Search

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 2 ; P P P P P 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.

Aims: To investigate whether manganese-enhancedmagnetic resonance imagingcan assess functional pancreatic beta-cellmass in people with type 1 diabetes mellitus.Methods: In a prospective case–controlstudy, 20 people with type 1 diabetesmellitus (10 with low (≥50 pmol/L) and 10 with very low (concentrations) and 15 healthy volunteers underwent manganese-enhancedmagnetic resonance imaging of the pancreas following an oral glucose load. Scan-rescanreproducibility was performed in 10 participants.Results: Mean pancreatic manganese uptake was 31 ± 6 mL/100 g of tissue/minin 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 peoplewith type1 diabetes mellitus (52 [44–61]years, 6 women) and low or very lowplasma C-peptideconcentrations respectively. Pancreatic manganese uptakecorrelated strongly with plasma C-peptideconcentrations in people with type1diabetes 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 manganeseuptake and age, body-massindex, or glycated haemoglobin. There was strongintra-observer(mean difference: 0.31 (limits of agreement −1.42 to 2.05) mL/100 gof tissue/min; intra-classcorrelation, ICC = 0.99), inter-observer(−1.23 (−5.74 to3.27) 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-enhancedmagnetic resonance imaging provides a potentialreproducible non-invasivemeasure of functional beta-cellmass in people with type1 diabetes mellitus. This holds major promise for investigating type 1 diabetes, monitoringdisease progression and assessing novel immunomodulatory interventions.

Takotsubo syndrome is a condition characterized by acute transient left ventricular systolic dysfunction, which at presentation can be challenging to distinguish from acute myocardial infarction. Although previously thought to be a benign, self-limiting condition, recent studies have confirmed that patients with takotsubo syndrome have persistent subtle ongoing cardiac dysfunction, and many continue to have limiting symptoms despite restoration of left ventricular ejection fraction. Moreover, these patients have a substantial burden of morbidity and mortality, as well, with high rates of subsequent major adverse cardiovascular events that approach those of patients with acute coronary syndrome. The mechanisms behind this condition remain elusive. Despite substantial research, the medical community continues to have an incomplete understanding of its underlying pathogenesis and pathophysiology. Catecholamine-induced myocardial injury is the most established and well-known theory, but this does not explain all the clinical features and presentations of the condition, and numerous other pathways and abnormalities are emerging. Because of the poor understanding of its underlying pathophysiology, there is a lack of evidence-based interventions to treat the acute episode, to avoid recurrences, and to prevent major adverse cardiovascular events. This highlights the need for further research to gain a better understanding of the underlying pathophysiology to inform appropriate randomized controlled trials of interventions targeting the causative pathways. Only then can evidence-based management strategies be established to improve clinical outcomes of this potentially lethal condition.

Background The transradial approach (TRA) for endovascular procedures has become a frequent practice in neurointervention. Advantages of the TRA include less access-site complications, early ambulation, and less postprocedural pain. The Rist 079 radial access guide catheter (Medtronic) is the first device designed specifically for neurointerventions performed through the TRA. In this study, we report our initial experience with the Rist catheter in a variety of neurointerventional procedures, aiming to evaluate the performance of this device and discuss its limitations. Methods A prospectively maintained database was retrospectively searched to identify patients who underwent procedures using the Rist catheter. Information on demographics, procedural details, and complications was recorded. Results Seventy-eight patients were included in the study, with a mean age of 60.3 years (range, 25–92 years); 45 (57.7%) were men. The interventional or diagnostic procedure was successfully completed in 77 patients (98.7%). The radial artery was the primary access-site choice in 71 patients (91%). The most frequent type of procedures performed were coiling or stent-assisted coiling (16.7%) and angioplasty and stenting (16.7%), followed by middle meningeal artery embolization (14.1%). Crossover to femoral artery access while maintaining use of the Rist was done in 5 cases (6.4%). Reasons for access or procedural failure included anatomical anomaly of the target vessel, unfavorable geometry of the great vessels, and proximal tortuosity of the supra-aortic vessels. Conclusion We demonstrated a high success rate with use of the Rist catheter system for a variety of procedures.

Myocardial fibrosis is the heart’s common healing response to injury. While initially seeking to optimize the strength of diseased tissue, fibrosis can become maladaptive, producing stiff poorly functioning and pro-arrhythmic myocardium. Different patterns of fibrosis are associated with different myocardial disease states, but the presence and quantity of fibrosis largely confer adverse prognosis. Current imaging techniques can assess the extent and pattern of myocardial scarring, but lack specificity and detect the presence of established fibrosis when the window to modify this process may have ended. For the first time, novel molecular imaging methods, including gallium-68 (68Ga)-fibroblast activation protein inhibitor positron emission tomography (68Ga-FAPI PET), may permit highly specific imaging of fibrosis activity. These approaches may facilitate earlier fibrosis detection, differentiation of active vs. end-stage disease, and assessment of both disease progression and treatment–response thereby improving patient care and clinical outcomes.

BackgroundAnthracycline-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.MethodsIn a multicenter prospective randomized open label blinded endpoint 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 non-randomized patients with cardiac troponin I concentrations in the lower two tertiles, we hypothesised the absence of a 6-month change in left ventricular ejection fraction (±2%).ResultsBetween October 2017 and June 2021, 175 patients (mean age 53 years; 87% female; 71% 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 adjusting for age, pre-treatment left ventricular ejection fraction and planned anthracycline dose, the estimated mean difference in 6-month left ventricular ejection fraction between cardioprotection and standard care groups was -0.37% (95% confidence interval, -3.59 to 2.85%; P=0.82). In low-risk non-randomized 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% confidence interval, 1.63 to 4.10%; P=0.92, not equivalent)ConclusionsCombination 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 non-randomized patients had similar declines in left ventricular ejection fraction questioning 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 needs to be better defined in patients receiving high-dose anthracycline regimes.REGISTRATIONEudraCT 2017-000896-99, ISRCTN24439460Clinical PerspectiveWhat is new?In this randomized controlled trial of patients at high risk of anthracycline cardiotoxicity, combined candesartan and carvedilol therapy did not protect against decline in 6-month left ventricular ejection fraction after completion of chemotherapy.Overall decline in 6-month left ventricular ejection fraction occurred irrespective of changes in cardiac troponin concentration during chemotherapy.What are the clinical implications?The Cardiac CARE trial findings do not support recent guideline recommendations advocating the use of cardiac troponin monitoring and early preventive neurohormonal blockade in patients at risk of anthracycline cardiotoxicity.Future studies should focus on factors determining transition to subsequent development of heart failure from initial mild and asymptomatic changes in cardiac function following anthracycline chemotherapy.

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.

Electrocardiography and high-sensitivity cardiac troponin testing are routinely applied as the initial step for clinical evaluation of patients with suspected non-ST-segment elevation myocardial infarction. Once diagnosed, patients with non-ST-segment elevation myocardial infarction are commenced on antithrombotic and secondary preventative therapies before undergoing invasive coronary angiography to determine the strategy of coronary revascularisation. However, this clinical pathway is imperfect and can lead to challenges in the diagnosis, management, and clinical outcomes of these patients. Computed tomography coronary angiography (CTCA) has increasingly been utilised in the setting of patients with suspected non-ST-segment elevation myocardial infarction, where it has an important role in avoiding unnecessary invasive coronary angiography and reducing downstream non-invasive functional testing for myocardial ischaemia. CTCA is an excellent gatekeeper for the cardiac catheterisation laboratory. In addition, CTCA provides complementary information for patients with myocardial infarction in the absence of obstructive coronary artery disease and highlights alternative or incidental diagnoses for those with cardiac troponin elevation. However, the routine application of CTCA has yet to demonstrate an impact on subsequent major adverse cardiovascular events. There are several ongoing studies evaluating CTCA and its associated technologies that will define and potentially expand its application in patients with suspected or diagnosed non-ST-segment elevation myocardial infarction. We here review the current evidence relating to the clinical application of CTCA in patients with non-ST-segment elevation myocardial infarction and highlight the areas where CTCA is likely to have an increasing important role and impact for our patients.

A closed fifth metacarpal neck fracture is a frequently encountered upper limb fracture that occurs when the bone breaks right below the little finger's knuckle. At the moment, there is no agreement on the best way to treat these fractures. This research seeks to look at the efficacy of buddy taping versus reduction and casting for non-operative management of uncomplicated closed fifth metacarpal neck fractures. A systematic review of PubMed, Medical Literature Analysis and Retrieval System Online (MEDLINE), PubMed Central (PMC), and the Cochrane Library databases was carried out using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to find relevant studies about buddy taping versus reduction and casting for non-operative management. Disabilities of the arm, shoulder, and hand (DASH) score; satisfaction score; visual analog scale (VAS); range of motion (ROM); strength; and other outcomes were reported in this study. We used Review Manager 5.4 (The Cochrane Collaboration, London, UK) for the meta-analysis. Seven trials with a total of 454 patients were considered in the review and four in the quantitative analysis. All the included studies were randomized controlled trials (RCTs). Our study concluded that buddy taping was effective for improving pain, range of motion, and strength. The DASH score and satisfaction score didn't show any significant difference. Thus, we recommend the use of buddy taping rather than plaster and immobilization for the management of uncomplicated closed fifth metacarpal neck fractures.

Patients with type 2 diabetes mellitus are at a higher risk of developing heart failure compared with the healthy population. In recent landmark clinical trials, sodium-glucose co-transporter 2 (SGLT2) inhibitor therapies improve blood glucose control and also reduce cardiovascular events and heart failure hospitalisations in patients with type 2 diabetes. Intriguingly, such clinical benefits have also been seen in patients with heart failure in the absence of type 2 diabetes although the underlying mechanisms are not clearly understood. Potential pathways include improved glycaemic control, diuresis, weight reduction and reduction in blood pressure, but none fully explain the observed improvements in clinical outcomes. More recently, novel mechanisms have been proposed to explain these benefits that include improved cardiomyocyte calcium handling, enhanced myocardial energetics, induced autophagy and reduced epicardial fat. We provide an up-to-date review of cardiac-specific SGLT2 inhibitor–mediated mechanisms and highlight studies currently underway investigating some of the proposed mechanisms of action in cardiovascular health and disease.

Myocardial infarction with non-obstructive coronary arteries (MINOCA) was first described over 80 years ago. The term has been widely and inconsistently used in clinical practice, influencing various aspects of disease classification, investigation and management. MINOCA encompasses a heterogenous group of conditions that include both atherosclerotic and non-atherosclerotic disease resulting in myocardial damage that is not due to obstructive coronary artery disease. In many ways, it is a term that describes a moment in the diagnostic pathway of the patient and is arguably not a diagnosis. Central to the definition is also the distinction between myocardial infarction and injury. The universal definition of myocardial infarction distinguishes acute myocardial infarction, including those with MINOCA, from other causes of myocardial injury by the presence of clinical evidence of ischaemia. However, these ischaemic features are often non-specific causing diagnostic confusion, and can create difficulties for patient management and follow-up. The purpose of this review is to summarise our current understanding of MINOCA and highlight important issues relating to the diagnosis, investigation and management of patients with MINOCA.

Background: Type 2 myocardial infarction is caused by myocardial oxygen supply-demand imbalance, and its diagnosis is increasingly common with the advent of high-sensitivity cardiac troponin assays. Although this diagnosis is associated with poor outcomes, widespread uncertainty and confusion remain among clinicians as to how to investigate and manage this heterogeneous group of patients with type 2 myocardial infarction. Methods: In a prospective cohort study, 8064 consecutive patients with increased cardiac troponin concentrations were screened to identify patients with type 2 myocardial infarction. We excluded patients with frailty or renal or hepatic failure. All study participants underwent coronary (invasive or computed tomography angiography) and cardiac (magnetic resonance or echocardiography) imaging, and the underlying causes of infarction were independently adjudicated. The primary outcome was the prevalence of coronary artery disease. Results: In 100 patients with a provisional diagnosis of type 2 myocardial infarction (median age, 65 years [interquartile range, 55–74 years]; 43% women), coronary and cardiac imaging reclassified the diagnosis in 7 patients: type 1 or 4b myocardial infarction in 5 and acute myocardial injury in 2 patients. In those with type 2 myocardial infarction, median cardiac troponin I concentrations were 195 ng/L (interquartile range, 62–760 ng/L) at presentation and 1165 ng/L (interquartile range, 277–3782 ng/L) on repeat testing. The prevalence of coronary artery disease was 68% (63 of 93), which was obstructive in 30% (28 of 93). Infarct-pattern late gadolinium enhancement or regional wall motion abnormalities were observed in 42% (39 of 93), and left ventricular systolic dysfunction was seen in 34% (32 of 93). Only 10 patients had both normal coronary and normal cardiac imaging. Coronary artery disease and left ventricular systolic dysfunction were previously unrecognized in 60% (38 of 63) and 84% (27 of 32), respectively, with only 33% (21 of 63) and 19% (6 of 32) on evidence-based treatments. Conclusions: Systematic coronary and cardiac imaging of patients with type 2 myocardial infarction identified coronary artery disease in two-thirds and left ventricular systolic dysfunction in one-third of patients. Unrecognized and untreated coronary or cardiac disease is seen in most patients with type 2 myocardial infarction, presenting opportunities for initiation of evidence-based treatments with major potential to improve clinical outcomes. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03338504.

Sickle Cell Disease (SCD) is a disease that affects many around the world and often accounts for frequent hospital admissions every year, secondary to uncontrolled pain. Marijuana is increasingly being used for its medicinal ability to treat pain in chronic medical conditions. Therefore, it is imperative to determine how effective it would be in providing pain relief to patients with SCD. We systematically screened five databases for relevant data: PubMed, Medline, PubMed Central (PMC), Cochrane Library, and Google Scholar. The inclusion and exclusion criteria were implemented. A quality appraisal was then done using the Cochrane Bias assessment for randomized controlled trials (RCTs), Newcastle-Ottawa tool for observational studies, and Scale for the Assessment of Narrative Review Articles (SANRA) checklist for traditional review articles. From seven articles, information was gathered; one systematic review, one RCT, two surveys, one cross-sectional study, one retrospective study, and one questionnaire-based study. Our review concluded that based on the literature assessed, marijuana use in SCD patients either worsened their painful crises or offered little to no help compared to opioids or hydroxyurea usage. There were limited RCTs published in addition to papers investigating the long-term effects of marijuana use in SCD. We hope that further data is gathered in these areas to sufficiently address whether cannabis use is efficacious for pain relief in patients with SCD.

The Authors’ reply We would like to thank Yalta et al 1 for their interest in our review. We share their enthusiasm for the potential metabolic benefits of sodium-glucose co-transporter 2 (SGLT-2) inhibition. We agree with Yalta et al that in patients with type 2 diabetes or heart failure, there is dysregulated fatty acid oxidation and impaired glucose uptake causing myocardial dysfunction. In this setting of restricted fuel selection and low energetic reserve, ketone bodies are a super-fuel producing Adenosine triphosphate (ATP) more efficiently than free fatty acids or glucose, which usually serve as fuels for …

Background Myocardial injury is associated with adverse outcomes in patients with COVID-19. However, the prognostic role of myocardial injury in COVID-19 compared to other acute illnesses and the underlying mechanisms of injury are poorly understood. Methods In a prospective, multi-centre, cohort study conducted in secondary and tertiary care hospitals in Scotland, all consecutive patients with suspected COVID-19 underwent cardiac troponin (ARCHITECTSTAT high-sensitive troponin I (hs-cTnI) assay; Abbott Laboratories) testing in plasma that was surplus to clinical requirements. The results were not reported unless required by the attending clinician. We evaluated the prevalence of myocardial injury, mechanisms and outcomes in all patients. In those with any hs-cTnI concentration above the sex-specific 99th centile the diagnosis was adjudicated according to the 4th Universal Definition of Myocardial Infarction. The primary outcome of all-cause mortality was compared in those with and without myocardial injury and COVID-19 by cox regression adjusted for age, sex, renal function and co-morbidities. Results A total of 2,916 (median age 69 [interquartile range, IQR 54–79] years, 53% women) consecutive patients with suspected COVID-19 were followed up for 228 [IQR 203–249] days. Myocardial injury occurred in 26% (750/2,916) with a median troponin concentration of 66 [35–178] ng/L; the prevalence was 41% (46/112) and 25% (704/2,804) in those with and without COVID-19, respectively. The most common mechanism was acute non-ischaemic myocardial injury occurring in 80% (37/46) and 71% (502/704) of patients with and without COVID-19, respectively. Type 1 myocardial infarction (2% and 4%), type 2 myocardial infarction (7% and 14%) and chronic myocardial injury (11% and 11%) were less common and only one patient had confirmed myocarditis. In patients with myocardial injury mortality was increased compared to those without (P Conclusion Myocardial injury is common in hospitalised patients with suspected COVID-19 whether or not COVID-19 was the cause of their presentation. The majority of patients had acute non-ischaemic myocardial injury rather than a defined cardiac condition. Despite this the presence of myocardial injury was an independent predictor of death in all hospitalised patients. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): British Heart Foundation Kaplan-Meier curve for all-cause death

It has been recommended that adults sleep a minimum of seven hours of sleep every night to maintain holistic health and well-being. A considerable fraction of the adult population suffers from sleep deprivation and related disorders. The stress of modern-day living may be the cause of this curtailment of sleep duration. The primary purpose of this study was to investigate the effects of reduced sleep on the development of insulin resistance and explore the possible mechanisms linking the two. We utilized databases like such as PubMed, PubMed Central (PMC), and Medical Literature Analysis and Retrieval System Online (MEDLINE) to systematically screen papers using keywords and Medical Subject Heading (MeSH) terms. A few articles were also retrieved from Cochrane Library. We applied inclusion/exclusion criteria after screening papers via title and abstracts. A quality appraisal check was doneperformed, and ten 10 related studies were strictly reviewed. Short sleep duration was significantly associated with insulin resistance. Inflammatory markers such as C-reactive protein (CRP) and serum amyloid A (SAA), biomarkers such as glucagon-like peptide-1 (GLP-1), and circadian misalignment may play a significant role in the pathogenesis of this association. To prevent metabolic complications such as type- 2 diabetes, adequate sleep (more than seven hours per night) is required in the adult population. The causal relationship between sleep deprivation and insulin resistance is multifactorial, and further studies are warranted to understand these mechanisms better.

ObjectivesTo determine the contribution of comorbidities on the reported widespread myocardial abnormalities in patients with recent COVID-19.MethodsIn 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.ResultsIn 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)%; pConclusionsPatients demonstrate right but not left ventricular dysfunction. Previous reports of left ventricular myocardial abnormalities following COVID-19 may reflect pre-existing comorbidities.Trial registration numberNCT04625075.

Background Widespread abnormalities of the myocardium have been reported in patients with COVID-19. However, these patients often have substantial co-morbidities and it is essential to understand whether cardiac abnormalities represent pre-existing disease or are the consequence of COVID-19. Objective To determine the contribution and cardiac impact of co-morbidities in patients who have recovered from COVID-19. Methods In a prospective observational study, adult patients hospitalized with confirmed COVID-19 were recruited from the Edinburgh Heart Centre between May and November 2020 and compared to healthy and co-morbidity-matched volunteers. Patients underwent gadolinium and manganese-enhanced magnetic resonance imaging and coronary computed tomography angiography. Results Twenty-three patients (54±11 years, 20 male) who recovered from COVID-19 were recruited. Half (n=11, 48%) required admission to the intensive care unit and a third (n=7, 31%) received non-invasive or invasive ventilation. Patients had a high prevalence of known cardiovascular disease (n=18, 78%), associated risk factors (n=11, 45%) and coronary artery disease (n=8, 35%). Compared with younger healthy volunteers (n=10), myocardial native T1 values (1202±25 versus 1162±27 ms, P=0.008, figure 1) and extracellular volume fraction (31.9±1.7 versus 29.8±0.5 %, P=0.001, figure 1) were higher with no differences in manganese uptake. Compared to co-morbidity-matched volunteers (n=20), there were no differences in native T1 values (1202±25 versus 1196±39 ms, P=0.61, figure 1), extracellular volume fraction (31.9±1.7 versus 31.0±0.5 %, P=0.11), presence of late gadolinium enhancement or manganese uptake. These findings remained irrespective of COVID-19 disease severity, presence of concomitant myocardial injury or coronary artery disease. Conclusions Patients who have recovered following hospitalization with COVID-19 have no evidence of a major excess in myocardial injury or dysfunction compared to co-morbidity-matched volunteers. The presence of co-morbidities likely explains many of the previously reported myocardial abnormalities. Conflict of Interest None

In an era of incremental gains in preventative cardiology, the ongoing pursuit of reduction in ischaemic events has led to advances in the antiplatelet armamentarium that is available for use after percutaneous coronary intervention (PCI). The protection offered by antithrombotic may be enhanced by extending their duration of use, or through the application of more potent drugs—longer, stronger or both. The corollary, of course, is the potential for increased bleeding, which may carry significant associated morbidity and mortality. What combination and duration of aspirin, clopidogrel, ticagrelor or prasugrel is optimal in a given patient? This is a nuanced question that is pertinent in both acute and chronic coronary syndromes. Current guidelines broadly recommend the use of dual antiplatelet therapy (DAPT) for at least 12 months in patients undergoing PCI for an acute coronary syndrome (ACS) and at least 6 months in chronic coronary syndrome, with the proviso that shorter duration DAPT may be considered in patients at high risk of bleeding.1 2 Within these boundaries, clinicians must gauge the ischaemic and bleeding risk of an individual patient in order to optimise their DAPT regime. The advent of potent P2Y12 inhibitors and iterative improvements in drug-eluting stents (DES), the latest of which have thinner struts, improved drug delivery and are associated with lower rates of stent thrombosis and restenosis, have raised the possibility of a shorter duration of DAPT after PCI, with the goal of minimising bleeding while offering non-inferior protection from ischaemic events. Multiple randomised trials have studied various combinations of drugs and DAPT duration, including short-term DAPT followed by aspirin monotherapy and short-term DAPT followed by P2Y12 inhibitor monotherapy.3–5 Although somewhat heterogenous, collectively, these data suggest that short-term DAPT may be considered as a safe option in selected individuals. The authors of the current paper conducted one …

ObjectiveIn a proof-of-concept study, to quantify myocardial viability in patients with acute myocardial infarction using manganese-enhanced MRI (MEMRI), a measure of intracellular calcium handling.MethodsHealthy volunteers (n=20) and patients with ST-elevation myocardial infarction (n=20) underwent late gadolinium enhancement (LGE) using gadobutrol and MEMRI using manganese dipyridoxyl diphosphate. Patients were scanned ≤7 days after reperfusion and rescanned after 3 months. Differential manganese uptake was described using a two-compartment model.ResultsAfter manganese administration, healthy control and remote non-infarcted myocardium showed a sustained 25% reduction in T1 values (mean reductions, 288±34 and 281±12 ms). Infarcted myocardium demonstrated less T1 shortening than healthy control or remote myocardium (1157±74 vs 859±36 and 835±28 ms; both p2=0.72 vs 0.55; p0.1) myocardium.ConclusionsThrough visualisation of intracellular calcium handling, MEMRI accurately differentiates infarcted, stunned and viable myocardium, and correlates with myocardial dysfunction better than LGE. MEMRI holds major promise in directly assessing myocardial viability, function and calcium handling across a range of cardiac diseases.Trial registration numbersNCT03607669; EudraCT number 2016-003782-25.

Background Cardiovascular magnetic resonance (CMR) is increasingly used for risk stratification in aortic stenosis (AS). However, the relative prognostic power of CMR markers and their respective thresholds remains undefined. Objectives Using machine learning, the study aimed to identify prognostically important CMR markers in AS and their thresholds of mortality. Methods Patients with severe AS undergoing AVR (n = 440, derivation; n = 359, validation cohort) were prospectively enrolled across 13 international sites (median 3.8 years’ follow-up). CMR was performed shortly before surgical or transcatheter AVR. A random survival forest model was built using 29 variables (13 CMR) with post-AVR death as the outcome. Results There were 52 deaths in the derivation cohort and 51 deaths in the validation cohort. The 4 most predictive CMR markers were extracellular volume fraction, late gadolinium enhancement, indexed left ventricular end-diastolic volume (LVEDVi), and right ventricular ejection fraction. Across the whole cohort and in asymptomatic patients, risk-adjusted predicted mortality increased strongly once extracellular volume fraction exceeded 27%, while late gadolinium enhancement >2% showed persistent high risk. Increased mortality was also observed with both large (LVEDVi >80 mL/m2) and small (LVEDVi ≤55 mL/m2) ventricles, and with high (>80%) and low (≤50%) right ventricular ejection fraction. The predictability was improved when these 4 markers were added to clinical factors (3-year C-index: 0.778 vs 0.739). The prognostic thresholds and risk stratification by CMR variables were reproduced in the validation cohort. Conclusions Machine learning identified myocardial fibrosis and biventricular remodeling markers as the top predictors of survival in AS and highlighted their nonlinear association with mortality. These markers may have potential in optimizing the decision of AVR.

Background The ability to characterize and to quantify the extent of coronary artery disease has the potential to improve the prognostic capability of coronary computed tomography angiography. Although reproducible techniques have been described in those with mild coronary disease, this has yet to be assessed in patients with advanced disease. Methods Twenty patients with known multivessel disease underwent repeated computed tomography coronary angiography, 2 weeks apart. Coronary artery segments were analysed using semi-automated software by two trained observers to determine intraobserver, interobserver and interscan reproducibility. Results Overall, 149 coronary arterial segments were analysed. There was excellent intraobserver and interobserver agreement for all plaque volume measurements (Lin’s coefficient 0.95 to 1.0). There were no substantial interscan differences (P ​> ​0.05 for all) for total (2063 ​± ​1246 ​mm3, mean of differences −35.6 ​mm3), non-calcified (1795 ​± ​910 ​mm3, mean of differences −4.3 ​mm3), calcified (298 ​± ​425 ​mm3, mean of differences −31.3 ​mm3) and low-attenuation (13 ​± ​13 ​mm3, mean of differences −2.6 ​mm3) plaque volumes. Interscan agreement was highest for total and noncalcified plaque volumes. Calcified and low-attenuation plaque (−236.6 to 174 ​mm3 and -15.8 to 10.5 ​mm3 respectively) had relatively wider 95% limits of agreement reflecting the lower absolute plaque volumes. Conclusion In the presence of advanced coronary disease, semi-automated plaque quantification provides excellent reproducibility, particularly for total and non-calcified plaque volumes. This approach has major potential to assess change in disease over time and optimize risk stratification in patients with established coronary artery disease.

Aims The aim of this study is to quantify altered myocardial calcium handling in non-ischaemic cardiomyopathy using magnetic resonance imaging. Methods and results Patients with dilated cardiomyopathy (n = 10) or hypertrophic cardiomyopathy (n = 17) underwent both gadolinium and manganese contrast-enhanced magnetic resonance imaging and were compared with healthy volunteers (n = 20). Differential manganese uptake (Ki) was assessed using a two-compartment Patlak model. Compared with healthy volunteers, reduction in T1 with manganese-enhanced magnetic resonance imaging was lower in patients with dilated cardiomyopathy [mean reduction 257 ± 45 (21%) vs. 288 ± 34 (26%) ms, P Conclusion The rate of manganese uptake in both dilated and hypertrophic cardiomyopathy provides a measure of altered myocardial calcium handling. This holds major promise for the detection and monitoring of dysfunctional myocardium, with the potential for early intervention and prognostication.

AIMS: High-risk plaque (HRP) and non-obstructive coronary artery disease independently predict adverse events, but their importance to future culprit lesions has not been resolved. We sought to determine in patients prior to confirmed acute coronary syndrome (ACS) the association between lesion percent diameter stenosis (%DS), and the absolute number and prevalence of HRP. The secondary objective was to examine the relative importance of non-obstructive HRP in future culprit lesions. METHODS AND RESULTS: Within the ICONIC study, a nested case–control study of patients undergoing coronary computed tomographic angiography (coronary CT), we included ACS cases with culprit lesions confirmed by invasive coronary angiography and coregistered to baseline coronary CT. Quantitative CT was used to evaluate obstructive (≥50%) and non-obstructive (

Aims To assess contemporary pre-test probability estimates for obstructive coronary artery disease in patients with stable chest pain. Methods and results In this substudy of a multicentre randomized controlled trial, we compared 2019 European Society of Cardiology (ESC)-endorsed pre-test probabilities with observed prevalence of obstructive coronary artery disease on computed tomography coronary angiography (CTCA). We assessed associations between pre-test probability, 5-year coronary heart disease death or non-fatal myocardial infarction and study intervention (standard care vs. CTCA). The study population consisted of 3755 patients (30–75 years, 46% women) with a median pre-test probability of 11% of whom 1622 (43%) had a pre-test probability of >15%. In those who underwent CTCA (n = 1613), the prevalence of obstructive disease was 22%. When divided into deciles of pre-test probability, the observed disease prevalence was similar but higher than the corresponding median pre-test probability [median difference 2.3 (1.3–5.6)%]. There were more clinical events in patients with a pre-test probability >15% compared to those at 5–15% and 15% (2.8% vs. 5.3%, log rank P = 0.01), although this interaction was not statistically significant on multivariable modelling. Conclusion The updated 2019 ESC guideline pre-test probability recommendations tended to slightly underestimate disease prevalence in our cohort. Pre-test probability is a powerful predictor of future coronary events and helps select those who may derive the greatest absolute benefit from CTCA.

Aortic stenosis is the most prevalent valvular heart disease worldwide, and rates are increasing with the growing and more elderly population. Although the precise mechanisms that underpin aortic valve stenosis are incompletely understood, pathological valvular calcification has emerged as a key instigator in mediating the biomechanical stiffening that can lead to symptoms, the need for aortic valve replacement, and death if left untreated. Here, we review the currently understood processes leading to aortic valve calcification, summarise the contemporary imaging assessments of valve calcification, and highlight how these might improve patient care and accelerate our pathological understanding and the development of an effective medical therapy.

How does language model pretraining help transfer learning? We consider a simple ablation technique for determining the impact of each pretrained layer on transfer task performance. This method, partial reinitialization, involves replacing different layers of a pretrained model with random weights, then finetuning the entire model on the transfer task and observing the change in performance. This technique reveals that in BERT, layers with high probing performance on downstream GLUE tasks are neither necessary nor sufficient for high accuracy on those tasks. Furthermore, the benefit of using pretrained parameters for a layer varies dramatically with finetuning dataset size: parameters that provide tremendous performance improvement when data is plentiful may provide negligible benefits in data-scarce settings. These results reveal the complexity of the transfer learning process, highlighting the limitations of methods that operate on frozen models or single data samples., Comment: Findings of EMNLP 2020

COVID-19 is the first major pandemic the modern world has faced since the Spanish influenza pandemic of 1918 and has had a profound impact on all aspects of society.1 Governments worldwide have established emergency plans to help tackle and reduce the rapid spread of the infection, with social isolation being implemented by most to varying degrees. Healthcare systems are facing unprecedented challenges and real-time restructuring and, as expected, this has resulted in an excess mortality worldwide.1 The first fatality with COVID-19 in the UK was reported on 2 March 2020, with subsequent nationwide lockdown on 23 March 2020. Public health concerns have focused on the increases in mortality directly attributable to COVID-19 and the indirect consequences of the pandemic on the healthcare system’s ability to manage non-COVID-19 related life-threatening illnesses due to diversion of established healthcare resources and capacity. This is a complex situation and there is also some overlap in direct and indirect causes of mortality. For example, as with other viral and respiratory illnesses, there is the potential for COVID-19 to trigger other fatal events that may not have otherwise happened. For example, it is well described that there is a 44% increase in myocardial infarction in the weeks after respiratory tract infections.2 There is also the concern that patients themselves may be reluctant to seek attention because of concerns regarding contracting COVID-19 in the hospital or burdening an overstretched healthcare system that is trying to cope with seriously ill patients with COVID-19. In the current issue of Heart , Wu and colleagues have assessed the impact of COVID-19 on both the population incidence and location of acute cardiovascular mortality that sheds light on some of these …

Importance Recent European guidance supports a diminished role for exercise electrocardiography (ECG) in the assessment of suspected stable angina. Objective To evaluate the utility of exercise ECG in contemporary practice and assess the value of combined functional and anatomical testing. Design, Setting, and Participants This is a post hoc analysis of the Scottish Computed Tomography of the Heart (SCOT-HEART) open-label randomized clinical trial, conducted in 12 cardiology chest pain clinics across Scotland for patients with suspected angina secondary to coronary heart disease. Between November 18, 2010, and September 24, 2014, 4146 patients aged 18 to 75 years with stable angina underwent clinical evaluation and 1417 of 1651 (86%) underwent exercise ECG prior to randomization. Statistical analysis was conducted from October 10 to November 5, 2019. Interventions Patients were randomized in a 1:1 ratio to receive standard care plus coronary computed tomography (CT) angiography or to receive standard care alone. The present analysis was limited to the 3283 patients who underwent exercise ECG alone or in combination with coronary CT angiography. Main Outcomes and Measures The primary clinical end point was death from coronary heart disease or nonfatal myocardial infarction at 5 years. Results Among the 3283 patients (1889 men; median age, 57.0 years [interquartile range, 50.0-64.0 years]), exercise ECG had a sensitivity of 39% and a specificity of 91% for detecting any obstructive coronary artery disease in those who underwent subsequent invasive angiography. Abnormal results of exercise ECG were associated with a 14.47-fold (95% CI, 10.00-20.41;P Conclusions and Relevance This study suggests that abnormal results of exercise ECG are associated with coronary revascularization and the future risk of adverse coronary events. However, coronary CT angiography more accurately detects coronary artery disease and is more strongly associated with future risk compared with exercise ECG. Trial Registration ClinicalTrials.gov Identifier:NCT01149590

We assessed myocardial calcium handling in patients with acute and established myocardial withmanganese-enhanced magnetic resonance imaging (MEMRI). Patients (n=20) with acute myocardial infarction and healthy volunteers (n=20) underwent gadolinium delayed enhanced MRI (DEMRI) and MEMRI (

We assessed myocardial calcium handling in patients with non-ischaemic cardiomyopathy usingmanganese-enhanced magnetic resonance imaging (MEMRI). Healthy volunteers (HV; n=20, 13 male, 42±11 yr), patients with hypertrophic (HCM; n=17, 10 male, 57±10 yr) or dilated (DCM; n=10, 6 male, 54±10 yr)