remodeling and causes of death including congestive heart failure and sudden cardiac death, often in a setting of vigorous exercise or stress. Cardiac modifications begin at cellular level, both metabolic and lipid depositions, resulting in overall changes in shape, size, geometry and function, with ventricular dysfunction and risk for arrhythmias at young age. Purpose Echocardiographic assessment of left ventricular (LV) shape and timing (especially the Isovolumic contraction time (IVCT)) can help us understand the pathophysiology during the remodeling process in this rare disease. Methods We included all the PA patients from the Amish plain Community seen in our center. Clinical data, including demographics, ECG and echo measurements were recorded. Results We included 22 patients, who were homozygous for the pathogenic variant for PA, (59% males, 20.3± 13.3 years old). ECG analysis showed mild tachycardia (92 ± 30bpm) with normal QRS (84± 18 msec) and QTc segments duration (424± 31 msec). Echocardiography demonstrated a globular LV with dilated base and apical segments, normal systolic function, and normal diastolic function. The Global Longitudinal Strain was mildly decreased (GLS −17±3.08) with a dispersion of the regional strain with apical sparing. (Figure 1). The mean LV IVCT (75 msec) was longer compared to mean RV IVCT (69 msec, Figure 1). Conclusion Patients with PA present with very specific remodeling, including an increase in sphericity of the heart and slightly decreased GLS with normal EF. The very long LV IVCT suggests a problem with pressure generation, potentially as a marker of decreased LV contractility, either at cellular level or with activation-contraction coupling. Together with the difference in timings between the LV and RV this might become a substrate for life-threatening arrhythmias. A contractility problem, together with the exercise induced arrhythmias suggest that PA patients might benefit from afterload reduction.

16α-OHE1, a novel oestrogen metabolite, attenuates dysfunction of left ventricle contractility via regulation of autophagy after myocardial ischemia and reperfusion

BackgroundMyocardial ischemia-reperfusion (MI/R) can exacerbate the initial cardiac damage in the myocardial functional changes, including dysfunction of left ventricular contractility. Oestrogen has been proven to protect the cardiovascular system. However, whether the oestrogen or its metabolites play the main role in attenuating dysfunction of left ventricular contractility is unknown. Methods and resultsThis study used the LC-MS/MS to detect oestrogen and its metabolites in clinical serum samples (n = 62) with heart diseases. After correlation analysis with markers of myocardial injury including cTnI (P < 0.01), CK-MB (P < 0.05), and D-Dimer (P < 0.001), 16α-OHE1 was identified. The result from LC-MS/MS in female and ovariectomised (OVX) rat serum samples (n = 5) matched the findings in patients. In MI/R model of animal, the recovery of left ventricular developed pressure (LVDP), rate pressure product (RPP), dp/dtmax and dp/dtmin after MI/R in OVX or male group were worsened than those in female group. Also, the infarction area of OVX or male group was larger than that in females (n = 5, p < 0.01). Furthermore, LC3 II in the left ventricle of OVX and male group was lower than that in females (n = 5, p < 0.01) by immunofluorescence. In H9C2 cells, after the application of 16α-OHE1, the number of autophagosomes was further increased and other organelles improved in MI/R. Simultaneously, LC3 II, Beclin1, ATG5, and p-AMPK/AMPK were increased, and p-mTOR/mTOR was decreased (n = 3, p < 0.01) by Simple Western. Conclusion16α-OHE1 could attenuate left ventricle contractility dysfunction via autophagy regulation after MI/R, which also offered fresh perspectives on therapeutical treatment for attenuating MI/R injury.

Human-umbilical cord matrix mesenchymal cells improved left ventricular contractility independently of infarct size in swine myocardial infarction with reperfusion.

Human umbilical cord matrix-mesenchymal stromal cells (hUCM-MSC) have demonstrated beneficial effects in experimental acute myocardial infarction (AMI). Reperfusion injury hampers myocardial recovery in a clinical setting and its management is an unmet need. We investigated the efficacy of intracoronary (IC) delivery of xenogeneic hUCM-MSC as reperfusion-adjuvant therapy in a translational model of AMI in swine. In a placebo-controlled trial, pot-belied pigs were randomly assigned to a sham-control group (vehicle-injection; n = 8), AMI + vehicle (n = 12) or AMI + IC-injection (n = 11) of 5 × 105 hUCM-MSC/Kg, within 30 min of reperfusion. AMI was created percutaneously by balloon occlusion of the mid-LAD. Left-ventricular function was blindly evaluated at 8-weeks by invasive pressure-volume loop analysis (primary endpoint). Mechanistic readouts included histology, strength-length relationship in skinned cardiomyocytes and gene expression analysis by RNA-sequencing. As compared to vehicle, hUCM-MSC enhanced systolic function as shown by higher ejection fraction (65 ± 6% vs. 43 ± 4%; p = 0.0048), cardiac index (4.1 ± 0.4 vs. 3.1 ± 0.2 L/min/m2; p = 0.0378), preload recruitable stroke work (75 ± 13 vs. 36 ± 4 mmHg; p = 0.0256) and end-systolic elastance (2.8 ± 0.7 vs. 2.1 ± 0.4 mmHg*m2/ml; p = 0.0663). Infarct size was non-significantly lower in cell-treated animals (13.7 ± 2.2% vs. 15.9 ± 2.7%; Δ = -2.2%; p = 0.23), as was interstitial fibrosis and cardiomyocyte hypertrophy in the remote myocardium. Sarcomere active tension improved, and genes related to extracellular matrix remodelling (including MMP9, TIMP1 and PAI1), collagen fibril organization and glycosaminoglycan biosynthesis were downregulated in animals treated with hUCM-MSC. Intracoronary transfer of xenogeneic hUCM-MSC shortly after reperfusion improved left-ventricular systolic function, which could not be explained by the observed extent of infarct size reduction alone. Combined contributions of favourable modification of myocardial interstitial fibrosis, matrix remodelling and enhanced cardiomyocyte contractility in the remote myocardium may provide mechanistic insight for the biological effect.

Characteristics of patients with chronic heart failure in different age groups

There are indications that the severity of clinical manifestations of chronic heart failure (CHF) is related to the age of patients, with older age groups characterized by a more severe course of CHF and more significant pathological changes in instrumental and laboratory parameters. In view of the above, the aim of the present study was to compare NT-proBNP level, other basic parameters of left ventricular myocardial contractility and the results of 6-min walk test, in CHF patients of different age. We investigated these parameters by dividing the total number of subjects into subgroups of young (18-44 years), middle-aged (45-59 years) and elderly (60-74 years) age according to WHO guidelines. There were 111 patients with CHF (82 men and 29 women) aged 20 to 74 years (mean age 60.4±1.25 years). The patients were divided into three subgroups: 1st - young age (21 patients), 2nd - middle age (37 patients) and 3rd - old age (53 patients). Echocardiographic examination, 6-minute walking test, determination of NT-proBNP level in blood plasma were used during the examination. The number of patients with decreased EF (&lt;35%) was significantly lower among young patients, while those with preserved EF was significantly higher among elderly patients. There were more patients with signs of pulmonary hypertension (high systolic pulmonary artery pressure (SPAP)) among elderly patients. The average distance walked during a 6-minute walk was relatively shorter in elderly patients, as well as a greater number of patients with higher (III-IV functional classes (FC)). The number of patients with elevated blood NT-proBNP levels as well as mean NT-proBNP levels were also relatively higher in the older age groups. Thus, the clinical course of CHF is characterized by a more severe course in elderly patients, despite the prevalence of patients with preserved EF, which is confirmed by more frequent occurrence of FC III-IV, clinical-instrumental and laboratory parameters, and is associated, at least partly, with more frequent occurrence of comorbid pathology.

Fetal Cardiac Function at Midgestation and Subsequent Development of Preeclampsia

To assess differences in cardiac morphology and function at midgestation in fetuses from pregnancies that subsequently developed preeclampsia (PE) or gestational hypertension (GH). This was a prospective study in 5,801 women with singleton pregnancies attending for a routine ultrasound examination at midgestation, including 179 (3.1%) who subsequently developed PE and 149 (2.6%) who developed GH. Conventional and more advanced echocardiographic modalities, such as speckle-tracking, were used to assess fetal cardiac function in the right and left ventricle. The morphology of the fetal heart was assessed by calculating the right and left sphericity index. In fetuses from the PE group (vs the no PE or GH group) there was a significantly higher left ventricular global longitudinal strain and lower left ventricular ejection fraction that could not be accounted for by fetal size. All other indices of fetal cardiac morphology and function were comparable between groups. There was no significant correlation between fetal cardiac indices and uterine artery pulsatility index multiple of the median or placental growth factor multiple of the median. At midgestation, fetuses of mothers at risk of developing PE, but not those at risk of GH, have mild reduction in left ventricular myocardial function. Although absolute differences were minimal and most likely not clinically relevant, these may suggest an early programming effect on left ventricular contractility in fetuses of mothers who develop PE.

Late left ventricular myocardial remodeling after pulmonary artery banding for end-stage dilated cardiomyopathy in infants: an imaging study

BackgroundUnderstanding the macroscopic biventricular changes induced by pulmonary artery banding (PAB) in children with dilated cardiomyopathy (DCM) represents the first step to unraveling the regenerative potential of the myocardium. We herein investigated the phases of left ventricular (LV) rehabilitation in PAB responders, using a systematic echocardiographic and cardiac magnetic imaging (CMRI) surveillance protocol. MethodsWe prospectively enrolled all patients with DCM treated with PAB from September-2015 at our institution. Among 9 patients, 7 positively responded to PAB and were selected. Transthoracic 2D echocardiography was performed before PAB; and 30, 60, 90, and 120 days after PAB; and at the last available follow-up. CMRI was performed before PAB (whenever possible) and one year after PAB. ResultsIn PAB responders, LV ejection fraction showed a modest 10% increase 30–60 days after PAB, followed by its almost complete normalization after 120 days (median of 20[10–26]% vs 56[44.5–63.5]%, at baseline and 120 days after PAB, respectively). Parallelly, the LV end-diastolic volume decreased from a median of 146(87–204)ml/m2 to 48(40–50)ml/m2. At the last available follow-up (median of 1.5 years from PAB), both echocardiography and CMRI showed a sustained positive LV response, although myocardial fibrosis was detected in all patients. ConclusionsEchocardiography and CMRI show that PAB can promote a LV remodeling process, which starts slowly and can culminate in the normalization of LV contractility and dimensions 4 months later. These results are maintained up to 1.5 years. However, CMRI showed residual fibrosis as evidence of a past inflammatory injury whose prognostic significance is still uncertain.