Cardiac Pump Function Research Articles

Correlation between cardiac index(CI) and cardio ankle vascular index(CAVI) at different degrees of head up tilt table

Background: Cardio Ankle Vascular Index (CAVI), a new index for arterial stiffness that can be measured by VaSera VS-1000 CAVI device. This is a new method for estimating the level of arteriosclerosis, which is relatively uninfluenced by changes of blood pressure. An association between some arterial fitness indices and cardiac function has been recently demonstrated. CI: is Cardiodynamic measure based on the Cardiac output (CO)which is normalized according to body size ,this is gained by dividing CO on body surface area. Aim: To establish if any significant interrelationship exists between indexed cardiac output (CI) and Cardio ankle vascular Index (CAVI). Further, to introduce a new index as a haemodynemic parameter, notably CI/CAVI. . Method: This study was carried out at Dr.Akeel Zwain private clinic, on 20 healthy male volunteers of a mean age of 30±5 year and BMI of 23.1±1.1 Kg/m². Measurement of cardiac output (CO) is accomplished by estimation of aortic diameter (D) and calculating the velocity time integral (VTI) of aortic flow by Doppler echocardiography, then utilizing the equation: CO=(VTI*D2 *0.785)*heart rate. Measurement of arterial stiffness index (CAVI) can be generated by VaSeraVS-1000 device. A motorized tilting table of incremental degrees; at 0º, 30º and 60º of head up tilt (HUT), was used to bring about peripheral sympathetic outflow modifications, together with postural changes in stroke volume, hence CO and CI. Results: This study demonstrated that there was a statistical significant negative correlation between CI and the degree of head up tilt. CI is significantly decreased relative to increase of HUT degree, in a stepwise manner; CI is significantly lower at 30 and 60 degrees than that at zero degree, (Pearson's correlation coefficient: r=0.63 for 0ºand 30º; r=0.81 for 0ºand 60º, p<0.001 for both; r= 0.71for 30ºand 60º; p<0.05 ). On the other hand, CAVI showed a statistical significant positive correlation relative to the degree of HUT. CAVI was significantly increased, in a stepwise fashion, at 30 and 60 degrees, than that at supine zero degree (Pearson's correlation coefficient: r =0.88 for 0º and 30º; r=0.83 for 0ºand 60º; r=0.81 for 30º and 60º ; p<0.001 for all). Correlation between CI and CAVI at different degrees of HUT was studied, the results demonstrated a significant negative correlation exists between CI and CAVI (r = - 0.47; p<0.05). The result of dividing the two indexes, by each other, CI/CAVI, yielded significant inverse inter relationship with respect to degree of HUT; being lower at 30ºand 60º than that obtained at 0ºtilt. It was significantly lower, in a slope wise pattern, at 60º than that at 30º of tilt (r =0.65 for 0º and 30º; r =0.78, for 0º and 60º; r =0.68, for 30º and 60º; p<0.001 for all). Conclusion: the present investigation reveals an inverse interrelationship between CI and CAVI; a decrease of CI is consistently associated with an increase of CAVI. A new index CI/CAVI may be proposed; it can be employed to early detect subclinical atherosclerosis impact on cardiac muscle pump function. This new integrated parameter could possibly serve for fitness assessment, and for cardiovascular risk stratification. Abbreviations: CAVI, cardio ankle vascular index; HUT: head up tilt; CI: cardiac index; CO: cardiac output; VTI: velocity time integral ; D: aortic diameter; SV ,stroke volume; HR, heart rate; Dd :change of diameter ; PS, systolic pressure ; Pd, diastolic pressure

Electro-energetics of Biventricular, Septal and Conduction System Pacing.

Abnormal electrical activation of the ventricles creates abnormalities in cardiac mechanics. Local contraction patterns, as reflected by strain, are not only out of phase, but also show opposing length changes in early and late activated regions. Consequently, the efficiency of cardiac pump function (the amount of stroke work generated by a unit of oxygen consumed), is approximately 30% lower in dyssynchronous than in synchronous hearts. Maintaining good cardiac efficiency appears important for long-term outcomes. Biventricular, left ventricular septal, His bundle and left bundle branch pacing may minimise the amount of pacing-induced dyssynchrony and efficiency loss when compared to conventional right ventricular pacing. An extensive animal study indicates maintenance of mechanical synchrony and efficiency during left ventricular septal pacing and data from a few clinical studies support the idea that this is also the case for left bundle branch pacing and His bundle pacing. This review discusses electro-mechanics and mechano-energetics under the various paced conditions and provides suggestions for future research.

Evaluation Of The Relationship Between Mitral Annular Plane Systolic Function (Mapse) and Syntax Score In Non-St Elevation Myocardial Infarction

Objective: Acute coronary syndromes (ACS) are still the main cause of mortality in the world. Scoring systems are important for risk evaluation in ACS. Angiographic The Synergy between Percutaneous Coronary Intervention (SYNTAX) score is universal. For cardiac pump function, left ventricular (LV) longitudinal shortening has a major role. It can be assessed by some echocardiographic parameters. Mitral annular plane systolic excursion (MAPSE) is well defined for the LV longitudinal function evaluation and clues with LV systolic function. In this study, we aimed to research the relationship between SYNTAX score and MAPSE in Non-ST elevation myocardial infarction (NSTEMI) patients.
 Methods: 138 consecutive patients who underwent coronary angiography after diagnosis of NSTEMI were included. Transthoracic echocardiography was performed to all patients by an experienced physician who was uninformed patient’s data. Coronary angiography via the femoral approach was performed for all patients within 48 hours. ≥ 50% coronary lesion stenosis in vessels ≥ 1.5 mm was scored separately and SYNTAX scores were obtained.
 Results: The median age was 64.5 (54.0-70.8) years and 80.4% were male. Hypertension was the most common risk factor (72.5%). Left anterior descending artery (LAD) stenosis was the most common artery stenosis (58.7%). The mean MAPSE was 14.0 (13.0-15.8) and the mean SYNTAX score was 10.0 (7.0-14). Correlation of our outcome variable SYNTAX score between physiological and clinical variables of age, troponin and LVEF were calculated. No significant p value was detected. The relationship between SYNTAX Score and categorical variables such as gender, hypertension, diabetes mellitus, hyperlipidemia, left main coronary artery (LMCA), LAD, right coronary artery (RCA), circumflex artery (CX), peripheral arterial disease (PAD) was evaluated. None of the variables included in the regression model were associated with the SYNTAX score
 Conclusion: In this study, we have investigated the relationship between MAPSE and SS in NSTEMI patients. No significant correlation was found between MAPSE and SS.

Pacemaker associated reduction of left ventricle systolic function

In recent years, data have been accumulated on the negative effect of right ventricular (RV) stimulation, leading to left ventricular (LV) asynchrony, proarrhythmias and progressive heart failure (HF). On the other hand, biventricular pacing has been shown to affect ventricular asynchrony, reduce HF manifestations, and improve prognosis in patients with LV dysfunction and wide QRS complex. The induced asynchrony from apical right ventricular pacing is unequivocally associated with changes in myocardial perfusion, LV dysfunction, and poorer prognosis for patients over time. This has led researchers for decades to look for an alternative position for electrode placement. The incidence of pacemaker-induced cardiomyopathy (PICM) ranges from 5.9 to 39% in patients with RV pacing, depending on the given definition and the limit for the degree of pacing. Upgrading to biventricular pacing has been shown to reverse the cardiomyopathy. Recently, there has been evidence of a positive effect of His bundle pacing (HBP) in the treatment of PICM even in patients with no improvement after biventricular pacing. The question about the pathogenetic mechanisms of PICM is currently unanswered. The connection between electrical asynchrony and the negative effect on cardiac pump function is clear. There is also evidence of an established relationship between asynchrony and coronary blood flow. The predisposing individual characteristics of the patient in which these negative effects are manifested are not clear. This is an issue that requires further studies.

ALM Fluid Therapy Shifts Sympathetic Hyperactivity to Parasympathetic Dominance in the Rat Model of Non-Compressible Hemorrhagic Shock.

Excessive sympathetic outflow following trauma can lead to cardiac dysfunction, inflammation, coagulopathy, and poor outcomes. We previously reported that buprenorphine analgesia decreased survival after hemorrhagic trauma. Our aim is to examine the underlying mechanisms of mortality in a non-compressible hemorrhage rat model resuscitated with saline or adenosine, lidocaine, magnesium (ALM). Anesthetized adult male Sprague-Dawley rats were randomly assigned to Saline control group or ALM therapy group (both n = 10). Hemorrhage was induced by 50% liver resection. After 15 min, 0.7 mL/kg 3% NaCl ± ALM intravenous bolus was administered, and after 60 min, 0.9% NaCl ± ALM was infused for 4 h (0.5 mL/kg/h) with 72 h monitoring. Animals received 6-12-hourly buprenorphine for analgesia. Hemodynamics, heart rate variability, echocardiography, and adiponectin were measured. Cardiac tissue was analyzed for adrenergic/cholinergic receptor expression, inflammation, and histopathology. Four ALM animals and one Saline control survived to 72 h. Mortality was associated with up to 97% decreases in adrenergic (β-1, α-1A) and cholinergic (M2) receptor expression, cardiac inflammation, myocyte Ca2+ loading, and histopathology, indicating heart ischemia/failure. ALM survivors had higher cardiac output and stroke volume, a 30-fold increase in parasympathetic/sympathetic receptor expression ratio, and higher circulating adiponectin compared to Saline controls. Paradoxically, Saline cardiac adiponectin hormone levels were higher than ALM, with no change in receptor expression, indicating intra-cardiac synthesis. Mortality appears to be a "systems failure" associated with CNS dysregulation of cardiac function. Survival involves an increased parasympathetic dominance to support cardiac pump function with reduced myocardial inflammation. Increased cardiac α-1A adrenergic receptor in ALM survivors may be significant, as this receptor is highly protective during heart dysfunction/failure.

Abstract 14091: Systemic Hypoxemia Induces Cardiomyocyte Cell Cycle Re-Entry but Few Myocytes Appear to Truly Divide

Rationale: The adult mammalian heart has a very limited capacity to regenerate cardiomyocytes that die from pathological damage. Several studies suggest that those few new myocytes found after injury are derived from pre-existing cardiomyocytes. A recent study suggests that systemic hypoxemia in adult mice can induce their cardiac myocytes to reenter the cell cycle and form two daughter cells. The goal of the present experiments was to determine if hypoxemia can induce adult murine cardiomyocytes to reenter the cell cycle and divide. Hypothesis: Hypoxia induces adult cardiomyocytes to complete the cell cycle and form new cardiac myocytes. Methods and Results: EdU mini pumps were implanted in 2-month-old C57BL/6 mice. Mice were then placed in a hypoxia chamber and the oxygen was lowered by 1% every day for 14 days to reach a final concentration of 7% oxygen. The animals remained in hypoxia (7% Oxygen) for 2 weeks and then were euthanized. Hypoxic mice had an increase in heart weight and echocardiography documented an increase in cardiac pump function and LV wall thickness when compared to control mice. Analysis of isolated cardiac myocytes in C57BL/6 animals showed an increase in EdU+ cardiomyocytes in hypoxemia and DAPI fluorescence intensity was also increased in these EdU+ myocytes which may indicate DNA synthesis. In fixed heart tissue sections, hypoxic mice contained more EdU+ myocytes and had an increase in the total amount of EdU+ cells in the heart. To further evaluate cardiomyocyte proliferation, we employed a mosaic mouse model with double markers (MADM) in which myocytes entering the cell cycle express both red fluorescent protein (RFP) and green fluorescent protein (GFP) and therefore are yellow in color. When cells complete the cell cycle and divide they express only RFP or GFP. MADM mice were exposed to hypoxia at 7% Oxygen as described above. MADM mice subjected to hypoxemia had increased numbers of yellow myocytes versus controls. There was a much smaller number of hypoxic myocytes with just RFP or GFP. Conclusion: Systemic hypoxia induces cardiac myocyte cell cycle re-entry and DNA synthesis, but it seems that very few of these myocytes complete the cell cycle and divide into two daughter cells.

The Initial Cardiac Tissue Response to Cryopreserved Allogeneic Adipose Tissue-Derived Mesenchymal Stromal Cells in Rats with Chronic Ischemic Cardiomyopathy.

Mesenchymal stromal cells have proven capable of improving cardiac pump function in patients with chronic heart failure, yet little is known about their mode of action. The aim of the study was to investigate the short-term effect of cryopreserved allogeneic rat adipose tissue-derived stromal cells (ASC) on cardiac composition, cellular subpopulations, and gene transcription in a rat model of chronic ischemic cardiomyopathy (ICM). Myocardial infarction (MI) was induced by permanent ligation of the left anterior descending coronary artery. After 6 weeks, the rats were treated with ASCs, saline, or no injection, using echo-guided trans-thoracic intramyocardial injections. The cardiac tissue was subsequently collected for analysis of cellular subpopulations and gene transcription 3 and 7 days after treatment. At day 3, an upregulation of genes associated with angiogenesis were present in the ASC group. On day 7, increases in CCR2+ and CD38+ macrophages (p = 0.047 and p = 0.021), as well as in the CD4/CD8 lymphocyte ratio (p = 0.021), were found in the ASC group compared to the saline group. This was supported by an upregulation of genes associated with monocytes/macrophages. In conclusion, ASC treatment initiated an immune response involving monocytes/macrophages and T-cells and induced a gene expression pattern associated with angiogenesis and monocyte/macrophage differentiation.

Systemic administration of dendrimer N-acetyl cysteine improves outcomes and survival following cardiac arrest.

Cardiac arrest (CA), the sudden cessation of effective cardiac pumping function, is still a major clinical problem with a high rate of early and long‐term mortality. Post‐cardiac arrest syndrome (PCAS) may be related to an early systemic inflammatory response leading to exaggerated and sustained neuroinflammation. Therefore, early intervention with targeted drug delivery to attenuate neuroinflammation may greatly improve therapeutic outcomes. Using a clinically relevant asphyxia CA model, we demonstrate that a single (i.p.) dose of dendrimer‐N‐acetylcysteine conjugate (D‐NAC), can target “activated” microglial cells following CA, leading to an improvement in post‐CA survival rate compared to saline (86% vs. 45%). D‐NAC treatment also significantly improved gross neurological score within 4 h of treatment (p < 0.05) and continued to show improvement at 48 h (p < 0.05). Specifically, there was a substantial impairment in motor responses after CA, which was subsequently improved with D‐NAC treatment (p < 0.05). D‐NAC also mitigated hippocampal cell density loss seen post‐CA in the CA1 and CA3 subregions (p < 0.001). These results demonstrate that early therapeutic intervention even with a single D‐NAC bolus results in a robust sustainable improvement in long‐term survival, short‐term motor deficits, and neurological recovery. Our current work lays the groundwork for a clinically relevant therapeutic approach to treating post‐CA syndrome.

Uptake of [68Ga]-NODAGA-E[(cRGDyK)]2 is related to improvement in pump function in rats with chronic ischemic cardiomyopathy treated with cell therapy

Abstract Background An increasing number of patients living with chronic ischemic cardiomyopathy (ICM) are potential candidates for cell therapy, including adipose tissue-derived mesenchymal stromal cells (ASC). However, proper assessment of clinical effects in relation to cellular effector mechanisms, such as angiogenesis, is currently lacking. Purpose To investigate the prognostic value of assessing angiogenesis non-invasively using novel PET imaging in terms of functional outcome after cell therapy in a homologous animal model of ICM. Methods Myocardial infarction was induced by permanent ligation of the left anterior descending coronary artery. Four weeks after infarction, the rats were scanned with [18F]-FDG and echocardiography, and based on left ventricular ejection fraction (LVEF) and infarct size randomized to allogeneic ASC treatment (n=14) or saline (n=9). Animals were treated using echo-guided trans-thoracic intramyocardial injections. Follow-up echocardiography was performed four weeks after treatment. Angiogenesis was assessed non-invasively using the [68Ga]-NODAGA-E[(cRGDyK)]2 (RGD) PET-tracer before treatment and two weeks after the treatment (Figure). The output was RGD-uptake by maximum standardized uptake value (SUVmax). Results RGD-uptake in the infarct area significantly decreased in the saline group (p=0.04), while this decline was not significant in the ASC group (p=0.58). There was no effect on LVEF of the cell therapy in this study (p=0.70). When the rats were grouped by RGD-uptake post treatment, the high RGD-uptake group (n=8) improved LVEF compared to the rats with medium or low RGD-uptake (n=15, p=0.04) irrespective of the treatment. This could indicate that non-invasive detection of a high degree of myocardial angiogenesis measured using RGD is predictive of improvement in cardiac pump function in ICM. Conclusions Following injection of ASC or saline, a high RGD-uptake precluded improvement in pump function. This is the first evidence of how uptake of the novel RGD tracer relates to changes in pump function in ICM and the results could affect the design of future clinical trials using regenerative therapy for ICM patients. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Aase and Ejnar Danielsens FondDoctor Sofus Carl Emil Friis and wife Olga Doris Friis' Scholarship Study design, RGD-uptake, and results

Left ventricular diastolic function during pregnancy: insights from conventional and speckle tracking echo parameters

Abstract Introduction Profound changes occur in the cardiovascular system during pregnancy, regarding to induce cardiac pumping function. Although LV systolic and diastolic function have been thoroughly studied using conventional indices, speckle tracking parameters of cardiac function are not well described. Purpose The aim of our study was to evaluate the LV diastolic function during an uncomplicated pregnancy using both traditional and newer speckle tracking parameters. Methods We prospectively enrolled 40 consecutive pregnant women in whom serial echocardiographic evaluation was performed in each pregnancy trimester (1st: 8th–12th week, 2nd: 22th–26th week, 3rd: 32–36th week) and 6 months after delivery. Mitral inflow velocities (E, A), mitral annulus TDI velocities (E', A'), ratio E/A and E/E' and untwisting velocity rate were measured after cautious selection of studies with legible images in. Results The peak E transmitral inflow velocity during early diastole decreased significantly during pregnancy especially between 2nd and 3rd trimester and increased again postpartum (p1-2=0.475, p2-3&amp;lt;0.05 p3-4&amp;lt;0.05). The peak A flow velocity during atrial contraction did not change significantly during pregnancy (p1-2=0.333, p2-3=0.952, p3-4=0.989). As a result, E/A ratio was decreasing as pregnancy was advancing (p1-2=0.964, p2-3&amp;lt;0.05, p3-4=0.240). TDI E' early diastolic velocity was decreased especially in the 3rd trimester and recovered postpartum (p1-2=0.138, p2-3&amp;lt;0.01, p3-4&amp;lt;0.01) while E/E' ratio was increased especially in the 2nd trimester (p1-2&amp;lt;0.05, p2-3=0.572, p3-4=0.021, p1-4=0.383) and also recovered postpartum. Peak untwisting velocity rate demontrated a progressive decrease during pregnancy, although not statistically significant. There was a trend towards recovery in the puerperium (p1-2=0.072, p2-3=0.679, p3-4=0.052, p1-4=0.929) (Table 1). Conclusion Our study demonstrated that diastolic function seems to be impaired during an uncomplicated pregnancy. However all the conventional and newer speckle tracking indices of diastolic function remain in normal range. Postpartum appears to be a recovery process in all parameters. Funding Acknowledgement Type of funding sources: None.

3-DIMENSIONAL CARDIOGENIC SHOCK SIMULATOR PHASE I: SUCCESSFUL DEVELOPMENT OF A LARGE ANIMAL CARDIOGENIC SHOCK MODEL

<h3>BACKGROUND</h3> Post-myocardial infarction (Post-MI) cardiogenic shock (CS) is a serious life-threatening condition that requires complex coordinated care. Despite this, early mortality remains as high as 50%, likely owing to still inadequate understanding of pathophysiology and the potential benefits of percutaneous ventricular assist devices (pVADs). Although all pVADs increase circulatory flow, they vary in their ability to help restore cardiac pump function. Additionally, shortcomings in terms of our understanding of the optimal timing of such devices in STEMI and shock algorithms likely contributes to the high mortality. Currently, preclinical pVAD evaluation is limited by the need for animal research where the induction of CS is often lethal before devices can be tested. We therefore plan to develop a high-fidelity simulator to facilitate device evaluation and help train clinical teams. The first phase to this program requires the elaboration of a stable animal post-MI CS model that can generate the physiologic data necessary for simulator validation. <h3>METHODS AND RESULTS</h3> Using 10 anesthetized 65-75kg female pigs, we sought to induce a large anterior infarct by percutaneous balloon occlusion of the left anterior descending artery with a provision for ethanol injection if CS was not observed within 2 hours of balloon occlusion. Continuous physiologic monitoring was ensured in order to record right and left heart and arterial pressures, mixed venous oxygen saturation, cardiac output, and serum lactate levels. Indices of myocardial contractility and relaxation were calculated at regular intervals. At the end of the experiment, Evans Blue was injected into the coronary circulation in order to determine the size of the myocardium at risk. The explanted heart was then stained with TTC mitochondrial stain and fixed with formaldehyde to determine the size of the infarct. A rate of survival of the anterior infarct of ≥50% and a rate of induction of CS in at least 50% of the survivors was considered necessary for the viability of the program. We successfully induced myocardial infarction in all 10 pigs and 5 pigs survived to develop cardiogenic shock. <h3>CONCLUSION</h3> While challenging, we successfully demonstrated that a large animal model of cardiogenic shock is possible and stable enough to generate the physiologic data necessary for the development of a CS simulator. The second phase will consist of the collection of detailed physiological data in a CS state with and without different pVAD support.

SLC7A11/xCT Prevents Cardiac Hypertrophy by Inhibiting Ferroptosis.

Systemic hypertension may induce adverse hypertrophy of the left cardiac ventricle. Pathological cardiac hypertrophy is a common cause of heart failure. We investigated the significance of ferroptosis repressor xCT in hypertrophic cardiomyopathy. xCT expression in angiotensin II (Ang II)-treated mouse hearts and rat cardiomyocytes was determined using qRT-PCR and Western blotting. Cardiac hypertrophy was induced by Ang II infusion in xCT knockout mice and their wildtype counterparts. Blood pressure, cardiac pump function, and pathological changes of cardiac remodeling were analyzed in these mice. Cell death, oxidative stress, and xCT-mediated ferroptosis were examined in Ang II-treated rat cardiomyocytes. After Ang II infusion, xCT was downregulated at day 1 but upregulated at day 14 at both mRNA and protein levels. It was also decreased in Ang II-treated cardiomyocytes, but not in cardiofibroblasts. Inhibition of xCT exacerbated cardiomyocyte hypertrophy and boosted the levels of ferroptosis biomarkers Ptgs2, malondialdehyde, and reactive oxygen species induced by Ang II, while overexpression of xCT opposed these detrimental effects. Furthermore, knockout of xCT aggravated Ang II-mediated mouse cardiac fibrosis, hypertrophy, and dysfunction. Ferrostatin-1, a ferroptosis inhibitor, alleviated the exacerbation of cardiomyocyte hypertrophy caused by inhibiting xCT in cultured rat cells or ablating xCT in mice. xCT acts as a suppressor in Ang II-mediated cardiac hypertrophy by blocking ferroptosis. Positive modulation of xCT may therefore represent a novel therapeutic approach against cardiac hypertrophic diseases.

Automated detection of shockable ECG signals: A review

• Shockable and non-shockable ECG signals are analyzed. • A review study for shockable ECG signal recognition is discussed. • Unique bispectrum and recurrence plots are proposed for shockable and non-shockable ECG signals. • Performance of nonlinear features for differentiating shockable and non-shockable. • ECG signals is compared. Sudden cardiac death from lethal arrhythmia is a preventable cause of death. Ventricular fibrillation and tachycardia are shockable electrocardiographic (ECG)rhythms that can respond to emergency electrical shock therapy and revert to normal sinus rhythm if diagnosed early upon cardiac arrest with the restoration of adequate cardiac pump function. However, manual inspection of ECG signals is a difficult task in the acute setting. Thus, computer-aided arrhythmia classification (CAAC) systems have been developed to detect shockable ECG rhythm. Traditional machine learning and deep learning methods are now progressively employed to enhance the diagnostic accuracy of CAAC systems. This paper reviews the state-of-the-art machine and deep learning based CAAC expert systems for shockable ECG signal recognition, discussing their strengths, advantages, and drawbacks. Moreover, unique bispectrum and recurrence plots are proposed to represent shockable and non-shockable ECG signals. Deep learning methods are usually more robust and accurate than standard machine learning methods but require big data of good quality for training. We recommend collecting large accessible ECG datasets with a meaningful proportion of abnormal cases for research and development of superior CAAC systems.

Heart failure in patients with high homocysteine levels

Increased levels of homocysteine (HHcy) can induce both systolic and diastolic left ventricular (LV) dysfunction that may evolve until chronic heart failure (HF). It is known that HHcy acts as an independent risk factor for atherosclerosis and hypercoagulation. This condition may cause coronary artery disease (CAD. Chronic reduction of oxygen supply to the myocardium can induce a reduction in LV contractility. These conditions can further evolve towards HF with reduced ejection fraction (HFrEF). But, HHcy can be also responsible for adverse cardiac remodeling for accumulation and proliferation of interstitial collagen, increased fibrosis and myocardial stiffness and preserved LV ejection fraction (HFpEF). Both HF can be further favoured by the advanced age, hypertension, diabetes and others. The administration of some nutrients, such as folic acid and B12 vitamin can delay or avoid these cardiac complications. However, the cellular mechanisms behind the adverse effects of Hcy on cardiac remodeling and pump function are not understood.

Modelling of fibre dispersion and its effects on cardiac mechanics from diastole to systole

Detailed fibre architecture plays a crucial role in myocardial mechanics both passively and actively. Strong interest has been attracted over decades in mathematical modelling of fibrous tissue (arterial wall, myocardium, etc.) by taking into account realistic fibre structures, i.e. from perfectly aligned one family of fibres, to two families of fibres, and to dispersed fibres described by probability distribution functions. It is widely accepted that the fibres, i.e. collage, cannot bear the load when compressed, thus it is necessary to exclude compressed fibres when computing the stress in fibrous tissue. In this study, we have focused on mathematical modelling of fibre dispersion in myocardial mechanics, and studied how different fibre dispersions affect cardiac pump function. The fibre dispersion in myocardium is characterized by a non-rotationally symmetric distribution using a pi -periodic Von Mises distribution based on recent experimental studies. In order to exclude compressed fibres for passive response, we adopted the discrete fibre dispersion model for approximating a continuous fibre distribution with finite fibre bundles, and then the general structural tensor was employed for describing dispersed active tension. We first studied the numerical accuracy of the integration of fibre contributions using the discrete fibre dispersion approach, then compared different mechanical responses in a uniaxially stretched myocardial sample with varied fibre dispersions. We finally studied the cardiac pump functions from diastole to systole in two heart models, a rabbit bi-ventricle model and a human left ventricle model. Our results show that the discrete fibre model is preferred for excluding compressed fibres because of its high computational efficiency. Both the diastolic filling and the systolic contraction will be affected by dispersed fibres depending on the in-plane and out-of-plane dispersion degrees, especially in systolic contraction. The in-plane dispersion seems affecting myocardial mechanics more than the out-of-plane dispersion. Despite different effects in the rabbit and human models caused by the fibre dispersion, large differences in pump function exist when fibres are highly dispersed at in-plane and out-of-plane. Our results highlight the necessity of using dispersed fibre models when modelling myocardial mechanics, especially when fibres are largely dispersed under pathological conditions, such as fibrosis.

Surrogate models based on machine learning methods for parameter estimation of left ventricular myocardium.

A long-standing problem at the frontier of biomechanical studies is to develop fast methods capable of estimating material properties from clinical data. In this paper, we have studied three surrogate models based on machine learning (ML) methods for fast parameter estimation of left ventricular (LV) myocardium. We use three ML methods named K-nearest neighbour (KNN), XGBoost and multi-layer perceptron (MLP) to emulate the relationships between pressure and volume strains during the diastolic filling. Firstly, to train the surrogate models, a forward finite-element simulator of LV diastolic filling is used. Then the training data are projected in a low-dimensional parametrized space. Next, three ML models are trained to learn the relationships of pressure–volume and pressure–strain. Finally, an inverse parameter estimation problem is formulated by using those trained surrogate models. Our results show that the three ML models can learn the relationships of pressure–volume and pressure–strain very well, and the parameter inference using the surrogate models can be carried out in minutes. Estimated parameters from both the XGBoost and MLP models have much less uncertainties compared with the KNN model. Our results further suggest that the XGBoost model is better for predicting the LV diastolic dynamics and estimating passive parameters than other two surrogate models. Further studies are warranted to investigate how XGBoost can be used for emulating cardiac pump function in a multi-physics and multi-scale framework.

Methods of Signal Analysis for Automatic Diagnosis of Shockable Cardiac Arrhythmias: A Review

Ventricular fibrillation is considered the most common cause of sudden cardiac arrest. The fibrillation, and ventricular tachycardia often preceding it, are cardiac rhythms that may respond to emergency electroshock therapy and return to normal sinus rhythm when diagnosed early after cardiac arrest with the restoration of adequate cardiac pumping function. However, manually checking ECG signals on the existence of a pattern of such arrhythmias is a risky and time-consuming task in stressful situations and practically impossible in the absence of a qualified medical specialist. Therefore, systems of the computer classification of arrhythmias with the function of making a decision on the necessity of electric cardioversion with the parameters of a high-voltage pulse calculated adaptively for each patient are widely used for the automatic diagnosis of such conditions. This paper discusses methods of analyzing the electrocardiographic signal taken from the electrodes of an external automatic or semi-automatic defibrillator in order to make a decision on the necessity for defibrillation, which are applicable in the embedded software of automatic and semiautomatic external defibrillators. The paper includes an overview of applicable filtering techniques as well as subsequent algorithms for extracting, classifying and compressing features for the ECG signal.

The efficacy of the combined antihypertensive and statin therapy in patients with hypertension and excessive body mass

Objective — to assess the effects of the of the combined therapy with fixed combinations of antihypertensive medications in combination with statin on the indices of systemic hemodynamics, lipid profile, carbohydrate metabolism and adipocytokines production in overweight patients with essential hypertension of II stage.Materials and methods. The investigation involved in-hospital 64 hypertensive (stage II) patients, the mean age 59.0 (48.0 — 63.0) years with excessive body mass (body mass index > 25 kg/m2), who were treated in the therapeutic department No. 1 of the medical and sanitary unit of JSC “Motor Sich” in the years 2016 — 2018. and met the study inclusion criteria. All patients underwent general clinical, laboratory and instrumental examination to verify the diagnosis, determine complications and comorbidities. The patients were randomized into two subgroups who were administered fixed combinations of antihypertensive drugs for 120 days. Patients of the first subgroup (n = 32) received a combined drug «Equator» («Gedeon Richter», Hungary) in an initial dose of 1 tablet (amlodipine — 5 mg and lisinopril — 10 mg) per day, patients of the second subgroup (n = 32) received Valodip (KRKA, Slovenia) in an initial dose of 1 tablet (amlodipine — 5 mg and valsartan — 80 mg) per day. Within 2 weeks, the dose of drugs was adjusted if necessary. All patients were administered Rosuvastatin (Roxera, KRKA) in a dose of 10 mg/day.Results. The change in the doses wasn’t required for 10 (31.3 %) patients from the first subgroup and 13 (40.6 %) from the second subgroup; for the rest of patients, the doses of drugs were increased as follows: Equator (amlodipine — 5 mg and lisinopril — 20 mg) 1 tablet per day and «Valodip» (amlodipine — 5 mg and valsartan — 160 mg) 1 tablet per day. The target blood pressure level (130/85 mm Hg) was achieved in 24 (75.0 %) patients in the first group and in 26 (81.3 %) in the second. During treatment in both subgroups, the following positive changes were observed: in systemic hemodynamic parameters there were normalization of systolic and diastolic blood pressure and improved cardiac pumping function; in lipid spectrum — the decreased levels of total cholesterol, low-density lipoprotein cholesterol against the background of an increase in high-density lipoprotein cholesterol. Moreover the carbohydrate metabolism improved (fasting blood glucose decreased) and adipocytes production normalized — the levels of proinflammatory cytokines (interleukin-1β (IL-1β) and tumor necrosis factor-α) decreased and anti-inflammatory IL-10, adiponectin increased.Conclusions. The reduced production of pro-inflammatory and increased production of anti-inflammatory cytokines and adiponectin against the background of normalization of the indices of systemic hemodynamics, the decrease of pro-atherogenic and raise in the antiatherogenic fraction of blood lipids, reduction of the glycemia level in the patients with hypertension and excessive body mass under the influence of the therapy with fixed combinations of antihypertensive drugs with the use of both angiotensin-converting inhibitors and sartans, with the addition of statins, showed the efficacy of such therapy and its capability to considerably reduce the cardiovascular risk in this category of patients.

Effect of infarct stiffness on non-infarcted left and right ventricular tissue remodeling: a computational study based on myocardial mechano-transduction

Abstract Background/Introduction The mechanical properties of infarcted myocardium are important determinants of cardiac pump function and risk of developing heart failure following myocardial infarction (MI). Purpose To better understand the effects of infarct stiffness on compensatory hypertrophy and dilation of non-infarcted tissue in the left (LV) and right ventricle (RV), by using a computational model. Methods The CircAdapt computational model of the human heart and circulation was applied to simulate an acute MI involving 20% of LV wall mass. The simulation was validated using previously published experimental data. Subsequently, two degrees of increased infarct stiffness were simulated. In all three simulations, a model of structural myocardial adaptation of the non-infarcted tissue was applied, based on sensing of mechanical loading of myocytes and extracellular matrix (ECM). Results Mild and severe stiffening of the infarct reduced the increase of LV end-diastolic volume (EDV) from +23 mL to +17 mL and +16 mL, respectively, and the increase of LV non-infarcted tissue mass from +31% to +21% and +18%. RV EDV decreased after adaptation, and mild and severe infarct stiffening reduced the decrease of RV EDV from −21 mL to −12 mL and −10 mL, respectively. Increase of RV tissue mass was reduced from +13% to +8% and +7% with mild and severe infarct stiffening. In the LV, reduced dilation and hypertrophy were driven mainly by a reduction of maximum stress in the ECM and a higher stress between the myocytes and ECM following infarct stiffening. The decreased RV hypertrophy, but not EDV reduction, was caused by a reduction of maximum RV ECM stress and maximum RV active myofiber stress. Conclusions Model simulations predicted that a stiffened LV infarct reduces both LV and RV non-infarcted tissue hypertrophy as well as LV dilation. In LV remodeling, maximum ECM stress and stress between myocyte and ECM played a more prominent role than in RV remodeling, while maximum active stress was more important in the RV. Overview of all model simulations Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This work was funded by the Netherlands Organisation for Scientific Research and the Dutch Heart Foundation.

Cardiomyocyte Transplantation after Myocardial Infarction Alters the Immune Response in the Heart.

We investigated the influence of syngeneic cardiomyocyte transplantation after myocardial infarction (MI) on the immune response and cardiac function. Methods and Results: We show for the first time that the immune response is altered as a result of syngeneic neonatal cardiomyocyte transplantation after MI leading to improved cardiac pump function as observed by magnetic resonance imaging in C57BL/6J mice. Interestingly, there was no improvement in the capillary density as well as infarct area as observed by CD31 and Sirius Red staining, respectively. Flow cytometric analysis revealed a significantly different response of monocyte-derived macrophages and regulatory T cells after cell transplantation. Interestingly, the inhibition of monocyte infiltration accompanied by cardiomyocyte transplantation diminished the positive effect of cell transplantation alone. The number of CD68+ macrophages in the remote area of the heart observed after four weeks was also different between the groups. Transcriptome analysis showed several changes in the gene expression involving circadian regulation, mitochondrial metabolism and immune responses after cardiomyocyte transplantation. Conclusion: Our work shows that cardiomyocyte transplantation alters the immune response after myocardial infarction with the recruited monocytes playing a role in the beneficial effect of cell transplantation. It also paves the way for further optimization of the efficacy of cardiomyocyte transplantation and their successful translation in the clinic.