Aim: The clinical effect of the injection of recombinant human prourokinase to infarction-related arteries during percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI) patients who have slow reflow/no reflow was investigated.

Methods: Data from STEMI patients who underwent emergency PCI at the Chest Pain Center of the First People’s Hospital of Changde City from April 2017 to December 2018 were collected for analysis.

Results: Whether the ST segment had decreased by more than 50% at 90 min and whether the creatine kinase isoenzyme and cardiac troponin I had decreased by more than 50% were investigated. There were no significant differences in the indexes of color Doppler echocardiography (left ventricular ejection fraction, left ventricular end-diastolic diameter, ventricular aneurysm, and ventricular thrombus) within seven days after surgery and in the ventricular tachycardia/ventricular fibrillation between the two groups (P > 0.05). There was no significant difference in major adverse cardiovascular event between the two groups within one month after surgery (P > 0.05), but, there were significant differences in the Thrombolysis in Myocardial Infarction (TIMI) classification, corrected TIMI frame count, creatine kinase peak value, and the third-degree atrioventricular block (P < 0.05).

Conclusion: The intracoronary injection of recombinant human prourokinase in patients with STEMI undergoing emergency PCI is safe and effective.

Aim: The management of aortic stenosis has seen momentous changes thanks to the introduction of transcatheter aortic valve implantation (TAVI, i.e., transcatheter aortic valve replacement). Indications to TAVI have expanded progressively to intermediate- and low-risk patients, but trends in life expectancy have led to an increase of elderly but fit individuals with aortic stenosis eligible for TAVI.

Methods: We reviewed the current evidence base on TAVI in the elderly by conducting an umbrella review (i.e., overview of systematic reviews), based on a formal bibliographic search for systematic reviews on TAVI in elderly patients (≥ 65 years). Key, study, patient, procedural, and outcome data were extracted, and validity formally appraised with the Oxman-Guyatt index.

Results: From 71 citations, eight reviews were included (totaling 39 studies and 8579 patients): five systematic reviews, and three meta-analyses. Topics of interest were cognitive function before and after TAVI, predictive role of muscle mass and frailty on post-TAVI outcomes, comparative safety and effectiveness of TAVI, and role of rehabilitation to improve patient outlook after TAVI. Thirty-three additional studies were retrieved by means of snowballing, emphasizing the role of multidimensional assessment of elderly patients scheduled for TAVI, in order to maximize its appropriateness, effectiveness, and safety.

Conclusion: It is crucial to consider frailty scores, as well as nutrition and functional status, in addition to established surgical risk scores, in elderly patients considered for TAVI to improve risk prediction, reinforcing the favorable impact of this therapy to improve cognitive function.

Osmotin, a natural plant protein found in tomato, potato, pepper, and tobacco, is a homolog of human adiponectin. It exerts multiple biological activities through adiponectin receptors in a variety of mammalian cells. The therapeutic properties of osmotin have recently been shown in the pathogenesis of atherosclerosis by in vitro and in vivo experiments. Osmotin suppresses the adhesion of monocytes to endothelial cells by downregulating inflammatory cytokines and adhesion molecules in both cells. It suppresses oxidized low-density lipoprotein-induced foam cell formation by downregulating cluster of differentiation 36 and acyl-coenzyme A:cholesterol acyltransferase 1 as well as upregulating ATP-binding cassette transporter A1 in monocyte-derived macrophages. In vascular smooth muscle cells, osmotin suppresses the migration, proliferation, and production of collagen 1, fibronectin, and matrix metalloproteinase 2 by decreasing the phosphorylation of extracellular signal-regulated protein kinase 1/2 and nuclear factor-κB as well as increasing AMP-activated protein kinase (AMPK) expression. Treatment with osmotin suppresses abdominal fat accumulation in C57BL/6 mice and prevents the development of aortic atherosclerotic lesions, improving vascular inflammation and plaque instability in apolipoprotein E-deficient (Apoe^-/-) mice. Osmotin protects against obesity- and diabetes-induced nonalcoholic fatty liver disease in leptin-deficient obese (ob/ob) and leptin receptor-deficient diabetic (db/db) mice. These effects are attributed to the stimulatory actions of osmotin on peroxisome proliferator-activated receptor-α and AMPK. Moreover, osmotin lowers serum levels of total cholesterol and triglyceride in non-diabetic and diabetic rats. These findings suggest that osmotin contributes to improving the extracellular risk factors for atherosclerosis and vascular intracellular and molecular responses. Therefore, the novel phytochemical osmotin may serve as a novel therapeutic target for atherosclerosis and related diseases.

Single internal mammary artery and supplementary saphenous vein grafts (SVG) continues to be used in approximately 95% of coronary surgery as of 2019. The late failure of SVG is very well documented yet remains the predominant conduit used - why? The left internal mammary artery almost never fails, and late angiography of patent radial artery grafts also appear entirely normal. Logic would suggest that avoiding the conduit known to progressively fail would lead to improved late outcome. Our studies have demonstrated such findings in large single centre and national registry datasets. We describe strategies to achievement of total arterial coronary revascularisation.

The tricuspid valve (TV) and right ventricle (RV) are a complex mechanical system. Tricuspid regurgitation impacts a growing and heterogeneous population, leading to right-sided volume overload and right heart failure if left untreated. In part because isolated surgical tricuspid valve repair (TVR) is performed infrequently and has a high mortality, several percutaneous TVR options are being developed. However, the mechanical effects of different types of percutaneous or surgical TVR are unclear. Both the quality of RV imaging and the power of cardiac computational modeling have increased, and accurate computational models of the TV + RV with simulated TVR are now possible. Computational models of TV + RV may aid in patient selection and procedural planning prior to surgical and percutaneous TVR.

Infective endocarditis is still a challenging clinical condition undergoing continuous epidemiologic changes, involving both the population at risk and the microbiological etiology. Antibiotic treatment alone is not effective in presence of structural abnormalities of native valves, leading to heart failure and/or to high embolic risk. Moreover, some patients despite being treated with antibiotics, their valve leaflets may undergo profound degenerative changes responsible for significant hemodynamic abnormalities. The resulting valve disease may lead to a decreased life expectancy. In these patients, surgery was the only independent factor associated with long-term survival. Valve repair in the last two decades has demonstrated to be a valuable alternative to valve replacement in mitral valve 0 endocarditis. Mitral valve repair was associated with decreased hospital and long-term mortality, recurrent endocarditis and overall need for reoperation in comparison to valve replacement. Furthermore, repair limits the risks related to prolonged anticoagulation. However, these results suffer from several limitations: results of repair are dependent on the experience of surgical team, valve damage is usually less extended in patients undergoing repair as well clinical and hemodynamic impairment are more severe in patients undergoing replacement. Therefore, although repair should be preferred when technically feasible caution must be paid to assess its absolute superiority in comparison to valve replacement.

The role of exosomes in different physiological and pathological settings is an emerging field of great current interest. One hallmark of exosomes is the promotion of blood vessel formation. Exosomes of different cellular origin have been shown to be enriched in angiogenic proteins which directly promote angiogenesis. In addition, exosomes are also efficacious producers of adenosine and potentially encapsulate adenosine in their lumen. The adenosine content of exosomes has been linked to their immunosuppressive effects. In this communication, we consider the possibility that adenosine production by tumor cell-derived exosomes may represent a novel pathway for stimulation of angiogenesis in the tumor microenvironment.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in adults and is one critical area of the medical sciences. Atherosclerosis is the main underlying pathology and is characterized by chronic inflammation of the arterial walls. The current treatment modalities for CVD target hypertension, hyperlipidemia and hemostasis, and suppress inflammation without directly addressing the origin of inflammation. Thus, many individuals with multiple classic risk factors for CVD do not experience acute ischemic events. Moreover, myocardial infarction and stroke continue to occur in up to two-thirds of all patients. Because many cardiovascular events have not been explained by genetics or other risk factors, and multiple epidemiologic studies have consistently suggested an infectious component, the introduction of entirely novel approaches for diagnostics and treatment that target infections are acutely needed. These complementary novel approaches addressing additional manageable risk factors such as infections will be based on the concept of personalized medicine to control CVD and achieve longevity, while also increasing the quality of life. There are a variety of avenues that could enable such novel approaches. These focus on the discovery and characterization of the infective component of atherosclerosis, the atherosclerosis microbiome. Specifically, we provide an update of the latest developments in the oral microbiome and its relation to CVD.

Pulmonary hypertension is a serious disorder with a high morbidity and mortality rate. The juxtaposition of endothelial cells and smooth muscle cells maintains vascular homeostasis. Vascular injury results in endothelial dysfunction, leading to impaired vascular relaxation, cell proliferation, and altered immune and metabolic states. In addition, injury induces pulmonary arterial endothelium and other cells to release increased levels of extracellular vesicles, including exosomes and microparticles that may be involved in enhancing the proliferation of apoptosis-resistant smooth muscle cells. These extracellular vesicles carry proteins, lipids, RNA, miRNA, chemokines cytokines and modulate immune function, inflammation, embryogenesis, regenerative processes, and serve as intercellular messengers. Importantly, mesenchymal stem cells-derived extracellular vesicles exert inhibitory effects on inflammation and restore homeostasis. This article reviews the pathophysiological role of extracellular vesicles in pulmonary hypertension.

Aim: Coronary artery bypass grafting (CABG) patients’ characteristics and surgical techniques associated with short-term (ST; < 1 year) mortality are well documented; however, the literature pinpointing factors predictive of longer-term (LT; ≥ 1 year) death rates are more limited. Thus, the CABG factors associated with ST vs. LT mortality were compared.

Methods: Using advanced PubMed search techniques, the factors associated with improved post-CABG mortality were compared for ST vs. LT prediction models; ST vs. LT models’ results were compared across three time periods: until 1997, 1998-2007, and 2007-2017.

Results: Of 156 post-CABG mortality risk models (n = 125 publications), 133 ST and 23 LT models were evaluated. Important predictors consistently included age, ejection fraction, and renal dysfunction/dialysis. The ST models more commonly identified surgical priority, gender, and prior cardiac surgery; however, the LT models more frequently included diabetes and peripheral arterial disease. Compared to ST mortality, patterns also emerged for cerebrovascular disease and chronic lung disease predicting LT mortality. As modifiable risks, body mass index or another marker of body habitus appeared in 31/133 (23%) of ST models; smoking or tobacco use was considered in only 4/133 (3%). No models evaluated compliance with ischemic heart disease guidelines. No time period-related differences were found.

Conclusion: Different risk factors predicted ST vs. LT post-CABG mortality; for LT death, debilitating chronic/complex comorbidities were more often reported. As few models focused on identifying modifiable patient risks or ischemic heart disease guideline compliance, future CABG LT risk modeling should address these knowledge gaps.

Aim: To predict the peak wall stress in abdominal aortic aneurysms (AAAs) considering both morphological factors (maximum diameter, asymmetry index, and wall thickness) and sex differences, in order to assess the risk of AAA rupture more accurately.

Methods: Basic models of AAA focusing on different sexes with a range of morphological parameters were constructed. Using the Design-expert software for three-factor response surface methodology, 20 experimental models were built as well with the SolidWorks software. Fluid-structure interaction analysis was used to obtain stress distribution along the AAA wall. Polynomial regression equations were fitted to peak stresses in all experimental models.

Results: Based on fluid-structure interaction simulation data in the nonlinear polynomial regression model, separate equations for peak wall stress in AAA with regard to males and females were obtained. Morphological factors and sex differences have significant influence on peak wall stress. In some models, even when the maximum AAA diameter was relatively small, the peak wall stress became high. For the same maximal transverse measurement, when the AAA wall was thin and the asymmetry index large, or the former was thick and the latter small, the peak wall stress observed in males was higher than that in females.

Conclusion: To evaluate the risk of rupture of AAA more precisely and specifically, the present study proposes a new prediction method (based on equations) that includes more indicators such as sex and morphology, based on numerical biomechanical simulations, which were confirmed as such. This study provides a sex-specific clinical reference to assess the aforementioned risk of AAA rupture.

The tumour vasculature plays an important role in tumour growth and metastasis. Tumour angiogenesis provides more oxygen and nutrients to growing tumour cells, is not as tightly regulated as embryonic angiogenesis, and do not follow any hierarchically ordered pattern. The heterogeneity of the vasculature, high interstitial fluid pressure, poor extravasation due to sluggish blood flow, and larger distances between exchange vessels are potential barriers to the delivery of therapeutic agents to tumours. The prevention of angiogenesis, normalization of tumour vasculature, and enhancement of blood perfusion through the use of monoclonal antibodies against receptor proteins that are overexpressed on proangiogenic tumour cells, and improved, tumour-targeted delivery of therapeutic agents can all be achieved using nanocarriers of appropriate size. Nanomedicines such as polymeric nanoparticles, lipid nanoparticles, micelles, mesoporous silica particles, metal nanoparticles, noisomes, and liposomes have been developed for the delivery of anticancer drugs in combination with antiangiogenic agents. Amongst them, liposomal delivery systems are mostly approved by the FDA for clinical use. In this review, the molecular pathways of tumour angiogenesis, the physiology of tumour vasculature, barriers to tumour-targeted delivery of therapeutic agents, and the different strategies to overcome these barriers are discussed.

Endothelial cell-derived extracellular vesicles are produced by both activated and apoptotic endothelial cells, and play a pivotal role in various physiological conditions such as inflammation, repair, programmed cell death, and immune responses. There is a large body of evidence on the dysregulation of synthesis and secretion of several types of endothelial cell-derived extracellular vesicles, which can then trigger microvascular inflammation, atherosclerotic plaque formation, plaque rupture, thrombosis and endothelial dysfunction. The development of atherosclerosis and cardiovascular events is associated with an increased number of apoptotic, endothelial cell-derived vesicles and a decrease in activated, endothelial cell-derived vesicles. This review depicts the role of endothelial cell-derived extracellular vesicles in the manifestation and progression of atherosclerosis. We also discuss the clinical use and benefits of altering the immune phenotypes of extracellular vesicles originating from endothelial cells, to function as predictive biomarkers in both asymptomatic and subclinical atherosclerosis.

Transcatheter aortic valve implantation is a well-proven effective treatment option for patients with severe symptomatic aortic valve stenosis requiring valve replacement in all risk classes. Frequently, however, other concomitant cardiovascular conditions demanding intervention are present, and a combined approach is required. Here, we discuss some of the most frequent combined settings. The decision about which approach (staged or simultaneous) is more suitable for each patient needs to be based on individual characteristics and clinical, anatomical, and procedure-related factors.

Malaria infections due to the Plasmodium parasite remains a major global health problem. Plasmodium falciparum is responsible for majority of the severe cases, resulting in more than 400,000 deaths per annum. Extracellular vesicles (EVs) released by vascular cells, including parasitised erythrocytes, have been detected with increased levels in patients with malaria. EVs are thought to be involved in the pathogenesis of severe malaria, particularly cerebral malaria, and represent a unique molecular signature for different forms of the infection. In this review, we will cover the known effects of EVs on the vasculature and discuss their potential use as a biomarker of disease severity.

Obesity is a global public health issue with serious health consequences and rising prevalence. It is a risk factor for a broad range of diseases, particularly atherosclerosis and cardiovascular disease. Long-term weight loss is difficult to achieve, even with diet, life-style changes and anti-obesity drugs. The causes of the association between obesity and atherosclerotic cardiovascular disease are the subject of ongoing investigation. It is known that a chronic surplus in nutritional intake results in expansion and remodeling of adipose tissue, leading to chronic inflammation. Lipid overloaded adipocytes secrete pro-inflammatory adipokines and other mediators that produce this inflammatory state that may in turn, promote atherosclerosis, which is considered an inflammatory disorder. This review discusses the potential role of exosomes from adipose tissue in accelerating atherosclerosis in the setting of obesity. Exosomes are small membrane-bound vesicles that circulate in body fluids and are important participants in intercellular communication both locally and at a distance. They can transfer their cargo of protein, DNA, RNA and microRNA between cells, thus impacting cellular function and signaling. Adipose tissue-derived exosomes may be involved in heightening of the atherogenic environment and, if so, suggests a therapeutic target for the treatment and prevention of cardiovascular complications of obesity.

Bicuspid aortic valves (BAV) can be associated with aortopathy and coronary anomalies. We report the case of a 60 year-old woman undergoing surgery for severe aortic stenosis due to BAV and an ascending aortic aneurysm. During the procedure, an uncommon anomalous origin of the left main coronary artery from the posterior commissure with intramural takeoff of the left coronary artery was found. Routine pre-operative coronary angiography had failed to identify this anomaly. To avoid ischemic events or left main coronary lesions, we placed the aortic bioprosthesis by respecting the commissures, not to occlude the anomalous coronary ostium. The association of BAV, aortopathy and coronary anomalies is a rare finding. Awareness of the anatomy of the coronary arteries in patients with BAV should be considered mandatory to avoid catastrophic consequences and to select the appropriate surgical procedure.

Oxidative stress plays a critical role in the pathogenesis of various disorders including cardiovascular diseases, such as ischemia/reperfusion (I/R) injury, atherosclerosis, dyslipidemia, chronic kidney disease (CKD), arrhythmia, and diabetic cardiovascular complications. Although reactive oxygen species (ROS) have been proposed as the key mediator of oxidative stress-induced cell injury, antioxidant therapies have failed in clinical trials, raising the possibility that some unknown mechanism other than ROS may be involved. In 2015, we reported a novel apoptosis-inducing humoral factor in conditioned medium from cardiac myocytes subjected to hypoxia/reoxygenation. This novel 69th tyrosine-sulfated eukaryotic translation initiation factor 5A (eIF5A) was rapidly secreted from cells in response to oxidative stress and then acted as an apoptosis-inducing ligand in an autocrine fashion. We termed the novel secreted form of eIF5A “Oxidative stress-Responsive Apoptosis-Inducing Protein” (ORAIP). Evidence has accumulated that ORAIP may be a common and dominant apoptosis-inducer among various cell types in response to different types of oxidative stress and is involved in a wide spectrum of acute and chronic disorders. Among them, here, I summarize knowledge regarding the possible roles of ORAIP in myocardial and cerebral I/R injury, dyslipidemia in terms of atherosclerosis, cardiovascular complications in diabetes mellitus, and CKD.

Takayasu arteritis (TA) is a chronic vasculitis involving large vessels of unknown aetiology, a disease that is more common among the Asian population and predominant in young women. Cardiac manifestations include hypertension and involvement of the cardiac valves, myocardium and coronary arteries. Surgery on these patients is always a challenge given the tissue quality and the disease activity. They are prone to long-term complications such as restenosis and graft occlusion, hence requiring lifelong surveillance. The prevalence of coronary artery disease (CAD) in TA ranges from 9 to 11%. Coronary artery bypass grafting is preferred to percutaneous coronary intervention, as the latter has a high rate of restenosis and major adverse cardiovascular events. As left subclavian artery is commonly involved, saphenous vein graft is advised as a conduit rather than internal mammary artery. Other surgical procedures described for CAD are surgical angioplasty of the left main coronary artery and transaortic coronary ostial endarterectomy. Aortic regurgitation in TA has an incidence of approximately 20%. These patients tend to have prosthetic valve detachment, paravalvular leak or pseudoaneurysm at the anastomotic site. Further repair of these valves have a high rate of failure. Considering these facts, it is advisable to do an aortic root replacement for TA patients than to consider an aortic valve replacement or David's procedure.

Platelet-derived growth factor (PDGF) receptors are expressed throughout the body, including the central nervous system (CNS). Although the physiological role of PDGF receptors in the developed CNS is not fully characterized, PDGF signaling appears to provide neuroprotective effects against several neuronal insults. One of the best-characterized neuroprotective effects of PDGF type-β receptors is against human immunodeficiency virus (HIV) protein-induced neurotoxicity, with potential physiological relevance to HAD. PDGFβ receptors are also neuroprotective against glutamate excitotoxicity, which is associated with both stroke and neurodegenerative diseases, including Alzheimer’s disease. The neuroprotective effects of PDGFβ receptors occur both via direct activation by ligand (PDGF-BB), as well as by PDGFβ receptors activated downstream of G protein-coupled receptor signaling. In addition to the involvement of PDGF signaling in various pathologies and potential therapies, there is also an emerging body of evidence that PDGF may serve as a biomarker for neurological or psychiatric diseases.

Aim: To evaluate the prognostic value of high-sensitivity cardiac troponin (hscTnT) levels in unselected emergency medical admissions.

Methods: We report on all hscTnT tests in emergency medical admissions, performed over an eight year period from 2011-2018. The prognostic significance of hscTnT was related to 30-day in-hospital mortality with multivariable logistic regression, adjusted for Acute Illness Severity Score, Comorbidity Score, Sepsis, and Deprivation Status.

Results: There were 52,214 admissions from 28,982 patients during the study period. HscTnT level was a univariate - odds ratios (OR) 1.67 [95% confidence intervals (CI): 1.60-1.73] and an independent risk predictor in the multivariable logistic regression model - OR = 1.23 (95%CI: 1.16-1.29). 30-day in-hospital mortality increased as a linear function of hscTnT; not performed = 3.6%, ≥ 25 ng/L = 5.3%, > 100 ng/L = 7.4%, > 1000 ng/L = 8.8%. Increasing Comorbidity Score exacerbated risk; 30-day in-hospital mortality at a Score of 6, 10 and 16 points for those with no hscTnT performed or hscTnT < 25 ng/L were 1.8%, 6.5% and 31.3% respectively; for hscTnT ≥ 25 ng/L these increased to 2.2%, 8.8% and 41.3%.

Conclusion: HscTnT is prognostic in acutely ill medical patients; incorporation into hospital mortality predictive algorithms appears warranted.

Sucrose nonfermenting 1-related kinase (SNRK) is a serine/threonine kinase and a member of the adenosine monophosphate (AMP)-activated protein kinase (AMPK) family that is involved in the metabolic regulatory mechanisms in various cell types. SNRK is an important mediator in maintaining cellular metabolic homeostasis. In this review, we discuss the role of SNRK in metabolic tissues where it is expressed, including heart and adipose tissue. We discuss its role in regulating inflammation in these tissues and the pathways associated with regulating inflammation. We also discuss SNRK’s role in vascular development and the processes associated with it. Finally, we review SNRK’s potential as a target in various metabolic dysfunction-associated diseases such as cardiovascular diseases, diabetes, obesity, and cancer. This comprehensive review on SNRK suggests that it has therapeutic value in the suppression of inflammation in cardiac and adipose tissue.

Utilization of contrast media to visualize vasculature structures in the setting of cardiovascular disorders (CVD) can lead to acute kidney injury, referred to as contrast-induced nephropathy (CIN). CIN can potentiate mortality and hospitalization in aged individuals, patients with CVD, nephropathy, enhancing kidney damage, and cardiac events. Preventing CIN by identifying risk factors is important. The underlying mechanisms of CIN pathology are unclear, but the key factors include direct cytotoxicity, oxidative stress, vascular and endothelial dysfunction and inflammatory processes. Reactive Oxygen Species and inflammatory mediators have been proposed as key factors influencing the development of CIN and CVD, and the elucidation of the interplay between the mechanisms evoked by them may provide a better understanding of the signaling processes happening in these conditions, thereby potentially enabling early identification, prevention and characterization of novel drug targets.

The vascular endothelium is a vital component in maintaining the structure and function of blood vessels. The endothelial cells (ECs) mediate vital regulatory functions such as the proliferation of cells, permeability of various tissue membranes, and exchange of gases, thrombolysis, blood flow, and homeostasis. The vascular endothelium also regulates inflammation and immune cell trafficking, and ECs serve as a replicative niche for many bacterial, viral, and protozoan infectious diseases. Endothelial dysfunction can lead to vasodilation and pro-inflammation, which are the hallmarks of many severe diseases. Exosomes are nanoscale membrane-bound vesicles that emerge from cells and serve as important extracellular components, which facilitate communication between cells and maintain homeostasis during normal and pathophysiological states. Exosomes are also involved in gene transfer, inflammation and antigen presentation, and mediation of the immune response during pathogenic states. Protozoa are a diverse group of unicellular organisms that cause many infectious diseases in humans. In this regard, it is becoming increasingly evident that many protozoan parasites (such as Plasmodium, Trypanosoma, Leishmania, and Toxoplasma) utilize exosomes for the transfer of their virulence factors and effector molecules into the host cells, which manipulate the host gene expression, immune responses, and other biological activities to establish and modulate infection. In this review, we discuss the role of the vascular endothelium and exosomes in and their contribution to pathogenesis in malaria, African sleeping sickness, Chagas disease, and leishmaniasis and toxoplasmosis with an emphasis on their actions on the innate and adaptive immune mechanisms of resistance.

Aim: To investigate whether patients with symptomatic heart failure and exercise-induced dynamic severe mitral regurgitation (MR) benefit from percutaneous mitral valve repair (PMVR).

Methods: We included patients who underwent PMVR with the MitraClip system in an all-comers observational study. Handgrip echocardiography was performed in patients with a discrepancy between symptoms and echocardiographic findings at rest, giving rise to the suspicion of an exercise-induced increase in MR severity. The primary endpoint of the study was a composite of all-cause mortality or admission for heart failure at 1-year follow-up. The secondary endpoint was the reduction in NYHA functional class.

Results: Two hundred twenty-one patients who underwent MitraClip implantation were included. Ninety-three patients with moderate to severe MR at rest received handgrip echocardiography prior to PMVR. The remaining 128 patients presented with severe MR at rest, making exercise echocardiography unnecessary. Handgrip exercise led to an increase in MR severity in 81% of patients with moderate MR at rest, irrespective of the subtype of MR. Following PMVR, patients with dynamic severe MR experienced comparable clinical improvement as patients with severe MR already at rest: During 1-year follow-up, 37 patients died, and 71 patients were re-admitted to the hospital because of heart failure. In this regard, 13 patients (30%) with dynamic severe MR experienced the combined endpoint, while 72 patients (43%) with severe MR at rest did as well (P = 0.121). Moreover, the majority of patients with dynamic severe MR similar to patients with severe MR at rest experienced clinical improvement from NYHA class III/IV to I/II (59% vs. 56%; P = 0.566).

Conclusion: The data presented provide evidence of a clinical benefit from PMVR using MitraClip in patients with moderate MR at rest who display exercise-induced increases in MR severity during handgrip exercise.

Granulomatosis with polyangiitis, microscopic polyangiitis and renal-limited anti-neutrophil cytoplasm antibody (ANCA) associated vasculitis are the main ANCA-associated vasculitidies (AAV). Multiple induction therapies for AAV exist and have proven successful in achieving disease remission. Azathioprine and methotrexate have been used to maintain remission of AAV, however, relapse rates and adverse effects with these medications remain high. Rituximab (RTX), a B cell depleting monoclonal antibody, was shown to be safe and effective in maintaining disease remission in AAV in early retrospective reviews. In 2014, the first randomized control trial to compare RTX and azathioprine in maintenance therapy of newly diagnosed AAV (MAINRITSAN trial), revealed that patients who received RTX after cyclophosphamide induction had higher rates of sustained remission, fewer adverse effects and, better overall survival rates as compared to azathioprine. MAINRITSAN 2 revealed that patients receiving tailored regimens of maintenance RTX received fewer infusions but did not have higher rates of relapse than patients who received fixed dose therapy. The RITAZAREM trial conveyed that patients who experienced AAV relapse after induction therapy that received induction and maintenance RTX were significantly less likely to develop a relapse at 24 months vs. patients who received maintenance therapy with azathioprine. Overall, these studies suggest that maintenance therapy with RTX represents an exceptional treatment option in patients with AAV in terms of safety and efficacy, resulting in lower relapse rates and less drug toxicity than conventional treatments. As a result, patients have fewer exposures to cytotoxic medications and thus, improved outcomes.

Carotid artery diseases can result in many extracranial manifestations. Tinnitus is a recognised symptom and has long been correlated with significant internal carotid artery stenosis. It has been largely classified into pulsatile and non-pulsatile types with variable management approaches and prognoses. Surgical and endovascular approaches to treat carotid artery stenosis have not only aimed to reduce stroke rates but also to manage such symptoms. The clinical and cognitive evidence of such practices are broad and managed in a combined spectrum with otolaryngologists. This literature review aims to focus on current evidence and practice with vascular surgeons on the importance of dealing with tinnitus in managing carotid artery stenosis.

The development of the frozen elephant trunk (FET) technique for a simplified treatment of complex lesions of the thoracic aorta originated as an evolution of the classic elephant trunk technique, described for the first time by Borst et al.^[1] in 1983. Novel technologies and standardization of the surgical approach produced a progressive improvement of early and late outcomes. Most of the time and for specific indications, FET procedure allows physicians to treat lesions involving extensive portions of the thoracic aorta in one single step. Spinal cord injury remains one of the main complications of this procedure, even though spinal protection strategies have led to better results. We hereby report our opinions and recommendations based on our experience started in 2007.

Thoracic aortic aneurysm represents a deadly condition, particularly when it evolves into rupture and dissection. Proper surgical timing is the key to positively influencing the survival of patients with this pathology. According to the most recent guidelines, ascending aorta size ≥ 55 mm and a rate of growth ≥ 0.5 cm per year are the most important factors for surgical indication. Nevertheless, a lot of evidence show that aortic ruptures and dissections might occur also in small size ascending aorta. In this review, we sought to analyze a new biological and morphological network behind the aortic diameter that need to be considered in order to identify the portion of patients with thoracic aortic aneurysm who are at increased risk of aortic complications, despite current aortic guidelines not advising surgical intervention in this group.

Circumflex aorta is an unusual form of congenital arch malformation with a retroesophageal arch segment. Circumflex aorta crosses the midline behind the oesophagus and above the level of carina to become continuous with the proximal descending aorta on the opposite side to form a true vascular ring with the arterial ligament. The term is often used to refer to the more common variant of circumflex aorta with a retroesophageal right-sided aortic arch with a left-sided descending aorta and left-sided ligamentum. Its mirror-form with a retroesophageal left-sided aortic arch is much rarer. Although originally described without obstruction, it may occur in association with aortic arch hypoplasia, adding to its clinical burden. This article describes the morphology of circumflex aorta and its clinical presentation, and provides review of surgical management of circumflex aortic arch.

Aim: Sodium-glucose cotransporter-2 (SGLT2)-inhibitors improve survival in adults with reduced ejection fraction. Clinical outcomes in adults with heart failure (HF) with preserved ejection fraction (HFpEF) have not been systematically reviewed.

Methods: We conducted a systematic rapid literature review and appraised the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation methodology.

Results: We identified post-hoc subgroup analyses of four randomized controlled clinical trials (RCTs) and unpublished results from 2 RCTs. In 2 RCTs vs. placebo, Canagliflozin reduced the risk of fatal or hospitalized HF in adults with HF and documented or assumed left ventricular ejection fraction (LVEF) ≥ 50% (hazard rate ratio, HR = 0.71, 95%CI: 0.52-0.97) but had no effect in a subpopulation with documented LVEF ≥ 50% (HR = 0.83, 95%CI: 0.55-1.25). Dapagliflozin or ertugliflozin did not improve all-cause or cardiovascular death or hospitalization for HF in adults with HF and LVEF > 45% in two pivotal RCTs vs. placebo. Empagliflozin did not improve exercise ability, patient-reported outcomes or congestion, diuretic use and all-cause healthcare resource utilization in unpublished RCT vs. placebo. Various definitions of HFpEF, post-hoc interaction analyses suggesting outcome improvement regardless of heart failure type, small number of events, and probable publication bias hampered the quality of evidence.

Conclusion: Existing evidence is insufficient to support definitive clinical recommendations for use of SGLT2- inhibitors in adults with HFpEF. Future research should employ consistent definitions of HFpEF and examine the effects from SGLT2- Inhibitors in patients with various HFpEF phenotypes and underlying causes.

Stroke is a leading cause of morbidity and mortality worldwide. There have been significant advances in the hyperacute treatment of patients with ischemic stroke with the advent and application of reperfusion therapies, including intravenous thrombolysis and endovascular thrombectomy. Endovascular thrombectomy involves the removal of thrombus from an artery using a mechanical retriever or aspiration with angiographic visualization. This review aims to outline the current evidence to support the use of endovascular thrombectomy and highlight areas of ongoing research.

Aim: Chronic venous disease (CVD) is very common in nurses. Noticeably, operating room (OR) nurses are predicted to have a major prevalence of varicose veins. We investigated whether the prevalence of CVD in OR nurses was more than non-OR nurses.

Methods: Study populations were OR nurses and non-OR nurses at the Faculty of Medicine, Chiang Mai University. Information was compiled by questionnaire. Physical examination was operated by examiners for CVD based on clinical finding using Comprehensive Classification System for Chronic Venous Disorders classification.

Results: 222 nurses were included. The prevalence of C0-C2 was notably different between the two groups (P < 0.001). The prevalence of C1 in OR nurses and non-OR nurses was 59.6% and 72.1% while the prevalence of C2 in OR nurses and non-OR nurses was 8.1% and 16.4%, respectively. Nevertheless, the quality of life was not remarkably different between the two groups.

Conclusion: The results demonstrated that CVD in non-OR nurses appear to be higher than OR nurses.

Aim: We aimed to assess the clinical outcomes of the internal iliac artery (IIA) coverage during endovascular abdominal aortic aneurysm repair (EVAR).

Methods: A retrospective observational study was conducted in patients managed with EVAR for the aorto-iliac aneurysmal disease. The IIA was sacrificed by extension of the stent-graft into the external iliac artery in the absence of the distal landing zone, while it was preserved if the landing zone was available.

Results: From 2002 to 2018, 540 patients underwent EVAR for aorto-iliac aneurysmal disease in our center. Sixty-five (12.04%, n = 65/540) had iliac aneurysm extension. Among these 65 cases, the IIA was not covered in 32 patients (IIA salvage/spared group), while they were covered in 33 patients (IIA sacrifice group). The IIA sacrifice group consisted of 25 unilateral and 8 bilateral coverages. There was 100% technical success and no 30-day mortality in both groups. The IIA sacrifice group had more postoperative complications in general when compared to the IIA salvage group, but they were not significant (P < 0.05). There were one patient with buttock claudication (P = 1.000) with bilateral IIA coverage, two cases of lower limb microembolization (P = 0.492) and one case of erectile dysfunction (P = 1.000) in IIA sacrifice group, while they were not seen in IIA salvage group. There was no ruptured iliac access, device-related malfunction, spinal cord ischemia or bowel ischemia in either group.

Conclusion: We found coverage of IIA aneurysmal extension during EVAR of AAA to be technically feasible and safe.

Aim: The effectual use of frozen elephant trunk (FET) has been for total aortic arch replacement (TAR) of acute aortic dissection because of positive aortic remodeling. However, the use of FET in the non-dissecting aortic arch aneurysm is still contr oversial. We aim to investigate the outcomes of TAR using the FET technique for distal aortic arch aneurysms.

Methods: Between August 2014 and February 2020, 40 patients (35 males, mean age 77.0 years) underwent TAR by using the FET technique with the J Graft Open Stent Graft for distal aortic arch aneurysms including 8 patients with shaggy aorta. In 5 of 40 patients, coronary bypass grafting was concomitantly performed. We followed up for 29.0 months.

Results: The mortality were 0%. Stroke occurred in three patients (7.5%) one of whom had shaggy aorta, paraparesis in one patient (2.5%) who recovered fully, and respiratory complication in two patients (5.0%). There was no recurrent nerve palsy. During the follow-up period, death had no relationship with aortic disease.

Conclusion: We conclude the FET has the potential to improve TAR for distal aortic arch aneurysms.

Commissural alignment during transcatheter aortic valve implantation (TAVI) has important clinical implications as TAVI expands to younger patients in whom lifetime treatment of aortic valve disease and coronary artery disease is of particular importance. Numerous studies have shown that lack of commissural alignment may adversely affect coronary reaccess and the feasibility of redo-TAVI in this patient population. To assess the risk of commissural misalignment more accurately, we have pioneered and validated the use of a preprocedural imaging protocol that determines valve orientation using multi-detector computed tomography-fluoroscopy co-registration. Furthermore, we have shown that a modified delivery system insertion technique during initial valve deployment results in improved commissural alignment and reduced coronary artery overlap following TAVI with a self-expanding device. However, numerous unanswered questions remain about the impact of commissural misalignment on balloon-expandable valve-in-valve TAVI, especially in patients with unfavorable aortic root anatomy. It is imperative that clinicians consider these anatomic, device-related, and procedure factors, among others, when evaluating patients for transcatheter therapies.

Transcatheter aortic valve implantation (TAVI) is a well-established treatment for symptomatic severe aortic stenosis in intermediate and high-risk patients. However, as TAVI indications increase, concerns regarding adverse events and complications rise in the same proportion. Stroke is one of the most feared TAVI complications and a hard endpoint present in all TAVI studies. TAVI-related stroke incidence becomes even more relevant with TAVI indications spreading to younger, low/intermediate-risk patients. Several devices have been developed to prevent this catastrophic event, some of them being broadly used. Nevertheless, the evidence for routine use of cerebral embolic protection devices is still controversial.

The use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors has garnered widespread attention in the medical community over the past ten years. A number of landmark trials have demonstrated the efficacy of PCSK9 inhibitors in lowering low-density lipoprotein (LDL) levels dramatically when added to background statin therapy. Importantly, their use has led to a significant reduction in adverse events in patients at risk and with established cardiovascular diseases. Published evidence is sparse in the heart failure (HF) population, especially in those with Stage D disease. While the use of PCSK9 inhibitors has not been reported in patients with durable mechanical circulatory support devices, limited data exist in heart transplant recipients. Management of dyslipidemia is critically important in post-heart transplant population as it contributes to the development of cardiac allograft vasculopathy (CAV). However, most 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) interfere with the metabolism of commonly used immunosuppressant agents, such as tacrolimus. Case studies in post-heart transplant patients demonstrated significant LDL reduction with PCSK9 inhibitor use, without significant drug-drug interactions or adverse events. Two trials are currently underway examining their efficacy in reducing CAV progression. This paper aims to review the available clinical evidence for PCSK9 inhibitor use in HF patients, with specific focus on the advanced heart failure group.