Aim: To describe the implementation of a high sensitivity (hsTn) assay at a large academically affiliated Veteran Affairs medical center.
Methods: Approximately 6 months time was utilised for adoption of a new hsTn assay in clinical practice at our facility. We assembled a multidisciplinary team of front-line clinicians to determine which actions would best prepare the facility for the transition. Identified goals included: maximizing sensitivity of the assay, minimizing confusion for clinicians, making adoption as easy as possible for the end users, and encouraging clinicians to use uniform terminology while referring to troponin results. One month prior to the new assay initiation, educational interventions included live learning sessions, pre-recorded lectures, slide decks, and printed materials. Communication to the entire clinical staff was accomplished through staff meetings and email announcements. An abbreviated “top things to remember about hsTn list” was widely shared.
Results: After adoption, the cardiology service received minimal consultation requests from clinicians unaware of the change or uncomfortable with how to interpret the hsTn results. In quantitative assessment, we observed no change in the rate of cardiology consultations, electrocardiograms or cardiac stress tests.
Conclusion: A multidisciplinary implementation focused on application by the bedside and ample education were effective in creating a seamless transition to hsTn.
Aim: The ability to predict outcomes can help clinicians to better triage and treat stroke patients. We aimed to build prediction models using clinical data at admission and discharge to assess predictors highly relevant to stroke outcomes.
Methods: A total of 37,094 patients from the Taiwan Stroke Registry (TSR) were enrolled to ascertain clinical variables and predict their mRS outcomes at 90 days. The performances (i.e., the area under the curves (AUCs)) of these independent predictors identified by logistic regression (LR) based on clinical variables were compared.
Results: Several outcome prediction models based on different patient subgroups were evaluated, and their AUCs based on all clinical variables at admission and discharge were 0.85-0.88 and 0.92-0.96, respectively. After feature selections, the input features decreased from 140 to 2-18 (including age of onset and NIHSS at admission) and from 262 to 2-8 (including NIHSS at discharge and mRS at discharge) at admission and discharge, respectively. With only a few selected key clinical features, our models can provide better performance than those previously reported in the literature.
Conclusion: This study proposed high performance prognostics outcome prediction models derived from a population-based nationwide stroke registry even with reduced LR-selected clinical features. These key clinical features can help physicians to better focus on stroke patients to triage for best outcome in acute settings.
The heart is one of the principal targets of thyroid hormones (TH) action, affecting cardiac contractility, heart rate, and diastolic function. Oxidative damage is pivotal for onset and development of cardiovascular disease (CVD) and heart failure. Specifically, free radical generation is associated to hyper-metabolic state in hyperthyroidism, whereas hypo-metabolic state induced by hypothyroidism leads to a decrease of oxidative stress. In the present review, the role of oxidative damage in CVD and failing heart-TH interplay will be considered. The main oxidative events leading to cardiac dysfunction and TH cardiac regulation at genomic and non-genomic levels will be discussed, as well as role of TH in cardioprotection and reversion of cardiac remodeling.
Age-related macular degeneration (AMD) is the leading cause of vision loss in adults over 60 years old globally. There are two forms of advanced AMD: “dry” and “wet”. Dry AMD is characterized by geographic atrophy of the retinal pigment epithelium and overlying photoreceptors in the macular region; whereas wet AMD is characterized by vascular penetrance from the choroid into the retina, known as choroidal neovascularization (CNV). Both phenotypes eventually lead to loss of central vision. The pathogenesis of AMD involves the interplay of genetic polymorphisms and environmental risk factors, many of which elevate retinal oxidative stress. Excess reactive oxygen species react with cellular macromolecules, forming oxidation-modified byproducts that elicit chronic inflammation and promote CNV. Additionally, genome-wide association studies have identified several genetic variants in the age-related maculopathy susceptibility 2/high-temperature requirement A serine peptidase 1 (ARMS2-HTRA1) locus associated with the progression of late-stage AMD, especially the wet subtype. In this review, we will focus on the interplay of oxidative stress and HTRA1 in drusen deposition, chronic inflammation, and chronic angiogenesis. We aim to present a multifactorial model of wet AMD progression, supporting HTRA1 as a novel therapeutic target upstream of vascular endothelial growth factor (VEGF), the conventional target in AMD therapeutics. By inhibiting HTRA1’s proteolytic activity, we can reduce pro-angiogenic signaling and prevent proteolytic breakdown of the blood-retina barrier. The anti-HTRA1 approach offers a promising alternative treatment option to wet AMD, complementary to anti-VEGF therapy.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) has gained extensive attention since the discovery of its role in mediating hepatic low-density lipoprotein (LDL)-receptor (LDLR) degradation, and therefore regulating plasma LDL cholesterol clearance. However, emerging studies have indicated that PCSK9 may have pleiotropic effects on the development of atherosclerosis and eventually cardiac dysfunction by mechanisms independent of the regulation of LDL cholesterol levels. In this review, we will discuss recent findings of how PCSK9 affects cellular responses and the pro-inflammatory microenvironment within the local atherosclerotic vascular wall, which are critical for atherosclerotic plaque progression. We will also discuss recent research on the potential direct effects of PCSK9 on cardiomyocyte viability and function. These pathways may be critical for understanding the mechanisms of PCSK9’s cardioprotective effects beyond LDL cholesterol lowering.
Transcatheter therapies for patients with severe mitral regurgitation are increasingly performed in recent years. While transcatheter mitral valve repair (TMVR) is now a consolidated intervention with > 100,000 procedures performed worldwide, TMV replacement (TMVRpl) is in its early stages and can only be offered by a few centers. The complexity of mitral valve anatomy requires careful evaluation when selecting the best approach and the most suitable device. At present, the clinical experience with TMVRpl is still in a preliminary phase. Most of the patients treated with this approach thus far are high-risk candidates who have undergone a very restrictive clinical and anatomical selection. Therefore, it is difficult to correctly define which patients might benefit more from TMVRpl than from TMVR. We review the clinical, pathophysiological, and technical factors to suggest when to prefer TMVR instead of a replacement technique.
Aim: The development of varicose veins is driven by risk factors that support the progression of venous hypertension, specifically, by chronically augmenting the circumferential tension of the venous wall. We have previously verified the relevance of this biomechanical stimulus for the activation of venous cells and the structural remodeling of the vein wall. Recent transcriptome analyses revealed an increase in the expression of the gene encoding prostaglandin-endoperoxide synthase 2 [cyclooxygenase 2 (COX-2)] in biomechanically stressed human vein endothelial cells. This observation prompted us to investigate the functional relevance of COX activity for the onset of pressure-induced venous remodeling.
Methods: For the in vitro experiments, isolated mouse veins were exposed to elevated intraluminal pressure levels to study the markers of cellular activation. For the in vivo experiments, pressure-dependent varicose remodeling of veins was induced by ligation of an efferent vein in the mouse auricle. Diclofenac was applied to inhibit the activity of COX.
Results: Short-term exposure to elevated pressure levels stimulated the abundance of activated matrix-metalloproteinase-2 (MMP-2) and mitogen activated protein kinase, ERK1/2, in isolated mouse veins, which was inhibited upon treatment with diclofenac. Transdermal application of diclofenac-containing phospholipid-micelles attenuated the corkscrew-like enlargement of veins and decreased the abundance of COX-2 and MMP-2 as well as cell proliferation in the venous wall.
Conclusion: The cyclooxygenase inhibitor, diclofenac, interferes with stress-induced activation of venous cells and attenuates venous remodeling in vivo. Additional research is warranted to investigate whether nonsteroidal anti-inflammatory drugs interfere with the processes promoting the onset of varicose vein development and biomechanical activation of venous cells.
More than half a century of research focused on ischemic brain injury mechanisms has failed to yield a widely accepted neuroprotective drug for the treatment of acute ischemic stroke (AIS). The absence of a therapeutic intervention targeted at neuroprotective mechanisms raises questions about the relevance of preclinical models in human stroke. Indeed, this failure of forward translation (traditional bench-to-bedside research) to bring candidate drugs into clinical use suggests that alternative or complementary approaches are needed. Here, we discuss the potential of reverse translational research - exploring a bedside-to-bench approach - utilizing big data genomics to discover novel AIS therapeutic targets. This approach might provide insights into new and old drug targets.
Stroke is the leading cause of neurological disability in adults worldwide and involves the significant impairment of sensory-motor function caused by cerebral ischemia and subsequent neuronal death. Owing to a lack of medical or surgical treatments to improve neurological function and neurogenesis, chronic stroke places a huge burden on patients, their families, and society. Over the past twenty years, increasing evidence from translational and clinical research has demonstrated the potential effectiveness of hematopoietic growth factors and stem cell administration or transplantation in the treatment of stroke. In particular, these studies have included granulocyte colony-stimulating factor, mesenchymal stem cells, autologous CD34+ peripheral blood stem cells, umbilical cord blood stem cells, and autologous adipose-derived mesenchymal stem cells. It is therefore important to consider the safety of these putative therapies whilst achieving the maximum benefit for patients with chronic stroke in terms of the route of administration and stem cell numbers. In this review, we discuss current evidence and the progress that has been made in our hospital, which paves the way for the next neurogenesis therapy for chronic stroke.
Mobile stroke units (MSU) are specially designed ambulances with CT imaging capability able to provide faster pre-hospital care to patients in the community. The Melbourne Mobile Stroke Unit is the first MSU service in the Australian region, commencing operations in 2017 in central metropolitan Melbourne. This review describes the challenges of setting up the MSU in a unique Australian setting and initial clinical efficacy of pre-hospital MSU treatment and triage on ischemic and hemorrhagic stroke. We also discuss the current technological and operational limitations of the MSU service and directions for future research.
The treatment in acute ischemic stroke has shown extensive improvement in these recent years by new endovascular devices and advanced imaging. Advanced imaging is mainly led by perfusion imaging and has been powered by automated analyzing software. In this manuscript, we describe the history and the technology of perfusion imaging, including parameters and analyzing methods that have evolved from positron emission tomography and single-photon computed tomography to computed tomography perfusion and magnetic resonance imaging perfusion. The immense clinical advantage of advanced imaging is expansion of the therapeutic window by various mismatch assessments. Of these, perfusion-weighted imaging - core mismatch has managed to demonstrate the evidence in randomized control trials. A unique understanding of conventional imaging such as diffusion-weighted image - fluid-attenuated inversion recovery mismatch has also played a role in expanding the therapeutic window to wake-up strokes or unwitnessed strokes. In this article, these mismatch assessed trials are described with future insights.
Transcatheter aortic valve implantation (TAVI) has become a safe and valid procedure in all surgical risk patients, expanding TAVI indications to a larger number of patients. However, while short- and mid-term follow up showed similar results compared to surgery, long-term durability remains unstudied. Concerns about TAVI longevity are mainly raised by early development of higher rates of bioprosthetic valve disfunction (BVD) and especially of paravalvular leaks (PVL), which have been previously related with long-term mortality. In this context, the definition of BVD, its relationship with the TAVI technology (balloon vs. self-expandable), and the prognostic role of mild PVL are a complex topic which has not been clarified yet, along with outcomes of valve-in-valve (ViV) intervention, which represents a valid therapeutic option in the case of severe BVD. The aim of this narrative review is to offer a general overview of the evolution of TAVI indications; show the differences between balloon and self-expandable prostheses performances; clarify the definition, classification, and prognostic role of BVD; and summarize current evidence about long-term TAVI durability.
Coronary artery disease (CAD) represents the leading cause of chronic heart failure in developed countries. Ischemic heart failure is mainly characterized by impairment of left ventricle systolic function which can result from scarring of myocardium after myocardial infarction, stunning myocardium and hibernating myocardium. Hibernating myocardium represents a cause of ischemic left ventricular dysfunction amenable to recovery after revascularization. Several viability imaging modalities are available but their role in the clinical decision-making process and the prognostic value of viability in patients undergoing revascularization are still debated. When available, cardiac magnetic resonance or positron emission tomography should be preferred over the others as they show higher performance in terms of sensitivity and higher spatial resolution. Several observational studies have supported a positive prognostic value to the presence of viable myocardium for patients undergoing revascularization. This was not confirmed in randomized clinical trials. This lack of evidence does not support a precise role of viability assessment in the clinical decision-making process, and therefore, myocardial viability should be only one of the several factors considered in the clinical decision-making process.
A relationship between inflammatory activity, on the one hand, and haemostasias, cardiovascular risk factors and multiple phases of atherothrombotic diseases, on the other hand, has been documented for decades, but only recently have four large trials tested whether anti-inflammatory drugs could prevent major cardiovascular events (MACE) in > 25,000 patients followed on average for 1.9-3.7 years. In patients with recent myocardial infarction (MI) and serum C-reactive protein (CRP) ≥ 2 mg/L, the CANTOS trial showed that subcutaneous three-monthly 300 mg canakinumab [a high-cost, monoclonal antibody to interleukin (IL)-1β] reduced MACE versus placebo, but it increased fatal infections. In patients with recent MI (COLCOT trial) and in patients with chronic coronary syndromes (LoDoCo2 trial), oral 0.5 mg daily colchicine [a low-cost inhibitor of nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain containing protein 3 (NLRP3) inflammasome] reduced MACE compared to placebo, with a small but significant increase in pneumonia (0.9% vs. 0.4% in COLCOT; not confirmed in LoDoCo2). In coronary artery disease patients with type 2 diabetes or metabolic syndrome, the CIRT trial found that oral 15-20 mg weekly methotrexate (an anti-rheumatic drug with multiple effects including inhibition of nuclear factor kB activity) compared to placebo did not reduce MACE, nor circulating IL-6 or CRP, while increasing the risk of non-basal cell skin cancer. Thus, three out of four large trials have now proven that drugs inhibiting the IL-1/IL-6 inflammatory axis can prevent MACE in patients with coronary artery disease. Colchicine, given its overall profile, is likely to become an integral part of secondary cardiovascular-disease prevention strategies.
The association of hyperuricemia with cardiovascular risk, hypertension, atherosclerosis, metabolic syndrome, mortality, and chronic kidney disease has been largely described in clinical studies. Several pathogenetic mechanisms explaining uric acid mediated renal damage have been hypothesized, including crystal deposition, oxidative stress, arteriolosclerosis, and glomerular hypertension. Currently, two explanations for hyperuricemia-induced renal injury are the most widely accepted. Firstly, the fact that uric acid is recognized by receptors involved in the innate immune response as a dangerous molecule appears to be a powerful trigger for the inflammatory cascade, which ultimately lead to renal fibrosis. Secondly, serum uric acid has been demonstrated to be implicated in the renin-angiotensin system activation and nitric oxide synthesis inhibition, which promote endothelial dysfunction and proliferation of vascular smooth muscle cells, resulting in glomerulosclerosis and interstitial fibrosis. In this review, we focus on experimental data demonstrating pathophysiological mechanisms linking uric acid to inflammation and oxidative stress, which contribute to the development and progression of renal injury. In addition, we describe endothelial and vascular dysfunction crucial playmakers in kidney impairment induced by uric acid.
Aim: Encoded by Aoc3 gene, Vascular Adhesion Protein-1 (VAP-1), also called semicarbazide-sensitive amine oxidase (SSAO), is a protein supporting leucocyte extravasation to inflammation sites and catalyzing the oxidation of primary amines. We previously observed that a genetically-modified mouse model lacking active VAP-1/SSAO is obese and hypercholesterolemic. Here, we further studied the alterations related to factors that increase or alleviate the risk of atherosclerosis.
Methods: Body weight and glucose tolerance were determined in mice homozygous for a null mutation of Aoc3 (AOC3KO) and fed standard or high-fat diet (HFD). White adipose tissue (WAT) inflammation was assessed by immunohistological observations. Cholesterol trafficking was explored by determining plasma and tissue levels and key enzyme expression. Vascular reactivity and VAP-1/SSAO activity were assessed via hydrogen peroxide release, uric acid and nitrate/nitrite levels.
Results: AOC3KO mice were devoid of VAP-1/SSAO protein and activity, while, in WT control, WAT was the richest anatomical location regarding the capacity to oxidize benzylamine. AOC3KO mice were obese but did not exhibit alteration of glucose tolerance or insulin secretion. The elevated plasma cholesterol of AOC3KO mice was further increased by HFD, with LDL cholesterol levels higher than in WT. An increased cholesteryl ester accumulation occurred in plasma, liver and WAT, with higher HMGCoA expression in WAT and slightly reduced SR-BI hepatic transporters. However, in AOC3KO mice, no sign of WAT inflammation was detected, while lower hydrogen peroxide release and higher nitrite levels were found in aorta and kidney.
Conclusion: The obesity of AOC3KO mice occurred with hypercholesterolemia but without other atherosclerosis risk factors, such as worsened insulin sensitivity, WAT inflammation, increased oxidative stress and reduced nitric oxide availability.
PCSK9 is a secreted protein that binds to the LDL receptor on the cell surface, is endocytosed along with the receptor, and interferes with its ability to recycle to the cell surface. Instead the receptor is directed to the lysosome where it is degraded, leading to decreased levels of the receptor on the cell surface and decreased internalization of LDL. In this review, we will discuss how mice deficient in the Pcsk9 gene or hepatic overexpression due to transgenesis or viral vector mediated expression contributed to our understanding of the in vivo role of PCSK9. In addition, we will discuss how the discovery of PCSK9 and its gain of function mutants has greatly facilitated the manipulation of animals modelling atherosclerosis to induce hypercholesterolemia and atherosclerosis.
Traditional on-pump coronary artery bypass grafting on an arrested heart using a single arterial graft carries 2 main potential drawbacks: the risk of perioperative neurological injury and the known failure rate of vein grafts. To address this, we describe a surgical technique of anaortic, off-pump coronary artery bypass that avoids all manipulation of the ascending aorta and uses multiple-arterial grafts to achieve complete revascularisation. This provides optimal short- and long-term outcomes and is particularly important in high-risk subgroups. The standard graft configuration is the left internal mammary artery to the anterior wall, and the right internal mammary artery is extended with the radial artery and brought through the transverse sinus to revascularise the lateral and inferior walls sequentially. Alternative configurations, including “T” grafts and using long saphenous vein, are considered if patients have factors limiting arterial conduit selection. Arterial conduits are harvested using a skeletonised technique. The radial artery may also be harvested endoscopically. Wide, bilateral retrothymic tunnels are formed for the internal mammary arteries. The pericardium is opened using specific incisions designed to facilitate positioning of the heart whilst maintaining venous return and cardiac output. There are 4 main positions for the heart during grafts (high-lateral wall, low-lateral wall, inferior wall and anterior wall). These are obtained using a combination of table position, wet sponges, two nylon sutures placed in the pericardium and the off-pump stabiliser. All distal anastomoses are performed using homemade intra-coronary silastic shunts, which provide optimal grafting conditions. Graft patency is confirmed using transit-flow time measurement.
This perspective focuses primarily on the fundamental part of phlebology, where most attention is paid to the genetic aspects of the pathogenesis of varicose vein disease and where the main breakthrough advances in this area of research are discussed. We propose a direction for further actions to replenish molecular genetic knowledge about the main drivers of pathological processes in varicose vein disease and to complete the creation of an entire picture of pathogenesis, which, in turn, may serve as a key for the development of treatment options in the future in order to translate research evidence into clinical practice.
The Fourth Universal Definition of Myocardial Infarction recognizes “myocardial injury” as a distinct entity with a milder form of myocardial necrosis leading to the release of detectable troponin. Myocardial injury after non-cardiac surgery (MINS) is the release of detectable troponin in the absence of symptoms within 30-day. MINS has been increasingly recognized as it has a prognostic bearing on outcomes. However, the diagnosis, interpretation, implication, and treatment strategies are yet to be resolved. Definitions of diagnosis have changed from the fourth generation to fifth-generation (high-sensitivity troponin), which still is proprietary and lack universal standardization; interpretation in studies have varied depending on definitions based on fourth or fifth generation troponin assays. Other than prognostic implications, either equivocal results or limited studies exist for the utility for prevention and screening of MINS. Additionally, the studied strategies and drugs to prevent MINS have either failed to translate in clinical trials in humans, or showed inconclusive results. We, as a result of this, in our review, highlight such facts regarding elevation in perioperative troponin faced by the practicing perioperative clinician regularly.
Stroke is the second leading cause of death and the third greatest cause of disability worldwide. In some countries, stroke disproportionally affects Indigenous Peoples, with greater incidence and mortality at younger ages, higher rates of conventional cardiovascular risk factors and lower treatment rates. Worldwide there are 470 million Indigenous Peoples, residing in 90 countries. Analogous to the general health of all populations, the cause of stroke and its outcomes are the result of complex interactions between factors that act at societal, service, and individual levels. Colonisation, including the cultural and material losses associated with it, is a major indirect driver of disparities in lifestyle, biological and other risk factors for stroke in Indigenous Peoples. In addition, structural racism and the inability to access culturally safe education, employment and health care, further contribute to stroke health inequities for Indigenous Peoples globally. In this narrative review we provide an outline of stroke incidence rates, common risk factors for stroke, treatment rates with intravenous thrombolysis and endovascular clot retrieval in adult Indigenous populations in comparison to the non-Indigenous population of the same region. Our objective is to describe the differences that exist between the Indigenous and non-Indigenous populations with stroke in a particular region and discuss potential solutions that support a “strengths-based” approach driven by Indigenous People.
Over the last few decades, a trend for increased specialization has been observed in all surgical domains. This has been driven by the advancement of medical knowledge and technology and by the realization of a clear association between higher volume of cases and better surgical outcomes. The field of cardiothoracic surgery has followed the same trend, but the most commonly performed operation, coronary artery bypass grafting, is still considered a generalist procedure and does not benefit from recognition as a formal subspecialty. There is robust evidence to support that a positive effect on outcomes can be achieved by both increased volume and better quality of surgical techniques and perioperative protocols. We hypothesize that a structured specialized coronary revascularization program can be initiated in every institution through a strong leadership focused on effective mentorship and training that will achieve the benchmark of less than 1% operative mortality following coronary revascularization. This review article makes a case for recognition of myocardial surgical revascularization as a subspecialty and proposes a strategy to overcome the barriers that preclude such a recognition.
Coronary artery bypass grafting may involve substantial manipulation of the ascending aorta, including aortic cannulation, antegrade cardioplegia line cannulation, and aortic clamping. These distortions of the ascending aorta can lead to disruption of soft or calcified plaques in the aortic wall, which can cause embolization. A relationship has been shown between the degree of aortic manipulation and the degree of cerebral embolization. Thus, it is clear that the risk of cerebral embolization can be reduced by alterations in the surgical technique. Such surgical alterations can be guided by epiaortic ultrasound by assisting the surgeon in identifying regions where atherosclerosis is present to avoid or minimize the degree of aortic manipulation in these regions. By using a previously published examination protocol, the atherosclerotic regions can be found more efficiently with an ultrasound examination than manual palpation, and the entire examination can be completed within 3-5 min. This review aims to outline the current evidence to support the use of epiaortic ultrasound for myocardial surgical revascularization.
Endovascular treatment of brain aneurysms with flow diverter device can be technically difficult. Obtaining distal access through the wide neck of a large or giant aneurysm may be challenging and sometimes the microcatheter needs to be looped inside the aneurysm. However, the inability to resolve this loop and to straighten the microcatheter can preclude flow diverter placement. This brief report presents four cases of large/giant aneurysms treated with flow diverter device, in which our innovative stent-retriever anchor technique was used to obtain the distal access of the parent artery. All procedures were technically successful, and no complications were recorded.
Severe mitral regurgitation is the second leading cause of cardiac valve intervention in Europe, reaching up to 10% of people older than 75 years. The mitral valve is an anatomically complex structure in which several underlying mechanisms for its malfunction could coexist. Nonetheless, over the last years, development of new techniques and devices, improved patient selection, and dedicated imaging assessment and guidance tools seem to offer novel alternatives for percutaneous mitral valve treatment. The present review aims to provide an update of the available percutaneous techniques for patients with severe mitral regurgitation.
Acute stroke is one of the most common causes of disability worldwide and numbers are projected to increase. Modern and successful recanalizing treatments are available, but timely access to these treatments is most often restricted to urban populations. This disparity affects nearly half of the world’s population, particularly those living in rural and remote areas, and most often affects people with indigenous background. We provide information on this disparity in acute stroke care between rural, remote, and urban areas. We discuss potential new management strategies which could facilitate the timely delivery of acute stroke care to those residents beyond the better serviced urban areas. We focus on the concept of a mobile stroke unit (MSU), especially an Air-MSU. This aircraft solution could provide an imaging capability and immediate clinical expertise via linked telemedicine to diagnose and treat acute stroke patients at the emergency site. The Air-MSU is not only envisioned to allow intravenous thrombolysis in the field but also to allow pre-hospital triage to comprehensive stroke centres through use of contrast imaging to diagnose large vessel occlusion, facilitating endovascular thrombectomy. Moreover, issues regarding optimal operating environment as well as novel imaging and diagnostic devices, which could facilitate the implementation of an Air-MSU are discussed. Innovative health care solutions are urgently needed to close the treatment gap for stroke patients living in rural and remote regions worldwide.
Coronary microvascular dysfunction (CMD) is an under-diagnosed condition characterized by functional alteration of the small coronary arterioles and the cardiac capillary bed. The vessels do not dilate appropriately in response to changes in cardiac oxygen demand, leading to chest pain and symptoms of angina. These blood vessels contain two major cell types: the endothelial cells, which line the blood vessels and detect changes in oxygen demand, and smooth muscle cells (SMC) which respond to these changes by contracting or relaxing to provide an optimal blood supply to the cardiac tissue. Many CMD studies have focused on the endothelial cells as these cells secrete vasorelaxants and vasoconstrictors. However, comparably fewer studies have examined SMC despite their functional role in contracting and relaxing. A variety of health conditions and lifestyle choices, such as diabetes, hypertension and cigarette smoking, can promote the development of both CMD and macrovascular coronary artery disease; a condition where SMC have been studied extensively. This review article will consider the influence of CMD on SMC phenotype. It will discuss the structural, cellular and molecular changes in CMD, and will summarise how co-morbidities can have differing effects on micro- and macro-vascular SMC phenotype and function, which complicates the development of new therapeutic avenues for CMD.
Cerebral cavernous malformation (CCM) is a rare disease of proven genetic origin characterized by vascular lesions affecting capillaries and small vessels of the central nervous system. CCM lesions occur in a range of different phenotypes, including wide differences in lesion number, size, and susceptibility to intracerebral hemorrhage. CCM lesion genesis requires loss of function of any of three genes, namely KRIT1 (CCM1),
Cardioplegia and cardiopulmonary bypass (CP/CPB) during cardiac surgery may cause systemic microvascular dysfunction. CP/CPB is associated with significant alterations in myogenic tone, agonist-induced vasomotor response, and endothelial function in various organs and vascular beds. These alterations can result in vessel spasm, organ malperfusion, and tissue damage. This review summarizes the current state of research in this field.
Cerebral cavernous malformations (CCM) can occur either as sporadic or familial form with autosomal dominant inheritance. Three CCM genes have been identified: CCM1 (KRIT1), CCM2 (MGC4607), and CCM3 (PDCD10). In this review, we provide an overall update on genetics of cerebral cavernous malformations. We discuss the main features of these three genes and provide an updated listing of the mutations identified so far. Most of them lead to a premature stop codon regardless of the nature of the variation, including nonsense mutations, small deletions/insertions, and intronic/exonic substitutions causing an altered splicing and a frame-shift. In addition, deletions or duplications of one or more exons of CCM genes can be responsible for the disease. We examine the use of different mutation screening methods to identify all these mutations, providing a comprehensive approach to CCM genetic diagnosis. We also report the main strategies to evaluate the actual impact of the mutations on the protein function. Moreover, we recapitulate the available data on penetrance, phenotype-genotype correlations, and founder effect. Finally, we discuss the main aspects of genetic counseling, including genetic risk assessment in family members, in sporadic patients with multiple CCMs, and in the case of de novo mutations.
Intraoperative graft assessment should be considered a vital step during surgical myocardial revascularization that is performed following completion of grafting. It provides the surgeon a tool to assess graft flow and quality. Hence, it reduces graft failure rates related to avoidable or correctable technical errors, leading to improved early and late postoperative outcomes. Additionally, modern intraoperative functional coronary flow tests facilitate decision-making regarding the indication for revascularization of a particular vessel based on the functional significance and degree of ischemia induced by a lesion in that coronary artery. A wider implementation of intraoperative graft assessment modalities has the potential to improve graft patency and outcomes following myocardial revascularization. However, further research in the field is required before it becomes the standard of care during coronary artery bypass graft surgery. This article provides a general review of strategies and methods of coronary artery graft flow assessment, focusing on their availability and feasibility as well as strengths and limitations.
Aim: Patients with atrial fibrillation (AF) are over-represented in endovascular thrombectomy (EVT) populations, due to a high prevalence of large vessel occlusions (LVO) and contraindication to intravenous thrombolysis. This study aimed to: (1) compare 90-day functional outcomes [modified Rankin Score (mRS) 0-2] and mortality in AF vs. non-AF patients receiving EVT; (2) compare 90-day functional outcomes and mortality in AF patients on therapeutic vs. non-therapeutic anticoagulation receiving EVT; and (3) identify factors influencing outcomes in AF patients receiving EVT.
Methods: A retrospective analysis of 394 consecutive patients who received EVT for anterior cerebral circulation LVO at an Australian comprehensive stroke center was performed. The main outcome measures [90-day dichotomized mRS (0-2 good; 3-6 poor functional outcome) and mortality] were compared between AF and non-AF patients, as well as between therapeutic and non-therapeutic anticoagulation cohorts.
Results: In total, 171 (49%) EVT patients had AF. Patients with AF were older, had higher NIHSS, and had lower rates of thrombolysis administration. AF patients showed improved 90-day mRS on multivariate analysis [aOR 1.988 (1.167-3.387)], with similar symptomatic intracranial hemorrhage (sICH) [aOR 0.364 (0.064-2.086)] and mortality [aOR 1.454 (0.785-2.696)]. There was no difference in 90-day mRS [aOR 1.402 (0.625-3.145)], successful reperfusion rates [aOR 3.761 (0.661-21.410)], or mortality [aOR 1.077 (0.429-2.705)] between AF patients on therapeutic vs. non-therapeutic anticoagulation. In patients with AF, advancing age and higher NIHSS were independent predictors of worse 90-day functional outcome (OR = 1.045, P = 0.020; OR = 1.086, P = 0.001) and mortality (OR = 1.138, P < 0.001; OR = 1.107, P = 0.002). On multivariate analysis, thrombolysis administration improved mortality (OR = 0.215, P = 0.016) but not functional outcomes.
Conclusion: Patients with AF showed improved 90-day functional outcome, with similar mortality and sICH, after EVT. Therapeutic anticoagulation did not adversely influence EVT outcomes.
Evaluation and treatment of acute ischemic stroke has undergone significant advancement since the 1990s, when acute systemic reperfusion with intravenous alteplase became the first approved method for achieving reperfusion. Until recently, 4.5 h after stroke onset appeared to be the maximum time window in which positive results from thrombolysis can be achieved. However, the advent of advanced imaging modalities, including multimodal magnetic resonance imaging and computed tomography perfusion has allowed clinicians to refine the evaluation of these patients by delineating areas of infarcted tissue, areas of potentially salvageable tissue given timely reperfusion, and areas of benign oligemia. Early work in extending the time window beyond this historical limit of 4.5 h has culminated in four positive trials that demonstrate the benefit of acute mechanical or systemic reperfusion therapy in an extended time window of up to 24 h, using advanced imaging criteria for patient selection. The implications of the success of advanced imaging suggest use of these modalities for disposition decisions and selection of greater numbers of patients for reperfusion but add complexity to individual patient evaluation. Despite this, many questions remain unanswered, including the best choice of thrombolysis agent, whether we can extend the time window further to 24 h, and the optimal combination of mechanical thrombectomy and bridging therapy in the late time window in patients with or without large vessel occlusion.
Aim: Mutations in 3 genes encoding proteins of the Cerebral Cavernous Malformations (CCM) ternary complex cause autosomal dominant cerebral vascular disease. Targets of CCM complex regulation have been identified; however, the molecular mechanisms connecting CCM3 to these downstream effectors remain elusive. We aim to determine the mechanism of CCM3 action by using a Drosophila model to elucidate the signaling pathway downstream of CCM3. Previously, we showed that CCM3 and its binding partner, Germinal Center Kinase 3, are required in tracheal terminal cells to prevent tube morphogenesis defects. Further, we established that GCKIII phosphorylates and directly activates a downstream kinase, Tricornered (Drosophila STK38/38L ortholog). Here we aim to test whether Tricornered-associated scaffolding protein, Furry, is required for CCM3-GCKIII signaling.
Methods: We utilized the FRT-FLP system to generate genetic mosaic Drosophila larvae and adults. Mitotic recombination was induced in embryos (trachea) or larvae (wing disc). The animals were heterozygous for the gene of interest (ccm3 or furry), but after recombination, homozygous mutant daughter cells were produced. In addition, the GAL4-UAS system was used to express dominant negative GCKIII in wing disc cells. Mutant cells were analyzed by brightfield and/or fluorescent microscopy.
Results: We find that wing cells mutant for ccm3, or expressing dominant negative GCKIII, produce wing hair defects characteristic of mutations in tricornered and furry. Likewise, tracheal terminal cells mutant for furry produce tube dilation defects characteristic of cells mutant for ccm3 or GCKIII.
Conclusion: CCM3 and GCKIII act upstream of Furry-Tricornered, suggesting the conservation from yeast of a Hippo-like signaling pathway that regulates morphogenesis. We speculate that some combination of Furry/Furrylike and STK38/38L are therefore likely to act downstream of CCM3 in endothelial cells.
Chronic venous disease (CVD) is a common venous disorder of the lower extremities. CVD can be manifested as varicose veins (VVs), with dilated and tortuous veins, dysfunctional valves and venous reflux. If not adequately treated, VVs could progress to chronic venous insufficiency (CVI) and lead to venous leg ulcer (VLU). Predisposing familial and genetic factors have been implicated in CVD. Additional environmental, behavioral and dietary factors including sedentary lifestyle and obesity may also contribute to CVD. Alterations in the mRNA expression, protein levels and proteolytic activity of matrix metalloproteinases (MMPs) have been detected in VVs and VLU. MMP expression/activity can be modulated by venous hydrostatic pressure, hypoxia, tissue metabolites, and inflammation. MMPs in turn increase proteolysis of different protein substrates in the extracellular matrix particularly collagen and elastin, leading to weakening of the vein wall. MMPs could also promote venous dilation by increasing the release of endothelium-derived vasodilators and activating potassium channels, leading to smooth muscle hyperpolarization and relaxation. Depending on VVs severity, management usually includes compression stockings, sclerotherapy and surgical removal. Venotonics have also been promoted to decrease the progression of VVs. Sulodexide has also shown benefits in VLU and CVI, and recent data suggest that it could improve venous smooth muscle contraction. Other lines of treatment including induction of endogenous tissue inhibitors of metalloproteinases and administration of exogenous synthetic inhibitors of MMPs are being explored, and could provide alternative strategies in the treatment of CVD.
Aim: The percentage variation of Resistance Index (△RI%) after reactive hyperemia test at the brachial artery is a marker of endothelial dysfunction that could be used as a surrogate indicator for the extent of coronary artery disease (CAD). We assessed flow-mediated dilatation (FMD) and △RI% in 39 consecutive patients undergoing coronary angiography.
Methods: Patients were classified in groups 0 to 3 according to the number of diseased vessels and the SYNTAX score was calculated. The hyperemia reactive test was performed 1 day before to 3 days after coronary angiography.
Results: Both FMD and △RI% decreased significantly from groups 0 to 3 (ANOVA P < 0.001 and P = 0.002, respectively). Reduced △RI% was linearly associated with SYNTAX score (β = 0.34, P = 0.036). At multivariable modeling, impaired △RI% was the only significant independent predictor of the presence of CAD (OR = 1.28, 95%CI: 1.06-1.54, P = 0.01).
Conclusion: This study shows that a reduced △RI% after reactive hyperemia test is observed in patients with CAD and that such reduction is related to the extent of the disease. Therefore, to evaluate FMD and △RI% at the brachial artery can reliably indicate the burden of CAD.
Aim: During a recent institutional transition between two high sensitivity troponin assays, we sought to evaluate the correlation and agreement in an unselected population presenting to the ED undergoing troponin measurement.
Methods: This was a prospective study of consecutive patients presenting to a single, academic institution that underwent troponin testing. Paired samples of two high sensitivity troponin assays, hs-cTnT (Gen 5 TnT; Roche Diagnostics, Indianapolis, IN) and hs-cTnI (High Sensitive Troponin I Architect i2000; Abbott, Abbott Park, Illinois) were assessed for overall correlation and agreement. We also evaluated the paired difference between the two assays stratified by gender and CKD stage. Further, we determined reclassification at the 99th percentile limit and the institutional established abnormal.
Results: A total of 1349 unique patient encounters were included in the study with median result value of 12.2 ng/L (IQR 6-29.5) for hs-cTnT and 4.7 ng/L (IQR 3.5-15.5) for hs-cTnI. Direct comparison of the two assays indicated a Spearman Rho of 0.79 with poor agreement especially when cTn results were elevated. Paired difference was smaller in women with a difference of medians of 0.9 ng/L (0.06-1.67, P < 0.01) and three significant clusters (CKD 1, CKD 2 and 3, CKD 4 and 5; P < 0.01) were found when stratifying by Chronic Kidney Disease stage Reclassification occurred in 276 patients when evaluated at the 99th percentile and 148 patients at the institution’s abnormal cut-off.
Conclusion: There was moderate correlation seen during our transition between the two high sensitivity troponins, but differential bias with lower hs-cTnI than hs-cTnT at low levels and higher hs-cTnI than hs-cTnT at high values. Without the appropriate system level recommendations and established diagnostic protocol this level of disagreement can potentially cause problems with interpretation to the end clinician who has become accustomed to a specific assay’s thresholds.
Stasis microangiopathy includes all the pathological changes in the microcirculation and interstitium due to venous hypertension. Venous valve incompetence occurring in the superficial or deep venous system or in both is the most common cause of venous hypertension, a pathological condition that plays a key role in most or all clinical signs of chronic venous disease, including edema and venous ulcers. The aim of the first and main part of this review is to focus on the various pathogenetic mechanisms of stasis microangiopathy triggered by venous hypertension, including hemodynamic and hemorheological alterations, inflammation, and functional alterations. The rationale underlying the current available treatment options of stasis microangiopathy is mentioned briefly in the second part of the review.
The incidence of degenerated mitral bioprosthesis is increasing in clinical practice due to a greater use of biological prostheses for mitral valve replacement compared to mechanical valves and increased life expectancy after cardiac surgery. Similarly, mitral valve repair can result in long-term recurrence of mitral valve disease requiring reintervention. Therefore, the number of failing surgical prosthesis or repaired valves will increase over the next years representing a new challenge in the corrective approach in the case of long-term structural valve degeneration. Those patients were generally managed with reoperative mitral valve surgery, but transcatheter interventional therapies, initially considered an option in patients who are ineligible for redo surgery, have been recently associated with excellent outcomes. The efficacy and safety of transcatheter mitral valve procedures have been reported in both failing ring annuloplasty or degenerated mitral bioprosthesis, but the use of non-dedicated devices remains associated with significant severe complications such as device malpositioning or left ventricular outflow tract obstruction requiring emergent conversion to open surgery. Both the careful selection of patients and pre/intra-procedural scheduling are warranted to maximize benefits and reduce issues. This review focuses on emerging transcatheter mitral valve replacement devices as therapeutic options for degenerated mitral bioprosthesis or failed mitral repair. This paper aims to summarize current interventional techniques and available evidence, comparing outcomes between transcatheter technologies and reoperative mitral valve surgery.
Ear, nose, and throat (ENT) involvement is a common feature in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), particularly in granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis. Over the last decade, substantial advancement has been made in understanding AAV pathogenesis, classification, and treatment. Typical ENT symptoms may include sinonasal, otologic, pharyngeal, and laryngeal manifestations. The otolaryngologic symptoms of AAV sometimes might be misdiagnosed in etiology as infectious or allergic. Thus, rapid recognition and early diagnosis of AAV as the cause of the symptoms prevent the risk of irreversible organ damage. The high impact of ENT symptoms on the quality of life of AAV patients confirms the importance of their early treatment through specific local and systemic approaches. Appropriate interdisciplinary management to early recognition of AAV and initiation of treatment may reduce morbidity in these patients. The purpose of this comprehensive review is to describe the clinical, histological, and radiological findings of ENT involvement in AAV and to update their surgical and therapeutic management, with a focus also on the role of a multidisciplinary team, involving the otorhinolaryngologist.
Acute ischemic stroke is a leading cause of death and disability. Treatment efficacy is highly time-dependent. Approximately 20% of acute ischaemic stroke occurs in the posterior circulation. Clinical presentation of posterior circulation stroke is subtle. Diagnosis is often delayed and frequently missed. CT perfusion has improved diagnostic accuracy and been integral to guiding acute therapy in patients with anterior circulation stroke. There are limited studies assessing the role of CT perfusion in posterior circulation stroke. This review provides a reference for interpretation of CT perfusion and summarises current evidence relating to applications in acute posterior circulation stroke.
Atherosclerosis is the main pathological basis of most cardiovascular diseases and the leading health threat in the world. Of note, lipid-lowering therapy cannot completely retard atherosclerosis progression, even in patients treated with combined statins and PCSK9 inhibitors. This failure further impels researchers to explore other underlying therapeutic strategies except for lipid-lowering. Monocytes and macrophages are the major immune cell groups in atherosclerotic plaques. They play important roles in all stages of atherosclerosis, including the occurrence, advance, and regression. It is interesting that macrophages are demonstrated to have plastic and heterogenous characteristics within the dynamic atherosclerotic plaque microenvironment. Furthermore, the phenotype of macrophages can switch upon different microenvironmental stimulus. Therefore, macrophages have become a potential therapeutic target for anti-atherosclerosis treatment. This article reviews the phenotypic diversity of macrophages and their roles in dynamic atherosclerotic plaque microenvironment, especially the related signaling pathways involved in macrophage polarization and compounds exhibiting therapeutic effects.
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are a group of systemic autoimmune diseases associated with serum ANCA positivity that affect small to medium vessels with inflammation and endothelial injury. This group includes several diseases: granulomatosis with polyangiitis (GPA), microscopic polyangiitis, eosinophilic GPA, and drug-induced AAV. A few AAVs are ANCA negative, but this form has decreased with the increase in detection methods. Different genetic, epigenetic, and environmental risk factors contribute to the pathogenesis of AAV. ANCA’s role in the origin of vasculitis has led to a better grasp of the disease. Research has also improved the treatment, more precisely to tune its intensity, translating into better outcomes. However, there is still a gap to be filled with new potential and testable biomarkers for diagnosis, disease activity, and prognosis, which we discuss here.
Aim: To determine the relationship between coronary vascular dysfunction and history of migraines in women with suspected ischemia and no obstructive coronary arteries (INOCA).
Methods: In the Women’s Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction study, 402 women with suspected INOCA answered baseline angina questionnaires, including the Seattle Angina Questionnaire (SAQ). Coronary function testing (CFT) performed in a subgroup of 252 women evaluated for nonendothelial and endothelial-dependent coronary vascular function. Wilcoxon rank sum test, t-test, and linear regression models were performed.
Results: Of the 252 women who underwent CFT, 126 (50%) women reported migraine history. Compared to women who reported no migraines, women with migraines were younger and more were premenopausal. They had more angina at rest, with strong emotions, and hot/cold temperatures, as well as angina that wakes them from sleep (P < 0.05 for all). Women with migraines also scored worse on SAQ angina frequency and quality of life
Conclusion: Among women with suspected INOCA, migraine history is prevalent and women with migraines have worse angina compared to those without migraines. Coronary vascular dysfunction diagnosed by CFT does not appear to relate to migraine history.
Ear, nose, and throat (ENT) symptoms represent the most frequent manifestations at the onset of granulomatosis with polyangiitis (GPA). The diagnosis of the localized form of GPA remains challenging thus contributing to the delay at the beginning of treatment. This could lead to major sequelae due to tissue destruction. Otolaryngologists play a key role in collaboration with rheumatologists in early GPA diagnosis and treatment. Clinicians should maintain a high index of suspicion and proceed to a more comprehensive evaluation in cases of imperfect response to treatment or with unexplained atypical findings. The challenging issue in localized organ involvement during GPA is to determine whether the non-specific local upper aerodigestive symptoms are caused by a specific or a non-specific inflammatory process. The role of surgery becomes crucial in cases of laryngeal involvement. Life-threatening airway compromise necessitates urgent surgical intervention. There is an emerging role in the local ENT therapies.
As is the case in many areas of medicine and science in general, there has been a dramatic acceleration in the acquisition of understanding during the last few decades. This is also the case for cerebral cavernous malformations (CCMs). We like to artificially divide the progress that we have personally witnessed into three phases: pre-magnetic resonance imaging (MRI), post-MRI, and molecular. We highlight the major leaps forward linked to the specific discovery.
Cerebral cavernous malformations (CCMs), one of the most common vascular malformations, are characterized by abnormally dilated intracranial microvascular capillaries resulting in increased susceptibility to hemorrhagic stroke. As an autosomal dominant disorder with incomplete penetrance, the majority of CCMs gene mutation carriers are largely asymptomatic, but, when symptoms occur, the disease has typically reached the stage of focal hemorrhage with irreversible brain damage, while the molecular “trigger” initiating the occurrence of CCM pathology remain elusive. Currently, the invasive neurosurgery removal of CCM lesions is the only option for the treatment, despite the recurrence of worse symptoms frequently occurring after surgery. Therefore, there is a grave need for the identification of molecular targets for therapeutic treatment and biomarkers as risk predictors for hemorrhagic stroke prevention. Based on the various perturbed angiogenic signaling cascades mediated by the CCM signaling complex (CSC) reported, there have been many proposed candidate drugs, targeting potentially angiogenic-relevant signaling pathways dysregulated by loss of function of one of the CCM proteins, which might not be enough to correct the pathological phenotype, hemorrhagic CCMs. In this review, we describe a new paradigm for the mechanism of hemorrhagic CCM lesions and propose a new concept for the assurance of CSC stability to prevent the devastating outcome of hemorrhagic CCMs.
In recent years, there has been important progress in the evolving field of coronary vasomotor disorders regarding diagnostic assessments and therapeutic strategies. It is now commonly accepted that patients with angina and unobstructed coronary arteries (ANOCA) frequently suffer from coronary vasomotor disorders. The latter can be reliably diagnosed using invasive diagnostic procedures. They comprise the detection of epicardial and/or microvascular spasm, impaired coronary vasodilatation, and enhanced microvascular resistance. As these mechanisms may overlap in one given patient, various endotypes of disease can be distinguished. Although evidence from randomized clinical trials in this setting is still sparse, it has been suggested that - in addition to strict risk factor control-targeted pharmacological therapies/treatments based on the identified mechanism of disease can improve symptoms and prognosis. In patients with coronary spasm as the predominant mechanism, first-line treatment consists of high-dose calcium channel blockers and nitrates. In patients with impaired vasodilatation or enhanced microvascular resistance, beta-blockers, angiotensin-converting enzyme inhibitors, and statins represent first-line treatment. In the group of patients with symptoms refractory to first-line medication, second-line drugs such as nicorandil, molsidomine, ranolazine, ivabradine, and others for microvascular dysfunction are available. Moreover, ongoing studies in this area are evaluating the usefulness of newer pharmacological agents such as endothelin-receptor antagonists or soluble guanylate cyclase stimulators. This article summarizes the currently available evidence for pharmacological treatment strategies in patients with ANOCA due to coronary microvascular dysfunction.
Amyloidosis is a disease characterized by the deposition of amorphous protein material in the extracellular space which leads to progressive dysfunction of the affected organ. The forms of amyloidosis that most frequently involve the heart are transthyretin amyloidosis (ATTR) and immunoglobulin light chain amyloidosis (AL). Nuclear medicine offers numerous imaging techniques for the evaluation of patients with cardiac amyloidosis, and in the last decade osteophilic tracer scintigraphy has assumed a fundamental role in the diagnostic process of this disease. New PET radiopharmaceuticals for the detection of amyloid deposits are proving very effective in diagnosing the presence of AL amyloidosis and could soon allow a differential diagnosis without the need for invasive and potentially risky techniques such as endomyocardial biopsy.
Systemic amyloidosis includes a group of disorders, characterized by deposition of insoluble aggregates of amyloid fibrils in various tissues that lead to disruption of normal tissue structure and impaired function. They are currently categorized as hereditary and secondary. Peripheral neuropathy is a frequent complication of systemic amyloidosis. The most common phenotype is a length-dependent sensorimotor polyneuropathy with autonomic dysfunction, but there are many atypical presentations that often lead to delayed diagnosis. In this review, we emphasize the neurological clinical aspects that induce a suspicion of amyloidosis, the possible differential diagnosis and the diagnostic pitfalls. An early diagnosis of the disease is crucial for rapid initiation of appropriate treatment that may change the course and the progression of the disease.
Transthyretin amyloidosis of the heart, or transthyretin amyloid cardiomyopathy (ATTR-CM), once thought to be a rare disease, is now increasingly recognized as a common causing of restrictive cardiomyopathy, particularly in elderly patients and patients with heart failure with preserved ejection fraction. ATTR-CM is caused by an aggregation of misfolded transthyretin (TTR) protein amyloid fibrils in the myocardium. The TTR protein itself can be either wild-type (ATTRwt) or one of many pathologic variants (ATTRv). Recognition of ATTR-CM has been aided by rapid advances in technologies to diagnose the disease more accurately. Several advances in pharmacotherapeutic treatments have significantly reduced the morbidity and mortality of the disease. Treatments broadly fall into three categories: (1) TTR silencing through mRNA knockdown or silencing; (2) TTR stabilization; and (3) TTR resorption or extraction. This review article provides a survey of the pharmacokinetic and clinical data on all currently available treatments.
Mitral regurgitation is one of the most common cardiac valve disorders worldwide and the second most frequent indication of cardiac surgery for heart valve disease. During the last decades, open-heart mitral valve repair and replacement have been considered the sole and gold standard invasive therapy for this complex disorder. However, a significant proportion of patients experiences recurrence of mitral regurgitation during long-term follow-up, which entails an important increase in morbidity and mortality. In this scenario, percutaneous therapies to treat mitral regurgitation have become an appealing alternative to conventional surgery given high risk for repeat surgery. The present review describes current evidence of transcatheter mitral valve repair and replacement therapies to treat mitral regurgitation recurrence after surgery.
The diagnosis of coronary microvascular disease (CMD) is vital in a subset of patients with symptoms of myocardial ischemia. The typical ischemic findings on resting electrocardiogram and echocardiogram are uncommon or absent in CMD. Therefore, a high clinical suspicion is essential. We aim to review the invasive and non-invasive diagnostic testing for CMD. The goal is to assess the endothelial dysfunction related to vasoconstriction or reduced coronary blood flow reserve. Non-invasive testing includes resting electrocardiogram, exercise electrocardiogram, transthoracic color Doppler echocardiography, myocardial contrast echocardiography, positron emission tomography, and cardiac magnetic resonance imaging. Comprehensive invasive assessment includes coronary angiography followed by fractional functional flow reserve assessment, coronary flow reserve testing with intravenous acetylcholine with or without intravenous adenosine.
The acute hypertensive response, elevated blood pressure in the acute phase of intracerebral hemorrhage, is very common and is associated with hematoma expansion, cerebral edema formation, intracranial pressure elevation, and poor long-term outcomes. This has led to the acceptance of antihypertensive treatment of acute hypertensive response as a mainstay of intacerebral hemorrhage management to reduce hematoma expansion and the associated disability and mortality. Intensive lowering of systolic blood pressure in the acute phase of intracerebral hemorrhage with varying intensity of systolic blood pressure reduction has been evaluated in several clinical trials. Some of these trials showed little benefit with intensive systolic blood pressure reduction compared with moderate or standard blood pressure reduction, while some showed no benefit and despite the large amount of literature, optimal approaches are not yet clear. In this review article, we summarized the current knowledge of the mechanisms underlying acute hypertensive response and the recent guidelines on the treatment of the acute hypertensive response provided by professional organizations and results of clinical trials and discussed incorporation of these concepts into clinical practice.
The coronary microcirculation is a key determinant of blood supply to the myocardium and outweighs the epicardial arteries in its abundance and distribution. Recent studies have shown the clinical benefit of assessing the microcirculation, and this practice has now been given a recommendation within the latest international guidelines and consensus statements. However, the uptake of assessing the microcirculation remains low. We continue to focus our efforts in diagnosing and managing epicardial coronary disease in the cardiac catheterisation laboratory and mostly ignore the microvasculature. This is in large part due to the lack of familiarity with available tools to perform these assessments. This review aims to summarise the various techniques available to invasively assess the coronary microcirculation in the catheterisation laboratory. The advantages, disadvantages, pitfalls and clinical implications of each method are discussed.