Publications by authors named "Anoop S V Shah"

100 Publications

Diagnostic performance of the combined nasal and throat swab in patients admitted to hospital with suspected COVID-19.

BMC Infect Dis 2021 Apr 6;21(1):318. Epub 2021 Apr 6.

BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, EH16 4SA, UK.

Background: Accurate diagnosis in patients with suspected coronavirus disease 2019 (COVID-19) is essential to guide treatment and limit spread of the virus. The combined nasal and throat swab is used widely, but its diagnostic performance is uncertain.

Methods: In a prospective, multi-centre, cohort study conducted in secondary and tertiary care hospitals in Scotland, we evaluated the combined nasal and throat swab with reverse transcriptase-polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in consecutive patients admitted to hospital with suspected COVID-19. Diagnostic performance of the index and serial tests was evaluated for a primary outcome of confirmed or probable COVID-19, and a secondary outcome of confirmed COVID-19 on serial testing. The diagnosis was adjudicated by a panel, who recorded clinical, laboratory and radiological features blinded to the test results.

Results: We enrolled 1368 consecutive patients (median age 68 [interquartile range, IQR 53-80] years, 47% women) who underwent a total of 3822 tests (median 2 [IQR 1-3] tests per patient). The primary outcome occurred in 36% (496/1368), of whom 65% (323/496) and 35% (173/496) had confirmed and probable COVID-19, respectively. The index test was positive in 255/496 (51%) patients with the primary outcome, giving a sensitivity and specificity of 51.4% (95% confidence interval [CI] 48.8 to 54.1%) and 99.5% (95% CI 99.0 to 99.8%). Sensitivity increased in those undergoing 2, 3 or 4 tests to 60.1% (95% CI 56.7 to 63.4%), 68.3% (95% CI 64.0 to 72.3%) and 77.6% (95% CI 72.7 to 81.9%), respectively. The sensitivity of the index test was 78.9% (95% CI 74.4 to 83.2%) for the secondary outcome of confirmed COVID-19 on serial testing.

Conclusions: In patients admitted to hospital, a single combined nasal and throat swab with RT-PCR for SARS-CoV-2 has excellent specificity, but limited diagnostic sensitivity for COVID-19. Diagnostic performance is significantly improved by repeated testing.
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http://dx.doi.org/10.1186/s12879-021-05976-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022129PMC
April 2021

High-Sensitivity Cardiac Troponin on Presentation to Rule Out Myocardial Infarction: A Stepped-Wedge Cluster Randomized Controlled Trial.

Circulation 2021 Mar 23. Epub 2021 Mar 23.

BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK; Usher Institute, University of Edinburgh, Edinburgh, UK.

High-sensitivity cardiac troponin assays enable myocardial infarction to be ruled out earlier, but the safety and efficacy of this approach is uncertain. We investigated whether an early-rule out pathway is safe and effective for patients with suspected acute coronary syndrome. We performed a stepped-wedge cluster randomized controlled trial in the Emergency Departments of seven acute care hospitals in Scotland. Consecutive patients presenting with suspected acute coronary syndrome between December 2014 and December 2016 were included. Sites were randomized to implement an early rule-out pathway where myocardial infarction was excluded if high-sensitivity cardiac troponin I concentrations were <5 ng/L at presentation. During a prior validation phase, myocardial infarction was ruled out where troponin concentrations were <99th centile at 6-12 hours after symptom onset. The co-primary outcome was length of stay (efficacy), and myocardial infarction or cardiac death after discharge at 30 days (safety). Patients were followed for 1 year to evaluate safety and other secondary outcomes. We enrolled 31,492 patients (59±17 years, 45% women) with troponin concentrations <99th centile at presentation. Length of stay was reduced from 10.1±4.1 to 6.8±3.9 hours (adjusted geometric mean ratio 0.78, 95% confidence interval [CI] 0.73 to 0.83, P<0.001) following implementation, and the proportion of patients discharged increased from 50% to 71% (adjusted odds ratio [aOR] 1.59, 95% CI 1.45 to 1.75). Non-inferiority was not demonstrated for the 30-day safety outcome (upper limit of one-sided 95% CI for adjusted risk difference 0.70%, non-inferiority margin 0.50%, P=0.068), but the observed differences favoured the early rule-out pathway (0.4% [57/14,700] versus 0.3% [56/16,792]). At 1 year, the safety outcome occurred in 2.7% (396/14,700) and 1.8% (307/16,792) of patients before and after implementation (aOR 1.02, 95% CI 0.74 to 1.40, P=0.894), and there were no differences in hospital reattendance or all-cause mortality. Implementation of an early rule-out pathway for myocardial infarction reduced length of stay and hospital admission. Whilst non-inferiority for the safety outcome was not demonstrated at 30 days, there was no increase in cardiac events at 1 year. Adoption of this pathway would have major benefits for patients and healthcare providers. URL: https://www.clinicaltrials.gov Unique Identifier: NCT03005158.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.052380DOI Listing
March 2021

Sharing a household with children and risk of COVID-19: a study of over 300 000 adults living in healthcare worker households in Scotland.

Arch Dis Child 2021 Mar 18. Epub 2021 Mar 18.

Public health Scotland, Glasgow, UK

Objective: Children are relatively protected from COVID-19, due to a range of potential mechanisms. We investigated if contact with children also affords adults a degree of protection from COVID-19.

Design: Cohort study based on linked administrative data.

Setting: Scotland.

Study Population: All National Health Service Scotland healthcare workers and their household contacts as of March 2020.

Main Exposure: Number of young children (0-11 years) living in the participant's household.

Main Outcomes: COVID-19 requiring hospitalisation, and any COVID-19 (any positive test for SARS-CoV-2) in adults aged ≥18 years between 1 March and 12 October 2020.

Results: 241 266, 41 198, 23 783 and 3850 adults shared a household with 0, 1, 2 and 3 or more young children, respectively. Over the study period, the risk of COVID-19 requiring hospitalisation was reduced progressively with increasing numbers of household children-fully adjusted HR (aHR) 0.93 per child (95% CI 0.79 to 1.10). The risk of any COVID-19 was similarly reduced, with the association being statistically significant (aHR per child 0.93; 95% CI 0.88 to 0.98). After schools reopened to all children in August 2020, no association was seen between exposure to young children and risk of any COVID-19 (aHR per child 1.03; 95% CI 0.92 to 1.14).

Conclusion: Between March and October 2020, living with young children was associated with an attenuated risk of any COVID-19 and COVID-19 requiring hospitalisation among adults living in healthcare worker households. There was no evidence that living with young children increased adults' risk of COVID-19, including during the period after schools reopened.
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http://dx.doi.org/10.1136/archdischild-2021-321604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985971PMC
March 2021

Excess deaths in people with cardiovascular diseases during the COVID-19 pandemic.

Eur J Prev Cardiol 2021 Feb 21. Epub 2021 Feb 21.

Institute of Health Informatics, University College London, 222 Euston Road, London, UK, NW1 1DA.

Aims: Cardiovascular diseases (CVDs) increase mortality risk from coronavirus infection (COVID-19). There are also concerns that the pandemic has affected supply and demand of acute cardiovascular care. We estimated excess mortality in specific CVDs, both 'direct', through infection, and 'indirect', through changes in healthcare.

Methods And Results: We used (i) national mortality data for England and Wales to investigate trends in non-COVID-19 and CVD excess deaths; (ii) routine data from hospitals in England (n = 2), Italy (n = 1), and China (n = 5) to assess indirect pandemic effects on referral, diagnosis, and treatment services for CVD; and (iii) population-based electronic health records from 3 862 012 individuals in England to investigate pre- and post-COVID-19 mortality for people with incident and prevalent CVD. We incorporated pre-COVID-19 risk (by age, sex, and comorbidities), estimated population COVID-19 prevalence, and estimated relative risk (RR) of mortality in those with CVD and COVID-19 compared with CVD and non-infected (RR: 1.2, 1.5, 2.0, and 3.0).Mortality data suggest indirect effects on CVD will be delayed rather than contemporaneous (peak RR 1.14). CVD service activity decreased by 60-100% compared with pre-pandemic levels in eight hospitals across China, Italy, and England. In China, activity remained below pre-COVID-19 levels for 2-3 months even after easing lockdown and is still reduced in Italy and England. For total CVD (incident and prevalent), at 10% COVID-19 prevalence, we estimated direct impact of 31 205 and 62 410 excess deaths in England (RR 1.5 and 2.0, respectively), and indirect effect of 49 932 to 99 865 deaths.

Conclusion: Supply and demand for CVD services have dramatically reduced across countries with potential for substantial, but avoidable, excess mortality during and after the pandemic.
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http://dx.doi.org/10.1093/eurjpc/zwaa155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928969PMC
February 2021

Prevalence and clinical implications of valvular calcification on coronary computed tomography angiography.

Eur Heart J Cardiovasc Imaging 2021 Feb;22(3):262-270

University of Edinburgh/British Heart Foundation Centre for Cardiovascular Science, Chancellor's Building, 49 Little France Crescent, Edinburgh EH164SB, UK.

Aims: Valvular heart disease can be identified by calcification on coronary computed tomography angiography (CCTA) and has been associated with adverse clinical outcomes. We assessed aortic and mitral valve calcification in patients presenting with stable chest pain and their association with cardiovascular risk factors, coronary artery disease, and cardiovascular outcomes.

Methods And Results: In 1769 patients (58 ± 9 years, 56% male) undergoing CCTA for stable chest pain, aortic and mitral valve calcification were quantified using Agatston score. Aortic valve calcification was present in 241 (14%) and mitral calcification in 64 (4%). Independent predictors of aortic valve calcification were age, male sex, hypertension, diabetes mellitus, and cerebrovascular disease, whereas the only predictor of mitral valve calcification was age. Patients with aortic and mitral valve calcification had higher coronary artery calcium scores and more obstructive coronary artery disease. The composite endpoint of cardiovascular mortality, non-fatal myocardial infarction, or non-fatal stroke was higher in those with aortic [hazard ratio (HR) 2.87; 95% confidence interval (CI) 1.60-5.17; P < 0.001] or mitral (HR 3.50; 95% CI 1.47-8.07; P = 0.004) valve calcification, but this was not independent of coronary artery calcification or obstructive coronary artery disease.

Conclusion: Aortic and mitral valve calcification occurs in one in six patients with stable chest pain undergoing CCTA and is associated with concomitant coronary atherosclerosis. Whilst valvular calcification is associated with a higher risk of cardiovascular events, this was not independent of the burden of coronary artery disease.
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http://dx.doi.org/10.1093/ehjci/jeaa263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899264PMC
February 2021

Ten Years of High-Sensitivity Cardiac Troponin Testing: Impact on the Diagnosis of Myocardial Infarction.

Clin Chem 2021 Jan;67(1):324-326

Central Diagnostic Laboratory, Maastricht University Medical Center, Maastricht, the Netherlands.

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http://dx.doi.org/10.1093/clinchem/hvaa272DOI Listing
January 2021

Ex vivo F-fluoride uptake and hydroxyapatite deposition in human coronary atherosclerosis.

Sci Rep 2020 11 19;10(1):20172. Epub 2020 Nov 19.

Department of Radiology and Centre for Heart Lung Innovation, St Paul's Hospital and University of British Columbia, Vancouver, Canada.

Early microcalcification is a feature of coronary plaques with an increased propensity to rupture and to cause acute coronary syndromes. In this ex vivo imaging study of coronary artery specimens, the non-invasive imaging radiotracer, F-fluoride, was highly selective for hydroxyapatite deposition in atherosclerotic coronary plaque. Specifically, coronary F-fluoride uptake had a high signal to noise ratio compared with surrounding myocardium that makes it feasible to identify coronary mineralisation activity. Areas of F-fluoride uptake are associated with osteopontin, an inflammation-associated glycophosphoprotein that mediates tissue mineralisation, and Runt-related transcription factor 2, a nuclear protein involved in osteoblastic differentiation. These results suggest that F-fluoride is a non-invasive imaging biomarker of active coronary atherosclerotic mineralisation.
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http://dx.doi.org/10.1038/s41598-020-77391-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677392PMC
November 2020

Estimates of the global burden of cervical cancer associated with HIV.

Lancet Glob Health 2021 02 16;9(2):e161-e169. Epub 2020 Nov 16.

Department of Global HIV, Hepatitis and STIs Programmes, World Health Organization, Geneva, Switzerland. Electronic address:

Background: HIV enhances human papillomavirus (HPV)-induced carcinogenesis. However, the contribution of HIV to cervical cancer burden at a population level has not been quantified. We aimed to investigate cervical cancer risk among women living with HIV and to estimate the global cervical cancer burden associated with HIV.

Methods: We did a systematic literature search and meta-analysis of five databases (PubMed, Embase, Global Health [CABI.org], Web of Science, and Global Index Medicus) to identify studies analysing the association between HIV infection and cervical cancer. We estimated the pooled risk of cervical cancer among women living with HIV across four continents (Africa, Asia, Europe, and North America). The risk ratio (RR) was combined with country-specific UNAIDS estimates of HIV prevalence and GLOBOCAN 2018 estimates of cervical cancer to calculate the proportion of women living with HIV among women with cervical cancer and population attributable fractions and age-standardised incidence rates (ASIRs) of HIV-attributable cervical cancer.

Findings: 24 studies met our inclusion criteria, which included 236 127 women living with HIV. The pooled risk of cervical cancer was increased in women living with HIV (RR 6·07, 95% CI 4·40-8·37). Globally, 5·8% (95% CI 4·6-7·3) of new cervical cancer cases in 2018 (33 000 new cases, 95% CI 26 000-42 000) were diagnosed in women living with HIV and 4·9% (95% CI 3·6-6·4) were attributable to HIV infection (28 000 new cases, 20 000-36 000). The most affected regions were southern Africa and eastern Africa. In southern Africa, 63·8% (95% CI 58·9-68·1) of women with cervical cancer (9200 new cases, 95% CI 8500-9800) were living with HIV, as were 27·4% (23·7-31·7) of women in eastern Africa (14 000 new cases, 12 000-17 000). ASIRs of HIV-attributable cervical cancer were more than 20 per 100 000 in six countries, all in southern Africa and eastern Africa.

Interpretation: Women living with HIV have a significantly increased risk of cervical cancer. HPV vaccination and cervical cancer screening for women living with HIV are especially important for countries in southern Africa and eastern Africa, where a substantial HIV-attributable cervical cancer burden has added to the existing cervical cancer burden.

Funding: WHO, US Agency for International Development, and US President's Emergency Plan for AIDS Relief.
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http://dx.doi.org/10.1016/S2214-109X(20)30459-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815633PMC
February 2021

Risk of hospital admission with coronavirus disease 2019 in healthcare workers and their households: nationwide linkage cohort study.

BMJ 2020 10 28;371:m3582. Epub 2020 Oct 28.

Public Health Scotland, Edinburgh, UK

Objective: To assess the risk of hospital admission for coronavirus disease 2019 (covid-19) among patient facing and non-patient facing healthcare workers and their household members.

Design: Nationwide linkage cohort study.

Setting: Scotland, UK, 1 March to 6 June 2020.

Participants: Healthcare workers aged 18-65 years, their households, and other members of the general population.

Main Outcome Measure: Admission to hospital with covid-19.

Results: The cohort comprised 158 445 healthcare workers, most of them (90 733; 57.3%) being patient facing, and 229 905 household members. Of all hospital admissions for covid-19 in the working age population (18-65 year olds), 17.2% (360/2097) were in healthcare workers or their households. After adjustment for age, sex, ethnicity, socioeconomic deprivation, and comorbidity, the risk of admission due to covid-19 in non-patient facing healthcare workers and their households was similar to the risk in the general population (hazard ratio 0.81 (95% confidence interval 0.52 to 1.26) and 0.86 (0.49 to 1.51), respectively). In models adjusting for the same covariates, however, patient facing healthcare workers, compared with non-patient facing healthcare workers, were at higher risk (hazard ratio 3.30, 2.13 to 5.13), as were household members of patient facing healthcare workers (1.79, 1.10 to 2.91). After sub-division of patient facing healthcare workers into those who worked in "front door," intensive care, and non-intensive care aerosol generating settings and other, those in front door roles were at higher risk (hazard ratio 2.09, 1.49 to 2.94). For most patient facing healthcare workers and their households, the estimated absolute risk of hospital admission with covid-19 was less than 0.5%, but it was 1% and above in older men with comorbidity.

Conclusions: Healthcare workers and their households contributed a sixth of covid-19 cases admitted to hospital. Although the absolute risk of admission was low overall, patient facing healthcare workers and their household members had threefold and twofold increased risks of admission with covid-19.
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http://dx.doi.org/10.1136/bmj.m3582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591828PMC
October 2020

Adverse health effects associated with household air pollution: a systematic review, meta-analysis, and burden estimation study.

Lancet Glob Health 2020 11;8(11):e1427-e1434

Department of Non-communicable Disease, London School of Hygiene & Tropical Medicine, London, UK. Electronic address:

Background: 3 billion people worldwide rely on polluting fuels and technologies for domestic cooking and heating. We estimate the global, regional, and national health burden associated with exposure to household air pollution.

Methods: For the systematic review and meta-analysis, we systematically searched four databases for studies published from database inception to April 2, 2020, that evaluated the risk of adverse cardiorespiratory, paediatric, and maternal outcomes from exposure to household air pollution, compared with no exposure. We used a random-effects model to calculate disease-specific relative risk (RR) meta-estimates. Household air pollution exposure was defined as use of polluting fuels (coal, wood, charcoal, agricultural wastes, animal dung, or kerosene) for household cooking or heating. Temporal trends in mortality and disease burden associated with household air pollution, as measured by disability-adjusted life-years (DALYs), were estimated from 2000 to 2017 using exposure prevalence data from 183 of 193 UN member states. 95% CIs were estimated by propagating uncertainty from the RR meta-estimates, prevalence of household air pollution exposure, and disease-specific mortality and burden estimates using a simulation-based approach. This study is registered with PROSPERO, CRD42019125060.

Findings: 476 studies (15·5 million participants) from 123 nations (99 [80%] of which were classified as low-income and middle-income) met the inclusion criteria. Household air pollution was positively associated with asthma (RR 1·23, 95% CI 1·11-1·36), acute respiratory infection in both adults (1·53, 1·22-1·93) and children (1·39, 1·29-1·49), chronic obstructive pulmonary disease (1·70, 1·47-1·97), lung cancer (1·69, 1·44-1·98), and tuberculosis (1·26, 1·08-1·48); cerebrovascular disease (1·09, 1·04-1·14) and ischaemic heart disease (1·10, 1·09-1·11); and low birthweight (1·36, 1·19-1·55) and stillbirth (1·22, 1·06-1·41); as well as with under-5 (1·25, 1·18-1·33), respiratory (1·19, 1·18-1·20), and cardiovascular (1·07, 1·04-1·11) mortality. Household air pollution was associated with 1·8 million (95% CI 1·1-2·7) deaths and 60·9 million (34·6-93·3) DALYs in 2017, with the burden overwhelmingly experienced in low-income and middle-income countries (LMICs; 60·8 million [34·6-92·9] DALYs) compared with high-income countries (0·09 million [0·01-0·40] DALYs). From 2000, mortality associated with household air pollution had reduced by 36% (95% CI 29-43) and disease burden by 30% (25-36), with the greatest reductions observed in higher-income nations.

Interpretation: The burden of cardiorespiratory, paediatric, and maternal diseases associated with household air pollution has declined worldwide but remains high in the world's poorest regions. Urgent integrated health and energy strategies are needed to reduce the adverse health impact of household air pollution, especially in LMICs.

Funding: British Heart Foundation, Wellcome Trust.
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http://dx.doi.org/10.1016/S2214-109X(20)30343-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564377PMC
November 2020

Serial troponin measurements to monitor risk and response to endothelin A antagonism in chronic kidney disease.

Nephrol Dial Transplant 2021 01;36(2):375-377

University/British Heart Foundation Centre of Research Excellence, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.

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http://dx.doi.org/10.1093/ndt/gfaa214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834594PMC
January 2021

Short-term exposure to carbon monoxide and myocardial infarction: A systematic review and meta-analysis.

Environ Int 2020 10 4;143:105901. Epub 2020 Jul 4.

BHF Centre for Cardiovascular Science, University of Edinburgh, United Kingdom; Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, United Kingdom. Electronic address:

Background: Previous studies suggest an association between short-term exposure to carbon monoxide and myocardial infarction. We performed a systematic review and meta-analysis to assess current evidence on this association to support the update of the World Health Organization (WHO) Global Air Quality Guidelines.

Methods: We searched Medline, Embase and Cochrane Central Register of Controlled Trials to update the evidence published in a previous systematic review up to 30th September 2018 for studies investigating the association between short-term exposure to ambient carbon monoxide (up to lag of seven days) and emergency department visits or hospital admissions and mortality due to myocardial infarction. Two reviewers assessed potentially eligible studies and performed data extraction independently. Random-effects meta-analysis was used to derive the pooled risk estimate per 1 mg/m increase in ambient carbon monoxide concentration. Risk of bias in individual studies was assessed using a domain-based assessment tool. The overall certainty of the body of evidence was evaluated using an adapted certainty of evidence assessment framework.

Results: We evaluated 1,038 articles from the previous review and our updated literature search, of which, 26 satisfied our inclusion criteria. Overall, myocardial infarction was associated with exposure to ambient carbon monoxide concentration (risk ratio of 1.052, 95% confidence interval 1.017-1.089 per 1 mg/m increase). A third of studies were assessed to be at high risk of bias (RoB) due to inadequate adjustment for confounding. Using an adaptation of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework, the overall evidence was assessed to be of moderate certainty.

Conclusions: This review demonstrated that the pooled risk ratio for myocardial infarction was 1.052 (95% CI 1.017-1.089) per 1 mg/m increase in ambient carbon monoxide concentration. However, very few studies originated from low- and middle-income countries.
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http://dx.doi.org/10.1016/j.envint.2020.105901DOI Listing
October 2020

Performance of the GRACE 2.0 score in patients with type 1 and type 2 myocardial infarction.

Eur Heart J 2020 Jun 9. Epub 2020 Jun 9.

Department of Medicine, Karolinska Institute, 171 77 Solna, Stockholm, Sweden.

Aims: The Global Registry of Acute Coronary Events (GRACE) score was developed to evaluate risk in patients with myocardial infarction. However, its performance in type 2 myocardial infarction is uncertain.

Methods And Results: In two cohorts of consecutive patients with suspected acute coronary syndrome from 10 hospitals in Scotland (n = 48 282) and a tertiary care hospital in Sweden (n = 22 589), we calculated the GRACE 2.0 score to estimate death at 1 year. Discrimination was evaluated by the area under the receiver operating curve (AUC), and compared for those with an adjudicated diagnosis of type 1 and type 2 myocardial infarction using DeLong's test. Type 1 myocardial infarction was diagnosed in 4981 (10%) and 1080 (5%) patients in Scotland and Sweden, respectively. At 1 year, 720 (15%) and 112 (10%) patients died with an AUC for the GRACE 2.0 score of 0.83 [95% confidence interval (CI) 0.82-0.85] and 0.85 (95% CI 0.81-0.89). Type 2 myocardial infarction occurred in 1121 (2%) and 247 (1%) patients in Scotland and Sweden, respectively, with 258 (23%) and 57 (23%) deaths at 1 year. The AUC was 0.73 (95% CI 0.70-0.77) and 0.73 (95% CI 0.66-0.81) in type 2 myocardial infarction, which was lower than for type 1 myocardial infarction in both cohorts (P < 0.001 and P = 0.008, respectively).

Conclusion: The GRACE 2.0 score provided good discrimination for all-cause death at 1 year in patients with type 1 myocardial infarction, and moderate discrimination for those with type 2 myocardial infarction.

Trial Registration: ClinicalTrials.gov number, NCT01852123.
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http://dx.doi.org/10.1093/eurheartj/ehaa375DOI Listing
June 2020

We all breathe the same air … and we are all mortal.

Cardiovasc Res 2020 Sep;116(11):1797-1799

University/BHF Centre for Cardiovascular Sciences, University of Edinburgh, Queens Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.

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http://dx.doi.org/10.1093/cvr/cvaa126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449551PMC
September 2020

Incidence, Microbiology, and Outcomes in Patients Hospitalized With Infective Endocarditis.

Circulation 2020 06 15;141(25):2067-2077. Epub 2020 May 15.

Edinburgh Heart Centre, Royal Infirmary of Edinburgh, United Kingdom (N.L.C.).

Background: Despite improvements in management, infective endocarditis remains associated with high mortality and morbidity. We describe temporal changes in the incidence, microbiology, and outcomes of infective endocarditis and the effect of changes in national antibiotic prophylaxis guidelines on incident infective endocarditis.

Methods: Using a Scotland-wide, individual-level linkage approach, all patients hospitalized with infective endocarditis from 1990 to 2014 were identified and linked to national microbiology, prescribing, and morbidity and mortality datasets. Linked data were used to evaluate trends in the crude and age- and sex-adjusted incidence and outcomes of infective endocarditis hospitalizations. From 2008, microbiology data and associated outcomes adjusted for patient demographics and comorbidity were also analyzed. An interrupted time series analysis was performed to evaluate incidence before and after changes to national antibiotic prophylaxis guidelines.

Results: There were 7638 hospitalizations (65±17 years, 51% females) with infective endocarditis. The estimated crude hospitalization rate increased from 5.3/100 000 (95% CI, 4.8-5.9) to 8.6/100 000 (95% CI, 8.1-9.1) between 1990 and 1995 but remained stable thereafter. There was no change in crude incidence following the 2008 change in antibiotic prophylaxis guidelines (relative risk of change 1.06 [95% CI, 0.94-1.20]). The incidence rate in patients >80 years of age doubled from 1990 to 2014 (17.7/100 000 [95% CI, 13.4-23.3] to 37.9/100 000 [95% CI, 31.5-45.5]). The predicted 1-year age- and comorbidity-adjusted case fatality rate for a 65-year-old patient decreased in women (27.3% [95% CI, 24.6-30.2] to 23.7% [95% CI, 21.1-26.6]) and men (30.7% [95% CI, 27.7-33.8] to 26.8% [95% CI, 24.0-29.7]) from 1990 to 2014. Blood culture data were available from 2008 (n=2267/7638, 30%), with positive blood cultures recorded in 42% (950/2267). Staphylococcus (403/950, 42.4%) and streptococcus (337/950, 35.5%) species were most common. and enterococcus had the highest 1-year mortality (adjusted odds ratio 4.34 [95% CI, 3.12-6.05] and 3.41 [95% CI, 2.04-5.70], respectively).

Conclusions: Despite changes in antibiotic prophylaxis guidelines, the crude incidence of infective endocarditis has remained stable. However, the incidence rate has doubled in the elderly. Positive blood cultures were observed in less than half of patients, with and enterococcus bacteremia associated with worse outcomes.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.044913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7306256PMC
June 2020

Biomechanical Assessment Predicts Aneurysm Related Events in Patients with Abdominal Aortic Aneurysm.

Eur J Vasc Endovasc Surg 2020 09 4;60(3):365-373. Epub 2020 Apr 4.

BHF Centre for Cardiovascular Science, The University of Edinburgh, Edinburgh, UK.

Objective: To test whether aneurysm biomechanical ratio (ABR; a dimensionless ratio of wall stress and wall strength) can predict aneurysm related events.

Methods: In a prospective multicentre clinical study of 295 patients with an abdominal aortic aneurysm (AAA; diameter ≥ 40 mm), three dimensional reconstruction and computational biomechanical analyses were used to compute ABR at baseline. Participants were followed for at least two years and the primary end point was the composite of aneurysm rupture or repair.

Results: The majority were male (87%), current or former smokers (86%), most (72%) had hypertension (mean ± standard deviation [SD] systolic blood pressure 140 ± 22 mmHg), and mean ± SD baseline diameter was 49.0 ± 6.9 mm. Mean ± SD ABR was 0.49 ± 0.27. Participants were followed up for a mean ± SD of 848 ± 379 days and rupture (n = 13) or repair (n = 102) occurred in 115 (39%) cases. The number of repairs increased across tertiles of ABR: low (n = 24), medium (n = 34), and high ABR (n = 44) (p = .010). Rupture or repair occurred more frequently in those with higher ABR (log rank p = .009) and ABR was independently predictive of this outcome after adjusting for diameter and other clinical risk factors, including sex and smoking (hazard ratio 1.41; 95% confidence interval 1.09-1.83 [p = .010]).

Conclusion: It has been shown that biomechanical ABR is a strong independent predictor of AAA rupture or repair in a model incorporating known risk factors, including diameter. Determining ABR at baseline could help guide the management of patients with AAA.
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http://dx.doi.org/10.1016/j.ejvs.2020.02.023DOI Listing
September 2020

Low-Attenuation Noncalcified Plaque on Coronary Computed Tomography Angiography Predicts Myocardial Infarction: Results From the Multicenter SCOT-HEART Trial (Scottish Computed Tomography of the HEART).

Circulation 2020 May 16;141(18):1452-1462. Epub 2020 Mar 16.

Cedars-Sinai Medical Centre, Los Angeles, CA (P.M., S.C., P.J.S., D.S.B., D.D.).

Background: The future risk of myocardial infarction is commonly assessed using cardiovascular risk scores, coronary artery calcium score, or coronary artery stenosis severity. We assessed whether noncalcified low-attenuation plaque burden on coronary CT angiography (CCTA) might be a better predictor of the future risk of myocardial infarction.

Methods: In a post hoc analysis of a multicenter randomized controlled trial of CCTA in patients with stable chest pain, we investigated the association between the future risk of fatal or nonfatal myocardial infarction and low-attenuation plaque burden (% plaque to vessel volume), cardiovascular risk score, coronary artery calcium score or obstructive coronary artery stenoses.

Results: In 1769 patients (56% male; 58±10 years) followed up for a median 4.7 (interquartile interval, 4.0-5.7) years, low-attenuation plaque burden correlated weakly with cardiovascular risk score (=0.34; <0.001), strongly with coronary artery calcium score (=0.62; <0.001), and very strongly with the severity of luminal coronary stenosis (area stenosis, =0.83; <0.001). Low-attenuation plaque burden (7.5% [4.8-9.2] versus 4.1% [0-6.8]; <0.001), coronary artery calcium score (336 [62-1064] versus 19 [0-217] Agatston units; <0.001), and the presence of obstructive coronary artery disease (54% versus 25%; <0.001) were all higher in the 41 patients who had fatal or nonfatal myocardial infarction. Low-attenuation plaque burden was the strongest predictor of myocardial infarction (adjusted hazard ratio, 1.60 (95% CI, 1.10-2.34) per doubling; =0.014), irrespective of cardiovascular risk score, coronary artery calcium score, or coronary artery area stenosis. Patients with low-attenuation plaque burden greater than 4% were nearly 5 times more likely to have subsequent myocardial infarction (hazard ratio, 4.65; 95% CI, 2.06-10.5; <0.001).

Conclusions: In patients presenting with stable chest pain, low-attenuation plaque burden is the strongest predictor of fatal or nonfatal myocardial infarction. These findings challenge the current perception of the supremacy of current classical risk predictors for myocardial infarction, including stenosis severity. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01149590.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.044720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7195857PMC
May 2020

Exploring Patient Experience of Chest Pain Before and After Implementation of an Early Rule-Out Pathway for Myocardial Infarction: A Qualitative Study.

Ann Emerg Med 2020 04 23;75(4):502-513. Epub 2020 Jan 23.

Usher Institute of Population Health Science and Informatics, University of Edinburgh, Edinburgh, United Kingdom; Centre for Biomedicine, Self and Society, University of Edinburgh, Edinburgh, United Kingdom.

Study Objective: High-sensitivity cardiac troponin assays enable myocardial infarction to be excluded in the emergency department (ED). As part of a prospective clinical trial, we explore how introducing an early rule-out pathway may affect patient experience of chest pain.

Methods: In a qualitative study, participants presenting to the ED with suspected acute coronary syndrome, and for whom the diagnosis of myocardial infarction was excluded, were interviewed before (n=23) or after (n=26) implementation of an early rule-out pathway. Preimplementation, diagnosis of myocardial infarction was excluded on serial troponin testing requiring admission to the hospital. Postimplementation, diagnosis could be excluded in the ED, enabling direct patient discharge. Semistructured interviews exploring the patients' illness experience were conducted approximately 1 week postdischarge, transcribed verbatim, and analyzed thematically. Themes emerging pre- and postimplementation are described.

Results: Common themes emerged across both pathways: participants commonly sought health care advice before presenting to the ED; a discordance may exist between the objective interpretation of troponin results by clinicians and the patients' experience of illness; and pretest information, trust in the clinician, and active listening may enhance reassurance gained from negative test results. Other themes related to the care pathway were that routine care procedures appeared to be a source of frustration for participants requiring hospital admission, and patients assessed with the early rule-out pathway appeared less likely to appraise their future health status.

Conclusion: The early rule-out of myocardial infarction may be enhanced by recognition of patient out-of-hospital experience and improved communication surrounding reassurance and future cardiovascular health goals.
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http://dx.doi.org/10.1016/j.annemergmed.2019.11.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105816PMC
April 2020

Walking the tightrope: cardiovascular risk prediction in patients after acute coronary syndrome.

Heart 2020 04 10;106(7):484-486. Epub 2020 Jan 10.

Usher Institute of Population Health Sciences and Informatics, Univerity of Edinburgh, Edinburgh, UK

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http://dx.doi.org/10.1136/heartjnl-2019-316189DOI Listing
April 2020

Sex associations and computed tomography coronary angiography-guided management in patients with stable chest pain.

Eur Heart J 2020 04;41(13):1337-1345

British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, 126 University Place, University of Glasgow, Glasgow G12 8TA, UK.

Aims: The relative benefits of computed tomography coronary angiography (CTCA)-guided management in women and men with suspected angina due to coronary heart disease (CHD) are uncertain.

Methods And Results: In this post hoc analysis of an open-label parallel-group multicentre trial, we recruited 4146 patients referred for assessment of suspected angina from 12 cardiology clinics across the UK. We randomly assigned (1:1) participants to standard care alone or standard care plus CTCA. Fewer women had typical chest pain symptoms (n = 582, 32.0%) when compared with men (n = 880, 37.9%; P < 0.001). Amongst the CTCA-guided group, more women had normal coronary arteries [386 (49.6%) vs. 263 (26.2%)] and less obstructive CHD [105 (11.5%) vs. 347 (29.8%)]. A CTCA-guided strategy resulted in more women than men being reclassified as not having CHD {19.2% vs. 13.1%; absolute risk difference, 5.7 [95% confidence interval (CI): 2.7-8.7, P < 0.001]} or having angina due to CHD [15.0% vs. 9.0%; absolute risk difference, 5.6 (2.3-8.9, P = 0.001)]. After a median of 4.8 years follow-up, CTCA-guided management was associated with similar reductions in the risk of CHD death or non-fatal myocardial infarction in women [hazard ratio (HR) 0.50, 95% CI 0.24-1.04], and men (HR 0.63, 95% CI 0.42-0.95; Pinteraction = 0.572).

Conclusion: Following the addition of CTCA, women were more likely to be found to have normal coronary arteries than men. This led to more women being reclassified as not having CHD, resulting in more downstream tests and treatments being cancelled. There were similar prognostic benefits of CTCA for women and men.
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http://dx.doi.org/10.1093/eurheartj/ehz903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109601PMC
April 2020

Guiding Therapy by Coronary CT Angiography Improves Outcomes in Patients With Stable Chest Pain.

J Am Coll Cardiol 2019 10;74(16):2058-2070

Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.

Background: Within the SCOT-HEART (Scottish COmputed Tomography of the HEART Trial) trial of patients with stable chest pain, the use of coronary computed tomography angiography (CTA) reduced the rate of death from coronary heart disease or nonfatal myocardial infarction (primary endpoint).

Objectives: This study sought to assess the consistency and mechanisms of the 5-year reduction in this endpoint.

Methods: In this open-label trial, 4,146 participants were randomized to standard care alone or standard care plus coronary CTA. This study explored the primary endpoint by symptoms, diagnosis, coronary revascularizations, and preventative therapies.

Results: Event reductions were consistent across symptom and risk categories (p = NS for interactions). In patients who were not diagnosed with angina due to coronary heart disease, coronary CTA was associated with a lower primary endpoint incidence rate (0.23; 95% confidence interval [CI]: 0.13 to 0.35 vs. 0.59; 95% CI: 0.42 to 0.80 per 100 patient-years; p < 0.001). In those who had undergone coronary CTA, rates of coronary revascularization were higher in the first year (hazard ratio [HR]: 1.21; 95% CI: 1.01 to 1.46; p = 0.042) but lower beyond 1 year (HR: 0.59; 95% CI: 0.38 to 0.90; p = 0.015). Patients assigned to coronary CTA had higher rates of preventative therapies throughout follow-up (p < 0.001 for all), with rates highest in those with CT-defined coronary artery disease. Modeling studies demonstrated the plausibility of the observed effect size.

Conclusions: The beneficial effect of coronary CTA on outcomes is consistent across subgroups with plausible underlying mechanisms. Coronary CTA improves coronary heart disease outcomes by enabling better targeting of preventative treatments to those with coronary artery disease. (Scottish COmputed Tomography of the HEART Trial [SCOT-HEART]; NCT01149590).
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http://dx.doi.org/10.1016/j.jacc.2019.07.085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899446PMC
October 2019

Sex-Specific Thresholds of High-Sensitivity Troponin in Patients With Suspected Acute Coronary Syndrome.

J Am Coll Cardiol 2019 10;74(16):2032-2043

British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom; Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, United Kingdom. Electronic address:

Background: Major disparities between women and men in the diagnosis, management, and outcomes of acute coronary syndrome are well recognized.

Objectives: The aim of this study was to evaluate the impact of implementing a high-sensitivity cardiac troponin I assay with sex-specific diagnostic thresholds for myocardial infarction in women and men with suspected acute coronary syndrome.

Methods: Consecutive patients with suspected acute coronary syndrome were enrolled in a stepped-wedge, cluster-randomized controlled trial across 10 hospitals. Myocardial injury was defined as high-sensitivity cardiac troponin I concentration >99th centile of 16 ng/l in women and 34 ng/l in men. The primary outcome was recurrent myocardial infarction or cardiovascular death at 1 year.

Results: A total of 48,282 patients (47% women) were included. Use of the high-sensitivity cardiac troponin I assay with sex-specific thresholds increased myocardial injury in women by 42% and in men by 6%. Following implementation, women with myocardial injury remained less likely than men to undergo coronary revascularization (15% vs. 34%) and to receive dual antiplatelet (26% vs. 43%), statin (16% vs. 26%), or other preventive therapies (p < 0.001 for all). The primary outcome occurred in 18% (369 of 2,072) and 17% (488 of 2,919) of women with myocardial injury before and after implementation, respectively (adjusted hazard ratio: 1.11; 95% confidence interval: 0.92 to 1.33), compared with 18% (370 of 2,044) and 15% (513 of 3,325) of men (adjusted hazard ratio: 0.85; 95% confidence interval: 0.71 to 1.01).

Conclusions: Use of sex-specific thresholds identified 5 times more additional women than men with myocardial injury. Despite this increase, women received approximately one-half the number of treatments for coronary artery disease as men, and outcomes were not improved. (High-Sensitivity Troponin in the Evaluation of Patients With Acute Coronary Syndrome [High-STEACS]; NCT01852123).
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http://dx.doi.org/10.1016/j.jacc.2019.07.082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6876271PMC
October 2019

High-Sensitivity Cardiac Troponin and the Universal Definition of Myocardial Infarction.

Circulation 2020 01 7;141(3):161-171. Epub 2019 Oct 7.

BHF Centre for Cardiovascular Science (A.R.C., P.D.A., A.S.V.S., A.A., F.E.S., A.V.F., K.K.L., K.A.A.F., D.E.N., N.L.M.), University of Edinburgh, United Kingdom.

Background: The introduction of more sensitive cardiac troponin assays has led to increased recognition of myocardial injury in acute illnesses other than acute coronary syndrome. The Universal Definition of Myocardial Infarction recommends high-sensitivity cardiac troponin testing and classification of patients with myocardial injury based on pathogenesis, but the clinical implications of implementing this guideline are not well understood.

Methods: In a stepped-wedge cluster randomized, controlled trial, we implemented a high-sensitivity cardiac troponin assay and the recommendations of the Universal Definition in 48 282 consecutive patients with suspected acute coronary syndrome. In a prespecified secondary analysis, we compared the primary outcome of myocardial infarction or cardiovascular death and secondary outcome of noncardiovascular death at 1 year across diagnostic categories.

Results: Implementation increased the diagnosis of type 1 myocardial infarction by 11% (510/4471), type 2 myocardial infarction by 22% (205/916), and acute and chronic myocardial injury by 36% (443/1233) and 43% (389/898), respectively. Compared with those without myocardial injury, the rate of the primary outcome was highest in those with type 1 myocardial infarction (cause-specific hazard ratio [HR] 5.64 [95% CI, 5.12-6.22]), but was similar across diagnostic categories, whereas noncardiovascular deaths were highest in those with acute myocardial injury (cause specific HR 2.65 [95% CI, 2.33-3.01]). Despite modest increases in antiplatelet therapy and coronary revascularization after implementation in patients with type 1 myocardial infarction, the primary outcome was unchanged (cause specific HR 1.00 [95% CI, 0.82-1.21]). Increased recognition of type 2 myocardial infarction and myocardial injury did not lead to changes in investigation, treatment or outcomes.

Conclusions: Implementation of high-sensitivity cardiac troponin assays and the recommendations of the Universal Definition of Myocardial Infarction identified patients at high-risk of cardiovascular and noncardiovascular events but was not associated with consistent increases in treatment or improved outcomes. Trials of secondary prevention are urgently required to determine whether this risk is modifiable in patients without type 1 myocardial infarction.

Clinical Trial Registration: https://www.clinicaltrials.gov. Unique identifier: NCT01852123.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.042960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6970546PMC
January 2020

High-Sensitivity Troponin and the Application of Risk Stratification Thresholds in Patients With Suspected Acute Coronary Syndrome.

Circulation 2019 11 1;140(19):1557-1568. Epub 2019 Sep 1.

British Heart Foundation Centre for Cardiovascular Science (A.B., K.K.L., S.S., A.V.F., A.R.C., L.M., F.E.S., D.E.N., A.S.V.S., N.L.M., A.A.), University of Edinburgh, United Kingdom.

Background: Guidelines acknowledge the emerging role of high-sensitivity cardiac troponin (hs-cTnl) for risk stratification and the early rule-out of myocardial infarction, but multiple thresholds have been described. We evaluate the safety and effectiveness of risk stratification thresholds in patients with suspected acute coronary syndrome.

Methods: Consecutive patients with suspected acute coronary syndrome (n=48 282) were enrolled in a multicenter trial across 10 hospitals in Scotland. In a prespecified secondary and observational analysis, we compared the performance of the limit of detection (<2 ng/L) and an optimized risk stratification threshold (<5 ng/L) using the Abbott high-sensitivity troponin I assay. Patients with myocardial injury at presentation, with ≤2 hours of symptoms or with ST-segment elevation myocardial infarction were excluded. The negative predictive value was determined in all patients and in subgroups for a primary outcome of myocardial infarction or cardiac death within 30 days. The secondary outcome was myocardial infarction or cardiac death at 12 months, with risk modeled using logistic regression adjusted for age and sex.

Results: In total, 32 837 consecutive patients (61±17 years, 47% female) were included, of whom 23 260 (71%) and 12,716 (39%) had hs-cTnl concentrations of <5 ng/L and <2 ng/L at presentation. The negative predictive value for the primary outcome was 99.8% (95% CI, 99.7%-99.8%) and 99.9% (95% CI, 99.8%-99.9%) in those with hs-cTnl concentrations of <5 ng/L and <2 ng/L, respectively. At both thresholds, the negative predictive value was consistent in men and women and across all age groups, although the proportion of patients identified as low risk fell with increasing age. Compared with patients with hs-cTnl concentrations of ≥5 ng/L but <99th centile, the risk of myocardial infarction or cardiac death at 12 months was 77% lower in those <5 ng/L (5.3% vs 0.7%; adjusted odds ratio, 0.23 [95% CI, 0.19-0.28]) and 80% lower in those <2 ng/L (5.3% vs 0.3%; adjusted odds ratio, 0.20 [95% CI, 0.14-0.29]).

Conclusions: Use of risk stratification thresholds for hs-cTnl identify patients with suspected acute coronary syndrome and at least 2 hours of symptoms as low risk at presentation irrespective of age and sex.

Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01852123.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.042866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6831036PMC
November 2019

Presenting Symptoms in Men and Women Diagnosed With Myocardial Infarction Using Sex-Specific Criteria.

J Am Heart Assoc 2019 09 20;8(17):e012307. Epub 2019 Aug 20.

BHF Centre for Cardiovascular Science University of Edinburgh United Kingdom.

Background Sex-specific criteria are recommended for the diagnosis of myocardial infarction, but the impact of these on presenting characteristics is unknown. Methods and Results We evaluated patient-reported symptoms in 1941 patients (39% women) with suspected acute coronary syndrome attending the emergency department in a substudy of a prospective trial. Standardized criteria defined typical and atypical presentations based on pain nature, location, radiation, and additional symptoms. Diagnosis of myocardial infarction was adjudicated using a high-sensitivity cardiac troponin I assay with sex-specific thresholds (>16 ng/L women, >34 ng/L men). Patients identified who were missed by the contemporary assay with a uniform threshold (≥50 ng/L) were reclassified by this approach. Type 1 myocardial infarction was diagnosed in 16% (184/1185) of men and 12% (90/756) of women, with 9 (5%) men and 27 (30%) women reclassified using high-sensitivity cardiac troponin I and sex-specific thresholds. Chest pain was the presenting symptom in 91% (1081/1185) of men and 92% (698/756) of women. Typical symptoms were more common in women than in men with myocardial infarction (77% [69/90] versus 59% [109/184]; P=0.007), and differences were similar in those reclassified (74% [20/27] versus 44% [4/9]; P=0.22). The presence of ≥3 typical features was associated with a positive likelihood ratio for the diagnosis of myocardial infarction in women (positive likelihood ratio, 1.18; 95% CI, 1.03-1.31) but not in men (positive likelihood ratio 1.09; 95% CI, 0.96-1.24). Conclusions Typical symptoms are more common and have greater predictive value in women than in men with myocardial infarction whether or not they are diagnosed using sex-specific criteria. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier NCT01852123.
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http://dx.doi.org/10.1161/JAHA.119.012307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6755854PMC
September 2019

Ticagrelor to Reduce Myocardial Injury in Patients With High-Risk Coronary Artery Plaque.

JACC Cardiovasc Imaging 2020 07 14;13(7):1549-1560. Epub 2019 Aug 14.

British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom; Christchurch Heart Institute, University of Otago, Christchurch, New Zealand.

Objectives: The goal of this study was to determine whether ticagrelor reduces high-sensitivity troponin I concentrations in patients with established coronary artery disease and high-risk coronary plaque.

Background: High-risk coronary atherosclerotic plaque is associated with higher plasma troponin concentrations suggesting ongoing myocardial injury that may be a target for dual antiplatelet therapy.

Methods: In a randomized, double-blind, placebo-controlled trial, patients with multivessel coronary artery disease underwent coronary F-fluoride positron emission tomography/coronary computed tomography scanning and measurement of high-sensitivity cardiac troponin I. Patients were randomized (1:1) to receive ticagrelor 90 mg twice daily or matched placebo. The primary endpoint was troponin I concentration at 30 days in patients with increased coronary F-fluoride uptake.

Results: In total, 202 patients were randomized to treatment, and 191 met the pre-specified criteria for inclusion in the primary analysis. In patients with increased coronary F-fluoride uptake (120 of 191), there was no evidence that ticagrelor had an effect on plasma troponin concentrations at 30 days (ratio of geometric means for ticagrelor vs. placebo: 1.11; 95% confidence interval: 0.90 to 1.36; p = 0.32). Over 1 year, ticagrelor had no effect on troponin concentrations in patients with increased coronary F-fluoride uptake (ratio of geometric means: 0.86; 95% confidence interval: 0.63 to 1.17; p = 0.33).

Conclusions: Dual antiplatelet therapy with ticagrelor did not reduce plasma troponin concentrations in patients with high-risk coronary plaque, suggesting that subclinical plaque thrombosis does not contribute to ongoing myocardial injury in this setting. (Dual Antiplatelet Therapy to Reduce Myocardial Injury [DIAMOND]; NCT02110303).
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http://dx.doi.org/10.1016/j.jcmg.2019.05.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7342015PMC
July 2020

Machine Learning to Predict the Likelihood of Acute Myocardial Infarction.

Circulation 2019 Aug 16. Epub 2019 Aug 16.

BHF Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh, United Kingdom; Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, United Kingdom.

Background: Variations in cardiac troponin concentrations by age, sex and time between samples in patients with suspected myocardial infarction are not currently accounted for in diagnostic approaches. We aimed to combine these variables through machine learning to improve the assessment of risk for individual patients.

Methods: A machine learning algorithm (myocardial-ischemic-injury-index [MI]) incorporating age, sex, and paired high-sensitivity cardiac troponin I concentrations, was trained on 3,013 patients and tested on 7,998 patients with suspected myocardial infarction. MI uses gradient boosting to compute a value (0-100) reflecting an individual's likelihood of a diagnosis of type 1 myocardial infarction and estimates the sensitivity, negative predictive value (NPV), specificity and positive predictive value (PPV) for that individual. Assessment was by calibration and area under the receiver-operating-characteristic curve (AUC). Secondary analysis evaluated example MI thresholds from the training set that identified patients as low-risk (99% sensitivity) and high-risk (75% PPV), and performance at these thresholds was compared in the test set to the 99th percentile and European Society of Cardiology (ESC) rule-out pathways.

Results: Myocardial infarction occurred in 404 (13.4%) patients in the training set and 849 (10.6%) patients in the test set. MI was well calibrated with a very high AUC of 0.963 [0.956-0.971] in the test set and similar performance in early and late presenters. Example MI thresholds identifying low-risk and high-risk patients in the training set were 1.6 and 49.7 respectively. In the test set, MI values were <1.6 in 69.5% with a NPV of 99.7% (99.5%-99.8%) and sensitivity of 97.8% (96.7-98.7%), and were ≥49.7 in 10.6% with a PPV of 71.8% (68.9-75.0%) and specificity of 96.7% (96.3-97.1%). Using these thresholds, MI performed better than the ESC 0/3-hour pathway (sensitivity 82.5% [74.5-88.8%], specificity 92.2% [90.7-93.5%]) and the 99th percentile at any time-point (sensitivity 89.6% [87.4-91.6%]), specificity 89.3% [88.6-90.0%]).

Conclusions: Using machine learning, MI provides an individualized and objective assessment of the likelihood of myocardial infarction, which can be used to identify low-risk and high-risk patients who may benefit from earlier clinical decisions.

Clinical Trial Registration: Unique Identifier: Australian New Zealand Clinical Trials Registry: ACTRN12616001441404. URL: https://www.anzctr.org.au.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.041980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6749969PMC
August 2019