scholarly journals Multimodal cardiovascular model for hemodynamic analysis: Simulation study on mitral valve disorders

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0247921
Author(s):  
Dibyendu Roy ◽  
Oishee Mazumder ◽  
Aniruddha Sinha ◽  
Sundeep Khandelwal
Keyword(s):  
Mitral Valve ◽  
Cardiovascular System ◽  
In Silico ◽  
Valvular Disease ◽  
Published Data ◽  
Hemodynamic Parameters ◽  
Cardiovascular Model ◽  
Cardiovascular Morbidity And Mortality ◽  
Valvular Heart Diseases ◽  
Holistic Understanding

Valvular heart diseases are a prevalent cause of cardiovascular morbidity and mortality worldwide, affecting a wide spectrum of the population. In-silico modeling of the cardiovascular system has recently gained recognition as a useful tool in cardiovascular research and clinical applications. Here, we present an in-silico cardiac computational model to analyze the effect and severity of valvular disease on general hemodynamic parameters. We propose a multimodal and multiscale cardiovascular model to simulate and understand the progression of valvular disease associated with the mitral valve. The developed model integrates cardiac electrophysiology with hemodynamic modeling, thus giving a broader and holistic understanding of the effect of disease progression on various parameters like ejection fraction, cardiac output, blood pressure, etc., to assess the severity of mitral valve disorders, naming Mitral Stenosis and Mitral Regurgitation. The model mimics an adult cardiovascular system, comprising a four-chambered heart with systemic, pulmonic circulation. The simulation of the model output comprises regulated pressure, volume, and flow for each heart chamber, valve dynamics, and Photoplethysmogram signal for normal physiological as well as pathological conditions due to mitral valve disorders. The generated physiological parameters are in agreement with published data. Additionally, we have related the simulated left atrium and ventricle dimensions, with the enlargement and hypertrophy in the cardiac chambers of patients with mitral valve disorders, using their Electrocardiogram available in Physionet PTBI dataset. The model also helps to create ‘what if’ scenarios and relevant analysis to study the effect in different hemodynamic parameters for stress or exercise like conditions.

scholarly journals A Clinical Study on the Pattern of Mitral Valvular Disease in a Peripheral Tertiary Hospital in Bangladesh

1970 ◽  
Vol 3 (1) ◽  
pp. 11-21 ◽  
Author(s):  
AKMM Islam ◽  
MA Azhar ◽  
MF Islam ◽  
MZ Haque ◽  
L Yeasmin
Keyword(s):  
Mitral Valve ◽  
Left Atrial ◽  
Previous History ◽  
Public Health Problem ◽  
Valvular Disease ◽  
Pulmonary Vasculature ◽  
College Hospital ◽  
Delay In Diagnosis ◽  
Cardiovascular Morbidity And Mortality ◽  
The Common

Background: Rheumatic mitral valvular disease (MVD) is a common cause of cardiovascular morbidity and mortality in Bangladesh. Many patients are diagnosed late, get maltreated, and develop complications, which can be minimized if early diagnosis could be made. Objectives: The study was carried out to determine the common symptoms and signs of mitral valvular disease in our population, to find out the incidence and pattern of complications, to list the pattern of valve lesions, to identify the common findings in different investigations and to find out the causes of delay in diagnosis. Methods: Fifty consecutive cases of isolated MVD of rheumatic origin admitted in Rajshahi Medical College Hospital, Rajshahi, Bangladesh, from July, 2002 to March, 2003 were included. Detailed history was taken, and clinical examination was performed. Chest skiagram, 12-lead ECG and echocardiography were performed in all patients. Other investigations include complete blood counts, anti-streptolysin O (ASO) titre, C-reactive protein (CRP), blood sugar, serum creatinine and routine urinalysis. Results: The peak incidence of MVD was found in the third decade (34%), 14 (28%) patients were <20 years of age. Thirty two (64%) patients had poor socio-economic condition. A previous history suggestive of rheumatic fever was found in 28 (56%). Twenty six (52%) patients received treatment from the registered medical practitioners and/or from the hospitals, 11 (22%) consulted with the quacks only, 5 (10%) had treatment from both sources. Significant delay was found in 28 (56%) patients. Illiteracy and ignorance was found to be the cause in 14 (28%) cases, poverty in 12 (24%) and misdiagnosis in 7 (14%). Six (12%) patients adopted indigenous treatment. Forty three (86%) patients experienced moderate to severe limitation of day-to-day activities all had breathlessness. Palpitation, fatigue and cough were found in 49 (98%), 45 (90%) and 42 (84%) cases respectively. Nineteen (38%) patients had haemoptysis, 15 (30%) had dysphagia. Apex beat was normally situated in 32 (64%), and shifted in 16 (32%) cases. Forty two (84%) patients had left parasternal heave and palpable P2 was found in 41 (82%) patients. Diastolic thrill was palpable in 28 (56%) cases, systolic thrill in 8 (16%) patients. The first heart sound (S1) was loud in 34 (68%) and soft in 8 (16%) cases. Mid-diastolic murmur of MS was audible in 46 (92%) cases, pansystolic murmur of mitral regurgitation in 19 (38%) patients and pansystolic murmur of tricuspid regurgitation in 10 (20%). Opening snap was found in 30 (60%), and presystolic accentuation in 27 (54%) cases. Roentgenographic study revealed moderate to huge enlargement of cardiac shadow in 29 (58%), straightening of the left border of the heart with fullness or outward bulging of the pulmonary conus in 43 (86%), double contour of the right border in 35 (70%), upper lobe diversion of pulmonary vasculature in 31 (62%), Kerley B lines in 10 (20%) and pulmonary oedema in 16 (32%) patients. The ECG showed P-mitrale in 32 (64%), atrial fibrillation in 14 (28%) and atrial flutter in 2 (4%) cases. Echocardiography revealed thickening of mitral valve leaflets in all patients, changes in subvalvular apparatus in 28 (56%) and calcification in mitral valve apparatus in 3 (6%) cases. Mitral valve area was <1 cm2 in 33 (66%), 1.0 to 1.4 cm2 in 14 (28%) and e”1.5 cm2 in 1 (2%) patients. The left atrial size was 41 to 50 mm in 20 (40%) and >50 mm in 10 (20%) cases. Two patients had left atrial thrombus. Evidence of pulmonary hypertension was found in 34 (68%) patients. Conclusion: Rheumatic MVD and the accompanying complications can be detected with an appreciable degree of accuracy by skillful clinical assessment and judicial use of simple investigations like roentgenography, electrocardiography and echocardiography which are available in many parts of our country at affordable costs. So every effort should be made to utilize these invaluable resources to tackle this public health problem more efficiently. Key Words: Rheumatic; Mitral valvular disease; Clinical. DOI: 10.3329/cardio.v3i1.6421Cardiovasc. j. 2010; 3(1): 11-21

CORONARY ARTERY LESIONS IN PATIENTS OVER 50 YEAR OLD WITH VALVULAR HEART DISEASES INDICATED FOR VALVE SURGERY

2016 ◽  
pp. 20-24
Author(s):  
Bang Giap Vo ◽  
Anh Binh Ho ◽  
Van Minh Huynh
Keyword(s):  
Coronary Artery ◽  
Mitral Valve ◽  
Heart Valve ◽  
Right Coronary Artery ◽  
Heart Diseases ◽  
Heart Valve Diseases ◽  
Coronary Artery Lesions ◽  
Circumflex Coronary Artery ◽  
Valvular Heart Diseases ◽  
Valve Diseases

Objectives: To investigate the features of coronary artery lesions in patients over 50 with heart valve diseases and to find out the relationship between the levels of coronary artery lesions and heart valve diseases. Results: In patients over 50 year old with heart valve diseases, the rate of significant coronary artery lesions is 55.5%. In which, significant lesions in the group of both mitral and aorta valve diseases is 44.19%, only mitral valve diseases is of 70%, only aortic valve diseases is of 51.85%. There is a relationship between the severity of mitral valve diseases and right coronary artery lesions (OR 3.74: 1.64 to 8.5, p = 0.0017) and circumflex coronary artery lesions (OR 2.59: 1.16 to 5.75, p = 0.0192). The severity of heart valve lesions in significant coronary artery lesions group is higher than insignificant coronary artery lesions group or normal group. Conclusion: Coronary artery lesions is common in patients > 50 years old with heart valve diseases, there is a relationship between the severity of mitral valve diseases and and right coronary artery lesions and circumflex coronary artery lesions. Key words: coronary artery lesions, mitral valvediseases

Gaussian Network Model Revisited: Effects of Mutation and Ligand Binding on Protein Behavior

2021 ◽  
Author(s):  
Burak Erman
Keyword(s):  
Ligand Binding ◽  
Network Model ◽  
Adjacency Matrix ◽  
In Silico ◽  
Coarse Grained ◽  
Published Data ◽  
Specific Information ◽  
Gaussian Network Model ◽  
Gaussian Network ◽  
Alpha Carbon

The coarse-grained Gaussian Network model, GNM, considers only the alpha carbons of the folded protein. Therefore it is not directly applicable to the study of mutation or ligand binding problems where atomic detail is required. This shortcoming is improved by including the local effect of heavy atoms in the neighborhood of each alpha carbon into the Kirchoff Adjacency Matrix. The presence of other atoms in the coordination shell of each alpha carbon diminishes the magnitude of fluctuations of that alpha carbon. But more importantly, it changes the graph-like connectivity structure, i.e., the Kirchoff Adjacency Matrix of the whole system which introduces amino acid specific and position specific information into the classical coarse-grained GNM which was originally modelled in analogy with phantom network theory of rubber elasticity. With this modification, it is now possible to make predictions on the effects of mutation and ligand binding on residue fluctuations and their pair-correlations. We refer to the new model as all-atom GNM. Using examples from published data we show that the all-atom GNM applied to in silico mutated proteins and to their laboratory mutated structures gives similar results. Thus, loss and gain of correlations, which may be related to loss and gain of function, may be studied by using simple in silico mutations only.

scholarly journals MicroRNAs in Valvular Heart Diseases: Biological Regulators, Prognostic Markers and Therapeutical Targets

2021 ◽  
Vol 22 (22) ◽  
pp. 12132
Author(s):  
Francesco Nappi ◽  
Adelaide Iervolino ◽  
Sanjeet Singh Avtaar Singh ◽  
Massimo Chello
Keyword(s):  
Mitral Valve ◽  
Mitral Valve Prolapse ◽  
Heart Diseases ◽  
Osteoblastic Differentiation ◽  
New Drugs ◽  
Expression Vectors ◽  
Chordae Tendineae ◽  
Valvular Heart Diseases

miRNAs have recently attracted investigators’ interest as regulators of valvular diseases pathogenesis, diagnostic biomarkers, and therapeutical targets. Evidence from in-vivo and in-vitro studies demonstrated stimulatory or inhibitory roles in mitral valve prolapse development, aortic leaflet fusion, and calcification pathways, specifically osteoblastic differentiation and transcription factors modulation. Tissue expression assessment and comparison between physiological and pathological phenotypes of different disease entities, including mitral valve prolapse and mitral chordae tendineae rupture, emerged as the best strategies to address miRNAs over or under-representation and thus, their impact on pathogeneses. In this review, we discuss the fundamental intra- and intercellular signals regulated by miRNAs leading to defects in mitral and aortic valves, congenital heart diseases, and the possible therapeutic strategies targeting them. These miRNAs inhibitors are comprised of antisense oligonucleotides and sponge vectors. The miRNA mimics, miRNA expression vectors, and small molecules are instead possible practical strategies to increase specific miRNA activity. Advantages and technical limitations of these new drugs, including instability and complex pharmacokinetics, are also presented. Novel delivery strategies, such as nanoparticles and liposomes, are described to improve knowledge on future personalized treatment directions.

scholarly journals Integrated experimental-computational analysis of a liver-islet microphysiological system for human-centric diabetes research

2021 ◽  
Author(s):  
Belén Casas ◽  
Liisa Vilén ◽  
Sophie Bauer ◽  
Kajsa Kanebratt ◽  
Charlotte Wennberg Huldt ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Computational Model ◽  
In Silico ◽  
Experimental Results ◽  
Published Data ◽  
Diabetes Research ◽  
Glucose Response ◽  
High Blood Glucose

Microphysiological systems (MPS) are powerful tools for emulating human physiology and replicating disease progression in vitro. MPS could be better predictors of human outcome than current animal models, but mechanistic interpretation and in vivo extrapolation of the experimental results remain significant challenges. Here, we address these challenges using an integrated experimental-computational approach. This approach allows for in silico representation and predictions of glucose metabolism in a previously reported MPS with two organ compartments (liver and pancreas) connected in a closed loop with circulating medium. We developed a computational model describing glucose metabolism over 15 days of culture in the MPS. The model was calibrated on an experiment-specific basis using data from seven experiments, where single-liver or liver-islet cultures were exposed to both normal and hyperglycemic conditions resembling high blood glucose levels in diabetes. The calibrated models reproduced the fast (i.e. hourly) variations in glucose and insulin observed in the MPS experiments, as well as the long-term (i.e. over weeks) decline in both glucose tolerance and insulin secretion. We also investigated the behavior of the system under hypoglycemia by simulating this condition in silico, and the model could correctly predict the glucose and insulin responses measured in new MPS experiments. Last, we used the computational model to translate the experimental results to humans, showing good agreement with published data of the glucose response to a meal in healthy subjects. The integrated experimental-computational framework opens new avenues for future investigations toward disease mechanisms and the development of new therapies for metabolic disorders.

scholarly journals Enhancing network activation in natural killer cells: predictions from in silico modeling

2020 ◽  
Vol 12 (5) ◽  
pp. 109-121
Author(s):  
Sahak Z Makaryan ◽  
Stacey D Finley
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
In Silico ◽  
Intracellular Signaling ◽  
Cell Activation ◽  
Nk Cell ◽  
Mechanistic Model ◽  
Cell Killing ◽  
Published Data ◽  
Network Activation

Abstract Natural killer (NK) cells are part of the innate immune system and are capable of killing diseased cells. As a result, NK cells are being used for adoptive cell therapies for cancer patients. The activation of NK cell stimulatory receptors leads to a cascade of intracellular phosphorylation reactions, which activates key signaling species that facilitate the secretion of cytolytic molecules required for cell killing. Strategies that maximize the activation of such intracellular species can increase the likelihood of NK cell killing upon contact with a cancer cell and thereby improve efficacy of NK cell-based therapies. However, due to the complexity of intracellular signaling, it is difficult to deduce a priori which strategies can enhance species activation. Therefore, we constructed a mechanistic model of the CD16, 2B4 and NKG2D signaling pathways in NK cells to simulate strategies that enhance signaling. The model predictions were fit to published data and validated with a separate dataset. Model simulations demonstrate strong network activation when the CD16 pathway is stimulated. The magnitude of species activation is most sensitive to the receptor’s initial concentration and the rate at which the receptor is activated. Co-stimulation of CD16 and NKG2D in silico required fewer ligands to achieve half-maximal activation than other combinations, suggesting co-stimulating these pathways is most effective in activating the species. We applied the model to predict the effects of perturbing the signaling network and found two strategies that can potently enhance network activation. When the availability of ligands is low, it is more influential to engineer NK cell receptors that are resistant to proteolytic cleavage. In contrast, for high ligand concentrations, inhibiting phosphatase activity leads to sustained species activation. The work presented here establishes a framework for understanding the complex, nonlinear aspects of NK cell signaling and provides detailed strategies for enhancing NK cell activation.

scholarly journals P1304 Is antibiotic profilaxis really not needed in mitral valve prolapse?

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
S Suma ◽  
S Coli ◽  
W Serra ◽  
I Spaggiari ◽  
A Botti ◽  
...  
Keyword(s):  
Mitral Valve ◽  
Antibiotic Therapy ◽  
Mitral Valve Prolapse ◽  
Valvular Disease ◽  
Posterior Leaflet ◽  
Class Iii ◽  
Level Of Evidence ◽  
Native Valve ◽  
Dental Procedures

Abstract Patient Presentation A 54 years old woman with dyslipidemia was admitted to the hospital due to the onset of persistent fever. She had no significant comorbidities and she had a known mitral valve prolapse, which was in clinical and echocardiographic follow-up since more than 15 years before. Two months before the hospitalization she underwent dental hygiene procedure without taking any antibiotic before. The procedure included scaling and polishing of the teeth, and she referred just a mild bleeding. After few days she reported the onset of fever and therefore she started to take amoxicilline/clavulanic acid but without any significant improvement of symptoms. Initial work up At the blood chemistry she had a mild leucocytosis with neutrophilia and a rise in inflammatory indices. The Chest x-ray was normal. A systolic murmur was evident at the physical examination. Therefore, Transthoracic Echocardiogram was performed, followed by Transesophageal Echocardiogram (see Figure). At the Echo there was a significant endocarditic involvement of the mitral valve with multiple vegetations, two on the posterior leaflet (scallop P1 and P3) and one on the anterior one (scallop A3); moreover, there was a flail of the posterior leaflet (scallop P1) with subsequent moderate to severe eccentric valve regurgitation. Diagnosis and management Diagnosis of Endocarditis was made and, thus, antibiotic therapy was started with gentamicin and daptomycin, then switched to ampicillin and ceftriaxone after the isolation at the blood culture of Enterococcus Faecalis sensitive to them. Cerebral CT was performed with no evidence of embolization. Finally, owing to the significant endocarditis of the mitral valve with associate moderate to severe regurgitation, the patient underwent surgical intervention with mitral valve replacement with bioprosthesis. Follow-up The post-operative period was regular with no significant complications. She had no more fever and the antibiotics were stopped after six weeks. Conclusion We reported the case of a severe endocarditic involvement of the mitral valve in a patient with known valvular prolapse, who did not take any antibiotic before a minor dental procedure. 2015 ESC guidelines on Endocarditis recommend to not perform antibiotic prophylaxis in patient with no valvular prosthesis but with other form of valvular disease, including mitral valve prolapse (Class III, level of evidence C). Most of the time, patients with other form of valvular disease (e.g. mitral valve prolapse, bicuspid aortic valve, calcific aortic stenosis) do not experience endocarditis, neither after dental procedures. However, this case shows that sometimes it can happen due to the abnormal conformation of the native valve and, hence, it makes us wonder whether the antibiotic therapy should be indicated before dental procedures in those kind of patients. Abstract P1304 Figure.

scholarly journals The Relationship between Serum Oxalic Acid, Central Hemodynamic Parameters and Colonization by Oxalobacter formigenes in Hemodialysis Patients

2015 ◽  
Vol 5 (3) ◽  
pp. 164-174 ◽  
Author(s):  
Baris Gulhan ◽  
Kultigin Turkmen ◽  
Merve Aydin ◽  
Murat Gunay ◽  
Aytekin Cıkman ◽  
...  
Keyword(s):  
Oxalic Acid ◽  
Linear Regression Analysis ◽  
Multivariate Linear Regression Analysis ◽  
Hemodynamic Parameters ◽  
Oxalobacter Formigenes ◽  
Cardiovascular Morbidity And Mortality ◽  
Central Hemodynamic ◽  
Blood Pressures ◽  
The Relationship

Background/Objective: Elevated pulse wave velocity (PWV) and central aortic blood pressures are independent predictors of increased cardiovascular morbidity and mortality in hemodialysis (HD) patients. Oxalic acid is a uremic retention molecule that is extensively studied in the pathogenesis of calcium oxalate stones. Oxalobacter formigenes, a member of the colon microbiota, has important roles in oxalate homeostasis. Data regarding the colonization by and the exact role of O. formigenes in the pathogenesis of oxalic acid metabolism in HD patients are scant. Hence, we aimed to determine the relationship between fecal O. formigenes colonization, serum oxalic acid and hemodynamic parameters in HD patients with regard to the colo-reno-cardiac axis. Methods: Fifty HD patients were enrolled in this study. PWV and central aortic systolic (cASBP) and diastolic blood pressures (cADBP) were measured with a Mobil-O-Graph (I.E.M. GmbH, Stolberg, Germany). Serum oxalic acid levels were assessed by ELISA, and fecal O. formigenes DNA levels were isolated and measured by real-time PCR. Results: Isolation of fecal O. formigenes was found in only 2 HD patients. One of them had 113,609 copies/ml, the other one had 1,056 copies/ml. Serum oxalic acid levels were found to be positively correlated with PWV (r = 0.29, p = 0.03), cASBP (r = 0.33, p = 0.001) and cADBP (r = 0.42, p = 0.002) and negatively correlated with LDL (r = -0.30, p = 0.03). In multivariate linear regression analysis, PWV was independently predicted by oxalic acid, glucose and triglyceride. Conclusions: This is the first study that demonstrates the absence of O. formigenes as well as a relation between serum oxalic acid and cASBP, cADBP and PWV in HD patients. Replacement of O. formigenes with pre- and probiotics might decrease serum oxalic acid levels and improve cardiovascular outcomes in HD patients.

Sign in / Sign up

Export Citation Format

Share Document