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.

HIV-Associated Cardiovascular Disease Pathogenesis: An Emerging Understanding Through Imaging and Immunology.

Cardiac abnormalities were identified early in the epidemic of AIDS, predating the isolation and characterization of the etiologic agent, HIV. Several decades later, the causation and pathogenesis of cardiovascular disease (CVD) linked to HIV infection continue to be the focus of intense speculation. Before the widespread use of antiretroviral therapy, HIV-associated CVD was primarily characterized by HIV-associated cardiomyopathy linked to profound immunodeficiency. With increasing antiretroviral therapy use, viral load suppression, and establishment of immune competency, the effects of HIV on the cardiovascular system are more subtle. Yet, people living with HIV still face an increased incidence of cardiovascular pathology. Advances in cardiac imaging modalities and immunology have deepened our understanding of the pathogenesis of HIV-associated CVD. This review provides an overview of the pathogenesis of HIV-associated CVD integrating data from imaging and immunologic studies with particular relevance to the HIV population originating from high-endemic regions, such as sub-Saharan Africa. The review highlights key evidence gaps in the field and suggests future directions for research to better understand the complex HIV-CVD interactions.

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.

Application of the Universal Definition of Myocardial Infarction in Clinical Practice in Scotland and Sweden.

Importance: Whether the diagnostic classifications proposed by the universal definition of myocardial infarction (MI) to identify type 1 MI due to atherothrombosis and type 2 MI due to myocardial oxygen supply-demand imbalance have been applied consistently in clinical practice is unknown. Objective: To evaluate the application of the universal definition of MI in consecutive patients with possible MI across 2 health care systems. Design, Setting, and Participants: This cohort study used data from 2 prospective cohorts enrolling consecutive patients with possible MI in Scotland (2013-2016) and Sweden (2011-2014) to assess accuracy of clinical diagnosis of MI recorded in hospital records for patients with an adjudicated diagnosis of type 1 or type 2 MI. Data were analyzed from August 2022 to February 2023. Main Outcomes and Measures: The main outcome was the proportion of patients with a clinical diagnosis of MI recorded in the hospital records who had type 1 or type 2 MI, adjudicated by an independent panel according to the universal definition. Characteristics and risk of subsequent MI or cardiovascular death at 1 year were compared. Results: A total of 50 356 patients were assessed. The cohort from Scotland included 28 783 (15 562 men [54%]; mean [SD] age, 60 [17] years), and the cohort from Sweden included 21 573 (11 110 men [51%]; mean [SD] age, 56 [17] years) patients. In Scotland, a clinical diagnosis of MI was recorded in 2506 of 3187 patients with an adjudicated diagnosis of type 1 MI (79%) and 122 of 716 patients with an adjudicated diagnosis of type 2 MI (17%). Similar findings were observed in Sweden, with 970 of 1111 patients with adjudicated diagnosis of type 1 MI (87%) and 57 of 251 patients with adjudicated diagnosis of type 2 MI (23%) receiving a clinical diagnosis of MI. Patients with an adjudicated diagnosis of type 1 MI without a clinical diagnosis were more likely to be women (eg, 336 women [49%] vs 909 women [36%] in Scotland; P < .001) and older (mean [SD] age, 71 [14] v 67 [14] years in Scotland, P < .001) and, when adjusting for competing risk from noncardiovascular death, were at similar or increased risk of subsequent MI or cardiovascular death compared with patients with a clinical diagnosis of MI (eg, 29% vs 18% in Scotland; P < .001). Conclusions and Relevance: In this cohort study, the universal definition of MI was not consistently applied in clinical practice, with a minority of patients with type 2 MI identified, and type 1 MI underrecognized in women and older persons, suggesting uncertainty remains regarding the diagnostic criteria or value of the classification.

The burden and natural history of cardiac pathology at TB diagnosis in a high-HIV prevalence district in Zambia: protocol for the TB-Heart study.

BACKGROUND: Tuberculosis (TB) continues to be a major cause of death across sub-Saharan Africa (SSA). In parallel, non-communicable disease and especially cardiovascular disease (CVD) burden has increased substantially in the region. Cardiac manifestations of TB are well-recognised but the extent to which they co-exist with pulmonary TB (PTB) has not been systematically evaluated. The aim of this study is to improve understanding of the burden of cardiac pathology in PTB in those living with and without HIV in a high-burden setting. METHODS: This is a cross-sectional and natural history study to evaluate the burden and natural history of cardiac pathology in participants with PTB in Lusaka, Zambia, a high burden setting for TB and HIV. Participants with PTB, with and without HIV will be consecutively recruited alongside age- and sex-matched TB-uninfected comparators on a 2:1 basis. Participants will undergo baseline assessments to collect clinical, socio-demographic, functional, laboratory and TB disease impact data followed by point-of-care and standard echocardiography. Participants with PTB will undergo further repeat clinical and functional examination at two- and six months follow-up. Those with cardiac pathology at baseline will undergo repeat echocardiography at six months. DISCUSSION: The outcomes of the study are to a) determine the burden of cardiac pathology at TB diagnosis, b) describe its association with patient-defining risk factors and biochemical markers of cardiac injury and stretch and c) describe the natural history of cardiac pathology during the course of TB treatment.

Could paramedics use the HEART Pathway to identify patients at low-risk of myocardial infarction in the prehospital setting?

In the Emergency Department, patients with suspected myocardial infarction can be risk stratified using the HEART pathway, which has recently been amended for prehospital use and modified for the incorporation of a high-sensitivity cardiac troponin test. In a prospective analysis, the performance of both HEART pathways in the prehospital setting, with a high-sensitivity cardiac troponin test using 3 different thresholds, was evaluated for major adverse cardiac events at 30 days. We found that both low-risk HEART pathways, when using the most conservative cardiac troponin thresholds, approached but did not reach accepted rule-out performance in the Emergency Department.

Uniform or Sex-Specific Cardiac Troponin Thresholds to Rule Out Myocardial Infarction at Presentation.

BACKGROUND: Myocardial infarction can be ruled out in patients with a single cardiac troponin measurement. Whether use of a uniform rule-out threshold has resulted in sex differences in care remains unclear. OBJECTIVES: The purpose of this study was to evaluate implementation of a uniform rule-out threshold in females and males with possible myocardial infarction, and to derive and validate sex-specific thresholds. METHODS: The implementation of a uniform rule-out threshold (<5 ng/L) with a high-sensitivity cardiac troponin I assay was evaluated in consecutive patients presenting with possible myocardial infarction. The proportion of low-risk patients discharged from the emergency department and incidence of myocardial infarction or cardiac death at 30 days were determined. Sex-specific thresholds were derived and validated, and proportion of female and male patients were stratified as low-risk compared with uniform threshold. RESULTS: In 16,792 patients (age 58 ± 17 years; 46% female) care was guided using a uniform threshold. This identified more female than male patients as low risk (73% vs 62%), but a similar proportion of low-risk patients were discharged from the emergency department (81% for both) with fewer than 5 (<0.1%) patients having a subsequent myocardial infarction or cardiac death at 30 days. Compared with a uniform threshold of <5 ng/L, use of sex-specific thresholds would increase the proportion of female (61.8% vs 65.9%) and reduce the proportion of male (54.8% vs 47.8%) patients identified as low risk. CONCLUSIONS: Implementation of a uniform rule-out threshold for myocardial infarction was safe and effective in both sexes. Sex-specific rule-out thresholds should be considered, but their impact on effectiveness and safety may be limited.

Kidney replacement therapy: trends in incidence, treatment, and outcomes of myocardial infarction and stroke in a nationwide Scottish study.

BACKGROUND AND AIMS: Patients with kidney failure have a higher risk of cardiovascular disease compared with the general population. Whilst temporal trends of myocardial infarction and stroke are declining in the general population, these have not been evaluated in patients with kidney failure. This study aimed to describe national trends in the incidence, treatment, and outcomes of myocardial infarction and stroke in patients with kidney failure (i.e. on dialysis or with a kidney transplant) over a 20-year period, stratified by age and sex. METHODS: In this retrospective national data linkage study, all patients with kidney failure in Scotland (UK) receiving kidney replacement therapy between January 1996 and December 2016 were linked to national hospitalization, prescribing, and death records. The primary outcomes were the incidence of myocardial infarction and stroke, and subsequent cardiovascular death. Generalized additive models were constructed to estimate age-standardized, sex-stratified incidence rates and trends in cardiovascular and all-cause death. RESULTS: Amongst 16 050 patients with kidney failure [52 (SD 15) years; 41.5% women], there were 1992 [66 (SD 12) years; 34.8% women] and 996 [65 (SD 13) years; 45.1% women] incident myocardial infarctions and strokes, respectively, between January 1996 and December 2016. During this period, the age-standardized incidence of myocardial infarction per 100 000 decreased in men {from 4376 [95% confidence interval (CI) 3998-4785] to 1835 (95% CI 1692-1988)} and women [from 3268 (95% CI 2982-3593) to 1369 (95% CI 1257-1491)]. Similarly, the age-standardized incidence of stroke per 100 000 also decreased in men [from 1978 (95% CI 1795-2175) to 799 (95% CI 729-875)] and women [from 2234 (95% CI 2031-2468) to 903 (95% CI 824-990)]. Compared with the general population, the incidence of myocardial infarction was four- to eight-fold higher in patients with kidney failure, whilst for stroke it was two- to four-fold higher. The use of evidence-based cardioprotective treatment increased over the study period, and the predicted probability of cardiovascular death within 1 year of myocardial infarction for a 66-year-old patient with kidney failure (mean age of the cohort) fell in men (76.6% to 38.6%) and women (76.8% to 38.8%), and also decreased in both sexes following stroke (men, from 63.5% to 41.4%; women, from 67.6% to 45.8%). CONCLUSIONS: The incidence of myocardial infarction and stroke has halved in patients with kidney failure over the past 20 years but remains significantly higher than in the general population. Despite improvements in treatment and outcomes, the prognosis of these patients following myocardial infarction and stroke remains poor.

Impact of Residential Social Deprivation on Prediction of Heart Failure in Patients With Type 2 Diabetes: External Validation and Recalibration of the WATCH-DM Score Using Real World Data.

BACKGROUND: Patients with type 2 diabetes are at risk of heart failure hospitalization. As social determinants of health are rarely included in risk models, we validated and recalibrated the WATCH-DM score in a diverse patient-group using their social deprivation index (SDI). METHODS: We identified US Veterans with type 2 diabetes without heart failure that received outpatient care during 2010 at Veterans Affairs medical centers nationwide, linked them to their SDI using residential ZIP codes and grouped them as SDI <20%, 21% to 40%, 41% to 60%, 61% to 80%, and >80% (higher values represent increased deprivation). Accounting for all-cause mortality, we obtained the incidence for heart failure hospitalization at 5 years follow-up; overall and in each SDI group. We evaluated the WATCH-DM score using the C statistic, the Greenwood Nam D'Agostino test χ2 test and calibration plots and further recalibrated the WATCH-DM score for each SDI group using a statistical correction factor. RESULTS: In 1 065 691 studied patients (mean age 67 years, 25% Black and 6% Hispanic patients), the 5-year incidence of heart failure hospitalization was 5.39%. In SDI group 1 (least deprived) and 5 (most deprived), the 5-year heart failure hospitalization was 3.18% and 11%, respectively. The score C statistic was 0.62; WATCH-DM systematically overestimated heart failure risk in SDI groups 1 to 2 (expected/observed ratios, 1.38 and 1.36, respectively) and underestimated the heart failure risk in groups 4 to 5 (expected/observed ratios, 0.95 and 0.80, respectively). Graphical evaluation demonstrated that the recalibration of WATCH-DM using an SDI group-based correction factor improved predictive capabilities as supported by reduction in the χ2 test results (801-27 in SDI groups I; 623-23 in SDI group V). CONCLUSIONS: Including social determinants of health to recalibrate the WATCH-DM score improved risk prediction highlighting the importance of including social determinants in future clinical risk prediction models.

Rationale and design of the THIRST Alert feasibility study: a pragmatic, single-centre, parallel-group randomised controlled trial of an interruptive alert for oral fluid restriction in patients treated with intravenous furosemide.

INTRODUCTION: Acute heart failure (HF) is a major cause of unplanned hospitalisation characterised by excess body water. A restriction in oral fluid intake is commonly imposed on patients as an adjunct to pharmacological therapy with loop diuretics, but there is a lack of evidence from traditional randomised controlled trials (RCTs) to support the safety and effectiveness of this intervention in the acute setting.This study aims to explore the feasibility of using computer alerts within the electronic health record (EHR) system to invite clinical care teams to enrol patients into a pragmatic RCT at the time of clinical decision-making. It will additionally assess the effectiveness of using an alert to help address the clinical research question of whether oral fluid restriction is a safe and effective adjunct to pharmacological therapy for patients admitted with fluid overload. METHODS AND ANALYSIS: THIRST (Randomised Controlled Trial within the electronic Health record of an Interruptive alert displaying a fluid Restriction Suggestion in patients with the treatable Trait of congestion) Alert is a single-centre, parallel-group, open-label pragmatic RCT embedded in the EHR system that will be conducted as a feasibility study at an National Health Service (NHS) hospital in London. The clinical care team will be invited to enrol suitable patients in the study using a point-of-care alert with a target sample size of 50 patients. Enrolled patients will then be randomised to either restricted or unrestricted oral fluid intake. Two primary outcomes will be explored (1) the proportion of eligible patients enrolled in the study and (2) the mean difference in oral fluid intake between randomised groups. A series of secondary outcomes are specified to evaluate the effectiveness of the alert, adherence to the randomised treatment allocation and the quality of data generated from routine care, relevant to the outcomes of interest. ETHICS AND DISSEMINATION: This study was approved by Riverside Research Ethics Committee (Ref: 22/LO/0889) and will be published on completion. TRIAL REGISTRATION NUMBER: NCT05869656.

Prevalence of hypertension and high-normal blood pressure among young adults in Zimbabwe: findings from a large, cross-sectional population-based survey.

BACKGROUND: Hypertension is the greatest driver of cardiovascular mortality and onset might be in youth. We aimed to investigate the prevalence of and risk factors for elevated blood pressure (hypertension ≥140 mm Hg systolic, ≥90 mm Hg diastolic, or both) and high-normal blood pressure (130-139 mm Hg systolic, 85-89 mm Hg diastolic, or both) among youth in Zimbabwe. METHODS: A population-based, cross-sectional survey of randomly sampled youth aged 18-24 years from 24 urban and peri-urban communities in three provinces (Harare, Bulawayo, and Mashonaland East) in Zimbabwe was conducted between Oct 4, 2021, and June 2, 2022. Standardised questionnaires were used by research assistants to collect sociodemographic, behavioural, and clinical data. Height, bodyweight, and blood pressure were recorded. Three seated blood pressure measurements were taken at standardised timepoints during participant interview using a digital sphygmomanometer and cuffs sized on mid-upper arm circumference. The association of potential risk factors with elevated blood pressure was examined using multivariable logistic regression. FINDINGS: 17 682 (94·4%) of 18 729 eligible participants were recruited, 17 637 (99·7%) of whom had complete data, and 16 883 (95·7%) of whom were included in the final study sample after excluding 754 (4·3%) pregnant women. The median age was 20 years (IQR 19-22), 9973 (59·1%) participants were female, and 6910 (40·9%) were male. The prevalence of hypertension was 7·4% (95% CI 7·0-7·8) and high-normal blood pressure was 12·2% (11·7-12·7). Overall, prevalence of hypertension was higher in men (8·7% [95% CI 8·2-9·6]) than in women (6·6% [6·0-6·9]), but with age increased to similar levels (at age 18 years 7·3% [6·2-8·6] and 4·3% [3·5-5·2]; at age 23-24 years 10·9% [9·3-12·6] and 9·5% [8·4-10·7] in men and women, respectively). After adjusting for factors associated with hypertension in the crude analysis, hypertension was associated with male sex (adjusted odds ratio 1·53 [95% CI 1·36-1·74]), increasing age (age 19-20 years 1·20 [1·00-1·44]; age 21-22 years 1·45 [1·20-1·75]; age 23-24 years 1·90 [1·57-2·30], vs age 18 years), and BMI of 30·0 kg/m2 or more (1·94 [1·53-2·47] vs 18·5-24·9 kg/m2). A BMI of 18·5 kg/m2 or less (0·79 [0·63-0·98] vs 18·5-24·9 kg/m2) and living with HIV (0·71 [0·55-0·92]) were associated with lower odds of hypertension. INTERPRETATION: Prevalence of elevated blood pressure is high among urban and peri-urban youth in Zimbabwe and increases rapidly with age. Further research is needed to understand drivers of blood pressure elevation and the extent of target organ damage in youth in Zimbabwe and similar sub-Saharan African settings, to guide implementation of prevention and management strategies. FUNDING: Wellcome Trust.

Multiple Cardiac Biomarkers to Improve Prediction of Cardiovascular Events: Findings from the Generation Scotland Scottish Family Health Study.

BACKGROUND: Many studies have investigated whether single cardiac biomarkers improve cardiovascular risk prediction for primary prevention but whether a combined approach could further improve risk prediction is unclear. We aimed to test a sex-specific, combined cardiac biomarker approach for cardiovascular risk prediction. METHODS: In the Generation Scotland Scottish Family Health Study, N-terminal pro-B-type natriuretic peptide (NT-proBNP), growth differentiation factor-15 (GDF-15), cardiac troponin I (cTnI), cardiac troponin T (cTnT), and C-reactive protein (CRP) were measured in stored serum using automated immunoassays. Sex-specific Cox models that included SCORE2 risk factors evaluated addition of single and combined biomarkers for prediction of major adverse cardiovascular events (MACE). Combined biomarker models were compared to a baseline model that included SCORE2 risk factors. RESULTS: The study population comprised 18 383 individuals (58.9% women, median age of 48 years [25th-75th percentile, 35-58 years]). During the median follow up of 11.6 (25th-75th percentile, 10.8-13.0) years, MACE occurred in 942 (5.1%) individuals. The greatest increase in discrimination with addition of individual biomarkers to the base model was for women GDF-15 and for men NT-proBNP (change in c-index: + 0.010 for women and +0.005 for men). For women, combined biomarker models that included GDF-15 and NT-proBNP (+0.012) or GDF-15 and cTnI (+0.013), but not CRP or cTnT, further improved discrimination. For men, combined biomarker models that included NT-proBNP and GDF-15 (+0.007), NT-proBNP and cTnI (+0.006), or NT-proBNP and CRP (+0.008), but not cTnT, further improved discrimination. CONCLUSIONS: A combined biomarker approach, particularly the use of GDF-15, NT-proBNP and cTnI, further refined cardiovascular risk estimates.

Artificial intelligence and machine learning for clinical pharmacology.

Artificial intelligence (AI) will impact many aspects of clinical pharmacology, including drug discovery and development, clinical trials, personalized medicine, pharmacogenomics, pharmacovigilance and clinical toxicology. The rapid progress of AI in healthcare means clinical pharmacologists should have an understanding of AI and its implementation in clinical practice. As with any new therapy or health technology, it is imperative that AI tools are subject to robust and stringent evaluation to ensure that they enhance clinical practice in a safe and equitable manner. This review serves as an introduction to AI for the clinical pharmacologist, highlighting current applications, aspects of model development and issues surrounding evaluation and deployment. The aim of this article is to empower clinical pharmacologists to embrace and lead on the safe and effective use of AI within healthcare.

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.

Implementation of a high sensitivity cardiac troponin I assay and risk of myocardial infarction or death at five years: observational analysis of a stepped wedge, cluster randomised controlled trial.

OBJECTIVE: To evaluate the impact of implementing a high sensitivity assay for cardiac troponin I on long term outcomes in patients with suspected acute coronary syndrome. DESIGN: Secondary observational analysis of a stepped wedge, cluster randomised controlled trial. SETTING: 10 secondary and tertiary care centres in Scotland, UK. PARTICIPANTS: 48 282 consecutive patients with suspected acute coronary syndrome. Myocardial injury was defined as any high sensitivity assay result for cardiac troponin I >99th centile of 16 ng/L in women and 34 ng/L in men. INTERVENTION: Hospital sites were randomly allocated to either early (n=5 hospitals) or late (n=5 hospitals) implementation of a high sensitivity cardiac troponin I assay with sex specific diagnostic thresholds. MAIN OUTCOME MEASURE: The main outcome was myocardial infarction or death at five years. RESULTS: 10 360 patients had cardiac troponin concentrations greater than the 99th centile, of whom 1771 (17.1%) were reclassified by the high sensitivity assay. The five year incidence of subsequent myocardial infarction or death before and after implementation of the high sensitivity assay was 29.4% (5588/18 978) v 25.9% (7591/29 304), respectively, in all patients (adjusted hazard ratio 0.97, 95% confidence interval 0.93 to 1.01), and 63.0% (456/720) v 53.9% (567/1051), respectively, in those reclassified by the high sensitivity assay (0.82, 0.72 to 0.94). After implementation of the high sensitivity assay, a reduction in subsequent myocardial infarction or death was observed in patients with non-ischaemic myocardial injury (0.83, 0.75 to 0.91) but not in those with type 1 or type 2 myocardial infarction (0.92, 0.83 to 1.01 and 0.98, 0.84 to 1.14). CONCLUSIONS: Implementation of a high sensitivity cardiac troponin I assay in the assessment of patients with suspected acute coronary syndrome was associated with a reduced risk of subsequent myocardial infarction or death at five years in those reclassified by the high sensitivity assay. Improvements in outcome were greatest in patients with non-ischaemic myocardial injury, suggesting a broader benefit beyond the identification of myocardial infarction. TRIAL REGISTRATION: ClinicalTrials.gov NCT01852123.

Burden, determinants, consequences and care of multimorbidity in rural and urbanising Telangana, India: protocol for a mixed-methods study within the APCAPS cohort.

INTRODUCTION: The epidemiological and demographic transitions are leading to a rising burden of multimorbidity (co-occurrence of two or more chronic conditions) worldwide. Evidence on the burden, determinants, consequences and care of multimorbidity in rural and urbanising India is limited, partly due to a lack of longitudinal and objectively measured data on chronic health conditions. We will conduct a mixed-methods study nested in the prospective Andhra Pradesh Children and Parents' Study (APCAPS) cohort to develop a data resource for understanding the epidemiology of multimorbidity in rural and urbanising India and developing interventions to improve the prevention and care of multimorbidity. METHODS AND ANALYSIS: We aim to recruit 2100 APCAPS cohort members aged 45+ who have clinical and lifestyle data collected during a previous cohort follow-up (2010-2012). We will screen for locally prevalent non-communicable, infectious and mental health conditions, alongside cognitive impairments, disabilities and frailty, using a combination of self-reported clinical diagnosis, symptom-based questionnaires, physical examinations and biochemical assays. We will conduct in-depth interviews with people with varying multimorbidity clusters, their informal carers and local healthcare providers. Deidentified data will be made available to external researchers. ETHICS AND DISSEMINATION: The study has received approval from the ethics committees of the National Institute of Nutrition and Indian Institute of Public Health Hyderabad, India and the London School of Hygiene and Tropical Medicine, UK. Meta-data and data collection instruments will be published on the APCAPS website alongside details of existing APCAPS data and the data access process (www.lshtm.ac.uk/research/centres-projects-groups/apcaps).