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.

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.

Detecting heart failure from B-mode ultrasound characterization of arterial pulse waves.

This study investigated the sensitivity and specificity of identifying heart failure with reduced ejection fraction (HFrEF) from measurements of the intensity and timing of arterial pulse waves. Previously validated methods combining ultrafast B-mode ultrasound, plane-wave transmission, singular value decomposition (SVD), and speckle tracking were used to characterize the compression and decompression ("S" and "D") waves occurring in early and late systole, respectively, in the carotid arteries of outpatients with left ventricular ejection fraction (LVEF) < 40%, determined by echocardiography, and signs and symptoms of heart failure, or with LVEF ≥ 50% and no signs or symptoms of heart failure. On average, the HFrEF group had significantly reduced S-wave intensity and energy, a greater interval between the R wave of the ECG and the S wave, a reduced interval between the S and D waves, and an increase in the S-wave shift (SWS), a novel metric that characterizes the shift in timing of the S wave away from the R wave of the ECG and toward the D wave (all P < 0.01). Receiver operating characteristics (ROCs) were used to quantify for the first time how well wave metrics classified individual participants. S-wave intensity and energy gave areas under the ROC of 0.76-0.83, the ECG-S-wave interval gave 0.85-0.88, and the S-wave shift gave 0.88-0.92. Hence the methods, which are simple to use and do not require complex interpretation, provide sensitive and specific identification of HFrEF. If similar results were obtained in primary care, they could form the basis of techniques for heart failure screening.NEW & NOTEWORTHY We show that heart failure with reduced ejection fraction can be detected with excellent sensitivity and specificity in individual patients by using B-mode ultrasound to detect altered pulse wave intensity and timing in the carotid artery.

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.

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.

Smartphone-Based Remote Monitoring for Chronic Heart Failure: Mixed Methods Analysis of User Experience From Patient and Nurse Perspectives.

BACKGROUND: Community-based management by heart failure specialist nurses (HFSNs) is key to improving self-care in heart failure with reduced ejection fraction. Remote monitoring (RM) can aid nurse-led management, but in the literature, user feedback evaluation is skewed in favor of the patient rather than nursing user experience. Furthermore, the ways in which different groups use the same RM platform at the same time are rarely directly compared in the literature. We present a balanced semantic analysis of user feedback from patient and nurse perspectives of Luscii, a smartphone-based RM strategy combining self-measurement of vital signs, instant messaging, and e-learning. OBJECTIVE: This study aims to (1) evaluate how patients and nurses use this type of RM (usage type), (2) evaluate patients' and nurses' user feedback on this type of RM (user experience), and (3) directly compare the usage type and user experience of patients and nurses using the same type of RM platform at the same time. METHODS: We performed a retrospective usage type and user experience evaluation of the RM platform from the perspective of both patients with heart failure with reduced ejection fraction and the HFSNs using the platform to manage them. We conducted semantic analysis of written patient feedback provided via the platform and a focus group of 6 HFSNs. Additionally, as an indirect measure of tablet adherence, self-measured vital signs (blood pressure, heart rate, and body mass) were extracted from the RM platform at onboarding and 3 months later. Paired 2-tailed t tests were used to evaluate differences between mean scores across the 2 timepoints. RESULTS: A total of 79 patients (mean age 62 years; 35%, 28/79 female) were included. Semantic analysis of usage type revealed extensive, bidirectional information exchange between patients and HFSNs using the platform. Semantic analysis of user experience demonstrates a range of positive and negative perspectives. Positive impacts included increased patient engagement, convenience for both user groups, and continuity of care. Negative impacts included information overload for patients and increased workload for nurses. After the patients used the platform for 3 months, they showed significant reductions in heart rate (P=.004) and blood pressure (P=.008) but not body mass (P=.97) compared with onboarding. CONCLUSIONS: Smartphone-based RM with messaging and e-learning facilitates bilateral information sharing between patients and nurses on a range of topics. Patient and nurse user experience is largely positive and symmetrical, but there are possible negative impacts on patient attention and nurse workload. We recommend RM providers involve patient and nurse users in platform development, including recognition of RM usage in nursing job plans.

Does 3D-speckle tracking echocardiography improve prediction of major cardiovascular events in a multi-ethnic general population? A Southall and Brent Revisited (SABRE) cohort study.

3D-speckle tracking echocardiography(3D-STE) allows simultaneous assessment of ejection fraction(EF) and multidirectional strains, but its prognostic utility in the general population is unknown. We investigated if 3D-STE strains predicted a composite of major cardiac endpoints(MACE) beyond cardiovascular risk factors(CVDRF), and whether they were superior to 3D-EF. 529 participants in SABRE, a UK-based tri-ethnic general population cohort (69±6y; 76.6% male) with acceptable 3D-STE imaging were studied. Associations between 3D-EF or multidirectional myocardial strains and MACE(coronary heart disease(fatal/non-fatal), heart failure hospitalization, new-onset arrhythmia and cardiovascular mortality) were determined using Cox regression including adjustment for CVDRF and 2D-EF. Whether 3D-EF, global longitudinal strain(3D-GLS) and principle tangential strain(3D-PTS/3D-strain) improved cardiovascular risk stratification over CVDRF was investigated using a likelihood ratio test on a series of nested Cox proportional hazards models and Harrell's C statistics. During follow-up(median, 12y), there were 92 events. 3D-EF, 3D-GLS and 3D-PTS and 3D-RS were associated with MACE in unadjusted and models adjusted for CVDRF but not CVDRF+2D-EF. Compared to 3D-EF, both 3D-GLS and 3D-PTS slightly improved the predictive value over CVDRF for MACE, but the improvement was modest(C statistic increased from 0.698(0.647, 0.749) to 0.715(0.663, 0.766) comparing CVDRF with CVDRF +3D-GLS). 3D-STE-derived LV myocardial strains predicted MACE in a multi-ethnic general population sample of elderly individuals from the UK; however the added prognostic value of 3D-STE myocardial strains was small.

Smartphone-Based Remote Monitoring in Heart Failure With Reduced Ejection Fraction: Retrospective Cohort Study of Secondary Care Use and Costs.

BACKGROUND: Despite effective therapies, the economic burden of heart failure with reduced ejection fraction (HFrEF) is driven by frequent hospitalizations. Treatment optimization and admission avoidance rely on frequent symptom reviews and monitoring of vital signs. Remote monitoring (RM) aims to prevent admissions by facilitating early intervention, but the impact of noninvasive, smartphone-based RM of vital signs on secondary health care use and costs in the months after a new diagnosis of HFrEF is unknown. OBJECTIVE: The purpose of this study is to conduct a secondary care health use and health-economic evaluation for patients with HFrEF using smartphone-based noninvasive RM and compare it with matched controls receiving usual care without RM. METHODS: We conducted a retrospective study of 2 cohorts of newly diagnosed HFrEF patients, matched 1:1 for demographics, socioeconomic status, comorbidities, and HFrEF severity. They are (1) the RM group, with patients using the RM platform for >3 months and (2) the control group, with patients referred before RM was available who received usual heart failure care without RM. Emergency department (ED) attendance, hospital admissions, outpatient use, and the associated costs of this secondary care activity were extracted from the Discover data set for a 3-month period after diagnosis. Platform costs were added for the RM group. Secondary health care use and costs were analyzed using Kaplan-Meier event analysis and Cox proportional hazards modeling. RESULTS: A total of 146 patients (mean age 63 years; 42/146, 29% female) were included (73 in each group). The groups were well-matched for all baseline characteristics except hypertension (P=.03). RM was associated with a lower hazard of ED attendance (hazard ratio [HR] 0.43; P=.02) and unplanned admissions (HR 0.26; P=.02). There were no differences in elective admissions (HR 1.03, P=.96) or outpatient use (HR 1.40; P=.18) between the 2 groups. These differences were sustained by a univariate model controlling for hypertension. Over a 3-month period, secondary health care costs were approximately 4-fold lower in the RM group than the control group, despite the additional cost of RM itself (mean cost per patient GBP £465, US $581 vs GBP £1850, US $2313, respectively; P=.04). CONCLUSIONS: This retrospective cohort study shows that smartphone-based RM of vital signs is feasible for HFrEF. This type of RM was associated with an approximately 2-fold reduction in ED attendance and a 4-fold reduction in emergency admissions over just 3 months after a new diagnosis with HFrEF. Costs were significantly lower in the RM group without increasing outpatient demand. This type of RM could be adjunctive to standard care to reduce admissions, enabling other resources to help patients unable to use RM.

Sex-differences in associations of LV structure and function measured by echocardiography with long-term risk of mortality and cardiovascular morbidity.

Background: Three-dimensional echocardiography (3DE) measures of the left ventricle (LV) predict outcomes in high risk individuals, but their prognostic value in the general population is unknown. We aimed to establish whether 3DE was associated with mortality and morbidity in a multi-ethnic community-based sample, if associations differed by sex, and explored potential mechanisms explaining sex differences. Methods: 922 individuals (69.7 ± 6.2 years; 717 men) from the SABRE study underwent a health examination including echocardiography. Associations between 3DE LV measures (ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV), LV remodeling index (LVRI) and LV sphericity index (LVSI), and all-cause mortality and a composite cardiovascular endpoint [comprising new onset (non)fatal coronary heart disease, heart failure hospitalization, new-onset arrhythmias and cardiovascular mortality] were determined using multivariable Cox regression over a median follow-up of 8 years (all-cause mortality) and 7 years (composite cardiovascular endpoint). Results: There were 123 deaths and 151 composite cardiovascular endpoints. Lower EF, higher LV volumes and LVSI were associated with increased all-cause mortality, and higher LV volumes were associated with the composite cardiovascular endpoint independent of potential confounders. Associations between LV volumes, LVRI, LVSI, and mortality differed by sex (p interaction <0.1). In men increased LV volumes and LVSI and decreased LVRI and EF were associated with higher mortality, but associations were null or reversed in women (hazard ratios (95% CI) men vs. women: EDV 1.25 (1.05, 1.48) vs. 0.54 (0.26, 1.10); ESV, 1.36 (1.12, 1.63) vs. 0.59 (0.33, 1.04); LVRI, 0.79 (0.64, 0.96) vs. 1.70 (1.03, 2.80); LVSI, 1.27 (1.05, 1.54) vs. 0.61 (0.32, 1.15); and EF, 0.78 (0.66, 0.93) vs. 1.27 (0.69, 2.33). Similar sex differences were observed for associations with the composite cardiovascular outcome. Adjustment for LV diastolic stiffness and arterial stiffness marginally attenuated these differences. Conclusions: 3DE measures of LV volume and remodeling are associated with all-cause mortality and cardiovascular morbidity; however, some associations differ by sex. Sex-differences in LV remodeling patterns may influence mortality and morbidity risk in the general population.

Glycaemic control in people with diabetes following acute myocardial infarction.

Diabetes is a highly prevalent disease associated with considerable cardiovascular end organ damage and mortality. Despite significant changes to the management of acute myocardial infarction over the last two decades, people with diabetes remain at risk of complications and mortality following a myocardial infarct for a multitude of reasons, including increased coronary atherosclerosis, associated coronary microvascular dysfunction, and diabetic cardiomyopathy. Dysglycaemia causes significant endothelial dysfunction and upregulation of inflammation within the vasculature and epigenetic changes mean that these deleterious effects may persist despite subsequent efforts to tighten glycaemic control. Whilst clinical guidelines advocate for the avoidance of both hyper- and hypoglcyaemia in the peri-infarct period, the evidence base is lacking, and currently there is no consensus on the benefits of glycaemic control beyond this period. Glycaemic variability contributes to the glycaemic milieu and may have prognostic importance following myocardial infarct. The use of continuous glucose monitoring means that glucose trends and parameters can now be captured and interrogated, and its use, along with newer medicines, may provide novel opportunities for intervention after myocardial infarction in people with diabetes.

Relationship Between Image Quality and Bias in 3D Echocardiographic Measures: Data From the SABRE (Southall and Brent Revisited) Study.

Background Image-quality (IQ) compromises left ventricle assessment by 3-dimensional echocardiography (3DE). Sicker/frailer patients often have suboptimal IQ, and therefore observed associations may be biased by IQ. We investigated its effect in an observational study of older people and when IQ was modified experimentally in healthy volunteers. Methods and Results 3DE feasibility by IQ was assessed in 1294 individuals who attended the second wave of the Southall and Brent Revisited study and was compared with 2-dimensional (2D)-echocardiography feasibility in 147 individuals. Upon successful analysis, means of ejection fraction (3D-EF) and global longitudinal strain (3D-GLS) (plus 2D-EF) were compared in individuals with poor versus good IQ. In 2 studies of healthy participants, 3DE-IQ was impaired by (1) intentionally poor echocardiographic technique, and (2) use of a sheet of ultrasound-attenuating material (neoprene rubber; 2-4 mm). The feasibility was 41% (529/1294) for 3DE versus 61% (89/147) for 2D-EF, P<0.0001. Among acceptable images (n=529), good IQ by the 2015 American Society of Echocardiography/European Association of Cardiovascular Imaging criteria was 33.6% (178/529) and 71.3% (377/529) for 3D-EF and 3D-GLS, respectively. Individuals with poor IQ had lower 3D-EF and 3D-GLS (absolute) than those with good IQ (3D-EF: 52.8±6.0% versus 55.7±5.7%, Mean-Δ -2.9 [-3.9, 1.8]; 3D-GLS: 18.6±3.2% versus 19.2±2.9%, Mean-Δ -0.6 [-1.1, 0.0]). In 2 experimental models of poor IQ (n=36 for both), mean differences were (-2.6 to -3.2) for 3D-EF and (-1.2 to -2.0) for 3D-GLS. Similar findings were found for other 3DE left ventricle volumes and strain parameters. Conclusions 3DE parameters have low feasibility and values are systematically lower in individuals with poor IQ. Although 3D-EF and 3D-GLS have potential advantages over conventional echocardiography, further technical improvements are required to improve the utility of 3DE in clinical practice.

Implications of elevated troponin on time-to-surgery in non-ST elevation myocardial infarction (NIHR Health Informatics Collaborative: TROP-CABG study).

Implications of elevated troponin on time-to-surgery in non-ST elevation myocardial infarction(NIHR Health Informatics Collaborative:TROP-CABG study). Benedetto et al. BACKGROUND: The optimal timing of coronary artery bypass grafting (CABG) in patients with non-ST elevation myocardial infarction (NSTEMI) and the utility of pre-operative troponin levels in decision-making remains unclear. We investigated (a) the association between peak pre-operative troponin and survival post-CABG in a large cohort of NSTEMI patients and (b) the interaction between troponin and time-to-surgery. METHODS AND RESULTS: Our cohort consisted of 1746 patients (1684 NSTEMI; 62 unstable angina) (mean age 69 ± 11 years,21% female) with recorded troponins that had CABG at five United Kingdom centers between 2010 and 2017. Time-segmented Cox regression was used to investigate the interaction of peak troponin and time-to-surgery on early (within 30 days) and late (beyond 30 days) survival. Average interval from peak troponin to surgery was 9 ± 15 days, with 1466 (84.0%) patients having CABG during the same admission. Sixty patients died within 30-days and another 211 died after a mean follow-up of 4 ± 2 years (30-day survival 0.97 ± 0.004 and 5-year survival 0.83 ± 0.01). Peak troponin was a strong predictor of early survival (adjusted P = 0.002) with a significant interaction with time-to-surgery (P interaction = 0.007). For peak troponin levels <100 times the upper limit of normal, there was no improvement in early survival with longer time-to-surgery. However, in patients with higher troponins, early survival increased progressively with a longer time-to-surgery, till day 10. Peak troponin did not influence survival beyond 30 days (adjusted P = 0.64). CONCLUSIONS: Peak troponin in NSTEMI patients undergoing CABG was a significant predictor of early mortality, strongly influenced the time-to-surgery and may prove to be a clinically useful biomarker in the management of these patients.

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.

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.

Phasic flow patterns of right versus left coronary arteries in patients undergoing clinical physiological assessment.

BACKGROUND: Coronary blood flow in humans is known to be predominantly diastolic. Small studies in animals and humans suggest that this is less pronounced or even reversed in the right coronary artery (RCA). AIMS: This study aimed to characterise the phasic patterns of coronary flow in the left versus right coronary arteries of patients undergoing invasive physiological assessment. METHODS: We analysed data from the Iberian-Dutch-English Collaborators (IDEAL) study. A total of 482 simultaneous pressure and flow measurements from 301 patients were included in our analysis. RESULTS: On average, coronary flow was higher in diastole both at rest and during hyperaemia in both the RCA and LCA (mean diastolic-to-systolic velocity ratio [DSVR] was, respectively, 1.85±0.70, 1.76±0.58, 1.53±0.34 and 1.58±0.43 for LCArest, LCAhyp, RCArest and RCAhyp, p<0.001 for between-vessel comparisons). Although the type of RCA dominance affected the DSVR magnitude (RCAdom=1.55±0.35, RCAco-dom=1.40±0.27, RCAnon-dom=1.35; standard deviation not reported as n=3), systolic flow was very rarely predominant (DSVR was greater than or equal to 1.00 in 472/482 cases [97.9%] overall), with equal prevalence in the LCA. Stenosis severity or microvascular dysfunction had a negligible impact on DSVR in both the RCA and LCA (DSVR x hyperaemic stenosis resistance R2 =0.018, p=0.03 and DSVR x coronary flow reserve R2 <0.001, p=0.98). CONCLUSIONS: In patients with coronary artery disease undergoing physiological assessment, diastolic flow predominance is seen in both left and right coronary arteries. Clinical interpretation of coronary physiological data should therefore not differ between the left and the right coronary systems.

Corrigendum: Imaging Protocol, Feasibility, and Reproducibility of Cardiovascular Phenotyping in a Large Tri-Ethnic Population-Based Study of Older People: The Southall and Brent Revisited (SABRE) Study.

[This corrects the article DOI: 10.3389/fcvm.2020.591946.].