Phenogrouping heart failure with preserved or mildly reduced ejection fraction using electronic health record data.

BACKGROUND: Heart failure (HF) with preserved or mildly reduced ejection fraction includes a heterogenous group of patients. Reclassification into distinct phenogroups to enable targeted interventions is a priority. This study aimed to identify distinct phenogroups, and compare phenogroup characteristics and outcomes, from electronic health record data. METHODS: 2,187 patients admitted to five UK hospitals with a diagnosis of HF and a left ventricular ejection fraction ≥ 40% were identified from the NIHR Health Informatics Collaborative database. Partition-based, model-based, and density-based machine learning clustering techniques were applied. Cox Proportional Hazards and Fine-Gray competing risks models were used to compare outcomes (all-cause mortality and hospitalisation for HF) across phenogroups. RESULTS: Three phenogroups were identified: (1) Younger, predominantly female patients with high prevalence of cardiometabolic and coronary disease; (2) More frail patients, with higher rates of lung disease and atrial fibrillation; (3) Patients characterised by systemic inflammation and high rates of diabetes and renal dysfunction. Survival profiles were distinct, with an increasing risk of all-cause mortality from phenogroups 1 to 3 (p < 0.001). Phenogroup membership significantly improved survival prediction compared to conventional factors. Phenogroups were not predictive of hospitalisation for HF. CONCLUSIONS: Applying unsupervised machine learning to routinely collected electronic health record data identified phenogroups with distinct clinical characteristics and unique survival profiles.

Obstetric Emergencies.

Human gestation and birthing result in many deviations from usual physiology that are nonetheless normal to be seen. However, on occasion, certain complications in the obstetric patient can be life-threatening to both mother and fetus. Timely recognition of these disorders and allocation of the appropriate resources are especially important. These conditions often require an intensive care unit admission for closer monitoring and supportive care. They can affect an array of physiological systems and can lead to significant morbidity. Such complications are discussed in greater detail in this article.

Mortality risk prediction of high-sensitivity C-reactive protein in suspected acute coronary syndrome: A cohort study.

BACKGROUND: There is limited evidence on the use of high-sensitivity C-reactive protein (hsCRP) as a biomarker for selecting patients for advanced cardiovascular (CV) therapies in the modern era. The prognostic value of mildly elevated hsCRP beyond troponin in a large real-world cohort of unselected patients presenting with suspected acute coronary syndrome (ACS) is unknown. We evaluated whether a mildly elevated hsCRP (up to 15 mg/L) was associated with mortality risk, beyond troponin level, in patients with suspected ACS. METHODS AND FINDINGS: We conducted a retrospective cohort study based on the National Institute for Health Research Health Informatics Collaborative data of 257,948 patients with suspected ACS who had a troponin measured at 5 cardiac centres in the United Kingdom between 2010 and 2017. Patients were divided into 4 hsCRP groups (<2, 2 to 4.9, 5 to 9.9, and 10 to 15 mg/L). The main outcome measure was mortality within 3 years of index presentation. The association between hsCRP levels and all-cause mortality was assessed using multivariable Cox regression analysis adjusted for age, sex, haemoglobin, white cell count (WCC), platelet count, creatinine, and troponin. Following the exclusion criteria, there were 102,337 patients included in the analysis (hsCRP <2 mg/L (n = 38,390), 2 to 4.9 mg/L (n = 27,397), 5 to 9.9 mg/L (n = 26,957), and 10 to 15 mg/L (n = 9,593)). On multivariable Cox regression analysis, there was a positive and graded relationship between hsCRP level and mortality at baseline, which remained at 3 years (hazard ratio (HR) (95% CI) of 1.32 (1.18 to 1.48) for those with hsCRP 2.0 to 4.9 mg/L and 1.40 (1.26 to 1.57) and 2.00 (1.75 to 2.28) for those with hsCRP 5 to 9.9 mg/L and 10 to 15 mg/L, respectively. This relationship was independent of troponin in all suspected ACS patients and was further verified in those who were confirmed to have an ACS diagnosis by clinical coding. The main limitation of our study is that we did not have data on underlying cause of death; however, the exclusion of those with abnormal WCC or hsCRP levels >15 mg/L makes it unlikely that sepsis was a major contributor. CONCLUSIONS: These multicentre, real-world data from a large cohort of patients with suspected ACS suggest that mildly elevated hsCRP (up to 15 mg/L) may be a clinically meaningful prognostic marker beyond troponin and point to its potential utility in selecting patients for novel treatments targeting inflammation. TRIAL REGISTRATION: ClinicalTrials.gov - NCT03507309.

Determinants of outcomes following surgery for type A acute aortic dissection: the UK National Adult Cardiac Surgical Audit.

AIMS: Operability of type A acute aortic dissections (TAAAD) is currently based on non-standardized decision-making process, and it lacks a disease-specific risk evaluation model that can predict mortality. We investigated patient, intraoperative data, surgeon, and centre-related variables for patients who underwent TAAAD in the UK. METHODS AND RESULTS: We identified 4203 patients undergoing TAAAD surgery in the UK (2009-18), who were enrolled into the UK National Adult Cardiac Surgical Audit dataset. The primary outcome was operative mortality. A multivariable logistic regression analysis was performed with fast backward elimination of variables and the bootstrap-based optimism-correction was adopted to assess model performance. Variation related to hospital or surgeon effects were quantified by a generalized mixed linear model and risk-adjusted funnel plots by displaying the individual standardized mortality ratio against expected deaths. Final variables retained in the model were: age [odds ratio (OR) 1.02, 95% confidence interval (CI) 1.02-1.03; P < 0.001]; malperfusion (OR 1.79, 95% CI 1.51-2.12; P < 0.001); left ventricular ejection fraction (moderate: OR 1.40, 95% CI 1.14-1.71; P = 0.001; poor: OR 2.83, 95% CI 1.90-4.21; P < 0.001); previous cardiac surgery (OR 2.29, 95% CI 1.71-3.07; P < 0.001); preoperative mechanical ventilation (OR 2.76, 95% CI 2.00-3.80; P < 0.001); preoperative resuscitation (OR 3.36, 95% CI 1.14-9.87; P = 0.028); and concomitant coronary artery bypass grafting (OR 2.29, 95% CI 1.86-2.83; P < 0.001). We found a significant inverse relationship between surgeons but not centre annual volume with outcomes. CONCLUSIONS: Patient characteristics, intraoperative factors, cardiac centre, and high-volume surgeons are strong determinants of outcomes following TAAAD surgery. These findings may help refining clinical decision-making, supporting patient counselling and be used by policy makers for quality assurance and service provision improvement.

Invasive versus non-invasive management of older patients with non-ST elevation myocardial infarction (SENIOR-NSTEMI): a cohort study based on routine clinical data.

BACKGROUND: Previous trials suggest lower long-term risk of mortality after invasive rather than non-invasive management of patients with non-ST elevation myocardial infarction (NSTEMI), but the trials excluded very elderly patients. We aimed to estimate the effect of invasive versus non-invasive management within 3 days of peak troponin concentration on the survival of patients aged 80 years or older with NSTEMI. METHODS: Routine clinical data for this study were obtained from five collaborating hospitals hosting NIHR Biomedical Research Centres in the UK (all tertiary centres with emergency departments). Eligible patients were 80 years old or older when they underwent troponin measurements and were diagnosed with NSTEMI between 2010 (2008 for University College Hospital) and 2017. Propensity scores (patients' estimated probability of receiving invasive management) based on pretreatment variables were derived using logistic regression; patients with high probabilities of non-invasive or invasive management were excluded. Patients who died within 3 days of peak troponin concentration without receiving invasive management were assigned to the invasive or non-invasive management groups based on their propensity scores, to mitigate immortal time bias. We estimated mortality hazard ratios comparing invasive with non-invasive management, and compared the rate of hospital admissions for heart failure. FINDINGS: Of the 1976 patients with NSTEMI, 101 died within 3 days of their peak troponin concentration and 375 were excluded because of extreme propensity scores. The remaining 1500 patients had a median age of 86 (IQR 82-89) years of whom (845 [56%] received non-invasive management. During median follow-up of 3·0 (IQR 1·2-4·8) years, 613 (41%) patients died. The adjusted cumulative 5-year mortality was 36% in the invasive management group and 55% in the non-invasive management group (adjusted hazard ratio 0·68, 95% CI 0·55-0·84). Invasive management was associated with lower incidence of hospital admissions for heart failure (adjusted rate ratio compared with non-invasive management 0·67, 95% CI 0·48-0·93). INTERPRETATION: The survival advantage of invasive compared with non-invasive management appears to extend to patients with NSTEMI who are aged 80 years or older. FUNDING: NIHR Imperial Biomedical Research Centre, as part of the NIHR Health Informatics Collaborative.

Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide and results in an economic and social burden that is both substantial and increasing. The natural history of COPD is punctuated by exacerbations, which have major short- and long-term implications on the patient and health care system. Evidence-based guidelines stipulate that early detection and prompt treatment of exacerbations are essential to ensure optimal outcomes and to reduce the burden of COPD. In this review, we provide a concise overview of COPD exacerbations and their risk factors and etiology (infection vs noninfectious), outlining the initial evaluation, triaging, and current management including invasive and noninvasive ventilation, in addition to the prognosis and the preventive strategies.

Impact of different selection policies on subcutaneous ICD implants and therapies.

BACKGROUND: Patients with existing or anticipated indications for cardiac resynchronisation therapy (CRT), bradycardia, or anti-tachycardia pacing should not be offered subcutaneous defibrillators (SQIDs) but it remains unclear how clinicians should predict future need for these therapies. METHODS: We applied three SQID selection policies to data collected retrospectively from transvenous implantable cardioverter defibrillator (TV-ICD) implants: (a) approach A, SQID used in inherited channelopathies and idiopathic ventricular fibrillation only; (b) approach B, as above, plus all hypertrophic cardiomyopathy and grown-up congenital heart disease patients; (c) approach C, as above, plus primary and secondary prevention (for ventricular fibrillation only) of SCD in patients with QRS <150 ms. Approach C reflects current ESC and AHA/ACC/HRS guidelines. RESULTS: 338 of 951 patients with TV-ICD were considered for SQID after excluding 613 patients with contraindications. Approaches A, B, and C yielded 45 (4.7%), 89 (9.4%), and 338 (35.5%) patients suitable for SQID, respectively. Use of SQID resulted in more frequent ICD shocks compared to TV-ICD with approach C only (0.43 vs 0.23 per 1000 patient-days; P = .03). Rates of CRT upgrade were comparable across selection criteria (0, 0.03, and 0.07 per 1000 patient-days for approaches A, B, and C, respectively; P = NS). Risk of early mortality was higher when more liberal inclusion criteria were used (P = .003). CONCLUSIONS: One in three patients receiving ICDs may be suitable for SQID under current ESC and AHA/ACC/HRS guidelines. This proportion is influenced significantly by the selection criteria used, and the criteria used by a physician should be informed by the estimated survival of the patient, risk of shocks for MVT, future pacing, and CRT requirements.

Outcomes with single-coil versus dual-coil implantable cardioverter defibrillators: a meta-analysis.

Aims: Dual-coil implantable cardioverter defibrillator (ICD) leads have traditionally been used over single-coil leads due to concerns regarding high defibrillation thresholds (DFT) and consequent poor shock efficacy. However, accumulating evidence suggests that this position may be unfounded and that dual-coil leads may also be associated with higher complication rates during lead extraction. This meta-analysis collates data comparing dual- and single-coil ICD leads. Methods and results: Electronic databases were systematically searched for randomized controlled trials (RCT) and non-randomized studies comparing single-coil and dual-coil leads. The mean differences in DFT and summary estimates of the odds-ratio (OR) for first-shock efficacy and the hazard-ratio (HR) for all-cause mortality were calculated using random effects models. Eighteen studies including a total of 138,124 patients were identified. Dual-coil leads were associated with a lower DFT compared to single coil leads (mean difference -0.83J; 95% confidence interval [CI] -1.39--0.27; P = 0.004). There was no difference in the first-shock success rate with dual-coil compared to single-coil leads (OR 0.74; 95%CI 0.45-1.21; P=0.22). There was a significantly lower risk of all-cause mortality associated with single-coil leads (HR 0.91; 95%CI 0.86-0.95; P < 0.0001). Conclusion: This meta-analysis suggests that single-coil leads have a marginally higher DFT but that this may be clinically insignificant as there appears to be no difference in first-shock efficacy when compared to dual-coil leads. The mortality benefit with single-coil leads most likely represents patient selection bias. Given the increased risk and complexity of extracting dual-coil leads, centres should strongly consider single-coil ICD leads as the lead of choice for routine new left-sided ICD implants.

Vascular Endothelial Growth Factor-A165b Is Protective and Restores Endothelial Glycocalyx in Diabetic Nephropathy.

Diabetic nephropathy is the leading cause of ESRD in high-income countries and a growing problem across the world. Vascular endothelial growth factor-A (VEGF-A) is thought to be a critical mediator of vascular dysfunction in diabetic nephropathy, yet VEGF-A knockout and overexpression of angiogenic VEGF-A isoforms each worsen diabetic nephropathy. We examined the vasculoprotective effects of the VEGF-A isoform VEGF-A165b in diabetic nephropathy. Renal expression of VEGF-A165b mRNA was upregulated in diabetic individuals with well preserved kidney function, but not in those with progressive disease. Reproducing this VEGF-A165b upregulation in mouse podocytes in vivo prevented functional and histologic abnormalities in diabetic nephropathy. Biweekly systemic injections of recombinant human VEGF-A165b reduced features of diabetic nephropathy when initiated during early or advanced nephropathy in a model of type 1 diabetes and when initiated during early nephropathy in a model of type 2 diabetes. VEGF-A165b normalized glomerular permeability through phosphorylation of VEGF receptor 2 in glomerular endothelial cells, and reversed diabetes-induced damage to the glomerular endothelial glycocalyx. VEGF-A165b also improved the permeability function of isolated diabetic human glomeruli. These results show that VEGF-A165b acts via the endothelium to protect blood vessels and ameliorate diabetic nephropathy.

Diagnostic and prognostic value of an ejection fraction adjusted for myocardial remodeling.

Introduction: Ejection fraction (EF) is widely used to evaluate heart function during heart failure (HF) due to its simplicity compared but it may misrepresent cardiac function during ventricular hypertrophy, especially in heart failure with preserved EF (HFpEF). To resolve this shortcoming, we evaluate a correction factor to EF, which is equivalent to computing EF at the mid-wall layer (without the need for mid-layer identification) rather than at the endocardial surface, and thus better complements other complex metrics. Method: The retrospective cohort data was studied, consisting of 2,752 individuals (56.5% male, age 69.3 ± 16.4 years) admitted with a request of a troponin test and undergoing echocardiography as part of their clinical assessment across three centres. Cox-proportional regression models were constructed to compare the adjusted EF (EFa) to EF in evaluating risk of heart failure admissions. Result: Comparing HFpEF patients to non-HF cases, there was no significant difference in EF (62.3 ± 7.6% vs. 64.2 ± 6.2%, p = 0.79), but there was a significant difference in EFa (56.6 ± 6.4% vs. 61.8 ± 9.9%, p = 0.0007). Both low EF and low EFa were associated with a high HF readmission risk. However, in the cohort with a normal EF (EF ≥ 50%), models using EFa were significantly more associative with HF readmissions within 3 years, where the leave one out cross validation ROC analysis showed a 18.6% reduction in errors, and Net Classification Index (NRI) analysis showed that risk increment classification of events increased by 12.2%, while risk decrement classification of non-events decreased by 16.6%. Conclusion: EFa is associated with HF readmission in patients with a normal EF.

Randomized Trial of Remote Assessment of Patients After an Acute Coronary Syndrome.

BACKGROUND: Telemedicine programs can provide remote diagnostic information to aid clinical decisions that could optimize care and reduce unplanned readmissions post-acute coronary syndrome (ACS). OBJECTIVES: TELE-ACS (Remote Acute Assessment of Patients With High Cardiovascular Risk Post-Acute Coronary Syndrome) is a randomized controlled trial that aims to compare a telemedicine-based approach vs standard care in patients following ACS. METHODS: Patients were suitable for inclusion with at least 1 cardiovascular risk factor and presenting with ACS and were randomized (1:1) before discharge. The primary outcome was time to first readmission at 6 months. Secondary outcomes included emergency department (ED) visits, major adverse cardiovascular events, and patient-reported symptoms. The primary analysis was performed according to intention to treat. RESULTS: A total of 337 patients were randomized from January 2022 to April 2023, with a 3.6% drop-out rate. The mean age was 58.1 years. There was a reduced rate of readmission over 6 months (HR: 0.24; 95% CI: 0.13-0.44; P < 0.001) and ED attendance (HR: 0.59; 95% CI: 0.40-0.89) in the telemedicine arm, and fewer unplanned coronary revascularizations (3% in telemedicine arm vs 9% in standard therapy arm). The occurrence of chest pain (9% vs 24%), breathlessness (21% vs 39%), and dizziness (6% vs 18%) at 6 months was lower in the telemedicine group. CONCLUSIONS: The TELE-ACS study has shown that a telemedicine-based approach for the management of patients following ACS was associated with a reduction in hospital readmission, ED visits, unplanned coronary revascularization, and patient-reported symptoms. (Telemedicine in High-Risk Cardiovascular Patients Post-ACS [TELE-ACS]; NCT05015634).

Prognostic significance of troponin in patients with malignancy (NIHR Health Informatics Collaborative TROP-MALIGNANCY study).

BACKGROUND: Cardiac troponin is commonly raised in patients presenting with malignancy. The prognostic significance of raised troponin in these patients is unclear. OBJECTIVES: We sought to investigate the relation between troponin and mortality in a large, well characterised cohort of patients with a routinely measured troponin and a primary diagnosis of malignancy. METHODS: We used the National Institute for Health Research (NIHR) Health Informatics Collaborative data of 5571 patients, who had troponin levels measured at 5 UK cardiac centres between 2010 and 2017 and had a primary diagnosis of malignancy. Patients were classified into solid tumour or haematological malignancy subgroups. Peak troponin levels were standardised as a multiple of each laboratory's 99th -percentile upper limit of normal (xULN). RESULTS: 4649 patients were diagnosed with solid tumours and 922 patients with haematological malignancies. Raised troponin was an independent predictor of mortality in all patients (Troponin > 10 vs. <1 adjusted HR 2.01, 95% CI 1.73 to 2.34), in solid tumours (HR 1.84, 95% CI 1.55 to 2.19), and in haematological malignancy (HR 2.72, 95% CI 1.99 to 3.72). There was a significant trend in increasing mortality risk across troponin categories in all three subgroups (p < 0.001). CONCLUSION: Raised troponin level is associated with increased mortality in patients with a primary diagnosis of malignancy regardless of cancer subtype. Mortality risk is stable for patients with a troponin level below the ULN but increases as troponin level increases above the ULN in the absence of acute coronary syndrome.

Changes in the investigation and management of suspected myocardial infarction and injury during COVID-19: a multi-centre study using routinely collected healthcare data.

Objective: The COVID-19 pandemic was associated with a reduction in the incidence of myocardial infarction (MI) diagnosis, in part because patients were less likely to present to hospital. Whether changes in clinical decision making with respect to the investigation and management of patients with suspected MI also contributed to this phenomenon is unknown. Methods: Multicentre retrospective cohort study in three UK centres contributing data to the National Institute for Health Research Health Informatics Collaborative. Patients presenting to the Emergency Department (ED) of these centres between 1st January 2020 and 1st September 2020 were included. Three time epochs within this period were defined based on the course of the first wave of the COVID-19 pandemic: pre-pandemic (epoch 1), lockdown (epoch 2), post-lockdown (epoch 3). Results: During the study period, 10,670 unique patients attended the ED with chest pain or dyspnoea, of whom 6,928 were admitted. Despite fewer total ED attendances in epoch 2, patient presentations with dyspnoea were increased (p < 0.001), with greater likelihood of troponin testing in both chest pain (p = 0.001) and dyspnoea (p < 0.001). There was a dramatic reduction in elective and emergency cardiac procedures (both p < 0.001), and greater overall mortality of patients (p < 0.001), compared to the pre-pandemic period. Positive COVID-19 and/or troponin test results were associated with increased mortality (p < 0.001), though the temporal risk profile differed. Conclusions: The first wave of the COVID-19 pandemic was associated with significant changes not just in presentation, but also the investigation, management, and outcomes of patients presenting with suspected myocardial injury or MI.

Implementation of a Digital Health Tool for Patients Awaiting Input From a Specialist Weight Management Team: Observational Study.

BACKGROUND: Digital tools are increasingly used on a population level as a weight loss strategy for people living with overweight and obesity. Evidence supports the feasibility of digital tools for the management of obesity in a community setting, but there is only emerging evidence for the feasibility of such tools in specialist weight management services. No study has assessed the uptake of digital tools among patients awaiting their first appointment with a specialist weight management service. OBJECTIVE: The objective of this study was to understand interest, acceptance, and engagement with a digital behavioral change platform to support specialist weight management. METHODS: This was an observational study registered as a service innovation. All patients on the waiting list for a first appointment in the tier 3 weight management service at University Hospitals Coventry and Warwickshire National Health Service (NHS) Trust were eligible to access the NHS-approved digital tool. Data on interest and engagement with the digital tool were collected. Routine clinical data were used to describe patient demographics. Focus groups were held to explore patients' views on the use of digital tools as part of a specialist weight management service. RESULTS: A total of 199 patients on the waiting list were informed about the available digital tool. Just over a half (n=102, 51.3%) of patients were interested in using the app, with over one-third (n=68, 34%) of all patients engaging with the app. Overall, a third of patients on the waiting list (n=63, 32%) did not respond to the invite and 34 (17%) of patients expressed no interest in the app. Emotional eating and higher BMI was associated with interest in the Gro Health app. Male gender was associated with reduced engagement with the app. There were no differences in interest in the Gro Health app according to age, ethnicity, metabolic measures of glycemia, and lipid profile. CONCLUSIONS: It is feasible to offer digital tools such as Gro Health to patients awaiting their first appointment with specialist weight management services. Future research should explore barriers and facilitators of engagement with digital tools. Additionally, there is a need to further evaluate the effectiveness of such tools in specialist weight management services.

The Relationship Between Cardiac Troponin in People Hospitalised for Exacerbation of COPD and Major Adverse Cardiac Events (MACE) and COPD Readmissions.

Background: No single biomarker currently risk stratifies chronic obstructive pulmonary disease (COPD) patients at the time of an exacerbation, though previous studies have suggested that patients with elevated troponin at exacerbation have worse outcomes. This study evaluated the relationship between peak cardiac troponin and subsequent major adverse cardiac events (MACE) including all-cause mortality and COPD hospital readmission, among patients admitted with COPD exacerbation. Methods: Data from five cross-regional hospitals in England were analysed using the National Institute of Health Research Health Informatics Collaborative (NIHR-HIC) acute coronary syndrome database (2008-2017). People hospitalised with a COPD exacerbation were included, and peak troponin levels were standardised relative to the 99th percentile (upper limit of normal). We used Cox Proportional Hazard models adjusting for age, sex, laboratory results and clinical risk factors, and implemented logarithmic transformation (base-10 logarithm). The primary outcome was risk of MACE within 90 days from peak troponin measurement. Secondary outcome was risk of COPD readmission within 90 days from peak troponin measurement. Results: There were 2487 patients included. Of these, 377 (15.2%) patients had a MACE event and 203 (8.2%) were readmitted within 90 days from peak troponin measurement. A total of 1107 (44.5%) patients had an elevated troponin level. Of 1107 patients with elevated troponin at exacerbation, 256 (22.8%) had a MACE event and 101 (9.0%) a COPD readmission within 90 days from peak troponin measurement. Patients with troponin above the upper limit of normal had a higher risk of MACE (adjusted HR 2.20, 95% CI 1.75-2.77) and COPD hospital readmission (adjusted HR 1.37, 95% CI 1.02-1.83) when compared with patients without elevated troponin. Conclusion: An elevated troponin level at the time of COPD exacerbation may be a useful tool for predicting MACE in COPD patients. The relationship between degree of troponin elevation and risk of future events is complex and requires further investigation.

A randomized controlled trial to investigate the use of acute coronary syndrome therapy in patients hospitalized with COVID-19: the COVID-19 Acute Coronary Syndrome trial.

BACKGROUND: Patients hospitalized with COVID-19 suffer thrombotic complications. Risk factors for poor outcomes are shared with coronary artery disease. OBJECTIVES: To investigate the efficacy of an acute coronary syndrome regimen in patients hospitalized with COVID-19 and coronary disease risk factors. METHODS: A randomized controlled, open-label trial across acute hospitals (United Kingdom and Brazil) added aspirin, clopidogrel, low-dose rivaroxaban, atorvastatin, and omeprazole to standard care for 28 days. Primary efficacy and safety outcomes were 30-day mortality and bleeding. The key secondary outcome was a daily clinical status (at home, in hospital, on intensive therapy unit admission, or death). RESULTS: Three hundred twenty patients from 9 centers were randomized. The trial terminated early due to low recruitment. At 30 days, there was no significant difference in mortality (intervention vs control, 11.5% vs 15%; unadjusted odds ratio [OR], 0.73; 95% CI, 0.38-1.41; p = .355). Significant bleeds were infrequent and were not significantly different between the arms (intervention vs control, 1.9% vs 1.9%; p > .999). Using a Bayesian Markov longitudinal ordinal model, it was 93% probable that intervention arm participants were more likely to transition to a better clinical state each day (OR, 1.46; 95% credible interval [CrI], 0.88-2.37; Pr [beta > 0], 93%; adjusted OR, 1.50; 95% CrI, 0.91-2.45; Pr [beta > 0], 95%) and median time to discharge to home was 2 days shorter (95% CrI, -4 to 0; 2% probability that it was worse). CONCLUSION: Acute coronary syndrome treatment regimen was associated with a reduction in the length of hospital stay without an excess in major bleeding. A larger trial is needed to evaluate mortality.

Comparing the longer-term effectiveness of a single dose of the Pfizer-BioNTech and Oxford-AstraZeneca COVID-19 vaccines across the age spectrum.

Background: A single dose strategy may be adequate to confer population level immunity and protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, especially in low- and middle-income countries where vaccine supply remains limited. We compared the effectiveness of a single dose strategy of the Oxford-AstraZeneca or Pfizer-BioNTech vaccines against SARS-CoV-2 infection across all age groups and over an extended follow-up period. Methods: Individuals vaccinated in North-West London, UK, with either the first dose of the Oxford-AstraZeneca or Pfizer-BioNTech vaccines between January 12, 2021 and March 09, 2021, were matched to each other by demographic and clinical characteristics. Each vaccinated individual was additionally matched to an unvaccinated control. Study outcomes included SARS-CoV-2 infection of any severity, COVID-19 hospitalisation, COVID-19 death, and all-cause mortality. Findings: Amongst matched individuals, 63,608 were in each of the vaccine groups and 127,216 were unvaccinated. Between 14 and 84 days of follow-up after matching, there were 534 SARS-CoV-2 infections, 65 COVID-19 hospitalisations, and 190 deaths, of which 29 were categorized as due to COVID-19. The incidence rate ratio (IRR) for SARS-CoV-2 infection was 0.85 (95% confidence interval [CI], 0.69 to 1.05) for Oxford-Astra-Zeneca, and 0.69 (0.55 to 0.86) for Pfizer-BioNTech. The IRR for both vaccines was the same at 0.25 (0.09 to 0.55) and 0.14 (0.02 to 0.58) for reducing COVID-19 hospitalization and COVID-19 mortality, respectively. The IRR for all-cause mortality was 0.25 (0.15 to 0.39) and 0.18 (0.10 to 0.30) for the Oxford-Astra-Zeneca and Pfizer-BioNTech vaccines, respectively. Age was an effect modifier of the association between vaccination and SARS-CoV-2 infection of any severity; lower hazard ratios for increasing age. Interpretation: A single dose strategy, for both vaccines, was effective at reducing COVID-19 mortality and hospitalization rates. The magnitude of vaccine effectiveness was comparatively lower for SARS-CoV-2 infection, although this was variable across the age range, with higher effectiveness seen with older adults. Our results have important implications for health system planning -especially in low resource settings where vaccine supply remains constrained.

Prognostic Significance of Ventricular Arrhythmias in 13 444 Patients With Acute Coronary Syndrome: A Retrospective Cohort Study Based on Routine Clinical Data (NIHR Health Informatics Collaborative VA-ACS Study).

Background A minority of acute coronary syndrome (ACS) cases are associated with ventricular arrhythmias (VA) and/or cardiac arrest (CA). We investigated the effect of VA/CA at the time of ACS on long-term outcomes. Methods and Results We analyzed routine clinical data from 5 National Health Service trusts in the United Kingdom, collected between 2010 and 2017 by the National Institute for Health Research Health Informatics Collaborative. A total of 13 444 patients with ACS, 376 (2.8%) of whom had concurrent VA, survived to hospital discharge and were followed up for a median of 3.42 years. Patients with VA or CA at index presentation had significantly increased risks of subsequent VA during follow-up (VA group: adjusted hazard ratio [HR], 4.15 [95% CI, 2.42-7.09]; CA group: adjusted HR, 2.60 [95% CI, 1.23-5.48]). Patients who suffered a CA in the context of ACS and survived to discharge also had a 36% increase in long-term mortality (adjusted HR, 1.36 [95% CI, 1.04-1.78]), although the concurrent diagnosis of VA alone during ACS did not affect all-cause mortality (adjusted HR, 1.03 [95% CI, 0.80-1.33]). Conclusions Patients who develop VA or CA during ACS who survive to discharge have increased risks of subsequent VA, whereas those who have CA during ACS also have an increase in long-term mortality. These individuals may represent a subgroup at greater risk of subsequent arrhythmic events as a result of intrinsically lower thresholds for developing VA.