CASE REPORT | doi:10.20944/preprints202102.0167.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: single coronary artery; aortic valve surgery, coronary artery bypass grafting surgery; case report
Online: 8 February 2021 (15:42:53 CET)
A single coronary artery is a very rare condition, commonly associated with other congenital anomalies. It could be generally classified as neither benign nor malignant form of congenital coronary artery anomalies since its pathophysiological and clinical implications grossly depend on different anatomical patterns defined by the site of origin and distribution of the branches. By presenting the patient with an isolated single coronary artery, who underwent successful combined aortic valve replacement and coronary artery bypass grafting surgery, we intend to distinguish casual from causal in this extremely rare clinical and surgical scenario. This is the first-ever case published, combining such underlying pathology, clinical presentation, and surgical treatment.
ARTICLE | doi:10.20944/preprints202209.0178.v1
Subject: Medicine & Pharmacology, Anesthesiology Keywords: chronic postoperative pain; erector spinae plane block; coronary artery bypass grafting; Neuropathic Pain Symptom Inventory
Online: 13 September 2022 (11:24:28 CEST)
Up to 56% of patients develop chronic postsurgical pain (CPSP) after coronary artery bypass grafting (CABG). CPSP can affect patients’ moods and decrease daily activities. The primary aim of this study was to investigate CPSP severity in patients following off-pump (OP)-CABG using the Neuropathic Pain Symptom Inventory (NPSI). This was a prospective cohort study conducted in a cardiac surgery department of a teaching hospital. Patients undergoing OP-CABG were enrolled in an erector spinae plane block (ESPB) group (n = 27) or a control (CON) group (n = 24). Before the induction of general anesthesia, ESPB was performed on both sides under ultrasound guidance using 0.375% ropivacaine. The secondary outcomes included cumulative oxycodone consumption, acute pain intensity, mechanical ventilation time, hospital length of stay, and postoperative complications. CPSP intensity was lower in the ESPB group than in the CON group 1, 3, and 6 months postsurgery (p < 0.001). Significant between-group differences were also observed in other outcomes, including postoperative pain severity, opioid consumption, mechanical ventilation time, and hospital length of stay in favor of the ESPB group. Preemptive ESPB appears to decrease the risk of CPSP development in patients undergoing OP-CABG. Reduced acute pain severity and shorter mechanical ventilation times and hospital stays should improve patients’ satisfaction and reduce perioperative complications.
ARTICLE | doi:10.20944/preprints201912.0378.v1
Subject: Medicine & Pharmacology, Anesthesiology Keywords: blood viscosity; transit-time flow measurement; coronary artery bypass surgery
Online: 29 December 2019 (10:22:23 CET)
Background: Transit-time flow measurement (TTFM) is frequently used to evaluate intraoperative quality control during coronary artery bypass grafting (CABG). Although TTFM has the ability to assess graft failure intraoperatively, the perioperative factors affecting TTFM during CABG surgery remain poorly understood. Methods: Patients who underwent CABG surgery at a single institution between July 2016 and May 2018 were prospectively evaluated. Patients’ demographic characteristics, previous medical history, Euroscore, the results of preoperative blood tests, and intraoperative data were recorded. TTFM and blood viscosity were measured hemodynamically, and mean flow (mL/min) and pulsatility index (PI) were recorded. Arterial blood gas was analyzed immediately after anastomosis of the left internal mammary artery (LIMA) to the left descending artery (LAD) and before sternal closure. Factors associated with TTFM were assessed by multiple linear regression analysis. Results: Of the 62 patients who underwent CABG surgery during the study period, 57 were evaluated, including 49 who underwent off-pump and eight who underwent on-pump surgery. Blood viscosity was not significantly associated with TTFM (p > 0.05). However, TTFM was significantly associated with body mass index (BMI), systolic blood pressure, and cardiac index (p < 0.05 each). Conclusions: Blood viscosity was not significantly associated with intraoperative graft flow. Blood flow of graft vessels, however, was significantly associated with BMI, systolic blood pressure, and cardiac index.
CASE REPORT | doi:10.20944/preprints202104.0337.v2
Subject: Medicine & Pharmacology, Cardiology Keywords: coronary artery disease, acute coronary syndrome, inflammation, case report
Online: 13 April 2021 (13:14:55 CEST)
Background: Although persistent systemic inflammation is considered to be predictive for future cardiovascular events, it remains unclear whether or not C-reactive protein (CrP) plays an active role in coronary-plaque instability. Here, we report a case of a patient with failed and super-infected renal allograft as a source for systemic inflammation presenting with repeat acute coronary syndromes. Case presentation: A 52-years-old male type-2 diabetic with a failed kidney transplant who was hospitalized for acute urinary-tract infection. In the presence of other, classic cardiovascular risk factors, peak values of CrP coincided with episodes of unstable angina treated by percutaneous coronary interventions. Besides pyelonephritis, the histological examination of the kidney transplant revealed signs of chronic rejection and the presence of a renal cell carcinoma in situ. Once the renal allograft has been removed, systemic inflammation was attenuated, the patient was not re-hospitalized for acute-coronary syndrome within the next 12 months. Conclusion: In this case, systemic inflammation was paralleled by instability of coronary plaques as documented by repeat percutaneous coronary interventions.
ARTICLE | doi:10.20944/preprints201806.0381.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: coronary tortuosity; myocardial ischemia; coronary artery disease; chronic stable angina.
Online: 25 June 2018 (11:02:03 CEST)
Background: Coronary tortuosity is a common angiographic finding. Scarce data is available on clinical profile of patients with coronary tortuosity (CT) and its relation with coronary artery disease (CAD). Method: A total 224 patients undergoing angiography for suspected CAD were included in the study. CT was defined by the presence of ≥3 consecutive bends of > 45 degree measured at end-diastole in an epicardial artery ≥2 mm in diameter. CT was present in 45(20.08%) patients in the study and another 45 patients without CT was randomly selected as control (NCT group). Clinical profile of CT and NCT group was compared. Results: Incidence of CT was significantly higher in females (p=0.000) and hypertensives (p=0.001) patients. CT was most commonly seen in Left circumflex coronary artery. Incidence of CAD was significantly lower in CT group as compare to NCT group (0.02). Risk factors for CAD was associated with reduced incidence of CT. Majority (88.46%) patient with CT without CAD presented with chronic stable angina out of which (65.21%) had an objective evidence of myocardial ischemia. Conclusion: CT is more commonly seen females and hypertensive patients. It has negative correlation with CAD. Risk factors of CAD do not predict CT. CT itself can lead to myocardial ischemia.
ARTICLE | doi:10.20944/preprints202001.0220.v1
Subject: Mathematics & Computer Science, Artificial Intelligence & Robotics Keywords: heart disease; coronary artery disease; machine learning; deep learning; predictive features; coronary artery disease diagnosis; health informatics
Online: 20 January 2020 (09:11:14 CET)
Heart disease is one of the most common diseases in middle-aged citizens. Among the vast number of heart diseases, coronary artery disease (CAD) is considered a common cardiovascular disease with a high death rate. The most popular tool for diagnosing CAD is the use of medical imaging, e.g., angiography. However, angiography is known for being costly and also associated with a number of side effects. Hence, the purpose of this study is to increase the accuracy of coronary heart disease diagnosis by selecting significant predictive features in order of their ranking. In this study, we propose an integrated method using machine learning. The machine learning methods of random trees (RTs), the decision tree of C5.0, support vector machine (SVM), the decision tree of Chi-squared automatic interaction detection (CHAID) are used in this study. The proposed method shows promising results and the study confirms that the RTs model outperforms other models.
REVIEW | doi:10.20944/preprints201802.0084.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: dual anti platelet therapy; acute coronary syndrome; stents
Online: 12 February 2018 (05:13:18 CET)
Percutaneous coronary intervention(PCI) with stenting for the treatment of acute coronary syndrome(ACS) is the contemporary standard of care. Such treatment is followed by Dual anti-platelet therapy(DAPT) comprising of aspirin and a P2Y12 inhibitor. The efficacy of this therapy has been well established but the optimal duration of DAPT remains elusive, and has thus far attracted a prodigious deal of scientific attention. Decision regarding DAPT duration can be challenging clinically in the modern era with the evolution of newer stents, more potent antiplatelet agents and novel anticoagulant drugs in addition to an older patient population with multiple comorbidities. Major societal guidelines have emphasized comprehensive assessment of ischemic and bleeding risk, in turn recommending individualization of DAPT duration, thus encouraging "shared decision making". The following review is aimed at critically evaluating the available evidence to help make these crucial clinical decisions regarding duration of DAPT and triple therapy.
ARTICLE | doi:10.20944/preprints202009.0085.v1
Subject: Mathematics & Computer Science, Other Keywords: 3D+t modeling; coronary artery; non-rigid registration; cage deformation; 4D CT
Online: 4 September 2020 (07:36:01 CEST)
Cardiovascular-related diseases are one of the leading causes of death worldwide. An understanding of heart movement based on images plays a vital role in assisting the procedure in the postoperative and postoperative processes. In particular, if the shape information can be provided in real-time using the electrocardiogram(ECG) signal using this information, the heart’s movement information can be used for cardiovascular analysis and imaging guides during surgery. In this paper, we propose creating a 3D+t cardiac coronary artery model that is rendered in real-time according to the ECG signal. Hierarchical cage-based deformation modeling is used to generate mesh deformation used during the procedure according to the ECG signal. We match the blood vessel’s lumen obtained from the ECG-gated 3D+t CT angiography taken at the multiple cardiac phases to derive the optimal deformation. Splines for 3D deformation control points were used to continuously represent the obtained deformation at the multi-view according to the ECG signal. To verify the proposed method, we compared the manually segmented lumen and results of the proposed method for eight patients. The average distance and dice coefficient between the two models was 0.543mm and 0.735, respectively. The required time for registration of the 3D coronary artery model is 23.53 seconds/model. rendering speed to derive the model according to the ECG signal after generating the 3D+t model is faster than 120 FPS.
ARTICLE | doi:10.20944/preprints202301.0201.v1
Subject: Life Sciences, Biophysics Keywords: FFR, Blood Flow Simulation, coronal stenosis, Coronary Computed Tomography Angiography (CCTA), OpenFOAM
Online: 11 January 2023 (11:56:16 CET)
A novel physiologically based algorithm (PBA) for the computation of fractional flow reserve (FFR) in coronary artery trees (CATs) using computational fluid dynamics (CFD) is proposed and developed. The PBA is based on the extension of Murray's law and additional inlet conditions prescribed iteratively, and is implemented in OpenFOAM for testing and validation. 3D models of CATs are created using CT scans and computational meshes, and the results are compared to in-vasive coronary angiographic (ICA) data to validate the accuracy and effectiveness of the PBA. The discrepancy between calculated and experimental FFR is within 2.33-5.26% in steady-state and transient simulations, respectively, when convergence is reached. The PBA is a reliable and physiologically sound technique compared to the current lumped parameter model (LPM), which is based on empirical scaling correlations and requires nonlinear iterative computing for conver-gence. The accuracy of the PBA method is further confirmed using the FDA nozzle, which demonstrates good alignment with CFD-validated values.
ARTICLE | doi:10.20944/preprints201608.0164.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: vitamin B12; coronary tortuosity; coronary angiography
Online: 17 August 2016 (10:51:56 CEST)
Background: Vitamin B 12 deficiency has been implicated in endothelial dysfunction and cardiovascular disease via hyperhomocysteinemia. Coronary tortuosity (CorT) is a common coronary angiography finding. The etiology, clinical implication and long term prognosis are still not well clarified. This study was conducted with the aim to evaluate the relationship between CorT and vitamin B12. Subjects and Method: The medical records of consecutive patients, who underwent coronary angiography, were retrospectively reviewed. The study group consisted of 1624 patients. Taking into consideration the inclusion criteria, 212 patients with CorT and 210 patients with normal coronary angiographies (control group) were included in the study. Vitamin B12, other biochemical parameters, clinical and echocardiographic parameters, and CorT score were evaluated in all patients. CorT is defined as fixed 3 bends during both systole and diastole, with each bend ≥45 °. Results: Patients with CorT had higher prevalence of older, female gender, hypertension, current smoking. Vitamin B12 was significantly decreased in patient with CorT (134.7±47.8 vs 239.6±53.8 p<0.001). On multivariate analysis age, female gender, hypertension, diabetes mellitus and vitamin B12 were independent predictors for CorT (OR 1.56; 95% CI: 1.247–1.962; p < 0.001, OR 1.628; 95% CI: 1.376-2.048; p<0.001, OR 1.865; 95% CI: 1.387-2.695; p<0.001, OR 1.362; 95% CI: 1.184-1.726; p<0.001, OR 1.862; 95% CI: 1.486-2.674; p<0.001, respectively). Conclusion: In our study, we have founded a significant relationship between vitamin B12 deficiency and CorT.
ARTICLE | doi:10.20944/preprints201908.0300.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: coronary dimensions; Poiseuille’s Equation; arteriovenous fistula; coronary dilatation; wall shear stress; coronary blood flow; atherosclerosis; angiogenesis
Online: 29 August 2019 (03:35:08 CEST)
Background: The purpose was to develop a novel hypothetical method to increase the size of coronary arteries. Methods: In the long-term observation the coronary sizes were dilated in three unexpected scenarios. The coronary artery sizes were observed in patients with mitral stenosis (n=59) by angiogram prior to percutaneous balloon mitral valvuloplasty or valve replacement surgery for severe mitral stenosis. The coronaries of patients with patent ductus arteriosus who underwent surgical closure in the past (n=12) were examined by echocardiogram. Patients with renal failure on long-term dialysis through peripheral arterio-venous fistula without left ventricular hypertrophy (n=17) were studied by echocardiography. Normal age, weight and sex matched coronary sizes served as controls in the study. All these observations were made over a period of 11.5 years. Results: The sizes of coronaries in patients with mitral stenosis, patients who underwent closure for patent ductus arteriosus, and in patients on hemodialysis through arteriovenous fistulas were higher than normal controls (p<0.05, for all). A hypothetical model to increase the coronary sizes could be developed based on the analysis of the differential equations of Poiseuille’s. The proposed method is creating a peripheral arterio-venous fistula, which could be closed later electively by a percutaneous method/surgery. The closure time needs to be determined by experimental studies. The other methods could be a continuous exercise program or usage of beta-blockers. Conclusion: A novel hypothetical method of peripheral arteriovenous fistula formation could potentially increase the size of the coronaries, and this could be closed later.
REVIEW | doi:10.20944/preprints202208.0295.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: coronary; atherosclerosis; cardiac CT; geometry
Online: 17 August 2022 (03:24:46 CEST)
Coronary artery disease (CAD) represents a modern pandemic associated with significant morbidity and mortality. The multi-faceted pathogenesis of this entity has long been investigated, highlighting the contribution of systemic factors such as hyperlipidemia and hypertension. Nevertheless, recent research has drawn light to the importance of geometrical features of coronary vasculature on the complexity and vulnerability of coronary atherosclerosis. Various parameters have been investigated so far, including vessel-length, cross-sectional area, curvature, and tortuosity, using primarily invasive angiography and recently non-invasive cardiac computed tomography angiography (CCTA). It is clear that there is correlation between geometrical parameters and both the haemodynamic alterations augmenting the atherosclerosis-prone environment and the extent of plaque burden. The purpose of this review is to discuss the currently available literature regarding this issue and propose a potential non-invasive imaging biomarker, the geometric risk score, which could be of importance to allow early detection of individuals at increased risk of developing CAD.
REVIEW | doi:10.20944/preprints202204.0292.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: Breakfast consumption; mortality; coronary diseases; obesity
Online: 29 April 2022 (08:20:22 CEST)
Epidemiological studies indicate that skipping breakfast as a universal behavior, may have adverse effects on cardiovascular diseases [CVDs}and metabolic diseases. However, eating breakfast regularly, may increase satiety, thereby reducing overeating later in the day which prevents weight gain. Recent studies indicate that skipping breakfast increases the risk of obesity, metabolic syndrome, hypertension, hypercholesterolemia, type 2 diabetes mellitus (T2DM), coronary artery disease (CAD), and cardiovascular mortality as well as all-cause mortality. However, many studies also reported that regular taking of breakfast decreases the risk of CVDs and T2DM and all-cause mortality. Previous studies reported that heavy breakfast, in particular eating western diet may increase circadian rhythm of CVDs and sudden cardiac death. It seems that those who do not eat breakfast, they tend to eat refined and sweetened products, possibly, more in the night resulting in to greater risk of CVDs and T2DM. Breakfast skipping and eating in the night, may be associated with circadian misalignment in the central and peripheral clocks, leading to oxidative stress and inflammation. Increased systemic inflammation damages the adipocytes, beta cells of pancreas, endothelial cells and smooth muscle cells as well as neurons, which may produce dysfunction in these cells resulting in to related diseases. The beneficial effects of breakfast, may also be, at least in part, due to nutrient dense foods rather than time of eating. Eating regular breakfast, in particular rich in Indo-Mediterranean foods; vegetables, whole grains, fruits, spices and nuts may be protective against circadian increase in oxidative stress in the morning, resulting in to significant decline in the risk of CVDs and T2DM.
ARTICLE | doi:10.20944/preprints202004.0092.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: Acute coronary syndrome; inflammation; neutrophil; outcome
Online: 7 April 2020 (11:18:03 CEST)
Aims: Clinical evidence indicates that innate immune cells may contribute to the onset and outcome of acute coronary syndrome (ACS). Our prospective study aimed at analysing neutrophil phenotypes in ACS and their role in predicting 1-year major cardiovascular events. Methods: Blood neutrophil phenotypes were analysed by flow cytometry. Differential blood cell count and plasma levels of soluble markers were recorded at admission and at 6-month follow-up. Results: 108 patients categorized in chronic stable coronary artery disease (n=37), unstable angina (UA) (n=19), Non-ST-Elevation Myocardial Infarction (NSTEMI) (n=25), and ST-Elevation Myocardial Infarction (STEMI) (n=27) were included. STEMI and NSTEMI patients displayed higher neutrophil count and neutrophil-to-lymphocyte ratio (NLR) than stable and UA patients (P<0.0001), which normalized at 6-month after MI. STEMI patients were characterized by elevated percentages of band cells in low-density neutrophils (P=0.007) and in high-density neutrophils (P=0.019) compared to the other patients. Multivariable logistic regression analysis revealed that plasma levels of total MPO was associated with STEMI when compared to stable (OR: 1.434; 95% CI: 1.119-1.837; P<0.0001), UA (1.47; 1.146-1.886; P=0.002), and NSTEMI (1.213; 1.1-1.134; P=0.0001) patients, while increased neutrophil SSC signal intensity was associated with NSTEMI compared to stable patients (3.828; 1.033-14.184; P=0.045). Based on multivariable Cox regression analysis, elevated plasma levels of PCSK9 and low-density neutrophil percentage predicted 1-year outcome independently of cardiovascular risk factors (c-index: 0.915; IQR: 0.908-0.929). Conclusions: Changes in neutrophil phenotype are concomitant to ACS. These changes may differ between STEMI and NSTEMI. They may also contribute to ACS risk and patient outcome.
REVIEW | doi:10.20944/preprints201912.0365.v1
Subject: Medicine & Pharmacology, Obstetrics & Gynaecology Keywords: Acute Coronary Syndrome; STEMI; Spontaneous Coronary Artery Dissection; NSTEMI; Vasospastic Angina; Preeclampsia; Eclampsia; Systemic Lupus Erythromatosus
Online: 27 December 2019 (10:41:42 CET)
In this study, we wanted to discuss the acute coronary syndromes in the pregnant womens which are very important for life ofthe fetus. Spontaneous coronary artery dissection and management, which is the most common cause of acute coronary syndrome in pregnant women is also discussed. About 300 articles were examined and 35 articles which published in high quality journals with high level of evidence were chosen and this review was prepared.
REVIEW | doi:10.20944/preprints202104.0114.v2
Subject: Medicine & Pharmacology, Allergology Keywords: Anxiety, complementary therapies, coronary artery disease, pain
Online: 15 April 2021 (12:56:29 CEST)
Cardiovascular disease is the first leading cause of death in the world. Patients with cardiovascular disease may experience various problems, including physiological and psychological problems. Apart from pharmacological therapy, complementary therapy is necessary as a support to conventional medicine. This review aims to describe complementary and alternative therapies for pain and anxiety in patients with cardiovascular disease. This review utilized data from ProQuest, ScienceDirect, and PubMed with search keywords of "Complementary" AND "Nursing" AND "Pain" AND "Anxiety" AND "Coronary artery disease". Ten articles that met the inclusion criteria were analyzed. The results show that nursing actions increasingly develop along with the patient needs. One form of holistic nursing action is complementary and alternative therapy (CAT) that consists of three categories: body-based methods, mind therapies, and sensory therapies. CAT has positive impacts on patients with heart disease. It can reduce anxiety and pain, lower blood pressure, and improve the quality of life. This review also shows that CAT has a positive impact on the recovery of patients with heart disease. Proper therapeutic management should be implemented to reduce the risks of physiological and psychological problems in patients.
Subject: Medicine & Pharmacology, Cardiology Keywords: acute coronary syndromes; myocardial infarction; STEMI; Covid-19, infectious disease; respiratory infections; pathophysiology; percutaneous coronary intervention; thrombolysis; drug treatment
Online: 7 May 2020 (12:49:39 CEST)
Since association between myocardial infarction (MI) and respiratory infections has been described for influenza-viruses and other respiratory viral agents, understanding possible physiopathological links between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and acute coronary syndromes (ACS) is of the greatest importance. First data suggest an underestimation of ACS cases all over the world, but acute MI still represents a major cause of morbidity and mortality worldwide and should not be overshadowed during the coronavirus disease (Covid-19) pandemic. No common consensus regarding the most adequate healthcare management policy for ACS is currently available. Indeed, important differences have been reported between the measures employed to treat ACS in China during the first disease outbreak and what currently represents clinical practice across Europe and the USA. This review aims to discuss: pathophysiological links between MI, respiratory infections, and Covid-19; epidemiological data related to ACS at the time of the Covid-19 pandemic; what emerged so far from several catheterization labs and coronary care units all over the world, in order to shed some light on the current strategies for optimal management of ACS patients with confirmed or suspected SARS-CoV-2 infection.
CASE REPORT | doi:10.20944/preprints202105.0220.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Post-cardiac injury syndrome; pericarditis; percutaneous coronary intervention.
Online: 10 May 2021 (15:48:46 CEST)
Background: Percutaneous coronary intervention (PCI) is known as a very rare possible trigger of pericarditis. Most frequently it develops after a latent period or early in case of periprocedural complications. In this report, we present an atypical early onset of pericarditis after the uncomplicated PCI. Case Summary: A 58-year-old man was admitted to the hospital for the PCI of the chronic total occlusion of left anterior descending (LAD) artery. An initial electrocardiogram (ECG) was unremarkable. PCI attempt was unsuccessful. There were no procedure related complications observed at the end of PCI attempt and patient was symptom free. Six hours after interventional procedure the patient complained of severe chest pain. The ECG demonstrated ST-segment elevation in anterior and lateral leads. Troponin I was mildly elevated but coronary angiogram did not reveal impairment of collateral blood flow to the LAD territory. Because of pericarditic chest pain, typical ECG findings and pericardial effusion with elevated C-reactive protein, the diagnosis of acute pericarditis was established, and a course of nonsteroidal anti-inflammatory drugs (NSAIDs) was initiated. Chest pain was relieved and ST-segment elevation almost completely returned to baseline after three days of treatment. The patient was discharged in stable condition without chest pain on the fourth day after symptom onset. Conclusions: Acute pericarditis is a rare complication of PCI. Despite the lack of specific clinical manifestation, post-traumatic pericarditis should be considered in patients with symptoms and signs of pericarditis and a prior history of iatrogenic injury or thoracic trauma.
ARTICLE | doi:10.20944/preprints201810.0171.v3
Subject: Medicine & Pharmacology, General Medical Research Keywords: genome-wide polygenic score; coronary artery disease; AUC
Online: 6 December 2018 (07:06:32 CET)
A recent study claimed that genome-wide polygenic scores (GPSs) for five common diseases could identify individuals with risk equivalent to monogenic mutations. Receiver operator curve analyses were reported to have areas under the curve (AUCs) ranging from 0.63 for inflammatory bowel disease up to 0.81 for coronary artery disease (CAD) but these models also included age and sex, themselves strong predictors of risk. The GPS for CAD identified 8% of the population at threefold increased risk, which it was claimed was comparable to the excess risk from monogenic mutations. In the present study attempts were made to model the distribution of the GPS for CAD to match the information provided. These models were based on the reported distribution of prevalence by centile of GPS and on the distribution of GPS in controls and cases and were fitted to the reported results using linear approximations to the distributions and using simulations of a liability-threshold model. It was impossible to produce a compatible model in which the GPS produced an AUC as high as 0.81 and the most plausible estimate was that the true AUC was only 0.65. The reported distributions of the GPS in cases and controls overlap so much that they are not compatible with an AUC of 0.7 or higher. The AUC of the GPS for these diseases is modest. Furthermore, the literature robustly demonstrates that true CAD risk associated with monogenic mutations is much higher than the threefold increase which is predicted by the GPS. Together, these findings cast doubt on the clinical utility of the GPS.
ARTICLE | doi:10.20944/preprints202203.0050.v1
Subject: Life Sciences, Biophysics Keywords: Coronary vasculature; lumped parameter model; fractional flow reserve; computational cardiology
Online: 2 March 2022 (12:34:43 CET)
Background. The treatment of coronary stenosis relies on invasive high risk surgical assessment to generate the fractional flow reserve diagnostics index, a ratio of distal to proximal pressures in respect of coronary atherosclerotic plaque causing stenosis. Non-invasive methods are therefore a need of the times. This study proposes an extensible mathematical description of the coronary vasculature that permits rapid estimation of the coronary fractional flow reserve. Methods. By adapting an existing closed loop model of human coronary blood flow, the effects of large vessel stenosis and microvascular disease on fractional flow reserve were quantified. Several simula-tions generated flow and pressure information which was used to compute fractional flow re-serve under a spectrum of conditions including focal stenosis, diffuse stenosis, and microvascular disease. Sensitivity analysis stratified the influence of model parameters on the index. The model was simulated as coupled non-linear ordinary differential equations and numerically solved us-ing an implicit higher order method. Results. Large vessel stenosis affected fractional flow re-serve. The model predicts that the presence, rather than severity, of microvascular disease affect coronary flow deleteriously. Sensitivity analysis revealed that heart rate may not affect the index. Conclusions. The model provides a computationally inexpensive instrument for future in silico coronary blood flow investigations as well as clinical-imaging decision making. A combination of focal and diffuse stenosis appears to be essential in reducing the index. In addition to pressure measurements in the large epicardial vessels, diagnosis of microvascular disease is essential. The independence of the index with respect to heart rate suggests that computationally inexpensive steady state simulations may provide sufficient information to reliably compute the index.
ARTICLE | doi:10.20944/preprints202110.0293.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: high coronary thrombus burden; tissue plasminogen activator; catheter-directed thrombolysis
Online: 20 October 2021 (12:53:10 CEST)
Background: High coronary thrombus burden has been associated with unfavorable outcomes in patients with ST-segment elevation myocardial infarction (STEMI), the optimal management of which has not yet to be established. Methods: We evaluated the safety and efficacy of adjunctive catheter-directed thrombolysis (CDT) during primary percutaneous coronary intervention (PCI) in patients with STEMI and high thrombus burden. Results: Among the 1,849 consecutive patients with STEMI, 263 had high thrombus burden. Moreover, 41 patients received intracoronary infusion of tissue plasminogen activator during primary PCI (CDT group), whereas 222 did not receive (non-CDT group). No significant differences in bleeding complications and in-hospital and long-term mortalities were observed (9.8% vs. 7.2%, p=0.53; 7.3% vs. 2.3%, p=0.11; and 12.6% vs. 17.5%, p=0.84, CDT vs. non-CDT). In patients who underwent antecedent aspiration thrombectomy during PCI (75.6%; CDT group and 87.4%; non-CDT group), thrombolysis in myocardial infarction grade 2 or 3 flow rate after thrombectomy was significantly lower in the CDT group than in the non-CDT group (32.2% vs. 61.0%, p<0.01). However, the final rates improved considerably without significant difference (90.3% vs. 97.4%, p=0.14). Conclusions: For STEMI patients with high thrombus burden, adjunctive CDT is safe and effective for improving coronary flow. CDT resulted in favorable coronary flow even after unsatisfactory aspiration thrombectomy.
ARTICLE | doi:10.20944/preprints201804.0140.v1
Subject: Social Sciences, Other Keywords: coronary heart disease risk factors; healthy lifestyle behaviors; physical fitness
Online: 11 April 2018 (07:40:50 CEST)
The purpose of the present study was to determine the relationship between healthy lifestyle behaviors, physical fitness and coronary risk factors in university students. 320 male and female (nm:171; nf:149) students from a university participated in this study voluntarily. For the determination of body composition and Body Mass Indexes (BMI), subjects’ height, body weight, and skinfold thickness were taken and body fat percentage (%Fat) was determined. Healthy lifestyle behaviors were determined using the healthy lifestyle behaviors questionnaire. Indicators of physical fitness included flexibility (sit-up) (F), muscle strength and endurance (isometric knee (KS), back strength (BS) and a total of shuttle (TS), sprint performance, BMI, and body fat percentage (%fat). Coronary heart disease risk factors included mean arterial blood pressure (systolic (SBP) and diastolic (DBP)), fasting blood levels of triglycerides (TG), total cholesterol (TC), hematocrit (HT), and hemoglobin (HM). Results indicated subjects have normal body mass index, body fat percentage, SBP, DBP, TG, TCF, BS, KS. The results of the Pearson Product Moment Correlation Analysis, indicated that SBP, DBP, TG, TCF, BS, KS for male and female was significantly correlated with flexibility (sit-up) (F), muscle strength and endurance (isometric knee (KS), back strength (BS) and total of shuttle (TS)), sprint performance. (p<0.01; p<0.05), In conclusion, the findings of the present study indicated that physical fitness and healthy lifestyle behaviors play a determinant role in coronary heart disease risk factors for male and female students from a university.
ARTICLE | doi:10.20944/preprints202203.0306.v1
Subject: Medicine & Pharmacology, Other Keywords: Atherogenesis; metabolic status; lipid index; coronary heart disease; medical check-up
Online: 23 March 2022 (03:34:35 CET)
We evaluated the usefulness of the novel cholesterol-triglyceride subgroup (CTS) indices that potentially reflect the metabolic status regarding risk of coronary heart disease (CHD) using a retrospective longitudinal study of the Japanese general population. We recruited 12,373 individuals from the annual users of our healthcare center. Among them, the first onset of CHD was recorded in 131 individuals between April, 2014 and March, 2020. The multivariate Cox proportional hazards regression analyses for all normalized lipid indices revealed that the CTSqnt index showed a comparable hazard ratio for the CHD outcome to non-high-density lipoprotein cholesterol (nonHDL-c) and triglycerides. The HR of the CTSqlt index was significantly lower than for CTSqnt, but still comparable to that for low-density lipoprotein cholesterol (LDL-c). In comparison with the other indices, CTSqlt is more sensitive to risk increment while the index value increases. Linear regression analyses for the CTS indices and previously known lipid indices suggest that the CTSqnt and CTSqlt indices reflect the quantity of atherogenic lipoproteins and size of smaller and denser LDLs, respectively. Furthermore, the CTSqnt/HDL-c index can be used as a comprehensive risk indicator that may represent the status of lipid metabolism determined by the CTSqlt and CTSqnt indices and thus may be useful for screening. The CTS indices can be used to evaluate the metabolic status of individuals, which may increase the risk of future CHD.
ARTICLE | doi:10.20944/preprints202110.0076.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: coronary artery disease; gut microbiome; dysbiosis; obesity; Bacteroidetes; LPS; indoxyl sulfate
Online: 5 October 2021 (10:33:24 CEST)
Gut dysbiosis, alongside with high-fat diet and cigarette smoking, is considered one of the factors promoting coronary arterial disease (CAD) development. The present study aimed to research whether gut dysbiosis can increase bacterial metabolites concentration in the blood of CAD patients and what impact these metabolites can exert on endothelial cells. The gut microbiome of 15 CAD patients and age-matched 15 healthy controls was analyzed by metagenome sequencing. The in vitro impact of LPS and indoxyl sulfate at concentrations present in patients sera on endothelial cells was investigated. A metagenome sequencing analysis revealed gut dysbiosis in CAD patients, further confirmed by elevated levels of LPS and indoxyl sulfate in patients sera. CAD was associated with depletion of Bacteroidetes and Alistipes. LPS and indoxyl sulfate in meager concentrations demonstrated co-toxicity to endothelial cells inducing reactive oxygen species, E-selectin, and monocyte chemoattractant protein-1 (MCP-1) production and promoting thrombogenicity of endothelial cells confirmed by monocyte adherence. The co-toxicity of LPS and indoxyl sulfate was associated with harmful effects on endothelial cells, strongly suggesting that gut dysbiosis-associated increased intestinal permeability can initiate or promote endothelial inflammation and atherosclerosis progression.
ARTICLE | doi:10.20944/preprints202108.0213.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: troponin; high-sensitivity; chronic kidney disease; renal insufficiency; myocardial infarction; acute coronary syndrome
Online: 10 August 2021 (08:45:07 CEST)
Background: Patients with severe chronic kidney disease (CKD G4-G5) often have chronically elevated high-sensitivity cardiac troponin T (hs-cTnT) values above the 99th percentile of the upper reference limit. In these patients, optimal cutoff levels for diagnosing non-ST-elevation acute cor-onary syndrome (NSTE-ACS) requiring revascularization remain undefined. Methods: Of 11,912 patients undergoing coronary angiography from 2012 to 2017 for suspected NSTE-ACS, 325 (3%) had severe CKD. Of these, 290 with available serial hs-cTnT measurements were included and 300 matched patients with normal renal function were selected as a control cohort. Results: Diagnostic performance for patients with severe CKD was high at presentation and similar to that of the control population (AUC, 95% CI: 0.81, 0.75-0.87 versus 0.85, 0.80-0.89, p=0.68) and the ROC-derived cutoff value at presentation was 4 times higher compared to the conventional 99th percentile. Combining the ROC-derived cutoff levels for hs-cTnT at presentation and absolute 3-hour changes, sensitivity increased to 98%, PPV and NPV improved up to 93% and 86%, re-spectively. (4) Conclusions: In patients with severe CKD and suspected ACS the diagnostic accu-racy of hs-cTnT for the diagnosis of NSTE-ACS requiring revascularization is improved by using higher assay specific cutoff levels combined with early absolute changes.
ARTICLE | doi:10.20944/preprints202108.0026.v1
Subject: Mathematics & Computer Science, Algebra & Number Theory Keywords: 1D haemodynamics, stenosis, systole variations, coronary circulation, tachycardia, boundary conditions, FFR, CFR, iFR.
Online: 2 August 2021 (12:08:24 CEST)
Haemodynamic indices are widely used in clinical practice for deciding on a particular type of treatment. Low quality of the CT data and tachycardia complicate interpretation of the measured or simulated values. In this work, we present a novel approach for evaluating resistances in terminal coronary arteries. Using 14 measurements from 10 patients, we show that this algorithm retains the accuracy of 1D haemodynamic simulations in less detailed (truncated) geometric models of coronary networks. We also apply the variable systole fraction model to study the effect of elevated heart rate on the values of FFR, CFR and iFR. We conclude that tachycardia may produce both overestimation or underestimation of coronary stenosis significance.
REVIEW | doi:10.20944/preprints202204.0057.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: atherosclerosis; biomechanics; border detection; coronary artery disease; optical coherence to-mography; stents; vulnerable plaque
Online: 7 April 2022 (08:13:34 CEST)
Coronary optical coherence tomography (OCT) is an intravascular, near-infrared light-based imaging modality capable of reaching axial resolutions of 10-20 µm. This resolution allows for accurate determination of high-risk plaque features, such as thin cap fibroatheroma; however, visualisation of morphological features alone still provides unreliable positive predictive capability for plaque progression or future major adverse cardiovascular events (MACE). Biomechanical simulation could assist in this prediction, but this requires extracting morphological features from intravascular imaging to construct accurate three-dimensional simulations of patients’ arteries. Extracting these features is a laborious process, often carried out manually by trained experts. To address this challenge, numerous techniques have emerged to automate these processes while simultaneously overcoming difficulties associated with OCT imaging, such as its limited penetration depth. This systematic review summarises advances in automated segmentation techniques from the past five years (2016-2021) with a focus on their application to the three-dimensional reconstruction of vessels and their subsequent simulation. We discuss four categories based on the feature being processed, namely: coronary lumen; plaque characteristics and subtypes; artery layers; and stents. Areas for future innovation are also discussed as well as their potential for future translation.
REVIEW | doi:10.20944/preprints202112.0363.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: Platelet; ACKR3/CXCR7; Thrombosis; Thrombo-inflammation; Anti-platelet therapy; Cardiovascular disease; Coronary artery disease
Online: 22 December 2021 (12:27:01 CET)
The manifold actions of the pro-inflammatory and regenerative chemokine CXCL12/SDF-1α are executed through the canonical GProteinCoupledReceptor CXCR4, and the non-canonical ACKR3/CXCR7. Platelets express CXCR4, ACKR3/CXCR7, and are a vital source of CXCL12/SDF-1α themselves. In recent years, a regulatory impact of the CXCL12-CXCR4-CXCR7 axis on platelet biogenesis i.e. megakaryopoiesis, thrombotic and thrombo-inflammatory ac-tions have been revealed through experimental and clinical studies. Platelet surface expression of ACKR3/CXCR7 is significantly enhanced following myocardial infarction (MI) in acute coro-nary syndrome (ACS) patients, also associated with improved functional recovery and progno-sis. The therapeutic implications of ACKR3/CXCR7 in myocardial regeneration and improved recovery following an ischemic episode, are well documented. Cardiomyocytes, cardi-ac-fibroblasts, endothelial lining of the blood vessels perfusing the heart, besides infiltrating platelets and monocytes, all express ACKR3/CXCR7. This review recapitulates ligand induced differential trafficking of platelet CXCR4-ACKR3/CXCR7 affecting their surface availability, and in regulating thrombo-inflammatory platelet functions and survival through CXCR4 or ACKR3/CXCR7. It emphasizes the pro-thrombotic influence of CXCL12/SDF-1α exerted through CXCR4, as opposed to the anti-thrombotic impact of ACKR3/CXCR7. Offering an innovative translational perspective, this review also discusses the advantages and challenges of utilizing ACKR3/CXCR7 as a potential anti-thrombotic strategy in platelet associated cardiovascular dis-orders, particularly in coronary artery disease (CAD) patients post-MI.
ARTICLE | doi:10.20944/preprints201807.0509.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: inflammation; coronary disease; mediterranean diet; low-fat diet; C-reactive protein; adiponectin; visceral fat; body composition
Online: 26 July 2018 (10:33:01 CEST)
The Mediterranean diet (MedDiet) is recognised to reduce risk of coronary heart disease (CHD), in part, via its anti-inflammatory properties. Diet efficacy via this mechanism is however unclear in patients with diagnosed CHD. This study aimed to determine the effect of MedDiet versus low-fat diet intervention on inflammatory biomarkers and adiposity in a pilot cohort of Australian patients post coronary event. Participants (62±9 years, 83% male) were randomised to the MedDiet (n=34) or low-fat diet (n=31). At 0-, 3- and 6-months, dietary counselling, anthropometry, body composition (Dual-energy X-ray Absorptiometry) and venepuncture was conducted. Participants adhered well to the MedDiet intervention, however, there were no significant changes in body composition or inflammatory biomarkers hs-C-reactive protein or hs-interleukin-6 in the MedDiet compared to the low-fat diet group after 6-months. Adiponectin, an anti-inflammatory adipokine, tended to increase in response to the MedDiet (+1.1±4.2ng/mL, p=0.11) and decrease in response to the low-fat diet (-0.9±3.3ng/mL, p=0.20). In the pooled cohort, participants with greatest improvement in MedDiet adherence score had significantly lower waist circumference and subcutaneous fat levels at 6-months. A clinically significant effect of the MedDiet on inflammation and adiposity in CHD patients may require a larger sample, adjunct exercise intervention and/or caloric restriction.
REVIEW | doi:10.20944/preprints202212.0086.v1
Subject: Behavioral Sciences, Other Keywords: Information; resources; coronary heart disease; digital health; education; cardiac rehabilitation; secondary prevention; text message; sensors; cardiovascular risk
Online: 6 December 2022 (02:09:28 CET)
A critical aspect of coronary heart disease (CHD) care and secondary prevention is ensuring patients have access to evidence-based information. The purpose of this review is to summarise the guiding principles, content, context and timing of information and education that is beneficial for supporting people with CHD and potential communication strategies including digital interventions. We conducted a scoping review involving searching four databases (Web of Science, PubMed, CINAHL, Medline) for articles published from January 2000 to August 2022. Literature was identified through title and abstract screening by expert reviewers. Evidence was synthesised according to the review aims. Results demonstrated that information-sharing, decision-making, goal-setting, positivity and practicality are important aspects of secondary prevention and should be patient-centred and evidenced based with consideration of patient need and preference. Initiation and duration of education is highly variable between and within people, but hence communication and support should be regular and ongoing. In conclusion, text messaging programs, smartphone applications and wearable devices are examples of digital health strategies that facilitate education and support for patients with heart disease. There is no one size fits all approach that suits all patients at all stages and hence flexibility and a suite of resources and strategies is optimal.
ARTICLE | doi:10.20944/preprints202106.0733.v1
Subject: Engineering, Automotive Engineering Keywords: Discrete multiphysics; smooth particle hydrodynamics; Lattice Spring Model; Fluid-structure interaction; particle-based method; Coronary stent; Atherosclerosis
Online: 30 June 2021 (11:55:59 CEST)
Stenting is a common method for treating atherosclerosis. A metal or polymer stent is deployed to open the stenosed artery or vein. After the stent is deployed, the blood flow dynamics influence the mechanics by compressing and expanding the structure. If the stent does not respond properly to the resulting stress, vascular wall injury or re-stenosis can occur. In this work, Discrete Multiphysics is used to study the mechanical deformation of the coronary stent and its relationship with the blood flow dynamics. The major parameters responsible for deforming the stent are sort in terms of dimensionless numbers and a relationship between the elastic forces in the stent and pressure forces in the fluid is established. The blood flow and the stiffness of the stent material contribute significantly to the stent deformation and affect the rate of deformation. The stress distribution in the stent is not uniform with the higher stresses occurring at the nodes of the structure.
REVIEW | doi:10.20944/preprints201809.0040.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: Triggering receptor expressed on myeloid cells, DNAX-activating protein 12, cardiovascular diseases, atherosclerosis, coronary arteries diseases, acute myocardial infract, endocarditis
Online: 3 September 2018 (14:50:17 CEST)
Cardiovascular Diseases (CVDs) are still menacing and killing adults worldwide, notwithstanding the tremendous effort, to decrease their related mortality and morbidity. Lately, a growing body of evidences indicated that inflammation plays a pivotal role in the pathogenesis and complications of CVDs. A receptor of the immunoglobulin superfamily, triggering receptor expressed on myeloid cells -1 (TREM-1) was shown to induce and to amplify the inflammation in both acute and chronic diseases pathogenesis and progression and hence it is one of the important factors that complicates CVDs. Thus, studies endeavored to investigate the role played by TREM-1 in CVDs with respect to their etiologies, complications and possible therapeutics. We examined here, for the first time, the most relevant studies regarding TREM-1 involvement in CVDs. We summarized the finding after critically analyzing them and made some suggestions for furtherance of the investigations with the aim to utilize TREM-1 and its pathways for diagnostic, management and prognosis of CVDs. Overall, TREM-1 was found to be involved in the pathogenesis of acute and chronic cardiovascular conditions like Acute myocardial infraction (AMI) and atherosclerosis as well. Although most therapeutic approaches are yet to be elucidated, present research outcome displays a promising future to utilize TREM-1 pathway as potential target to understand and manage CVDs.
ARTICLE | doi:10.20944/preprints202006.0199.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: C-reactive protein; platelet to lymphocyte ratio; neutrophil to lymphocyte ratio; hematocrit; red blood cell distribution width; contrast induced nephropathy; coronary intervention
Online: 16 June 2020 (07:51:20 CEST)
Background: Strong indicators of inflammation, such as C-reactive protein (CRP), hypersensitive CRP (hs-CRP), and a series of hematological indices, including platelet to lymphocyte ratio (PLR), neutrophil to lymphocyte ratio (NLR), hematocrit (HCT) and red blood cell distribution width (RDW), are regarded related with the incidence of contrast induced nephropathy (CIN) closely. Whereas, it remains unclear whether they can function as predictors of CIN onset. The objective of this meta-analysis was to determine the relationship between above indicators and CIN incidence among patients receiving coronary intervention. Methods: Clinical studies were retrieved from the electronic databases of PubMed, EMBASE, Google Scholar, Clinical Trials, and science direct from their inception to June 3rd, 2020. Meta-analysis was performed on pool eligible studies. Two reviewers screened all titles and abstracts and independently assessed all articles. Results: A total of 26 studies involving 29,454 patients were included in the meta-analysis. Pooled analysis results revealed that patients with higher CRP (odds ratio [OR]=1.06, 95% confidence interval [CI]: 1.01–1.12, P=0.02), hs-CRP (OR=1.03, 95% CI: 1.01–1.06, P=0.004), NLR (OR=1.11, 95% CI: 1.01–1.20, P=0.02), RDW (OR=1.35, 95% CI: 1.19–1.53, P<0.00001), and lower HCT (OR=0.94, 95% CI: 0.92–0.97, P=0.0003) all exhibited significantly higher CIN rates, but there was no significant association between PLR and CIN risk (OR=1.12, 95% CI: 0.99–1.26, P=0.07). Conclusion: The meta-analysis reported here demonstrates that pre-angiography CRP/hs-CRP and some hematological indices are associated with CIN.
ARTICLE | doi:10.20944/preprints202108.0157.v1
Subject: Life Sciences, Cell & Developmental Biology Keywords: reptile, ventricular septation, endocardial cushions, semilunar valves, outflow tract, cartilage, foramen of Panizza, left aorta, right aorta, pulmonary trunk, pharyngeal arch arteries, coronary arter
Online: 6 August 2021 (11:08:56 CEST)
The outflow tract of crocodilians resembles that of birds and mammals as ventricular septation is complete. The arterial anatomy however, presents with a pulmonary trunk originating from the right ventricular cavum, and two aortae originating from either the right or left ventricular cavum. Mixing of blood in crocodilians cannot occur at ventricular level as in other reptiles, but instead takes place at aortic root level by a shunt, the Foramen of Panizza, the opening of which is guarded by two facing semilunar leaflets of both bicuspid aortic valves. Methods. Developmental stages of Alligator mississipiensis, Crocodilus niloticus and Caiman latirostris, have been studied. Results and Conclusions. The outflow tract septation complex can be divided into 2 components. The aorto-pulmonary septum divides the pulmonary trunk from both aortae, whereas the interaortic septum divides the systemic from the visceral aorta. Neural crest cells are most likely involved in the formation of both components. Remodeling of the endocardial cushions and both septa results in the formation of bicuspid valves in all three arterial trunks. The foramen of Panizza originates intracardially as a channel in the septal endocardial cushion.
ARTICLE | doi:10.20944/preprints201808.0463.v1
Subject: Chemistry, Medicinal Chemistry Keywords: Factor Xa ( F-Xa), Cardiovascular diseases (CD), Coronary heart disease (CHD), Tissue plasminogen activator (t-PA), Urokinase (UK), Streptokinase (SK), N,N-Dimethyl formamide (DMF)
Online: 27 August 2018 (14:54:10 CEST)
A new series of 1,3,4-oxadiazoles derivatives was synthesized, characterized and evaluated for their in vitro and in vivo anti-thrombotic activity. Compounds (3a-3i) exhibited significant clot lysis with respect to negative control and reference drug streptokinase (30,000 IU) while enhanced clotting time (CT) values were observed (130-342 sec) for these tested compounds than the standard drug heparin (110 sec.). High affinity towards 1NFY with greater docking score was observed for the compounds (3a, 3i, 3e, 3d and 3h) than the control ligand RPR200095. In addition, very good inhibitory potential against factor Xa (F-Xa) was observed with higher docking scores (5612-6270) with ACE values (–189.68 to –352.28 kcal/mol) than the control ligand RPR200095 (Docking score 5192; ACE –197.81 kcal/mol. In vitro, in vivo and in silico results proposed that these newly synthesized compounds can be used as anti-coagulant agents.
ARTICLE | doi:10.20944/preprints201809.0082.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: atherosclerosis; coronary aortic disease; gene set enrichment analysis; heart disease; Apoe mouse; transcriptomics; RNA-seq analysis; pathway enrichment analysis; mouse; precision medicine; New Zealand White rabbit
Online: 5 September 2018 (04:49:40 CEST)
The central promise of personalized medicine is individualized treatments that target molecular mechanisms underlying the physiological changes and symptoms arising from disease. We demonstrate a bioinformatics analysis pipeline as a proof-of-principle to test the feasibility and practicality of comparative transcriptomics to classify two of the most popular in vivo diet-induced models of coronary atherosclerosis, apolipoprotein E null mice and New Zealand White rabbits. Transcriptomics analyses indicate the two models extensively share dysregulated genes albeit with some unique pathways. For instance, while both models have alterations in the mitochondrion, the biochemical pathway analysis revealed, Complex IV in the electron transfer chain is higher in mice, whereas the rest of the electron transfer chain components are higher in the rabbits. Several fatty acids anabolic pathways are expressed higher in mice, whereas fatty acids and lipids degradation pathways are higher in rabbits. This reflects the differences between two translational models of atherosclerosis. This study validates transcriptome analysis as a potential method to precisely identify altered cellular and molecular pathways in atherosclerotic disease, which can be used to individualize treatment even in the absence of genetic data.