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This study assessed Lavandula stoechas flower extract's impact on Isoprenaline-induced myocardial necrosis in rats. Five groups of five rats each were used. Group I received 1 ml/kg normal saline orally for 13 days, Group II received 10 ml/kg normal saline orally, Group III received 200 mg/kg Lavandula stoechas extract orally, Group IV received 400 mg/kg Lavandula stoechas extract orally, and Group V received 10 mg/kg Metoprolol orally. On days 14 and 15, Group I received 0.5 ml/kg subcutaneous normal saline, and Groups II to V received 85 mg/kg Isoprenaline subcutaneously. On day 16, rats were weighed, and cardiac blood samples were collected. Serum was analyzed for total protein, triglycerides, and cardiac enzymes (cardiac injury markers). Rats were sacrificed, and heart tissues were histologically examined. Results showed significant serum marker enzyme reductions (p < 0.01) in Lavandula stoechas-treated rats. Total protein and triglyceride levels (p < 0.01) decreased, and heart weight-to-body weight ratio (p < 0.05) decreased in Lavandula stoechas-treated rats. Histopathology confirmed the extract's protective effect. In conclusion, Lavandula stoechas flower extract offers protection against Isoprenaline-induced myocardial infarction in rats. [ABSTRACT FROM AUTHOR]

Objective: In this paper, we propose an algorithm for the generation of a patient-specific cardiac vascular network starting from segmented epicardial vessels down to the arterioles. Method: We extend a tree generation method based on satisfaction of functional principles, named constrained constructive optimization, to account for multiple, competing vascular trees. The algorithm simulates angiogenesis under vascular volume minimization with flow-related and geometrical constraints adapting the simultaneous tree growths to patient priors. The generated trees fill the entire left ventricle myocardium up to the arterioles. Results: From actual vascular tree models segmented from CT images, we generated networks with 6000 terminal segments for six patients. These networks contain between 33 and 62 synthetic trees. All vascular models match morphometry properties previously described. Conclusion and significance: Image-based models derived from CT angiography are being used clinically to simulate blood flow in the coronary arteries of individual patients to aid in the diagnosis of disease and planning treatments. However, image resolution limits vessel segmentation to larger epicardial arteries. The generated model can be used to simulate the blood flow and derived quantities from the aorta into the myocardium. This is an important step for diagnosis and treatment planning of coronary artery disease. [ABSTRACT FROM AUTHOR]

In transposition of the great arteries (TGA), certain coronary patterns have been associated with major adverse events early after the arterial switch operation (ASO). We sought to determine the impact of preoperative echocardiographic (ECHO) diagnosis on the intra­ and postoperative morbidity. All patients with TGA born between June 2001 and June 2017 and who underwent ASO were reviewed. Data on presumed coronary anatomy (CA) preoperatively were obtained from the preoperative ECHO report. Intraoperative CA was categorized according to Yacoub classification. Major postoperative morbidity included at least one of the following: delayed sternal closure (DSC), prolonged (> 72 h) mechanical ventilation, reintubation, peritoneal dialysis (PD), ECMO, reoperation, and readmission within 30 days after surgery. 240 patients with median age of 5 days (range 1-614) and mean weight at surgery was 3.6 kg (1.8-8.4) were included. Preoperative ECHO assessment of CA was available in 228 patients. Intraoperatively, 181 patients (75%) were found to have type A, 25 patients had type B or C or intramural (B-C-IM; 10%), and 34 patients had type D or E (D-E; 14%). Patients with types B, C, and intramural coronary (B-C-IM) had increased risk for delayed sternum closure (9/25 vs. 20/181 in type A and 8/34 in type D-E; p = 0.04), peritoneal dialysis (4/25 vs. 8/181 and 1/34; p = 0.04), and ECMO (2/25 vs. 1/131 and 1/34; p = 0.02). Within the B-C-IM group, preoperative ECHO raised suspicion of type A in 13 patients (i.e., incorrect diagnosis, ID; 52%), whereas non-A CA was suspected in 12 patients (i.e., correct diagnosis, CD; 48%). With the exception of reoperation, which was seen only in the ID subgroup (4/12 vs. 0/10 in the CD subgroup; p = 0.04), the intraoperative (cardiopulmonary bypass time and cross-clamp time) and postoperative morbidity indices were comparable in both ID and CD subgroups (p > 0.1). Although there is a significant risk for early postoperative morbidity in TGA patients with single, interarterial, and intramural CA, there seems to be relatively limited influence of preoperative ECHO assessment of coronary anatomy on this morbidity burden. [ABSTRACT FROM AUTHOR]

Background: The arterial switch operation (ASO) is the gold standard operative correction of neonates with transposition of the great arteries and intact ventricular septum, with excellent operative survival. The associations between patient and surgeon characteristics and outcomes are well understood, but the associations between variation in preoperative care and outcomes are less well studied.Methods: A multicenter retrospective cohort study of infants undergoing neonatal ASO between January 2010 and September 2015 at hospitals contributing data to the Pediatric Health Information Systems database was performed. The association between preoperative care (timing of ASO, preoperative use of balloon atrial septostomy, prostaglandin infusion, mechanical ventilation, and vasoactive agents) and operative outcomes (mortality, length of stay, and cost) was studied with multivariable mixed-effects models.Results: Over the study period, 2159 neonates at 40 hospitals were evaluated. Perioperative mortality was 2.8%. Between hospitals, the use of adjuvant therapies and timing of ASO varied broadly. At the subject level, older age at ASO was associated with higher mortality risk (age >6 days: odds ratio, 1.90; 95% CI, 1.11-3.26; P=0.02), cost, and length of stay. Receipt of a balloon atrial septostomy was associated with lower mortality risk (odds ratio, 0.32; 95% CI, 0.17-0.59; P<0.001), cost, and length of stay. Later hospital median age at ASO was associated with higher odds of mortality (odds ratio, 1.15 per day; 95% CI, 1.02-1.29; P=0.03), longer length of stay ( P<0.004), and higher cost ( P<0.001). Other hospital factors were not independently associated with the outcomes of interest.Conclusions: There was significant variation in preoperative care between hospitals. Some potentially modifiable aspects of perioperative care (timing of ASO and septostomy) were significantly associated with mortality, length of stay, and cost. Further research on the perioperative care of neonates is necessary to determine whether modifying practice on the basis of the observed associations translates into improved outcomes. [ABSTRACT FROM AUTHOR]

We summarize the evidence on the new strategies for coronary artery bypass grafting (CABG). Hybrid CABG implies surgical grafting of the left anterior descending artery and percutaneous treatment of the other target vessels, with the promise of combining the durable benefits of surgery with the less invasive approach of percutaneous coronary interventions. Robotic CABG and minimally invasive CABG are performed through minimal incision or port access with dedicated equipment and instruments. Anaortic coronary artery bypass refers to off-pump CABG using only in-situ grafts. The use of multiple arterial grafts has been shown to improve patency and is potentially associated with better clinical outcomes. All these techniques require dedicated training and are more complex than conventional CABG but can significantly improve the results of surgery. Validation of the results of these new approaches in large randomized trials is a priority for the surgical community. [ABSTRACT FROM AUTHOR]

Background: Coronary lesions with low fractional flow reserve (FFR) that are treated medically are associated with higher revascularization rates. High wall shear stress (WSS) has been linked with increased plaque vulnerability.Objectives: This study investigated the prognostic value of WSS measured in the proximal segments of lesions (WSSprox) to predict myocardial infarction (MI) in patients with stable coronary artery disease (CAD) and hemodynamically significant lesions. The authors hypothesized that in patients with low FFR and stable CAD, higher WSSprox would predict MI.Methods: Among 441 patients in the FAME II (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation II) trial with FFR ≤0.80 who were randomized to medical therapy alone, 34 (8%) had subsequent MI within 3 years. Patients with vessel-related MI and adequate angiograms for 3-dimensional reconstruction (n = 29) were propensity matched to a control group with no MI (n = 29) by using demographic and clinical variables. Coronary lesions were divided into proximal, middle, and distal, along with 5-mm upstream and downstream segments. WSS was calculated for each segment.Results: Median age was 62 years, and 46 (79%) were male. In the marginal Cox model, whereas lower FFR showed a trend (hazard ratio: 0.084; p = 0.064), higher WSSprox (hazard ratio: 1.234; p = 0.002, C-index = 0.65) predicted MI. Adding WSSprox to FFR resulted in a significant increase in global chi-square for predicting MI (p = 0.045), a net reclassification improvement of 0.69 (p = 0.005), and an integrated discrimination index of 0.11 (p = 0.010).Conclusions: In patients with stable CAD and hemodynamically significant lesions, higher WSS in the proximal segments of atherosclerotic lesions is predictive of MI and has incremental prognostic value over FFR. [ABSTRACT FROM AUTHOR]

Introduction: In this analysis, we aimed to systematically compare percutaneous coronary intervention (PCI) versus coronary artery bypass surgery (CABG) in terms of adverse outcomes utilizing data from a recent (2015-2017) population of patients with type 2 diabetes mellitus (T2DM).Methods: An electronic search of recent studies (2015-2017) was carried out using ‘diabetes mellitus,’ ‘coronary artery bypass surgery,’ and ‘percutaneous coronary intervention’ as the main search terms. Uncomplicated T2DM patients with stable coronary artery disease (CAD), left main CAD, and multi-vessel disease were included. RevMan software (version 5.3) was used to calculate odds ratios (OR) and 95% confidence intervals (CIs).Results: Among a total of 13,114 T2DM patients, CABG and PCI patients did not differ significantly in their rates of mortality (OR 0.90, 95% CI 0.61-1.31; P = 0.57) and cardiac death (OR 1.00, 95% CI 0.78-1.30; P = 0.98). However, rates of major adverse events, repeat revascularization, and myocardial infarction were significantly higher in the PCI group. Stroke rates did not significantly differ between the two groups.Conclusion: Mortality (1-5 years) did not significantly differ between the CABG and PCI patients with T2DM. However, rates of other major adverse events were significantly higher in the PCI patients, suggesting that CABG is more advantageous than PCI in patients with T2DM. [ABSTRACT FROM AUTHOR]

The article presents an argument stating that there is not a scientific rationale supporting the value of exercise for the cardiovascular health of children. According to the article, there is no convincing evidence available that either improving physical activity or increasing fitness in normal healthy, nonobese children will alter risk factors for adult coronary artery disease. While there are reasons to suppose that regular exercise habits will prevent the development of risk factors in healthy individuals over time, there is no scientific basis to assume that is true. The article discusses a rationale suggested by S. N. Blair and colleagues.

The article presents support for a scientific rationale supporting the value of exercise for the cardiovascular health of children. The article discusses definitions of cardiovascular health and exercise, risk factors associated with coronary artery disease, how exercise influences cardiovascular health, and examples of various medical studies researching cardiovascular health. According to the article, while many studies have failed to show exercise to have a beneficial effect on risk factors for coronary artery disease, flaws in many of the studies may account for some of the null results. Children develop habits, attitudes, and physiologic characteristics that have a long-term impact on future behaviors and qualities.

In the present work, an ischaemic process, mainly focused on the reperfusion stage, is studied using the informational causal entropy-complexity plane. Ischaemic wall behavior under this condition was analyzed through wall thickness and ventricular pressure variations, acquired during an obstructive flow maneuver performed on left coronary arteries of surgically instrumented animals. Basically, the induction of ischaemia depends on the temporary occlusion of left circumflex coronary artery (which supplies blood to the posterior left ventricular wall) that lasts for a few seconds. Normal perfusion of the wall was then reestablished while the anterior ventricular wall remained adequately perfused during the entire maneuver. The obtained results showed that system dynamics could be effectively described by entropy-complexity loops, in both abnormally and well perfused walls. These results could contribute to making an objective indicator of the recovery heart tissues after an ischaemic process, in a way to quantify the restoration of myocardial behavior after the supply of oxygen to the ventricular wall was suppressed for a brief period. [ABSTRACT FROM AUTHOR]

Objective: Studies have suggested a beneficial effect of angiotensin-converting enzyme (ACE) inhibition. To explore whether the ACE inhibitor ramipril has a direct effect on the microvasculature beyond the blood pressure (BP) lowering effect, we investigated whether ramipril improved coronary microvascular function in normotensive women with coronary microvascular dysfunction (CMD). Methods: We included 63 normotensive women with angina, no epicardial stenosis>50% and CMD defined as a coronary flow velocity reserve (CFVR)<2.2 assessed by adenosine stress-echocardiography in a randomized double-blinded, superiority trial with 1:1 allocation to placebo or ramipril (maximum dose 10 mg depending on blood pressure) for 24±6 weeks. Primary outcome was CFVR. Secondary outcomes were left ventricular systolic and diastolic function and symptoms evaluated by Seattle Angina Questionnaire (clinicaltrials.gov, NCT02525081). Results: Follow-up was available on 55 patients. BP remained unchanged during treatment in both groups. CFVR improved in both the ramipril (p = 0.004) and placebo group (p = 0.026) with no difference between groups (p = 0.63). Symptoms improved in both groups with no significant between-group differences. No changes were detected in parameters of systolic and diastolic function. No serious adverse reactions were reported. Conclusions: In normotensive women with angina and CMD, treatment with ramipril had no significant effect on CFVR or symptoms compared with placebo. The effect of ACE inhibition previously reported may be mediated by blood pressure reduction. [ABSTRACT FROM AUTHOR]

Background. In cardiology, the paths of the arteries penetrating the septomarginal trabecula (SMT) are especially important. They provide blood supply to the apparatus of the right atrioventricular orifice and often form anastomoses with the system of the right coronary artery. Despite this, only a few publications discuss the morphological aspect of the septomarginal trabecula, and available histological analyses seldom deal with its blood supply. Objectives. The aim of this study was to analyze the vessel structure of the septomarginal trabecula in terms of the variability of the area of the cross-section of the lumen and the muscular layer of the artery. Material and methods. The study was carried out on the material of 50 human hearts from adults of both sexes. The material was divided into 4 morphological types. Histological examinations were conducted by means of classic staining methods. Results. At the initial cross-section of the septomarginal trabecula, the area of the cross-section increased to half of the length of the trabecula, and then it started to decrease. This is connected with the thickening of the inner muscular layer of the artery, which proportionally takes up more area of the cross-section of the whole artery of the SMT. The total area of the cross-section of all vessels in both types examined was also the largest in the middle part of the SMT. Furthermore, the results of this study confirm the presence of a connection between both systems of coronary arteries. Conclusions. As the septomarginal trabecula passes through the lumen of the right ventricle, its arteries become exposed to the influence of the factors which may evoke a biological response from the walls of this vessel, causing the thickening of the muscular layer and, as a result, of the section of the whole artery, in particular its middle part. [ABSTRACT FROM AUTHOR]

Key points: Coronary wave intensity analysis (WIA) is an emerging technique for assessing upstream and downstream influences on myocardial perfusion. It is thought that a dominant backward decompression wave (BDWdia) is generated by a distal suction effect, while early‐diastolic forward decompression (FDWdia) and compression (FCWdia) waves originate in the aorta. We show that wave reflection also makes a substantial contribution to FDWdia, FCWdia and BDWdia, as quantified by a novel method. In 18 sheep, wave reflection accounted for ∼70% of BDWdia, whereas distal suction dominated in a computer model representing a hypertensive human. Non‐linear addition/subtraction of mechanistically distinct waves (e.g. wave reflection and distal suction) obfuscates the true contribution of upstream and downstream forces on measured waves (the ‘smoke and mirrors’ effect). The mechanisms underlying coronary WIA are more complex than previously thought and the impact of wave reflection should be considered when interpreting clinical and experimental data. Abstract: Coronary arterial wave intensity analysis (WIA) is thought to provide clear insight into upstream and downstream forces on coronary flow, with a large early‐diastolic surge in coronary flow accompanied by a prominent backward decompression wave (BDWdia), as well as a forward decompression wave (FDWdia) and forward compression wave (FCWdia). The BDWdia is believed to arise from distal suction due to release of extravascular compression by relaxing myocardium, while FDWdia and FCWdia are thought to be transmitted from the aorta into the coronary arteries. Based on an established multi‐scale computational model and high‐fidelity measurements from the proximal circumflex artery (Cx) of 18 anaesthetized sheep, we present evidence that wave reflection has a major impact on each of these three waves, with a non‐linear addition/subtraction of reflected waves obscuring the true influence of upstream and downstream forces through concealment and exaggeration, i.e. a ‘smoke and mirrors’ effect. We also describe methods, requiring additional measurement of aortic WIA, for unravelling the separate influences of wave reflection versus active upstream/downstream forces on coronary waves. Distal wave reflection accounted for ∼70% of the BDWdia in sheep, but had a lesser influence (∼25%) in the computer model representing a hypertensive human. Negative reflection of the BDWdia at the coronary–aortic junction attenuated the Cx FDWdia (by ∼40% in sheep) and augmented Cx FCWdia (∼5‐fold), relative to the corresponding aortic waves. We conclude that wave reflection has a major influence on early‐diastolic WIA, and thus needs to be considered when interpreting coronary WIA profiles. [ABSTRACT FROM AUTHOR]

One of the most important problems in patients with aortic coarctation after aortic arch repair is future cardiovascular disease. We have previously reported that the enhancement of aortic pressure wave reflection in patients could be one of the causes of future cardiovascular diseases, because it results in an increase of the left ventricular workload and is disadvantageous for coronary circulation. Seventeen patients who had undergone aortic arch repair without pressure gradient in their aortic arch were enrolled. An ascending aortic pressure waveform was recorded by a pressure-sensor-mounted catheter, and a subendocardial viability ratio, which measures cardiac blood supply–workload balance, was calculated. The values were compared with those in age-matched controls. The patients’ mean age was 6.8 ± 2.8 years. The mean ascending aortic systolic pressure was higher (100.4 ± 12.9 vs. 90.2 ± 8.9 mmHg, p = 0.0011) and the pulse pressure was wider (38.1 ± 7.1 vs. 32.5 ± 5.4 mmHg, p = 0.0072) in patients than in control subjects. There was no difference in the mean subendocardial viability ratio (1.01 ± 0.25 vs. 1.01 ± 0.24, ns), while the mean tension time index (27.4 ± 5.6 vs. 23.0 ± 3.3, p = 0.0001) and diastolic pressure time index (28.4 ± 11.1 vs. 23.6 ± 8.0, p = 0.0082) were higher in patients than in controls. The cardiac blood supply–workload balance was preserved in patients after aortic arch repair, despite an increase in their cardiac workload. [ABSTRACT FROM AUTHOR]

Initial angiogenesis within the first 3 days is critical for healing ischemic diseases such as myocardial infarction. Recently, decellularized extracellular matrix (dECM) has been reported to provide tissue-derived ECM components and can be used as a scaffold for cell delivery for angiogenesis in tissue engineering. Decellularization by various detergents such as sodium dodecyl sulfate (SDS) and triton X-100 can remove the cell nuclei in tissue organs. However, this leads to ECM structure denaturation, decreased presence of various ECM proteins and cytokines, and loss of mechanical properties. To overcome these limitations, in this study, we developed a supercritical carbon dioxide and ethanol co-solvent (scCO 2 -EtOH) decellularization method, which is a detergent-free system that prevents ECM structure disruption and retains various angiogenic proteins in the heart dECM, and tested on rat heart tissues. The heart tissue was placed into the scCO 2 reactor and decellularized at 37 °C and 350 bar. After scCO 2 -EtOH treatment, the effects were evaluated by DNA, collagen, and glycosaminoglycan (GAG) quantification and hematoxylin and eosin and immunofluorescence staining to determine the absence of nucleic acids and preservation of heart ECM components. Similar to the native group, the scCO 2 -EtOH group contained more ECM components such as collagen, GAGs, collagen I, laminin, and fibronectin and angiogenic factors including vascular endothelial growth factor, fibroblast growth factor, and platelet-derived growth factor and others in comparison to the detergent group. In addition, to estimate angiogenesis of the dECM hydrogels, the neutralized dECM solution was injected in a rat subcutaneous layer (n = 6 in each group: collagen, scCO 2 -EOH, and detergent group), after which the solution naturally formed gelation in the subcutaneous layer. After 3 days, the gels were harvested and estimated by immunofluorescence staining and the ImageJ program for angiogenesis analysis. Consequently, blood vessel formation and density of vWF and α-SMA in the scCO 2 -EtOH group were significantly greater than that in the collagen group. Here we suggest that heart-derived decellularized extracellular matrix (dECM) with scCO 2 -EtOH treatment is a highly promising angiogenic material for healing in ischemic disease. Statement of Significance Supercritical carbon dioxide (scCO 2 ) in a supercritical phase has low viscosity and high diffusivity between gas and liquid properties and is known to be affordable, non-toxic, and eco-friendly. Therefore, scCO 2 extraction technology has been extensively used in commercial and industrial fields. Recently, decellularized extracellular matrix (dECM) was applied to tissue engineering and regenerative medicine as a scaffold, therapeutic material, and bio-ink for 3D printing. Moreover, the general decellularization method using detergents has limitations including eliminating tissue-derived ECM components and disrupting their structures after decellularization. To overcome these limitations, heart tissues were treated with scCO 2 -EtOH for decellularization, resulting in preserving of tissue due to the various ECM and angiogenic factors derived. In addition, initiation of angiogenesis was highly induced even after 3 days of injection. [ABSTRACT FROM AUTHOR]

Myeloperoxidase (MPO) is an oxidative hemoprotein compound expressed in polymorphonuclear leukocytes that contributes to inflammatory responses. Coronary artery disease (CAD), as the most prevalent form of heart disease, is considered to originate from an interaction between genetic and environmental factors. In the present study, the potential associations between MPO-463G/A and -129G/A polymorphisms with CAD were investigated in a Turkish population using a polymerase chain reaction-based restriction fragment length polymorphism (RFLP) assay technique. To the best of our knowledge, the study was the first to examine the association of MPO-463G/A and -129G/A with patient survival rate in a Turkish population. The study population consisted of 201 patients with CAD and 201 healthy controls. The results indicated that there was a significant association of the GA genotype of MPO-463G/A with the case population (P=0.048). Meanwhile, in the patients with CAD, the frequency distributions of the MPO-129A allele (P=0.006) and GA genotype (P=0.001) were significantly increased compared with the G allele and GG genotype, respectively, in CAD patients. Additionally, compared with the GG genotype, the frequency distribution of MPO-129A was significantly increased in the patient group regarding smoking status (P=0.001) and the presence of hypercholesterolemia (P=0.028). However, survival analysis did not detect an effect of either polymorphism on the survival rate of the CAD patients (P>0.05). Therefore, the MPO-129GA genotype may be a significant risk factor for the development of CAD. [ABSTRACT FROM AUTHOR]

Humans with a patent foramen ovale (PFO) have a higher esophageal temperature (Tesoph) than humans without a PFO (PFO+). Thus the presence of a PFO might also be associated with differences in thermal responsiveness to passive cooling and heating such as shivering and hyperpnea, respectively. The purpose of this study was to determine whether thermal responses to passive cooling and heating are different between PFO+ subjects and subjects with a PFO (PFO+). We hypothesized that compared with PFO+ subjects PFO+ subjects would cool down more rapidly and heat up slower and that PFO+ subjects who experienced thermal hyperpnea would have a blunted increase in ventilation. Twenty-seven men (13 PFO+) completed two trials separated by ±48 h: 1) 60 min of cold water immersion (19.5 ± 0.9°C) and 2) 30 min of hot water immersion (40.5 ± 0.2°C). PFO+ subjects had a higher Tesoph before and during cold water and hot water immersion (P < 0.05). However, the rate of temperature change was similar between groups for each condition. Within a subset of 18 subjects (8 PFO+) who experienced thermal hyperpnea, PFO+ subjects experienced thermal hyperpnea at a higher absolute Tesoph but with a blunted magnitude compared with PFO+ subjects. These data suggest that PFO+ subjects have a higher Tesoph at rest and have blunted thermal hyperpnea during passive heating. NEW & NOTEWORTHY Patent foramen ovale (PFO) is found in ~25-40% of the population. The presence of a PFO appears to be associated with a greater core body temperature and blunted ventilatory responses during passive heating. The reason for this blunted ventilatory response to passive heating is unknown but may suggest differences in thermal sensitivity in PFO+ subjects compared with PFO+ subjects. [ABSTRACT FROM AUTHOR]

Coronary arterial stenoses, particularly serial stenoses in a single branch, are responsible for complex hemodynamic properties of the coronary arterial trees, and the uncertain prognosis of invasive intervention. Critical information of the blood flow redistribution in the stenotic arterial segments is required for the adequate treatment planning. Therefore, in this study, an image based non-invasive functional assessment is performed to investigate the hemodynamic significances of serial stenoses. Twenty patient-specific coronary arterial trees with different combinations of stenoses were reconstructed from the computer tomography angiography for the evaluation of the hemodynamics. Our results showed that the computed FFR based on CTA images (FFRCT) pullback curves with wall shear stress (WSS) distribution could provide more effectively examine the physiological significance of the locations of the segmental narrowing and the curvature of the coronary arterial segments. The paper thus provides the diagnostic efficacy of FFRCT pullback curve for noninvasive quantification of the hemodynamics of stenotic coronary arteries with serial lesions, compared to the gold standard invasive FFR, to provide a reliable physiological assessment of significant amount of coronary artery stenosis. Further, we were also able to demonstrate the potential of carrying out virtual revascularization, to enable more precise PCI procedures and improve their outcomes. [ABSTRACT FROM AUTHOR]

Angiogenesis assays are important tools for studying both the mechanisms of cardiac angiogenesis and the potential development of therapeutic strategies to ischemic heart diseases. Currently, various assays have been used to quantitate cardiac tubule formation, yet no consensus has been reached regarding a suitable assay for evaluating the efficacy of angiogenic stimulants or inhibitors. Most in vivo angiogenesis assays are complex and difficult to interpret, whereas traditional in vitro angiogenesis models measure only one aspect of this process. To bridge the gap between in vivo and in vitro angiogenesis assays, here, we have developed a novel modified cardiac explants matrigel assay. We observed the morphology of vascular sprouts formed in three forms of cardiac angiogenesis assays then used quantitative image analyses to further compare the morphological features of vascular sprouts formed in two cardiac explants angiogenesis assays. Vascular sprouts formed in the fibronectin group were less and short, whereas those formed in the matrigel group were significantly longer, consisting of more area and branch points. Moreover, we found the benefits of this matrigel model by observing the ability of cardiac explants to form vascular sprouts under normoxia or hypoxia condition in the presence of angiogenic stimulant and inhibitor, VEGF and PEDF. In summary, the above analyses revealed that the morphology of vascular sprouts formed in this model appears more representative of myocardial capillary formation in vivo, and this accessible, reliable angiogenic assay is a more physiologically relevant assay which allows further assessment of pharmacologic compounds on cardiac angiogenesis. [ABSTRACT FROM AUTHOR]

Objectives: Thoracic endovascular aortic repair (TEVAR) has been shown to lead to increased aortic stiffness. The aim of this study was to investigate the effect of stent graft type and stent graft length on aortic stiffness in a controlled, experimental setting. Methods: Twenty porcine thoracic aortas were connected to a pulsatile mock loop system. Intraluminal pressure was recorded at two sites in order to measure pulse wave velocity (PWV) for each aorta: before stent graft deployment (t1); after deployment of a 100-mm long stent graft (t2); and after distal extension through deployment of a second 100-mm long stent graft (t3). Four different types of stent grafts (Conformable Gore® TAG® Device, Bolton Relay® Device, Cook Zenith Alpha™, and Medtronic Valiant®) were evaluated. Results: For the total cohort of 20 aortas, PWV increased by a mean 0.6 m/s or 8.9% of baseline PWV after deployment of a 100-mm proximal stent graft (P<0.001), and by a mean 1.4 m/s or 23.0% of baseline PWV after distal extension of the stent graft (P<0.001). Univariable regression analysis showed a significant correlation between aortic PWV and extent of stent graft coverage, (P<0.001), but no significant effect of baseline aortic length, baseline aortic PWV, or stent graft type on the percentual increase in PWV at t2 or at t3. Conclusions: In this experimental set-up, aortic stiffness increased significantly after stent graft deployment with each of the four types of stent graft, with the increase in aortic stiffness depending on the extent of stent graft coverage. [ABSTRACT FROM AUTHOR]

Background: red cell distribution width is a marker associated with increased mortality and morbidity in cardiac patients, however it's relation with coronary artery calcium score (CACS) is not well studied yet. Aim of the work: this study aimed to assess the relation between red cell distribution width (RDW) and coronary artery calcium score (CACS) in the diabetic patients undergoing coronary CT angiography. Patients and methods: this study was conducted on 60 patients presented for assessment of coronary artery disease (CAD) by coronary CT angiography and they were categorized into 2 groups, group (A) diabetics(30 patients),group(B)non-diabetics (30 patients), All patients included in this study were subjected to: History Taking, complete physical examination, multi-slice CT coronary angiography (MSCT) including calcium score(CACS), laboratory investigations including complete blood count (CBC) including RDW(SD&CV), serum calcium level(total and ionized), erythrocyte sedimentation rate (ESR), lipid profile. Results: higher RDW(SD) was associated with the presence of greater coronary complexity of CAD and higher calcium score. In our study total serum calcium and RDW (SD) were found to be independent predictors of high Ca score more than 100, while ionized calcium and systolic blood pressure(SBP) were independent predictors of high Calcium score more than 400. Cut off value of RDW to predict high calcium score (more than 100) was RDW(CV) more than 13.45 & RDW(SD) more than44.45, while Cut off value of RDW to predict high calcium score (more than 400) was RDW(SD) more than 45.1. Conclusions: a greater baseline RDW(SD) value was independently associated with the presence of a greater coronary complexity of CAD and higher calcium score. [ABSTRACT FROM AUTHOR]

In the past years, a number of cardiac electromechanics models have been developed to better understand the excitation–contraction behavior of the heart. However, there is no agreement on whether inertial forces play a role in this system. In this study, we assess the influence of mass in electromechanical simulations, using a fully coupled finite element model. We include the effect of mechano-electrical feedback via stretch activated currents. We compare five different models: electrophysiology, electromechanics, electromechanics with mechano-electrical feedback, electromechanics with mass, and electromechanics with mass and mechano-electrical feedback. We simulate normal conduction to study conduction velocity and spiral waves to study fibrillation. During normal conduction, mass in conjunction with mechano-electrical feedback increased the conduction velocity by 8.12% in comparison to the plain electrophysiology case. During the generation of a spiral wave, mass and mechano-electrical feedback generated secondary wavefronts, which were not present in any other model. These secondary wavefronts were initiated in tensile stretch regions that induced electrical currents. We expect that this study will help the research community to better understand the importance of mechano-electrical feedback and inertia in cardiac electromechanics. [ABSTRACT FROM AUTHOR]

A method to estimate the hemodynamics parameters of a network of vessels using an Ensemble Kalman filter is presented. The elastic moduli (Young's modulus) of blood vessels and the terminal boundary parameters are estimated as the solution of an inverse problem. Two synthetic test cases and a configuration where experimental data are available are presented. The sensitivity analysis confirms that the proposed method is quite robust even with a few numbers of observations. The simulations with the estimated parameters recovers target pressure or flow rate waveforms at given specific locations, improving the state-of-the-art predictions available in the literature. This shows the effectiveness and efficiency of both the parameter estimation algorithm and the blood flow model. [ABSTRACT FROM AUTHOR]

Objective: To investigate the impact of gender difference in early postoperative outcomes in elderly patients (aged 70 or older) undergoing coronary artery bypass grafting surgery. Methods: Between October 2009 and December 2013, a total of 223 elderly patients (aged 70 or older) undergoing isolated primary coronary artery bypass grafting surgery were included in this retrospective observational cohort study. Patients were divided into two groups according to their gender. The patients' medical records were collected, their baseline preoperative characteristics, operative data, and postoperative outcomes were retrospectively reviewed, and the effect of gender difference in the early postoperative outcomes was analyzed. Results: Group 1 (female patients) and Group 2 (male patients) consisted of 71 and 152 patients, respectively. Mean age of patients was 74.4±3.6 years (range: 70-84 years). The level of EuroSCORE I, the incidence of hypertension and hyperlipidemia were significantly higher in Group 1, while the rate of smoking was significantly higher in Group 2. Mean postoperative intubation time, length of intensive care unit and hospital stay were longer in female patients than in male patients, but these differences were not statistically significant. No statistically significant difference between two groups in terms of the transfusion of blood products was observed. The rates of in-hospital mortality and major postoperative complications were statistically similar between the two groups. Conclusion: In conclusion, the female gender was not associated with worse early postoperative outcomes in elderly patients undergoing coronary artery bypass grafting surgery. [ABSTRACT FROM AUTHOR]

Kawasaki disease (KD) is an acute systemic vasculitis complicated by development of coronary artery lesions. PECAM-1 is a kind of cell adhesion molecule, which plays an important role in coronary artery disease. The relationship between PECAM-1 gene polymorphisms and their susceptibility to Kawasaki diseases (KD) is still unclear. In our study, we examined the PECAM-1 gene polymorphisms in 44 KD patients and 59 healthy children and revealed the correlation of PECAM-1 gene polymorphisms in KD children with and without coronary artery lesions (CAL). [ABSTRACT FROM AUTHOR]

Background Among endocannabinoid (EC)-related mediators, Oleoyl-ethanolamide (OEA) and Palmitoyl-ethanolamide (PEA), two endogenous PPARα agonists with lipolytic and anti-inflammatory action, respectively, are being actively investigated. Here, we assessed the potential association between plasma levels of PEA and OEA and coronary function in a cohort including normal, overweight, obese, and morbidly obese (MOB) individuals. Methods Myocardial perfusion and endothelium-related myocardial blood flow (MBF) responses to cold pressor test (CPT) and during pharmacological vasodilation with dipyridamole were measured with 13 N-ammonia positron emission tomography/computed tomography. OEA and PEA were extracted from human plasma by liquid-liquid extraction, separated by liquid chromatography and quantified by mass spectrometry. Serum levels of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 (VCAM-1) were measured by colorimetric enzyme-linked immunosorbent assay. Results Circulating levels of PEA and VCAM-1 were increased in MOB as compared to normal weight subjects. Circulating levels of OEA and PEA were associated with body mass index, but not with adhesion molecules. Increases of PEA levels were associated with and predictive of worsened coronary function in MOB and the overall cohort studied. Conclusion Plasma levels of PEA are increased in MOB patients and associated with coronary dysfunction as a functional precursor of CAD process. Larger trials are needed to confirm PEA as a potential circulating biomarker of coronary dysfunction in both MOB patients and the general population. [ABSTRACT FROM AUTHOR]

This work presents a computational framework to perform a systematic and comprehensive assessment of the morphometry of coronary arteries from in vivo medical images. The methodology embraces image segmentation, arterial vessel representation, characterization and comparison, data storage, and finally analysis. Validation is performed using a sample of 48 patients. Data mining of morphometric information of several coronary arteries is presented. Results agree to medical reports in terms of basic geometric and anatomical variables. Concerning geometric descriptors, inter-artery and intra-artery correlations are studied. Data reported here can be useful for the construction and setup of blood flow models of the coronary circulation. Finally, as an application example, similarity criterion to assess vasculature likelihood based on geometric features is presented and used to test geometric similarity among sibling patients. Results indicate that likelihood, measured through geometric descriptors, is stronger between siblings compared with non-relative patients. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

OBJECTIVES: We evaluated long-term results of two different repair strategies of anomalous origin of left coronary artery from pulmonary artery (ALCAPA) in two German surgical centres. METHODS: We performed a retrospective review of patients who underwent ALCAPA repair between November 1980 and October 2012. Ventricular function was assessed by standardized transthoracic echocardiographic studies. RESULTS: A total of 30 patients with a median age of 0.4 years (range 0.05-37.6 years) underwent ALCAPA repair. Nineteen patients received coronary transfer, 9 underwent Takeuchi repair (creation of an intrapulmonary tunnel) and 2 were treated by closure of the ALCAPA. There was one concomitant mitral valve repair. The total follow-up was 244.8 years with a mean follow-up of 8.16 ± 6.7 years (range 0.06-24.3 years). There was no late mortality. None of the patients treated with coronary transfer or Takeuchi repair died. One moribund patient who received coronary ligation in the 1980s died perioperatively. The 10-year rate of freedom from reoperation was 94.1% for patients treated with coronary transfer. For patients with Takeuchi repair, the 10-year rate of freedom from reoperation was 71.1% (P = 0.146). At last followup, left ventricular end-diastolic diameter (LVEDD) and function measured by fractional shortening was normal in all patients. The mean shortening fraction improved from 20.25 ± 10.86% to 35.7 ± 4.8%, with the most remarkable change taking place in the first year, and the mean LVEDD indexed to normal improved from 42 ± 34% above normal values preoperatively to 3 ± 12% at the last follow-up (P < 0.01). The number of patients with moderate-to-severe mitral regurgitation (MR) improved from 50% to 6.7% (2 of 30) at the last followup. In all children receiving ALCAPA repair under the age of 6 months, MR was absent or trivial at the last follow-up. Eight years after Takeuchi repair, 79.9% of these patients suffered from at least moderate pulmonary regurgitation, in contrast to 0% after coronary transfer (P < 0.001). CONCLUSIONS: Survival rates and long-term left ventricular function were excellent for both surgical strategies. Mitral regurgitation resolved in all patients operated during their first year of life independent of the type of repair. Takeuchi repair, however, led to significant pulmonary regurgitation. [ABSTRACT FROM AUTHOR]

The objectives were to compare the performance of a segmentation algorithm, based on the minimization of an uncertainty function, to delineate contours of external elastic membrane and lumen of human coronary arteries imaged with 40 and 60 MHz IVUS, and to use values of this function to delineate portions of contours with highest uncertainty. For 8 patients, 40 and 60 MHz IVUS coronary data acquired pre- and post-interventions were used, for a total of 68,516 images. Manual segmentations of contours (on 2312 images) performed by experts at three core laboratories were the gold-standards. Inter-expert variability was highest on contour points with largest values of the uncertainty function (p < 0.001). Inter-expert variability was lower at 60 than 40 MHz for external elastic membrane (p = 0.013) and lumen (p = 0.024). Average differences in plaque (and atheroma) burden between algorithmic contours and experts’ contours were within inter-expert variability (p < 0.001). [ABSTRACT FROM AUTHOR]

Decellularization is a proposed method of preparing nonautologous biological arterial vascular scaffolding; however, the fate of the supporting medial elastic fiber, which is important in preserving the vascular structural integrity, is uncertain. The influence of losartan on preserving the medial elastic fiber integrity in decellularized small diameter vascular conduits (SDVC) was investigated. Decellularized infrarenal abdominal aortic allografts were implanted in Sprague-Dawley rats treated either with (study rats, n = 6) or without oral losartan (control rats, n = 6) and graded 8 weeks later according to a remodeling scoring system (1-mild, 2-moderate, 3-severe) which we devised based on the intimal hyperplasia degree, morphologic changes, and elastic fiber fragmentation of the conduits. DAPI immunohistochemistry analysis was performed in 47 (25 decellularization only and 22 losartan treatment) cross-sectional slide specimens. The losartan versus decellularization only SDVC showed a significantly lower medial elastic fragmentation score (1.32 vs. 2.24, P < 0.001), superior medial layer preservation, and relatively more normal appearing intimal cellular morphology. The results suggested rats receiving decellularized SDVCs treated with losartan may yield superior medial layer elastic fiber preservation. [ABSTRACT FROM AUTHOR]

Transit time flow measurement (TTFM) is a quality control tool for intraoperative graft evaluation in coronary artery bypass graft (CABG) surgery. A critical review of the literature available using TTFM in CABG surgery is the focus of this article. The main objectives will be to detail precise parameters for flow evaluation, to show limitations of TTFM and to prove its predictive impact on postoperative graft failure rate. Publications listed in the PubMed database were reviewed, searching for intraoperative graft verification in coronary surgery by TTFM, with postoperative imaging follow-up (FU) modality and with a special focus on publications released after European guidelines from 2010. Nine included publications revealed an overall graft failure rate of ∼12%. Mean graft flow had a positive predictive value in the largest study, and cut-offs, of at least 20 ml/min for internal mammary artery (IMA) grafts, therein partially confirming guidelines, and 30-40 ml/min for saphenous venous grafts (SVGs) were proposed. An explicit correlation between graft flow, patency rate and severity of coronary stenosis, by indicating the fractional flow reserve, was found for IMA grafts. Increased pulsatility index and increased systolic reverse flow probably predict worse outcome and may help identifying competitive flow. Diastolic filling, rarely indicated, could not be confirmed as the predictive marker. No significant correlation of TTFM and graft failure rate for radial and other arterial grafts could be found, partially due to the small number of these types of grafts analysed. Larger target vessels and lower postoperative CK-MB levels may predict better graft patency rates. Low sensitivity for TTFM to reliably detect graft failure is certainly a major issue, as found in randomized analyses. However, methodical limitations and varying threshold values for TTFM render a general consensus difficult. Influence of quantity (vessel territory distribution) and quality (myocardial scar) of the graft perfusion area, on TTFM and FU outcome, was not included by anyone and should be part of future research. TTFM is probably not the tool of choice to detect progressive late graft failure of SVG. Peroperative TTFM values should be correlated with one type of conduit, differentiating between early and late graft failure (by applying a uniform, appropriated definition), to precise and confirm threshold values. [ABSTRACT FROM AUTHOR]

Background: Excessive bleeding and blood transfusion are associated with adverse outcome after cardiac surgery, but their mechanistic effects are difficult to disentangle in patients with increased operative risk. This study aimed to evaluate the incidence and prognostic impact of bleeding and transfusion of blood products in low-risk patients undergoing coronary artery bypass grafting (CABG).Study Design and Methods: Sixteen tertiary European centers of cardiac surgery contributed to the prospective European registry of CABG (E-CABG). The severity of bleeding was defined by the E-CABG bleeding severity classification and universal definition of perioperative bleeding (UDPB) classification.Results: Of 1213 patients with EuroSCORE II of less than 2% (mean, 1.1 ± 0.4%), 18.5% suffered from mild bleeding (E-CABG bleeding Grade 1) and 3.4% experienced severe bleeding (E-CABG bleeding Grade 2-3). Similarly, 19.7% had UDPB Class 2 and 5.9% had UDPB Classes 3 and 4. Mild and severe bleeding defined by the E-CABG and UDPB classifications were associated with an increased risk of several adverse events as adjusted by multiple covariates. The risk of death, stroke, and acute kidney injury was particularly increased in patients with severe bleeding.Conclusion: Severe bleeding is rather uncommon in low-risk patients undergoing CABG, but it is associated with an increased risk of major adverse events. Prevention of excessive perioperative bleeding and patient blood management may improve the outcome of cardiac surgery also in low-risk patients. [ABSTRACT FROM AUTHOR]

New Findings What is the central question of this study? In this study, we sought to investigate whether cardiovascular responses to peripheral chemoreflex activation of rats recovered from protein restriction are related to activation of AT1 receptors., What is the main finding and its importance? This study highlights the fact that angiotensinergic mechanisms activated by AT1 receptors do not support increased responses to peripheral chemoreflex activation by KCN in rats recovered from protein restriction. Also, we found that protein restriction led to increased resting ventilation in adult rats, even after recovery., The effects of a low-protein diet followed by recovery on cardiorespiratory responses to peripheral chemoreflex activation were tested before and after systemic angiotensin II type 1 (AT1) receptor antagonism. Male Fischer rats were divided into control and recovered (R-PR) groups after weaning. The R-PR rats were fed a low-protein (8%) diet for 35 days and recovered with a normal protein (20%) diet for 70 days. Control rats received a normal protein diet for 105 days (CG105). After cannulation surgery, mean arterial pressure, heart rate, respiratory frequency, tidal volume and minute ventilation were acquired using a digital recording system in freely moving rats. The role of angintensin II was evaluated by systemic antagonism of AT1 receptors with losartan (20 mg kg−1 i.v.). The peripheral chemoreflex was elicited by increasing doses of KCN (20-160 μg kg min−1, i.v.). At baseline, R-PR rats presented increased heart rate and minute ventilation (372 ± 34 beats min−1 and 1.274 ± 377 ml kg−1 min−1) compared with CG105 animals (332 ± 22 beats min−1 and 856 ± 112 ml kg−1 min−1). Mean arterial pressure was not different between the groups. Pressor and bradycardic responses evoked by KCN (60 μg kg−1) were increased in R-PR (+45 ± 13 mmHg and −77 ± 47 beats min−1) compared with CG105 rats (+25 ± 17 mmHg and −27 ± 28 beats min−1), but no difference was found in the tachypnoeic response. These differences were preserved after losartan. The data suggest that angiotensin II acting on AT1 receptors may not be associated with the increased heart rate, increased minute ventilation and acute cardiovascular responses to peripheral chemoreflex activation in rats that underwent postweaning protein restriction followed by recovery. [ABSTRACT FROM AUTHOR]

Introduction: Although global deformation parameters have been increasingly used for myocardial function analysis, there are sparse data concerning segmental deformation of the left ventricle (LV). Moreover, some studies suggest heterogeneity of strain among LV segments, which may be especially significant during stress echocardiography. We assessed quantitatively regional LV function in the setting of dobutamine stress echocardiography (DSE), to examine differences of longitudinal strain between basal, mid and apical LV segments and to compare variability of regional deformation between rest and the peak stage of DSE.Material and Methods: Among 250 patients examined by DSE applied for diagnosis of ischemia, a subset of 111 patients without significant coronary stenoses in angiography was selected (68 females, mean age: 60 ±10 years). Systolic longitudinal strain (SLS) in individual LV segments at baseline and the peak stage of DSE was analyzed with speckle tracking echocardiography.Results: Inhomogeneity of SLS among the LV segments (p < 0.001) was observed at baseline and the peak stage. Dispersion indices were higher at the peak stage of DSE than at baseline (p < 0.001), and the lowest heterogeneity was observed among mid segments. The analysis of changes in SLS during DSE showed SLS reduction in basal and mid-ventricular segments and an increase in apical segments.Conclusions: Significant heterogeneity of strain and the opposite direction of the longitudinal strain changes during DSE between apical and basal LV segments were observed. This variability among non-ischemic LV segments ought to be considered in quantification of LV function during DSE. [ABSTRACT FROM AUTHOR]

The aim of this study was to identify potential changes that could occur during histological evaluations of CLAWN miniature swine, with potential consequences for subsequent experiments. The systemic organs from male and female CLAWN miniature swine (16.3-42.3 months old) that had been used in long-term studies of coronary stent implantation were examined histologically. Commonly observed histopathological findings were testicular/epididymal atrophy, cyst-like follicles in the ovaries, hemosiderin deposition in the spleen, lipofuscin deposition in the proximal tubular epithelia and presence of eosinophilic globules in the Bowman's space and the lumen of the proximal tubules in the kidneys, and cellular infiltration in several organs, including the eyelids, respiratory organs, and digestive tract. However, none of these changes were serious enough to indicate a significant impact on research. In conclusion, this study identified CLAWN miniature swine as a suitable animal model for various experiments. [ABSTRACT FROM AUTHOR]

In blood vessels situated just after the heart, an irregular blood flow occurs due to some specific structural elements of the tunica media. The current paper describes the histological aspects of some post-cardiac arterial sections in lamb. The tissue samples were collected from five 30 days old male lambs (Țurcană breed). Histological specimens from different regions of the aorta were harvested (i.e., the ascending aorta, aortic arch, thoracic and abdominal regions of the descending aorta). From the specified regions, small pieces (cca. 0.5 cm) were fixed in neutral 10% buffered formalin. The tissues were subsequently embedded in paraffin wax, sectioned at 5 µm, and stained with Goldner's trichrome and Verhoeff methods. Tissue analysis was performed using an Olympus system for image acquisition and analysis. Histological appearance of the assessed segments of the aorta in lamb is unusual. Major changes occur in tunica media of the aorta. In the ascending aorta, aortic arch and thoracic regions of the aorta, the histological outline is somewhat the same. The internal region of the media possesses the typical lamellar arrangement. Concerning the outer part of tunica media, the smooth muscle has a tendency to form bundles of various sizes. The muscle islands are not present in the media of abdominal region of the aorta, which exhibits the classic pattern of elastic arteries. [ABSTRACT FROM AUTHOR]

Cardiac hemodynamics can be computed from medical imaging data, and results could potentially aid in cardiac diagnosis and treatment optimization. However, simulations are often based on simplified geometries, ignoring features such as papillary muscles and trabeculae due to their complex shape, limitations in image acquisitions, and challenges in computational modeling. This severely hampers the use of computational fluid dynamics in clinical practice. The overall aim of this study was to develop a novel numerical framework that incorporated these geometrical features. The model included the left atrium, ventricle, ascending aorta, and heart valves. The framework used image registration to obtain patient-specific wall motion, automatic remeshing to handle topological changes due to the complex trabeculae motion, and a fast interpolation routine to obtain intermediate meshes during the simulations. Velocity fields and residence time were evaluated, and they indicated that papillary muscles and trabeculae strongly interacted with the blood, which could not be observed in a simplified model. The framework resulted in a model with outstanding geometrical detail, demonstrating the feasibility as well as the importance of a framework that is capable of simulating blood flow in physiologically realistic hearts. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of our study is to verify, whether percutaneous mitral annuloplasty results in reverse remodeling in patients with functional mitral regurgitation (FMR) and impaired ejection fraction (EF) and to investigate which echo parameters may help in prediction of the efficacy of the procedure.Background: FMR exacerbates left ventricular (LV) dilatation and contributes to both LV remodeling and heart failure.Methods: We analyzed baseline and 1 month follow-up data in 22 consecutive patients with FMR, who underwent successful percutaneous trans-coronary venous mitral annuloplasty with the Carillon device.Results: Significant reduction of FMR echo parameters, including vena contracta (VC), effective regurgitant orifice area (EROA), and regurgitant volume (RV) were observed and maintained throughout 1 month follow up and did not correlate with baseline annular, LV or with the left atrial diameters. Baseline mitral tenting area correlated negatively with the relative improvement (% difference) of EROA (r = -0.5898) and RV (r = -0.4363), but not with VC (r = 0.1341). In addition, increased EF as well as a significant reduction in left ventricular diameters were noted. The increase in EF negatively correlated with the change in EROA (r = -0.50058), PISA (r = -0.5327), and RV (r = -0.5457). Baseline mitral tenting area significantly correlated with the 1 month change in EF (r = 0.5946) and stroke volume (r = 0.6913).Conclusions: The improvement of FMR after treatment with the Carillon device is associated with LV reverse remodeling and an increase in systolic performance, that correlates with the reduction in mitral regurgitation, being not dependent on baseline heart diameters. Mitral tenting area seems to be an important parameter in prediction of benefit from percutaneous mitral annuloplasty. [ABSTRACT FROM AUTHOR]

Background: Increased levels of interleukin-18 (IL-18) and high mobility group box 1 protein (HMGB1) have been reported in patients with calcific aortic valve disease (CAVD). However, the role of IL-18 and HMGB1 in the modulation of the valvular interstitial cell (VIC) phenotype remains unclear. We hypothesized that HMGB1 mediates IL-18-induced myofibroblastic transition of VICs. Methods: The expression of IL-18, HMGB1 and α-smooth muscle actin (α-SMA) in human aortic valves was evaluated by immunohistochemical staining, real-time polymerase chain reaction and immunoblotting. Plasma concentrations of IL-18 and HMGB1 were measured using the ELISA kit. Cultured human aortic VICs were used as an in vitro model. Results: Immunohistochemistry and immunoblotting revealed increased levels of IL-18, HMGB1 and α-SMA in calcific valves. Circulating IL-18 and HMGB1 levels were also higher in CAVD patients. In vitro, IL-18 induced upregulation of HMGB1 and α-SMA in VICs. Moreover, IL-18 induced secretion of HMGB1 to the extracellular space and activation of nuclear factor kappa-B (NF-κB). Blockade of NF-κB abrogated the upregulation and release of HMGB1 induced by IL-18. Whereas HMGB1 inhibition attenuated the IL-18-induced expression of α-SMA, HMGB1 enhanced the effect of IL-18. Conclusions: We demonstrated for the first time that both tissue and plasma levels of IL-18 and HMGB1 were increased in patients with CAVD. Mechanically, HMGB1 mediated IL-18-induced VIC myofibroblastic transition. [ABSTRACT FROM AUTHOR]

Haemophilus parosuis (HPS) is one of the most important bacterial infectious diseases harming China's pig industry for the last few years. To understand the prevalence status of glasser's disease in China, the disease samples submitted by Shandong, Henan, Heilongjiang, Jiangxi, Liaoning, Guangdong, Shaanxi and Sichuan provinces were isolated and identified. The synovial fluid, lung, brain tissue, heart blood and nasal cavity of sick pigs in 194 pig farms collected from 2006 to 2009 were detected, and 47 strains of HPS were eventually isolated, with the separation rale of 24.2%. Serotypes of the isolates were identified through KRG (Kieletein-Rapp-Gabriedson) agar diffusion method. There were 13 strains of serotype 4 (27.7%), 10 strains of serotype 5 (21.3%), 8 strains of serotype 12 (17%) and 7 strains of serotype 13 (14.9%), indicating the major serotypes of HPS in China were serotype 4, serotype 5, serotype 12 and serotype 13. [ABSTRACT FROM AUTHOR]

Importance: Among patients with suspected coronary heart disease (CHD), rates of invasive angiography are considered too high.Objective: To test the hypothesis that among patients with suspected CHD, cardiovascular magnetic resonance (CMR)-guided care is superior to National Institute for Health and Care Excellence (NICE) guidelines-directed care and myocardial perfusion scintigraphy (MPS)-guided care in reducing unnecessary angiography.Design, Setting, and Participants: Multicenter, 3-parallel group, randomized clinical trial using a pragmatic comparative effectiveness design. From 6 UK hospitals, 1202 symptomatic patients with suspected CHD and a CHD pretest likelihood of 10% to 90% were recruited. First randomization was November 23, 2012; last 12-month follow-up was March 12, 2016.Interventions: Patients were randomly assigned (240:481:481) to management according to UK NICE guidelines or to guided care based on the results of CMR or MPS testing.Main Outcomes and Measures: The primary end point was protocol-defined unnecessary coronary angiography (normal fractional flow reserve >0.8 or quantitative coronary angiography [QCA] showing no percentage diameter stenosis ≥70% in 1 view or ≥50% in 2 orthogonal views in all coronary vessels ≥2.5 mm diameter) within 12 months. Secondary end points included positive angiography, major adverse cardiovascular events (MACEs), and procedural complications.Results: Among 1202 symptomatic patients (mean age, 56.3 years [SD, 9.0]; women, 564 [46.9%] ; mean CHD pretest likelihood, 49.5% [SD, 23.8%]), number of patients with invasive coronary angiography after 12 months was 102 in the NICE guidelines group (42.5% [95% CI, 36.2%-49.0%])], 85 in the CMR group (17.7% [95% CI, 14.4%-21.4%]); and 78 in the MPS group (16.2% [95% CI, 13.0%-19.8%]). Study-defined unnecessary angiography occurred in 69 (28.8%) in the NICE guidelines group, 36 (7.5%) in the CMR group, and 34 (7.1%) in the MPS group; adjusted odds ratio of unnecessary angiography: CMR group vs NICE guidelines group, 0.21 (95% CI, 0.12-0.34, P < .001); CMR group vs the MPS group, 1.27 (95% CI, 0.79-2.03, P = .32). Positive angiography proportions were 12.1% (95% CI, 8.2%-16.9%; 29/240 patients) for the NICE guidelines group, 9.8% (95% CI, 7.3%-12.8%; 47/481 patients) for the CMR group, and 8.7% (95% CI, 6.4%-11.6%; 42/481 patients) for the MPS group. A MACE was reported at a minimum of 12 months in 1.7% of patients in the NICE guidelines group, 2.5% in the CMR group, and 2.5% in the MPS group (adjusted hazard ratios: CMR group vs NICE guidelines group, 1.37 [95% CI, 0.52-3.57]; CMR group vs MPS group, 0.95 [95% CI, 0.46-1.95]).Conclusions and Relevance: In patients with suspected angina, investigation by CMR resulted in a lower probability of unnecessary angiography within 12 months than NICE guideline-directed care, with no statistically significant difference between CMR and MPS strategies. There were no statistically significant differences in MACE rates.Trial Registration: Clinicaltrials.gov Identifier: NCT01664858. [ABSTRACT FROM AUTHOR]

The post-mortem diagnosis of acute myocardial ischemia remains a challenge for both clinical and forensic pathologists. We performed an experimental study (ligation of left anterior descending coronary artery in rats) in order to identify early markers of myocardial ischemia, to further apply to forensic and clinical pathology in cases of sudden cardiac death. Using immunohistochemistry, Western blots, and gene expression analyses, we investigated a number of markers, selected among those which are currently used in emergency departments to diagnose myocardial infarction and those which are under investigation in basic research and autopsy pathology studies on cardiovascular diseases. The study was performed on 44 adult male Lewis rats, assigned to three experimental groups: control, sham-operated, and operated. The durations of ischemia ranged between 5 min and 24 h. The investigated markers were troponins I and T, myoglobin, fibronectin, C5b-9, connexin 43 (dephosphorylated), JunB, cytochrome c, and TUNEL staining. The earliest expressions (≤30 min) were observed for connexin 43, JunB, and cytochrome c, followed by fibronectin (≤1 h), myoglobin (≤1 h), troponins I and T (≤1 h), TUNEL (≤1 h), and C5b-9 (≤2 h). By this investigation, we identified a panel of true early markers of myocardial ischemia and delineated their temporal evolution in expression by employing new technologies for gene expression analysis, in addition to traditional and routine methods (such as histology and immunohistochemistry). Moreover, for the first time in the autopsy pathology field, we identified, by immunohistochemistry, two very early markers of myocardial ischemia: dephosphorylated connexin 43 and JunB. [ABSTRACT FROM AUTHOR]

Monitoring the levels of the ceramides (Cer) d18:1/16:0, Cer d18:1/18:0, Cer d18:1/24:0, and Cer d18:1/24:1 and ratios thereof in human plasma empowers the prediction of fatal outcome of coronary artery disease (CAD). We describe a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) methodology for clinical-scaled measurement of the four distinct ceramides. Rapid plasma precipitation was accomplished in 96-well format. Excellent extraction recoveries in the range of 98-109 % were achieved for each ceramide. Addition of corresponding D-labeled ceramide standards facilitated precise quantification of each plasma ceramide species utilizing a novel short 5-min LC-MS/MS method. Neither matrix interference nor carryover was observed. Robust intra- and inter-assay accuracy and precision <15 % at five different concentrations were obtained. Linear calibration lines with regressions, R > 0.99, were achieved for all analytes. Short-term bench top, long-term plasma, and extract stability demonstrated that the distinct ceramides were stable in the conditions evaluated. The validity of the methodology was demonstrated by determining the precise ceramide concentrations in a small CAD case-control study. Thus, our LC-MS/MS methodology features simple sample preparation and short analysis time for accurate quantification of Cer d18:1/16:0, Cer d18:1/18:0, Cer d18:1/24:0, and Cer d18:1/24:1, designed for routine analysis. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Many investigators have reported that the total amount of coronary calcium correlates with the overall magnitude of atherosclerotic plaque burden in the entire coronary tree and is a powerful predictor of future cardiovascular events. However, the development and spatial distribution of coronary calcifications remain unclear. We investigated the spatial distribution of calcifications throughout the coronary tree during coronary artery evaluation using coronary computed tomography angiography (CTA). A further aim was to assess the progression of existing calcifications and the development of new deposits in a follow-up study. The study population consisted of 287 patients for the cross-sectional study using CTA to evaluate the spatial distribution of calcifications by parent coronary arteries. Next, we analyzed a CTA dataset of 57 patients who had undergone two CTA examinations. In this group, the two CTA images were used for assessing the progression of existing calcifications and the development of new deposits. The coronary calcifications tended to be clustered within the proximal and middle portions. Moreover, in the proximal left anterior descending coronary artery (LAD), small calcifications were located more toward the inner pericardial side. Finally, new calcium deposits developed within the proximal and middle portions of the LAD and left circumflex coronary artery, but those in the right coronary artery were likely to appear evenly from the proximal to the distal portion. This study shows the characteristic patterns of the longitudinal and circumferential distribution of calcifications by parent coronary arteries. [ABSTRACT FROM AUTHOR]