Immunoglobulin E Sensitization to Mammalian Oligosaccharide Galactose-α-1,3 (α-Gal) Is Associated With Noncalcified Plaque, Obstructive Coronary Artery Disease, and ST-Segment-Elevated Myocardial Infarction.

BACKGROUND: Treating known risk factors for coronary artery disease (CAD) has substantially reduced CAD morbidity and mortality. However, a significant burden of CAD remains unexplained. Immunoglobulin E sensitization to mammalian oligosaccharide galactose-α-1,3-galactose (α-Gal) was recently associated with CAD in a small observational study. We sought to confirm that α-Gal sensitization is associated with CAD burden, in particular noncalcified plaque. Additionally, we sort to assess whether that α-Gal sensitization is associated with ST-segment-elevated myocardial infarction (STEMI) Methods: We performed a cross-sectional analysis of participants enrolled in the BioHEART cohort study. We measured α-Gal specific-immunoglobulin E antibodies in serum of 1056 patients referred for CT coronary angiography for suspected CAD and 100 selected patients presenting with STEMI, enriched for patients without standard modifiable risk factors. CT coronary angiograms were assessed using coronary artery calcium scores and segmental plaque scores. RESULTS: α-Gal sensitization was associated with presence of noncalcified plaque (odds ratio, 1.62 [95% CI, 1.04-2.53], P=0.03) and obstructive CAD (odds ratio, 2.05 [95% CI, 1.29-3.25], P=0.002), independent of age, sex, and traditional risk factors. The α-Gal sensitization rate was 12.8-fold higher in patients with STEMI compared with matched healthy controls and 2.2-fold higher in the patients with STEMI compared with matched stable CAD patients (17% versus 1.3%, P=0.01 and 20% versus 9%, P=0.03, respectively). CONCLUSIONS: α-Gal sensitization is independently associated with noncalcified plaque burden and obstructive CAD and occurs at higher frequency in patients with STEMI than those with stable or no CAD. These findings may have implications for individuals exposed to ticks, as well as public health policy. Registration: URL: https://www.anzctr.org.au; Unique identifier: ACTRN12618001322224.

Single Atom Dynamics in Chemical Reactions.

Many heterogeneous chemical reactions involve gases catalyzed over solid surfaces at elevated temperatures and play a critical role in the production of energy, healthcare, pollution control, industrial products, and food. These catalytic reactions take place at the atomic level, with active structures forming under reaction conditions. A fundamental understanding of catalysis at the single atom resolution is therefore a major advance in a rational framework upon which future catalytic processes can be built. Visualization and analysis of gas-catalyst chemical reactions at the atomic level under controlled reaction conditions are key to understanding the catalyst structural evolution and atomic scale reaction mechanisms crucial to the performance and the development of improved catalysts and chemical processes. Increasingly, dynamic single atoms and atom clusters are believed to lead to enhanced catalyst performance, but despite considerable efforts, reaction mechanisms at the single atom level under reaction conditions of gas and temperature are not well understood. The development of the atomic lattice resolution environmental transmission electron microscope (ETEM) by the authors is widely used to visualize gas-solid catalyst reactions at this atomic level. It has recently been advanced to the environmental scanning TEM (ESTEM) with single atom resolution and full analytical capabilities. The ESTEM employs high-angle annular dark-field imaging where intensity is approximately proportional to the square of the atomic number (Z). In this Account, we highlight the ESTEM development also introduced by the authors for real time in situ studies to reliably discern metal atoms on lighter supports in gas and high temperature environments, evolving oxide/metal interfaces, and atomic level reaction mechanisms in heterogeneous catalysts more generally and informatively, with utilizing the wider body of literature. The highlights include platinum/carbon systems of interest in fuel cells to meet energy demands and reduce environmental pollution, in reduction/oxidation (redox) mechanisms of copper and nickel nanoparticles extensively employed in catalysis, electronics, and sensors, and in the activation of supported cobalt catalysts in Fischer-Tropsch (FT) synthesis to produce fuels. By following the dynamic reduction process at operating temperature, we investigate Pt atom migrations from irregular nanoparticles in a carbon supported platinum catalyst and the resulting faceting. We outline the factors that govern the mechanism involved, with the discovery of single atom interactions which indicate that a primary role of the nanoparticles is to act as reservoirs of low coordination atoms and clusters. This has important implications in supported nanoparticle catalysis and nanoparticle science. In copper and nickel systems, we track the oxidation front at the atomic level as it proceeds across a nanoparticle, by directly monitoring Z-contrast changes with time and temperature. Regeneration of deactivated catalysts is key to prolong catalyst life. We discuss and review analyses of dynamic redox cycles for the redispersion of nickel nanoparticles with single atom resolution. In the FT process, pretreatment of practical cobalt/silica catalysts reveals higher low-coordination Co0 active sites for CO adsorption. Collectively, the ESTEM findings generate structural insights into catalyst dynamics important in the development of efficient catalysts and processes.

Prognostic impact of collaterals in patients with a coronary chronic total occlusion: A meta-analysis of over 3,000 patients.

OBJECTIVES: To assess the prognostic implications of the degree of coronary collaterals on outcomes in patients with a CTO. BACKGROUND: Coronary chronic total occlusions (CTO) are identified frequently in patients undergoing coronary angiography and have been associated with poorer prognosis. Whether the degree of coronary collaterals, the hallmark of CTOs impacts prognosis, is unknown. METHODS: A search of EMBASE, MEDLINE, and Cochrane Library was conducted to identify studies reporting on coronary collaterals and risk of all-cause mortality, acute myocardial infarction (AMI) and successful percutaneous coronary intervention (PCI). Patients with Rentrop grade 0 or 1 collaterals were defined as poor collaterals, while Rentrop grade 2 or 3 were defined as robust collaterals. RESULTS: Twelve studies with a total of 3,369 were included. Patients with robust collaterals did not have lower rates of AMI (OR: 0.89, 95%CI: 0.39-2.04) or lower rates of all-cause mortality (OR: 0.81, 95% CI: 0.42-1.58), however were more likely to have successful PCI (OR: 4.04, 95%CI: 1.10-14.85). CONCLUSION: The presence of robust collaterals is not associated with lower rates of AMI or mortality, but does increase the likelihood of successful CTO PCI. These results have importance implications with respect to the indications for CTO PCI as well as selecting appropriate patients to undergo the procedure.

Visualizing single atom dynamics in heterogeneous catalysis using analytical in situ environmental scanning transmission electron microscopy.

Progress is reported in analytical in situ environmental scanning transmission electron microscopy (ESTEM) for visualizing and analysing in real-time dynamic gas-solid catalyst reactions at the single-atom level under controlled reaction conditions of gas environment and temperature. The recent development of the ESTEM advances the capability of the established ETEM with the detection of fundamental single atoms, and the associated atomic structure of selected solid-state heterogeneous catalysts, in catalytic reactions in their working state. The new data provide improved understanding of dynamic atomic processes and reaction mechanisms, in activity and deactivation, at the fundamental level; and in the chemistry underpinning important technological processes. The benefits of atomic resolution-E(S)TEM to science and technology include new knowledge leading to improved technological processes, reductions in energy requirements and better management of environmental waste. This article is part of a discussion meeting issue 'Dynamic in situ microscopy relating structure and function'.

Influence of gas environment and heating on atomic structures of platinum nanoparticle catalysts for proton-exchange membrane fuel cells.

Atomic-scale relaxations of platinum nanoparticles (Pt NPs) for fuel-cell catalysts are evaluated by spherical-aberration corrected environmental transmission electron microscopy (ETEM) under reference high-vacuum and N2 atmospheres, and then under reactive H2, CO and O2 atmospheres, combined with ex situ durability test using an electrochemical half-cell. In high-vacuum, increasing roughness due to continuous relaxation of surface-adsorbed Pt atoms is quantified in real-space. Under H2 and N2 atmospheres at a critical partial pressure of 1 × 10-2 Pa the stability of the surface facets is for the first time found to be improved. The adsorption behaviour of CO molecules is investigated using experimentally measured Pt-Pt bond lengths on the topmost surface layer of Pt NPs. The deactivation of Pt NPs in the anode environment of a proton-exchange-membrane fuel-cell is demonstrated at the atomic-scale in the ETEM, and the transformation of NPs into disordered nanoclusters is systematically quantified using the partial size distribution of Pt atomic clusters under controlled heating experiments at 423, 573 and 723 K.

Indications for Percutaneous Coronary Intervention (PCI) in Chronic Total Occlusion (CTO): Have We Reached a DECISION or Do We Continue to EXPLORE After EURO-CTO?

A coronary chronic total occlusion (CTO) is a common finding during coronary angiography and is associated with increased mortality and poorer cardiovascular prognosis. Technological developments in percutaneous strategies for revascularisation have resulted in increased interest in this area. However, until recently, there has been a paucity of robust scientific randomised data comparing the efficacy of medical management with percutaneous strategies. Both observational data, and to a lesser extent, randomised data, suggest that CTO percutaneous coronary intervention (PCI) should be considered in symptomatic patients. However, in the absence of any randomised data, CTO PCI should not be performed for prognostic benefit. Ongoing trials are needed to confirm these findings as well as to identify the optimal timing and strategy of such interventions.

Visualizing the Cu/Cu2(O) Interface Transition in Nanoparticles with Environmental Scanning Transmission Electron Microscopy.

Understanding the oxidation and reduction mechanisms of catalytically active transition metal nanoparticles is important to improve their application in a variety of chemical processes. In nanocatalysis the nanoparticles can undergo oxidation or reduction in situ, and thus the redox species are not what are observed before and after reactions. We have used the novel environmental scanning transmission electron microscope (ESTEM) with 0.1 nm resolution in systematic studies of complex dynamic oxidation and reduction mechanisms of copper nanoparticles. The oxidation of copper has previously been reported to be dependent on its crystallography and its interaction with the substrate. By following the dynamic oxidation process in situ in real time with high-angle annular dark-field imaging in the ESTEM, we use conditions ideal to track the oxidation front as it progresses across a copper nanoparticle by following the changes in the atomic number (Z) contrast with time. The oxidation occurs via the nucleation of the oxide phase (Cu2O) from one area of the nanoparticle which then progresses unidirectionally across the particle, with the Cu-to-Cu2O interface having a relationship of Cu{111}//Cu2O{111}. The oxidation kinetics are related to the temperature and oxygen pressure. When the process is reversed in hydrogen, the reduction process is observed to be similar to the oxidation, with the same crystallographic relationship between the two phases. The dynamic observations provide unique insights into redox mechanisms which are important to understanding and controlling the oxidation and reduction of copper-based nanoparticles.

Routine aspiration thrombectomy improves the diagnosis and management of embolic myocardial infarction.

OBJECTIVES: Assess the effect of aspiration thrombectomy on diagnosis and management of embolic acute myocardial infarction. BACKGROUND: Discrimination of embolic acute myocardial infarction from atherosclerotic plaque rupture/erosion prompts oral anticoagulation treatment of source of embolus, as well as avoiding unnecessary stenting and dual antiplatelet therapy. However, detection is difficult without aspiration. METHODS: We compared rates of diagnosis of embolic infarction for 2.5 years prior to (pre-RAT) and 2.5 years post routine aspiration thrombectomy (post-RAT). Baseline demographics, outcomes, and treatment strategies were also compared between the embolic infarction and atherosclerotic infarction. RESULTS: Diagnosed embolic infarction rose from 1.2% in the pre-RAT era to 2.8% in the post-RAT period (P < 0.05). In addition, more successful removal of thrombus by aspiration led to less stenting (20% vs. 55% P < 0.05) in the post-RAT period thus avoiding the hazards of "triple therapy." Embolic infarction was more frequently associated with atrial fibrillation (55% vs. 8%), had higher mortality (17% vs. 4%), and had higher rates of embolic stroke (13% vs. 0.3%) when compared with atherosclerotic MI (all P < 0.05). CONCLUSIONS: Routine aspiration thrombectomy more readily identifies embolic infarction allowing more specific therapy and avoidance of stenting and triple anticoagulant therapy.

Dynamic wet-ETEM observation of Pt/C electrode catalysts in a moisturized cathode atmosphere.

The gas injection line of the latest spherical aberration-corrected environmental transmission electron microscope has been modified for achieving real-time/atomic-scale observations in moisturised gas atmospheres for the first time. The newly developed Wet-TEM system is applied to platinum carbon electrode catalysts to investigate the effect of water molecules on the platinum/carbon interface during deactivation processes such as sintering and corrosion. Dynamic in situ movies obtained in dry and 24% moisturised nitrogen environments visualize the rapid rotation, migration and agglomeration of platinum nanoparticles due to the physical adsorption of water and the hydroxylation of the carbon surface. The origin of the long-interconnected aggregation of platinum nanoparticles was discovered to be a major deactivation process in addition to conventional carbon corrosion.

Endothelial progenitor cells for diabetic cardiac and kidney disease.

The management of diabetes mellitus and its resultant end organ dysfunction represents a major challenge to global health-care systems. Diabetic cardiac and kidney disease commonly co-occur and are significant contributors to the morbidity and mortality of patients with diabetes, carrying a poor prognosis. The tight link of these parallel end organ manifestations suggests a deeper common underlying pathology. Here, we outline the mechanistic link between diabetic cardiac and kidney disease, providing evidence for the role of endothelial dysfunction in both processes and the potential for cellular therapy to correct these disorders. Specifically, we review the preclinical and clinical evidence for endothelial progenitor cell therapy in cardiac, kidney, and cardio-renal disease applications. Finally, we outline novel approaches to endothelial progenitor cell therapy through cell enhancement and the use of extracellular vesicles, discussing published and future work.

Canadian Cardiovascular Society Clinical Practice Update on Contemporary Management of the Patient with Hypertrophic Cardiomyopathy.

Numerous guidelines on the diagnosis and management of hypertrophic cardiomyopathy (HCM) have been published, by learned societies, over the last decade. While helpful they are often long and less adapted to non-experts. This writing panel was challenged to produce a document that grew as much from years of practical experience as it did from the peer-reviewed literature. As such, rather than produce yet another set of guidelines, we aim here to deliver a concentrate of our own experiential learning and distil for the reader the essence of effective and appropriate HCM care. This Clinical Practice Update on HCM is therefore aimed at general cardiologists and other cardiovascular practitioners rather than for HCM specialists. We set the stage with a description of the condition and its clinical presentation; discuss the central importance of 'obstruction' and how to look for it; review the role of cardiac magnetic resonance imaging; reflect on the appropriate use of genetic testing; review the treatment options for symptomatic HCM - crucially including cardiac myosin inhibitors; and deal concisely with practical issues surrounding risk assessment for sudden cardiac death, and management of the end-stage HCM patient. Uniquely, we have captured the pediatric experience on our panel to discuss appropriate differences in the management of younger patients with HCM. We ask the reader to remember that this document represents expert consensus opinion rather than dogma and to use their best judgement when dealing with the HCM patient in front of them.

Strength in numbers: growth of Canadian clinician investigator training in the 21st century.

PURPOSE: Enhancing clinician-investigator (CI) training at Canadian medical schools is urgently needed to bolster the dwindling work force of medical professionals carrying out patient-oriented research in a wide array of medical fields. The purpose of this study is to obtain, from the 15 Canadian medical schools that offer one or more CI training programs, data on the number of trainees, funding levels, attrition rates or other important metrics to evaluate the outcomes of such training efforts. METHODS: All Canadian CI programs were surveyed to collect demographic information for the academic year 2010-2011 and compared this to historical data collected by the Association of Faculties of Medicine of Canada (AFMC) and MD/PhD program funding data from the Canadian Institutes of Health Research (CIHR). RESULTS: Over the past decade, enrolment in Canadian CI training programs has increased approximately four-fold. Program-specific funding (CIHR) has also increased, but nearly 50% of MD/PhD trainees are still not supported through dedicated CIHR funding. CONCLUSION: It is too early to know to what extent this increase in both CI and funding will sustain the workforce of Canadian researchers carrying out patient-oriented research. Monitoring of CI training demographics across Canada, beyond this baseline study, will be essential to measure outcomes from CI training programs and to guide response from funding bodies and policy-makers.

Nitric oxide synthase gene transfer restores activity of circulating angiogenic cells from patients with coronary artery disease.

Circulating angiogenic cells (CACs), represent a potential new therapeutic tool for the treatment of cardiovascular diseases, but their regenerative function is impaired in patients with coronary artery disease (CAD) and cardiac risk factors. The objective of this study is to assess the effect of lentiviral overexpression of endothelial nitric oxide synthase (eNOS) on the activity of CACs from patients with CAD and cardiac risk factors. In vitro and in vivo assays were employed to evaluate the regenerative capacity of the cells compared to CACs derived from healthy volunteers. Lentiviral eNOS transduction of cells from CAD patients significantly improved chemotactic migration compared with sham transduction, and increased the ability of CACs to induce angiogenic tube formation when cocultured with human umbilical vein endothelial cells (HUVECs) on Matrigel. In addition, eNOS transduction restored the ability of patient-derived CACs to enhance neovascularization and improve ischemic hind limb perfusion, approaching the efficacy of cells from healthy donors. These data indicate that CAC dysfunction seen in high-risk patients can be partially reversed by eNOS overexpression, suggesting that ex vivo gene delivery may improve the efficacy of autologous cell therapy for cardiovascular disease.

Long-term tracking of bone marrow progenitor cells following intracoronary injection post-myocardial infarction in swine using MRI.

Magnetic resonance imaging (MRI) can track progenitor cells following direct intramyocardial injection. However, in the vast majority of post-myocardial infarction (MI) clinical trials, cells are delivered by the intracoronary (IC) route, which results in far greater dispersion within the myocardium. Therefore, we assessed whether the more diffuse distribution of cells following IC delivery could be imaged longitudinally with MRI. In 11 pigs (7 active, 4 controls), MI was induced by 90-min balloon occlusion of the left anterior descending coronary artery. Seven (0) days [median (interquartile range)] following MI, bone marrow progenitor cells (BMCs) were colabeled with an iron-fluorophore and a cell viability marker and delivered to the left anterior descending coronary artery distal to an inflated over-the-wire percutaneous transluminal coronary angioplasty balloon. T2*-weighted images were used to assess the location of the magnetically labeled cells over a 6-wk period post-MI. Immediately following cell delivery, hypointensity characteristic of the magnetic label was observed in the infarct border rather than within the infarct itself. At 6 wk, the cell signal hypointensity persisted, albeit with significantly decreased intensity. BMC delivery resulted in significant improvement in infarct volume and ejection fraction (EF): infarct volume in cell-treated animals decreased from 7.1 +/- 1.5 to 4.9 +/- 1.0 ml (P < 0.01); infarct volume in controls was virtually unchanged at 4.64 +/- 2.1 to 4.39 +/- 2.1 ml (P = 0.7). EF in cell-treated animals went from 30.4 +/- 5.2% preinjection to 34.5 +/- 2.5% 6 wk postinjection (P = 0.013); EF in control animals went from 34.3 +/- 4.7 to 31.9 +/- 6.8% (P = 0.5). Immunohistochemical analysis revealed intracellular colocalization of the iron fluorophore and cell viability dye with the labeled cells continuing to express the same surface markers as at baseline. MRI can track the persistence and distribution of magnetically labeled BMCs over a 6-wk period following IC delivery. Signal hypointensity declines with time, particularly in the first week following delivery. These cells maintain their original phenotype during this time course. Delivery of these cells appears safe and results in improvement in infarct size and left ventricular ejection fraction.

Rationale and design of Enhanced Angiogenic Cell Therapy in Acute Myocardial Infarction (ENACT-AMI): the first randomized placebo-controlled trial of enhanced progenitor cell therapy for acute myocardial infarction.

BACKGROUND: Despite the widespread use of pharmacological and/or interventional reperfusion therapies, recovery of cardiac function in myocardial infarction (MI) patients is often modest or even absent. Unlike classical pharmacological treatments, the use of progenitor cells could potentially restore functional tissue in regions that otherwise would form only scar. However, a major limitation of autologous cell therapy is the deleterious influence of age and cardiac risk factors on progenitor cell activity. TRIAL DESIGN: The ENACT-AMI trial is a phase IIb, double-blind, randomized placebo-controlled trial, using transplantation of autologous early endothelial progenitor cells (EPCs) for patients who have suffered large MI. Circulating mononuclear cells (MNCs) are obtained by apheresis and subjected to differential culture for 3 days to select a population of highly regenerative, endothelial-like, culture modified MNCs (E-CMMs), often referred to as "early EPCs." A total of 99 patients will be randomized to placebo (Plasma-Lyte A), autologous E-CMMs, or E-CMMs transfected with human endothelial nitric oxide synthase delivered by coronary injection into the infarct-related artery. The primary efficacy end point is change from baseline to 6 months in global left ventricular ejection fraction by cardiac MRI; secondary endpoints include regional wall motion, wall thickening, infarct volume, time to clinical worsening, and quality of life. CONCLUSIONS: This will be the first clinical trial to include a strategy designed to enhance the function of autologous progenitor cells by overexpressing endothelial nitric oxide synthase, and the first to use combination gene and cell therapy for the treatment of cardiac disease.

Insulin increases reendothelialization and inhibits cell migration and neointimal growth after arterial injury.

OBJECTIVE: Insulin has both growth-promoting and protective vascular effects in vitro, however the predominant effect in vivo is unclear. We investigated the effects of insulin in vivo on neointimal growth after arterial injury. METHODS AND RESULTS: Rats were given subcutaneous control (C) or insulin implants (3U/d;I) 3 days before arterial (carotid or aortic) balloon catheter injury. Normoglycemia was maintained by oral glucose and, after surgery, by intraperitoneal glucose infusion (saline in C). Insulin decreased intimal area (P<0.01) but did not change intimal cell proliferation or apoptosis. However, insulin inhibited cell migration into the intima (P<0.01) and increased expression of smooth muscle cell (SMC) differentiation markers (P<0.05). Insulin also increased reendothelialization (P<0.01) and the number of circulating progenitor cells (P<0.05). CONCLUSIONS: These results are the first demonstration that insulin has a protective effect on both SMC and endothelium in vivo, resulting in inhibition of neointimal growth after vessel injury.

Feasibility study of noninvasive ventilation with helium-oxygen gas flow for chronic obstructive pulmonary disease during exercise.

BACKGROUND: Individually, noninvasive ventilation (NIV) and helium-oxygen gas mixtures (heliox) diminish ventilatory workload and improve exercise tolerance in patients with chronic obstructive pulmonary disease (COPD). NIV in combination with heliox may have additive effects on exercise tolerance in severe COPD. METHODS: We assessed the safety, tolerability, and efficacy of heliox and NIV during exercise in patients with severe COPD. SETTING: Pulmonary rehabilitation facility in an academic tertiary-care medical center. PROTOCOL: Twelve patients with severe COPD were enrolled. Using a sequential randomized placebo-controlled crossover study design, the patients performed 4 separate constant-work stationary bicycle cardiopulmonary exercise studies at 80% of maximal workload during application of sham NIV, NIV, 60:40 heliox with sham NIV, and 60:40 heliox with NIV. Tolerability, safety, and exercise duration as determined by constant-work cardiopulmonary exercise test were the primary outcome measures. Secondary outcome measures at peak exercise and iso-time included rate of perceived exertion, dyspnea, leg pain, heart rate, respiratory rate, systolic and diastolic blood pressure, tympanic temperature, and oxyhemoglobin saturation. RESULTS: No adverse effects occurred during or after application of NIV, heliox, or NIV with heliox. Exercise duration using heliox with NIV was significantly longer than both heliox (P = .01) and NIV (P = .007), but not placebo (P = .09). Relative to placebo, all treatment arms permitted lower respiratory rates at peak exercise. Heliox, with or without NIV, was associated with significant improvements in oxyhemoglobin saturation at peak exercise, relative to placebo or NIV alone. CONCLUSIONS: The adjunctive use of NIV with heliox during exercise proved both safe and tolerable in patients with severe COPD. The lack of demonstrable efficacy to any of the treatment arms relative to placebo (P = .09) may be the result of the small sample size (ie, type 2 error)-a conclusion emphasized by the large standard deviations and differences in treatment group variances in exercise duration alone.

Applicability and Interpretation of Coronary Physiology in the Setting of a Chronic Total Occlusion.

Concurrent coronary artery disease in a vessel remote from a chronic total occlusion (CTO) is common and presents a management dilemma. While the use of adjunctive coronary physiology to guide revascularization is now commonplace in the catheterization laboratory, the presence of a CTO provides a unique and specific situation whereby the physiological assessment is more complex and relies on theoretical assumptions. Broadly, the physiological assessment of a CTO relies on assessing the function and regression of collaterals, the assessment of the microcirculation, the impact of collateral steal as well as assessing the severity of a lesion in the donor vessel (the vessel supplying the majority of collaterals to the CTO). Recent studies have shown that physiological assessment of the donor vessel in the setting of a CTO may overestimate the severity of stenosis, and that after revascularization of a CTO, the index of ischemia may increase, potentially altering the need for revascularization. In this review article, we present the current literature on physiological assessment of patients with a CTO, management recommendations and identify areas for ongoing research.

Silent left ventricular apical ballooning and Takotsubo cardiomyopathy in an Australian intensive care unit.

AIMS: Recent reports have shown a high incidence of silent left ventricular apical ballooning (LVAB) in the intensive care unit (ICU) setting with potential implications for safe use of inotropes and vasopressors. We examined the incidence, predictors, and associated outcomes of LVAB in patients in a contemporary tertiary Australian ICU. METHODS AND RESULTS: In a prospective cohort study, patients were screened within 24 h of admission to the ICU and enrolled if they were deemed critically unwell based on mechanical ventilation, administration of >5 mg/min of noradrenaline, or need for renal replacement therapy. Exclusion criteria were a primary diagnosis of Takotsubo cardiomyopathy, admission to ICU after cardiac surgery, or with acute myocardial infarction or heart failure. Echocardiography was performed, and the presence/absence of LVAB was documented. A total of 116 patients were enrolled of whom four had LVAB (3.5%, 95% confidence interval 0.9-8.6%). Female sex was the only baseline demographic or clinical characteristic associated with incident LVAB. Medical history, ICU admission indication, and choice of inotropes were not associated with increased risk. Patients with LVAB had no deaths and had similar lengths of ICU and hospital stay compared with patients with no LVAB. CONCLUSIONS: The incidence of silent LVAB suggestive of TC was substantially lower in this study than recently reported in other international ICU settings. We did not observe a suggestion of worse outcomes. A larger, multi-centre study, prospectively screening for LVAB may help understand any variation between centres and regions, with important implications for ICU management.