Systematic hand-held echocardiography in patients hospitalised with acute coronary syndrome.

AIMS: Transthoracic echocardiography is recommended in all patients with acute coronary syndrome but is time-consuming and lacks an evidence base. We aimed to assess the feasibility, diagnostic accuracy and time-efficiency of hand-held echocardiography in patients with acute coronary syndrome and describe the impact of echocardiography on clinical management in this setting. METHODS AND RESULTS: Patients with acute coronary syndrome underwent both hand-held and transthoracic echocardiography with agreement between key imaging parameters assessed using kappa statistics. The immediate clinical impact of hand-held echocardiography in this population was systematically evaluated.Overall, 262 patients (65±12 years, 71% male) participated. Agreement between hand-held and transthoracic echocardiography was good-to-excellent (kappa 0.60-1.00) with hand-held echocardiography having an overall negative predictive value of 95%. Hand-held echocardiography was performed rapidly (7.7±1.6 min) and completed a median of 5 [interquartile range 3-20] hours earlier than transthoracic echocardiography. Systematic hand-held echocardiography in all patients with acute coronary syndrome identified an important cardiac abnormality in 50% and the clinical management plan was changed by echocardiography in 42%. In 85% of cases, hand-held echocardiography was sufficient for patient decision-making and transthoracic echocardiography was no longer deemed necessary. CONCLUSIONS: In patients with acute coronary syndrome, hand-held echocardiography provides comparable results to transthoracic echocardiography, can be more rapidly applied and gives sufficient imaging information for decision-making in the vast majority of patients. Systematic echocardiography has clinical impact in half of patients, supporting the clinical utility of echocardiography in this population, and providing an evidence-base for current guidelines.

First-in-human controlled inhalation of thin graphene oxide nanosheets to study acute cardiorespiratory responses.

Graphene oxide nanomaterials are being developed for wide-ranging applications but are associated with potential safety concerns for human health. We conducted a double-blind randomized controlled study to determine how the inhalation of graphene oxide nanosheets affects acute pulmonary and cardiovascular function. Small and ultrasmall graphene oxide nanosheets at a concentration of 200 µg m-3 or filtered air were inhaled for 2 h by 14 young healthy volunteers in repeated visits. Overall, graphene oxide nanosheet exposure was well tolerated with no adverse effects. Heart rate, blood pressure, lung function and inflammatory markers were unaffected irrespective of graphene oxide particle size. Highly enriched blood proteomics analysis revealed very few differential plasma proteins and thrombus formation was mildly increased in an ex vivo model of arterial injury. Overall, acute inhalation of highly purified and thin nanometre-sized graphene oxide nanosheets was not associated with overt detrimental effects in healthy humans. These findings demonstrate the feasibility of carefully controlled human exposures at a clinical setting for risk assessment of graphene oxide, and lay the foundations for investigating the effects of other two-dimensional nanomaterials in humans. Clinicaltrials.gov ref: NCT03659864.

Plasticity in inhibitory networks improves pattern separation in early olfactory processing.

Distinguishing between nectar and non-nectar odors presents a challenge for animals due to shared compounds in complex mixtures, where changing ratios often signify differences in reward. Changes in nectar production throughout the day and potentially many times within a forager's lifetime add to the complexity. The honeybee olfactory system, containing less than a 1000 of principal neurons in the early olfactory relay, the antennal lobe (AL), must learn to associate diverse volatile blends with rewards. We used a computational network model and live imaging of the honeybee's AL to explore the neural mechanisms and functions of the AL plasticity. Our findings revealed that when trained with a set of rewarded and unrewarded odors, the AL inhibitory network suppresses shared chemical compounds while enhancing responses to distinct compounds. This results in improved pattern separation and a more concise and efficient neural code. Our Ca2+ imaging data support our model's predictions. Furthermore, we applied these contrast enhancement principles to a Graph Convolutional Network (GCN) and found that similar mechanisms could enhance the performance of artificial neural networks. Our model provides insights into how plasticity at the inhibitory network level reshapes coding for efficient learning of complex odors.

Multicenter, Prospective, Randomized Controlled Trial of High-Sensitivity Cardiac Troponin I-Guided Combination Angiotensin Receptor Blockade and Beta-Blocker Therapy to Prevent Anthracycline Cardiotoxicity: The Cardiac CARE Trial.

BACKGROUND: Anthracycline-induced cardiotoxicity has a variable incidence, and the development of left ventricular dysfunction is preceded by elevations in cardiac troponin concentrations. Beta-adrenergic receptor blocker and renin-angiotensin system inhibitor therapies have been associated with modest cardioprotective effects in unselected patients receiving anthracycline chemotherapy. METHODS: In a multicenter, prospective, randomized, open-label, blinded end-point trial, patients with breast cancer and non-Hodgkin lymphoma receiving anthracycline chemotherapy underwent serial high-sensitivity cardiac troponin testing and cardiac magnetic resonance imaging before and 6 months after anthracycline treatment. Patients at high risk of cardiotoxicity (cardiac troponin I concentrations in the upper tertile during chemotherapy) were randomized to standard care plus cardioprotection (combination carvedilol and candesartan therapy) or standard care alone. The primary outcome was adjusted change in left ventricular ejection fraction at 6 months. In low-risk nonrandomized patients with cardiac troponin I concentrations in the lower 2 tertiles, we hypothesized the absence of a 6-month change in left ventricular ejection fraction and tested for equivalence of ±2%. RESULTS: Between October 2017 and June 2021, 175 patients (mean age, 53 years; 87% female; 71% with breast cancer) were recruited. Patients randomized to cardioprotection (n=29) or standard care (n=28) had left ventricular ejection fractions of 69.4±7.4% and 69.1±6.1% at baseline and 65.7±6.6% and 64.9±5.9% 6 months after completion of chemotherapy, respectively. After adjustment for age, pretreatment left ventricular ejection fraction, and planned anthracycline dose, the estimated mean difference in 6-month left ventricular ejection fraction between the cardioprotection and standard care groups was -0.37% (95% CI, -3.59% to 2.85%; P=0.82). In low-risk nonrandomized patients, baseline and 6-month left ventricular ejection fractions were 69.3±5.7% and 66.4±6.3%, respectively: estimated mean difference, 2.87% (95% CI, 1.63%-4.10%; P=0.92, not equivalent). CONCLUSIONS: Combination candesartan and carvedilol therapy had no demonstrable cardioprotective effect in patients receiving anthracycline-based chemotherapy with high-risk on-treatment cardiac troponin I concentrations. Low-risk nonrandomized patients had similar declines in left ventricular ejection fraction, bringing into question the utility of routine cardiac troponin monitoring. Furthermore, the modest declines in left ventricular ejection fraction suggest that the value and clinical impact of early cardioprotection therapy need to be better defined in patients receiving high-dose anthracycline. REGISTRATION: URL: https://doi.org; Unique identifier: 10.1186/ISRCTN24439460. URL: https://www.clinicaltrialsregister.eu/ctr-search/search; Unique identifier: 2017-000896-99.

Women in cardiovascular imaging: a call for action to address ongoing challenges.

AIMS: The EACVI Scientific Initiatives Committee and the EACVI women's taskforce conducted a global survey to evaluate the barriers faced by women in cardiovascular imaging (WICVi). METHODS AND RESULTS: In a prospective international survey, we assessed the barriers faced at work by WICVi. Three hundred fourteen participants from 53 countries responded. The majority were married (77%) and had children (68%), but most reported no flexibility in their work schedule during their pregnancy or after their maternity leave. More than half of the women reported experiencing unconscious bias (68%), verbal harassment (59%), conscious bias (51%), anxiety (70%), lack of motivation (60%), imposter syndrome (54%), and burnout (61%) at work. Furthermore, one in five respondents had experienced sexual harassment, although this was rarely reported formally. The majority reported availability of mentorship (73%), which was mostly rated as 'good' or 'very good'. While more than two-thirds of respondents (69%) now reported being well trained and qualified to take on leadership roles in their departments, only one-third had been afforded that opportunity. Despite the issues highlighted by this survey, >80% of the participating WICVi would still choose cardiovascular imaging if they could restart their career. CONCLUSION: The survey has highlighted important issues faced by WICVi. While progress has been made in areas such as mentorship and training, other issues including bullying, bias, and sexual harassment are still widely prevalent requiring urgent action by the global cardiovascular imaging community to collectively address and resolve these challenges.

Current clinical use of speckle-tracking strain imaging: insights from a worldwide survey from the European Association of Cardiovascular Imaging (EACVI).

AIMS: Speckle-tracking echocardiography (STE) strain imaging has been a major advancement in myocardial function quantification. We aimed to explore current worldwide clinical application of STE. METHODS AND RESULTS: Access, feasibility, access, and clinical implementation of STE were investigated with a worldwide open-access online survey of the European Association of Cardiovascular Imaging. Participants (429 respondents and 77 countries) from tertiary centres (46%), private clinics, or public hospitals (54%) using different vendors for data acquisition and analysis were represented. Despite almost universal access (98%) to STE, only 39% of the participants performed and reported STE results frequently (>50%). Incomplete training and time constraints were the main reasons for not using STE more regularly. STE was mainly used to assess the LV (99%) and less frequently the right ventricular (57%) and the left atrial (46%) function. Cardiotoxicity (88%) and cardiac amyloidosis (87%) were the most frequent reasons for the clinical use of LV STE. Left atrial STE was used most frequently for the diagnosis of diastolic dysfunction and right ventricular STE for the assessment of right ventricle (RV) function in pulmonary hypertension (51%). Frequency of STE use, adherence to optimal techniques, and clinical appropriateness of STE differed according to training experience and across vendors. Key suggestions outlined by respondents to increase the clinical use of STE included improved reproducibility (48%) and standardization of strain values across vendors (42%). CONCLUSION: Although STE is now readily available, it is underutilized in the majority of centres. Structured training, improved reproducibility, and inter-vendor standardization may increase its uptake.

Bone Grafting Outcomes in Smokers Undergoing High Tibial Osteotomy: A Systematic Review.

This systematic review summarises the findings in the literature available to show outcomes of high tibial osteotomy (HTO) with bone grafting in smokers. It also studies the trend of complications, outcome measures used and overall outcomes like union, non-union or the need to perform revision surgeries. The aim is to find out if HTO done with bone grafting improves outcomes in smokers. Articles were shortlisted using Population, Intervention, Control, and Outcomes (PICO) search design and quality assessment was completed using Jadad, STROBE (Strengthening the Reporting of Observational studies in Epidemiology), Delphi, and Critical Appraisal Skills Program (CASP) followed by data extraction by two independent authors. There was union in 97.6% of smokers who received HTO with bone grafting. A case of non-union was treated with removal of metalwork and distraction osteogenesis. Three cases of unknown demographics had arthroplasty in the time frame from HTO with bone grafting to follow up. The commonest complication post surgery was metalwork causing soft tissue irritation and lateral proximal tibial cortex fracture. Following this review we can conclude that HTO with bone grafting could be considered as an option to achieve better outcomes in smokers. Bone grafting helps healing across osteotomy sites in smokers whose healing potential is poor. Autogenous Iliac crest bone grafting is ideal due to its osteoinductive and osteoconductive properties, but has the disadvantage of donor site morbidity.

Non-invasive imaging of functional pancreatic islet beta-cell mass in people with type 1 diabetes mellitus.

AIMS: To investigate whether manganese-enhanced magnetic resonance imaging can assess functional pancreatic beta-cell mass in people with type 1 diabetes mellitus. METHODS: In a prospective case-control study, 20 people with type 1 diabetes mellitus (10 with low (≥50 pmol/L) and 10 with very low (<50 pmol/L) C-peptide concentrations) and 15 healthy volunteers underwent manganese-enhanced magnetic resonance imaging of the pancreas following an oral glucose load. Scan-rescan reproducibility was performed in 10 participants. RESULTS: Mean pancreatic manganese uptake was 31 ± 6 mL/100 g of tissue/min in healthy volunteers (median 32 [interquartile range 23-36] years, 6 women), falling to 23 ± 4 and 13 ± 5 mL/100 g of tissue/min (p ≤ 0.002 for both) in people with type1 diabetes mellitus (52 [44-61] years, 6 women) and low or very low plasma C-peptide concentrations respectively. Pancreatic manganese uptake correlated strongly with plasma C-peptide concentrations in people with type1 diabetes mellitus (r = 0.73, p < 0.001) but not in healthy volunteers (r = -0.054, p = 0.880). There were no statistically significant correlations between manganese uptake and age, body-mass index, or glycated haemoglobin. There was strong intra-observer (mean difference: 0.31 (limits of agreement -1.42 to 2.05) mL/100 g of tissue/min; intra-class correlation, ICC = 0.99), inter-observer (-1.23 (-5.74 to 3.27) mL/100 g of tissue/min; ICC = 0.85) and scan-rescan (-0.72 (-2.9 to 1.6) mL/100 g of tissue/min; ICC = 0.96) agreement for pancreatic manganese uptake. CONCLUSIONS: Manganese-enhanced magnetic resonance imaging provides a potential reproducible non-invasive measure of functional beta-cell mass in people with type 1 diabetes mellitus. This holds major promise for investigating type 1 diabetes, monitoring disease progression and assessing novel immunomodulatory interventions.

Olfactory receptor neurons generate multiple response motifs, increasing coding space dimensionality.

Odorants binding to olfactory receptor neurons (ORNs) trigger bursts of action potentials, providing the brain with its only experience of the olfactory environment. Our recordings made in vivo from locust ORNs showed that odor-elicited firing patterns comprise four distinct response motifs, each defined by a reliable temporal profile. Different odorants could elicit different response motifs from a given ORN, a property we term motif switching. Further, each motif undergoes its own form of sensory adaptation when activated by repeated plume-like odor pulses. A computational model constrained by our recordings revealed that organizing responses into multiple motifs provides substantial benefits for classifying odors and processing complex odor plumes: each motif contributes uniquely to encode the plume's composition and structure. Multiple motifs and motif switching further improve odor classification by expanding coding dimensionality. Our model demonstrated that these response features could provide benefits for olfactory navigation, including determining the distance to an odor source.

Manganese-Enhanced Magnetic Resonance Imaging of the Heart.

Manganese-based contrast media were the first in vivo paramagnetic agents to be used in magnetic resonance imaging (MRI). The uniqueness of manganese lies in its biological function as a calcium channel analog, thus behaving as an intracellular contrast agent. Manganese ions are taken up by voltage-gated calcium channels in viable tissues, such as the liver, pancreas, kidneys, and heart, in response to active calcium-dependent cellular processes. Manganese-enhanced magnetic resonance imaging (MEMRI) has therefore been used as a surrogate marker for cellular calcium handling and interest in its potential clinical applications has recently re-emerged, especially in relation to assessing cellular viability and myocardial function. Calcium homeostasis is central to myocardial contraction and dysfunction of myocardial calcium handling is present in various cardiac pathologies. Recent studies have demonstrated that MEMRI can detect the presence of abnormal myocardial calcium handling in patients with myocardial infarction, providing clear demarcation between the infarcted and viable myocardium. Furthermore, it can provide more subtle assessments of abnormal myocardial calcium handling in patients with cardiomyopathies and being excluded from areas of nonviable cardiomyocytes and severe fibrosis. As such, MEMRI offers exciting potential to improve cardiac diagnoses and provide a noninvasive measure of myocardial function and contractility. This could be an invaluable tool for the assessment of both ischemic and nonischemic cardiomyopathies as well as providing a measure of functional myocardial recovery, an accurate prediction of disease progression and a method of monitoring treatment response. EVIDENCE LEVEL: 5: TECHNICAL EFFICACY: STAGE 5.

Manganese-Enhanced Magnetic Resonance Imaging in Takotsubo Syndrome.

BACKGROUND: Takotsubo syndrome is an acute cardiac emergency characterized by transient left ventricular systolic dysfunction typically following a stressful event. Despite its rapidly rising incidence, its pathophysiology remains poorly understood. Takotsubo syndrome may pass unrecognized, especially if timely diagnostic imaging is not performed. Defective myocardial calcium homeostasis is a central cause of contractile dysfunction and has not been explored in takotsubo syndrome. We aimed to investigate myocardial calcium handling using manganese-enhanced magnetic resonance imaging during the acute and recovery phases of takotsubo syndrome. METHODS: Twenty patients with takotsubo syndrome (63±12 years of age; 90% female) and 20 volunteers matched on age, sex, and cardiovascular risk factors (59±11 years of age; 70% female) were recruited from the Edinburgh Heart Centre between March 2020 and October 2021. Patients underwent gadolinium and manganese-enhanced magnetic resonance imaging during index hospitalization with repeat manganese-enhanced magnetic resonance imaging performed after at least 3 months. RESULTS: Compared with matched control volunteers, patients had a reduced left ventricular ejection fraction (51±11 versus 67±8%; P<0.001), increased left ventricular mass (86±11 versus 57±14 g/m2; P<0.001), and, in affected myocardial segments, elevated native T1 (1358±49 versus 1211±28 ms; P<0.001) and T2 (60±7 versus 38±3 ms; P<0.0001) values at their index presentation. During manganese-enhanced imaging, kinetic modeling demonstrated a substantial reduction in myocardial manganese uptake (5.1±0.5 versus 8.2±1.1 mL/[100 g of tissue ·min], respectively; P<0.0001), consistent with markedly abnormal myocardial calcium handling. After recovery, left ejection fraction, left ventricular mass, and T2 values were comparable with those of matched control volunteers. Despite this, native and postmanganese T1 and myocardial manganese uptake remained abnormal compared with matched control volunteers (6.6±0.5 versus 8.2±1.1 mL/[100 g of tissue ·min]; P<0.0001). CONCLUSIONS: In patients with takotsubo syndrome, there is a profound perturbation of myocardial manganese uptake, which is most marked in the acute phase but persists for at least 3 months despite apparent restoration of normal left ventricular ejection fraction and resolution of myocardial edema, suggesting abnormal myocardial calcium handling may be implicated in the pathophysiology of takotsubo syndrome. Manganese-enhanced magnetic resonance imaging has major potential to assist in the diagnosis, characterization, and risk stratification of patients with takotsubo syndrome. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04623788.

EACVI survey on the multi-modality imaging assessment of the right heart.

AIMS: The European Association of Cardiovascular Imaging (EACVI) Scientific Initiatives Committee performed a global survey to evaluate the use of different cardiac imaging modalities for the evaluation of the right heart. METHODS AND RESULTS: Delegates from 250 EACVI registered centres were invited to participate in a survey which was also advertised on the EACVI bulletin and on social media. One hundred and thirty-eight respondents from 46 countries across the world responded to the survey. Most respondents worked in tertiary centres (79%) and echocardiography was reported as the commonest imaging modality used to assess the right ventricle (RV). The majority of survey participants (78%) included RV size and function in >90% of their echocardiographic reports. The RV basal diameter obtained from the apical four-chamber view and the tricuspid annular plane systolic excursion were the commonest parameters used for the echocardiographic assessment of RV size and function as reported by 82 and 97% respondents, respectively. Survey participants reported arrhythmogenic cardiomyopathy as the commonest condition (88%) where cardiac magentic resonance (CMR) imaging was used for right heart assessment. Only 52% respondents included RV volumetric and ejection fraction assessments routinely in their CMR reports, while 30% of respondents included these parameters only when RV pathology was suspected. Finally, 73% of the respondents reported pulmonary hypertension as the commonest condition where right heart catheterization was performed. CONCLUSION: Echocardiography remains the most frequently used imaging modality for the evaluation of the right heart, while the use of other imaging techniques, most notably CMR, is increasing.

Thoracic Aortic 18F-Sodium Fluoride Activity and Ischemic Stroke in Patients With Established Cardiovascular Disease.

BACKGROUND: Aortic atherosclerosis represents an important contributor to ischemic stroke risk. Identifying patients with high-risk aortic atheroma could improve preventative treatment strategies for future ischemic stroke. OBJECTIVES: The purpose of this study was to investigate whether thoracic 18F-sodium fluoride positron emission tomography (PET) could improve the identification of patients at the highest risk of ischemic stroke. METHODS: In a post hoc observational cohort study, we quantified thoracic aortic and coronary 18F-sodium fluoride activity in 461 patients with stable cardiovascular disease undergoing PET combined with computed tomography (CT). Progression of atherosclerosis was assessed by change in aortic and coronary CT calcium volume. Clinical outcomes were determined by the occurrence of ischemic stroke and myocardial infarction. We compared the prognostic utility of 18F-sodium fluoride activity for predicting stroke to clinical risk scores and CT calcium quantification using survival analysis and multivariable Cox regression. RESULTS: After 12.7 ± 2.7 months, progression of thoracic aortic calcium volume correlated with baseline thoracic aortic 18F-sodium fluoride activity (n = 140; r = 0.31; P = 0.00016). In 461 patients, 23 (5%) patients experienced an ischemic stroke and 32 (7%) a myocardial infarction after 6.1 ± 2.3 years of follow-up. High thoracic aortic 18F-sodium fluoride activity was strongly associated with ischemic stroke (HR: 10.3 [95% CI: 3.1-34.8]; P = 0.00017), but not myocardial infarction (P = 0.40). Conversely, high coronary 18F-sodium fluoride activity was associated with myocardial infarction (HR: 4.8 [95% CI: 1.9-12.2]; P = 0.00095) but not ischemic stroke (P = 0.39). In a multivariable Cox regression model including imaging and clinical risk factors, thoracic aortic 18F-sodium fluoride activity was the only variable associated with ischemic stroke (HR: 8.19 [95% CI: 2.33-28.7], P = 0.0010). CONCLUSIONS: In patients with established cardiovascular disease, thoracic aortic 18F-sodium fluoride activity is associated with the progression of atherosclerosis and future ischemic stroke. Arterial 18F-sodium fluoride activity identifies localized areas of atherosclerotic disease activity that are directly linked to disease progression and downstream regional clinical atherothrombotic events. (DIAMOND-Dual Antiplatelet Therapy to Reduce Myocardial Injury [DIAMOND], NCT02110303; Study Investigating the Effect of Drugs Used to Treat Osteoporosis on the Progression of Calcific Aortic Stenosis [SALTIRE II], NCT02132026; Novel Imaging Approaches To Identify Unstable Coronary Plaques, NCT01749254; and Role of Active Valvular Calcification and Inflammation in Patients With Aortic Stenosis, NCT01358513).

EACVI survey on burnout amongst cardiac imaging specialists during the 2019 coronavirus disease pandemic.

AIMS: The European Association of Cardiovascular Imaging Scientific Initiatives Committee conducted a global survey to evaluate the impact of the 2019 coronavirus disease (COVID-19) pandemic on the mental well-being of cardiac imaging specialists. METHODS AND RESULTS: In a prospective international survey performed between 23 July 2021 and 31 August 2021, we assessed the mental well-being of cardiac imaging specialists ∼18 months into the COVID-19 pandemic. One-hundred-and-twenty-five cardiac imaging specialists from 34 countries responded to the survey. More than half described feeling anxious during the pandemic, 34% felt melancholic, 27% felt fearful, and 23% respondents felt lonely. A quarter of respondents had increased their alcohol intake and more than half reported difficulties in sleeping. Two-thirds of respondents described worsening features of burnout during the past 18 months, 44% considered quitting their job. One in twenty respondents had experienced suicidal ideation during the pandemic. Despite these important issues, the majority of participants (57%) reported having no access to any formal mental health support at work. CONCLUSION: The survey has highlighted important issues regarding the mental well-being of cardiac imaging specialists during the COVID-19 pandemic. This is a major issue in our sub-specialty, which requires urgent action and prioritization so that we can improve the mental health of cardiovascular imaging specialists.

Air pollution and cardiovascular disease: the Paul Wood Lecture, British Cardiovascular Society 2021.

Air pollution is associated with up to 8.8 million excess deaths worldwide each year and is a major contributor to the global burden of disease. Cardiovascular conditions are the predominant cause for air pollution-related deaths and there is an urgent need to address the silent pandemic of air pollution on cardiovascular health. Air pollution exposure is associated with acute events like acute coronary syndrome and stroke, and with chronic conditions, such as atherosclerosis and heart failure. Several potential mechanisms have been proposed that link particle inhalation to cardiovascular disease including oxidative stress and inflammation, changes in autonomic balance and neuroendocrine regulation and the particle translocation into the circulation itself. This, in turn, can cause endothelial, vasomotor and fibrinolytic dysfunction and increased thrombogenicity and blood pressure which are implicated in the mediation of adverse cardiovascular events. Certain interventions can help mitigate these adverse effects. At an individual level, this includes the use of a facemask and indoor air purification systems. At an environmental level, interventions reducing the generation or release of combustion-derived pollutants are key and include public health policies to facilitate active transport, cleaner sources of energy and reductions in vehicular and fossil fuel emissions. In this review, we summarise the key pathways and mechanisms that draw together how air pollution can lead to adverse cardiovascular effects, as well as explore potential interventions to reduce the burden of air pollution-induced cardiovascular morbidity and mortality.

MRI and CT coronary angiography in survivors of COVID-19.

OBJECTIVES: To determine the contribution of comorbidities on the reported widespread myocardial abnormalities in patients with recent COVID-19. METHODS: In a prospective two-centre observational study, patients hospitalised with confirmed COVID-19 underwent gadolinium and manganese-enhanced MRI and CT coronary angiography (CTCA). They were compared with healthy and comorbidity-matched volunteers after blinded analysis. RESULTS: In 52 patients (median age: 54 (IQR 51-57) years, 39 males) who recovered from COVID-19, one-third (n=15, 29%) were admitted to intensive care and a fifth (n=11, 21%) were ventilated. Twenty-three patients underwent CTCA, with one-third having underlying coronary artery disease (n=8, 35%). Compared with younger healthy volunteers (n=10), patients demonstrated reduced left (ejection fraction (EF): 57.4±11.1 (95% CI 54.0 to 60.1) versus 66.3±5 (95 CI 62.4 to 69.8)%; p=0.02) and right (EF: 51.7±9.1 (95% CI 53.9 to 60.1) vs 60.5±4.9 (95% CI 57.1 to 63.2)%; p≤0.0001) ventricular systolic function with elevated native T1 values (1225±46 (95% CI 1205 to 1240) vs 1197±30 (95% CI 1178 to 1216) ms;p=0.04) and extracellular volume fraction (ECV) (31±4 (95% CI 29.6 to 32.1) vs 24±3 (95% CI 22.4 to 26.4)%; p<0.0003) but reduced myocardial manganese uptake (6.9±0.9 (95% CI 6.5 to 7.3) vs 7.9±1.2 (95% CI 7.4 to 8.5) mL/100 g/min; p=0.01). Compared with comorbidity-matched volunteers (n=26), patients had preserved left ventricular function but reduced right ventricular systolic function (EF: 51.7±9.1 (95% CI 53.9 to 60.1) vs 59.3±4.9 (95% CI 51.0 to 66.5)%; p=0.0005) with comparable native T1 values (1225±46 (95% CI 1205 to 1240) vs 1227±51 (95% CI 1208 to 1246) ms; p=0.99), ECV (31±4 (95% CI 29.6 to 32.1) vs 29±5 (95% CI 27.0 to 31.2)%; p=0.35), presence of late gadolinium enhancement and manganese uptake. These findings remained irrespective of COVID-19 disease severity, presence of myocardial injury or ongoing symptoms. CONCLUSIONS: Patients demonstrate right but not left ventricular dysfunction. Previous reports of left ventricular myocardial abnormalities following COVID-19 may reflect pre-existing comorbidities. TRIAL REGISTRATION NUMBER: NCT04625075.

Implementation of an early rule-out pathway for myocardial infarction using a high-sensitivity cardiac troponin T assay.

OBJECTIVES: Patients with suspected acute coronary syndrome and high-sensitivity cardiac troponin (hs-cTn) concentrations below the limit of detection at presentation are low risk. We aim to determine whether implementing this approach facilitates the safe early discharge of patients. METHODS: In a prospective single-centre cohort study, consecutive patients with suspected acute coronary syndrome were included before (standard care) and after (intervention) implementation of an early rule-out pathway. During standard care, myocardial infarction was ruled out if hs-cTnT concentrations were <99th centile (14 ng/L) at presentation and at 6-12 hours after symptom onset. In the intervention, patients were ruled out if hs-cTnT concentrations were <5 ng/L at presentation and symptoms present for ≥3 hours or were ≥5 ng/L and unchanged within the reference range at 3 hours. We compared duration of stay (efficacy) and all-cause death at 1 year (safety) before and after implementation. RESULTS: We included 10 315 consecutive patients (64±16 years, 46% women) with 6642 (64%) and 3673 (36%) in the standard care and intervention groups, respectively. Duration of stay was reduced from 534 (IQR, 220-2279) to 390 (IQR, 218-1910) min (p<0.001) after implementation. At 1 year, all-cause death occurred in 10.9% (721 of 6642) and 10.4% (381 of 3673) of patients in the standard care group (referent) and intervention group, respectively (adjusted OR 1.02, 95% CI 0.88 to 1.18). CONCLUSION: In patients with suspected acute coronary syndrome, implementing an early rule-out pathway using hs-cTnT concentrations <5 ng/L at presentation reduced the duration of stay in hospital without compromising safety.

The Role of SGLT2 Inhibitors in Heart Failure: A Systematic Review and Meta-Analysis.

AIMS: Recent randomised controlled trials (RCTs) have shown a significant prognostic benefit of sodium-glucose cotransporter 2 (SGLT2) inhibitors in the cardiovascular (CV) profile of patients with diabetes. This systematic review and meta-analysis aim to provide a concise evaluation of all the available evidence for the use of these agents in patients with heart failure (HF) regardless of their baseline diabetes status. METHODS AND RESULTS: PubMed, Web of Science, and Cochrane library databases were systematically searched from inception until November 20th 2020. Eight studies consisting of 13,275 patients were included in the meta-analysis. For the total population, SGLT2 inhibitors reduced the risk of all-cause mortality (HR: 0.83; 95% CI: 0.75-0.91; I 2 0%), hospitalisation for HF (HR: 0.68; 95% CI: 0.61-0.75; I 2: 0%), CV death (HR: 0.82; 95% CI: 0.74-0.92; I 2: 0%), and hospitalisation for HF or CV death (HR: 0.72; 95% CI: 0.66-0.78; I 2: 0%). Subgroup analyses of the total population according to the diabetes status showed that SGLT2 inhibitors significantly reduced the risk of hospitalisation for HF (HR: 0.68; 95% CI: 0.61, 0.75; I 2: 0%), as well as the risk of hospitalisation for HF or CV death (HR: 0.72; 95% CI: 0.66, 078; I 2: 0%) and CV death (HR: 0.82; 95% CI: 0.74, 0.91; I 2: 0%). CONCLUSIONS: The results of this meta-analysis confirm the growing evidence in the literature of the favourable profile of SGLT2 inhibitors in cardiovascular outcomes and mortality in patients with heart failure regardless of the baseline diabetes status. This systematic review has been registered with PROSPERO (CRD42021224777).