The relationship between parameters measured using intravoxel incoherent motion and dynamic contrast-enhanced MRI in patients with breast cancer undergoing neoadjuvant chemotherapy: a longitudinal cohort study.

Purpose: The primary aim of this study was to explore whether intravoxel incoherent motion (IVIM) can offer a contrast-agent-free alternative to dynamic contrast-enhanced (DCE)-MRI for measuring breast tumor perfusion. The secondary aim was to investigate the relationship between tissue diffusion measures from DWI and DCE-MRI measures of the tissue interstitial and extracellular volume fractions. Materials and methods: A total of 108 paired DWI and DCE-MRI scans were acquired at 1.5 T from 40 patients with primary breast cancer (median age: 44.5 years) before and during neoadjuvant chemotherapy (NACT). DWI parameters included apparent diffusion coefficient (ADC), tissue diffusion (Dt), pseudo-diffusion coefficient (Dp), perfused fraction (f), and the product f×Dp (microvascular blood flow). DCE-MRI parameters included blood flow (Fb), blood volume fraction (vb), interstitial volume fraction (ve) and extracellular volume fraction (vd). All were extracted from three tumor regions of interest (whole-tumor, ADC cold-spot, and DCE-MRI hot-spot) at three MRI visits: pre-treatment, after one, and three cycles of NACT. Spearman's rank correlation was used for assessing between-subject correlations (r), while repeated measures correlation was employed to assess within-subject correlations (rrm) across visits between DWI and DCE-MRI parameters in each region. Results: No statistically significant between-subject or within-subject correlation was found between the perfusion parameters estimated by IVIM and DCE-MRI (f versus vb and f×Dp versus Fb; P=0.07-0.81). Significant moderate positive between-subject and within-subject correlations were observed between ADC and ve (r=0.461, rrm=0.597) and between Dt and ve (r=0.405, rrm=0.514) as well as moderate positive within-subject correlations between ADC and vd and between Dt and vd (rrm=0.619 and 0.564, respectively) in the whole-tumor region. Conclusion: No correlations were observed between the perfusion parameters estimated by IVIM and DCE-MRI. This may be attributed to imprecise estimates of fxDp and vb, or an underlying difference in what IVIM and DCE-MRI measure. Care should be taken when interpreting the IVIM parameters (f and f×Dp) as surrogates for those measured using DCE-MRI. However, the moderate positive correlations found between ADC and Dt and the DCE-MRI parameters ve and vd confirms the expectation that as the interstitial and extracellular volume fractions increase, water diffusion increases.

Associations of health-related quality of life with major adverse cardiovascular and cerebrovascular events for individuals with ischaemic heart disease: systematic review, meta-analysis and evidence mapping.

OBJECTIVE: To investigate the association between health-related quality of life (HRQoL) and major adverse cardiovascular and cerebrovascular events (MACCE) in individuals with ischaemic heart disease (IHD). METHODS: Medline(R), Embase, APA PsycINFO and CINAHL (EBSCO) from inception to 3 April 2023 were searched. Studies reporting association of HRQoL, using a generic or cardiac-specific tool, with MACCE or components of MACCE for individuals with IHD were eligible for inclusion. Risk of bias was assessed using the Newcastle-Ottawa Quality Assessment Scale to assess the quality of the studies. Descriptive synthesis, evidence mapping and random-effects meta-analysis were performed stratified by HRQoL measures and effect estimates. Between-study heterogeneity was assessed using the Higgins I2 statistic. RESULTS: Fifty-one articles were included with a total of 134 740 participants from 53 countries. Meta-analysis of 23 studies found that the risk of MACCE increased with lower baseline HeartQoL score (HR 1.49, 95% CI 1.16 to 1.93) and Short Form Survey (SF-12) physical component score (PCS) (HR 1.39, 95% CI 1.28 to 1.51). Risk of all-cause mortality increased with a lower HeartQoL (HR 1.64, 95% CI 1.34 to 2.01), EuroQol 5-dimension (HR 1.17, 95% CI 1.12 to 1.22), SF-36 PCS (HR 1.29, 95% CI 1.19 to 1.41), SF-36 mental component score (HR 1.18, 95% CI 1.08 to 1.30). CONCLUSIONS: This study found an inverse association between baseline values or change in HRQoL and MACCE or components of MACCE in individuals with IHD, albeit with between-study heterogeneity. Standardisation and routine assessment of HRQoL in clinical practice may help risk stratify individuals with IHD for tailored interventions. PROSPERO REGISTRATION NUMBER: CRD42021234638.

Cohort profile: Evaluation of the Methods and Management of Acute Coronary Events (EMMACE) Longitudinal Cohort.

AIMS: The Evaluation of the Methods and Management of Acute Coronary Events (EMMACE) longitudinal cohort study aims to investigate health trajectories of individuals following hospitalization for myocardial infarction (MI). METHODS AND RESULTS: EMMACE is a linked multicentre prospective cohort study of 14 899 patients with MI admitted to 77 hospitals in England who participated in the EMMACE-3 and -4 studies between 1st November 2011 and 24th June 2015. Long-term follow-up of the EMMACE cohorts was conducted through the EMMACE-XL (27th September 2020 to 31st March 2022) and EMMACE-XXL (1st July 2021 to 1st July 2023) studies. EMMACE collected individual participant data for health-related quality of life (HRQoL) measured by three-level EuroQol five-dimension and visual analogy scale at admission, 1 month, 6 months, 12 months, and 10 years follow-up, as well as medications, medication adherence, beliefs about medicines, Satisfaction with Information about Medicines Scale, and illness perceptions. Participant data were deterministically linked to the Myocardial Infarction National Audit Project (MINAP) for information on baseline treatments and comorbidities, Hospital Episode Statistics Admitted Patient Care (for cause-specific hospitalization data), and the Office for National Statistics (for mortality data) up to 2020. CONCLUSION: EMMACE is a nationwide prospective cohort that will provide unique insights into fatal and non-fatal outcomes, medication adherence, and HRQoL following MI.Trial registration: ClinicalTrials.gov NCT01808027 and NCT01819103.

Association of beta-blockers beyond 1 year after myocardial infarction and cardiovascular outcomes.

OBJECTIVE: Beta-blockers (BB) are an established treatment following myocardial infarction (MI). However, there is uncertainty as to whether BB beyond the first year of MI have a role in patients without heart failure or left ventricular systolic dysfunction (LVSD). METHODS: A nationwide cohort study was conducted including 43 618 patients with MI between 2005 and 2016 in the Swedish register for coronary heart disease. Follow-up started 1 year after hospitalisation (index date). Patients with heart failure or LVSD up until the index date were excluded. Patients were allocated into two groups according to BB treatment. Primary outcome was a composite of all-cause mortality, MI, unscheduled revascularisation and hospitalisation for heart failure. Outcomes were analysed using Cox and Fine-Grey regression models after inverse propensity score weighting. RESULTS: Overall, 34 253 (78.5%) patients received BB and 9365 (21.5%) did not at the index date 1 year following MI. The median age was 64 years and 25.5% were female. In the intention-to-treat analysis, the unadjusted rate of primary outcome was lower among patients who received versus not received BB (3.8 vs 4.9 events/100 person-years) (HR 0.76; 95% CI 0.73 to 1.04). Following inverse propensity score weighting and multivariable adjustment, the risk of the primary outcome was not different according to BB treatment (HR 0.99; 95% CI 0.93 to 1.04). Similar findings were observed when censoring for BB discontinuation or treatment switch during follow-up. CONCLUSION: Evidence from this nationwide cohort study suggests that BB treatment beyond 1 year of MI for patients without heart failure or LVSD was not associated with improved cardiovascular outcomes.

Attainment of NICE blood pressure targets among older people with newly diagnosed hypertension: nationwide linked electronic health records cohort study.

BACKGROUND: it is not known if clinical practice reflects guideline recommendations for the management of hypertension in older people and whether guideline adherence varies according to overall health status. AIMS: to describe the proportion of older people attaining National Institute for Health and Care Excellence (NICE) guideline blood pressure targets within 1 year of hypertension diagnosis and determine predictors of target attainment. METHODS: a nationwide cohort study of Welsh primary care data from the Secure Anonymised Information Linkage databank including patients aged ≥65 years newly diagnosed with hypertension between 1st June 2011 and 1st June 2016. The primary outcome was attainment of NICE guideline blood pressure targets as measured by the latest blood pressure recording up to 1 year after diagnosis. Predictors of target attainment were investigated using logistic regression. RESULTS: there were 26,392 patients (55% women, median age 71 [IQR 68-77] years) included, of which 13,939 (52.8%) attained a target blood pressure within a median follow-up of 9 months. Success in attaining target blood pressure was associated with a history of atrial fibrillation (OR 1.26, 95% CI 1.11, 1.43), heart failure (OR 1.25, 95% CI 1.06, 1.49) and myocardial infarction (OR 1.20, 95% CI 1.10, 1.32), all compared to no history of each, respectively. Care home residence, the severity of frailty, and increasing co-morbidity were not associated with target attainment following adjustment for confounder variables. CONCLUSIONS: blood pressure remains insufficiently controlled 1 year after diagnosis in nearly half of older people with newly diagnosed hypertension, but target attainment appears unrelated to baseline frailty, multi-morbidity or care home residence.

Sex differences in health-related quality of life trajectories following myocardial infarction: national longitudinal cohort study.

OBJECTIVES: To investigate sex-based differences in baseline values and longitudinal trajectories of health-related quality of life (HRQoL) in a large cohort of myocardial infarction (MI) survivors after adjusting for other important factors. DESIGN: Longitudinal cohort study. SETTING: Population-based longitudinal study the Evaluation of the Methods and Management of Acute Coronary Events study linked with national cardiovascular registry. Data were collected from 77 hospitals in England between 1 November 2011 and 24 June 2015. PARTICIPANTS: 9551 patients with MI. Patients were eligible for the study if they were ≥18 years of age. PRIMARY AND SECONDARY OUTCOME MEASURES: HRQoL was measured by EuroQol five-dimension, visual analogue scale (EQ-5D, EQ VAS) survey at baseline, 1, 6 and 12 months after discharge. Multi-level linear and logistic regression models coupled with inverse probability weighted propensity scoring were used to evaluate sex differences in HRQoL following MI. RESULTS: Of the 9551 patients with MI and complete data on sex, 25.1% (2,397) were women. At baseline, women reported lower HRQoL (EQ VAS (mean (SD) 59.8 (20.4) vs 64.5 (20.9)) (median (IQR) 60.00 (50.00-75.00) vs 70.00 (50.00-80.00))) (EQ-5D (mean (SD) 0.66 (0.31) vs 0.74 (0.28)) (median (IQR) 0.73 (0.52-0.85) vs 0.81 (0.62-1.00))) and were more likely to report problems in each HRQoL domain compared with men. In the covariate balanced and adjusted multi-level model sex differences in HRQoL persisted during follow-up, with lower EQ VAS and EQ-5D scores in women compared with men (adjusted EQ VAS model sex coefficient: -4.41, 95% CI -5.16 to -3.66 and adjusted EQ-5D model sex coefficient: -0.07, 95% CI -0.08 to -0.06). CONCLUSIONS: Women have lower HRQoL compared with men at baseline and during 12 months follow-up after MI. Tailored interventions for women following an MI could improve their quality of life. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT04598048, NCT01808027, NCT01819103.

Evaluation of Monoexponential, Stretched-Exponential and Intravoxel Incoherent Motion MRI Diffusion Models in Early Response Monitoring to Neoadjuvant Chemotherapy in Patients With Breast Cancer-A Preliminary Study.

BACKGROUND: There has been a growing interest in exploring the applications of stretched-exponential (SEM) and intravoxel incoherent motion (IVIM) models of diffusion-weighted imaging (DWI) in breast imaging, with the focus on differentiation of breast lesions. However, the use of SEM and IVIM models to predict early response to neoadjuvant chemotherapy (NACT) has received less attention. PURPOSE: To investigate the value of monoexponential, SEM, and IVIM models to predict early response to NACT in patients with primary breast cancer. STUDY TYPE: Prospective. POPULATION: Thirty-seven patients with primary breast cancer (aged 46 ± 11 years) due to undergo NACT. FIELD STRENGTH/SEQUENCES: A 1.5-T MR scanner, T1 -weighted three-dimensional spoiled gradient-echo, two-dimensional single-shot spin-echo echo-planar imaging sequence (DWI) at six b-values (0-800 s mm-2 ). ASSESSMENT: Tumor volume, apparent diffusion coefficient, tissue diffusion (Dt ), pseudo-diffusion coefficient (Dp ), perfusion fraction (f), distributed diffusion coefficient, and alpha (α) were extracted, following volumetric sampling of the tumors, at three time-points: pretreatment, post one and three cycles of NACT. STATISTICAL TESTS: Mann-Whitney test, receiver operating characteristic (ROC) curve. Statistical significance level was P < 0.05. RESULTS: Following NACT, 17 patients were determined to be pathological responders and 20 nonresponders. Tumor volume was significantly larger in nonresponders at each MRI time-point and demonstrated reasonable performance in predicting response (area under the ROC curve [AUC] = 0.83-0.87). No significant differences between groups were found in the diffusion coefficients at each time-point (P = 0.09-1). The parameters α (SEM), f, and f × Dp (IVIM) were able to differentiate between response groups after one cycle of NACT (AUC = 0.73, 0.72, and 0.74, respectively). CONCLUSION: Diffusion coefficients derived from the monoexponential, SEM, and IVIM models did not predict pathological response. However, the IVIM-derived parameters f and f × Dp and the SEM-derived parameter α were able to predict response to NACT in breast cancer patients following one cycle of NACT. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

Association of treatments for acute myocardial infarction and survival for seven common comorbidity states: a nationwide cohort study.

BACKGROUND: Comorbidity is common and has a substantial negative impact on the prognosis of patients with acute myocardial infarction (AMI). Whilst receipt of guideline-indicated treatment for AMI is associated with improved prognosis, the extent to which comorbidities influence treatment provision its efficacy is unknown. Therefore, we investigated the association between treatment provision for AMI and survival for seven common comorbidities. METHODS: We used data of 693,388 AMI patients recorded in the Myocardial Ischaemia National Audit Project (MINAP), 2003-2013. We investigated the association between comorbidities and receipt of optimal care for AMI (receipt of all eligible guideline-indicated treatments), and the effect of receipt of optimal care for comorbid AMI patients on long-term survival using flexible parametric survival models. RESULTS: A total of 412,809 [59.5%] patients with AMI had at least one comorbidity, including hypertension (302,388 [48.7%]), diabetes (122,228 [19.4%]), chronic obstructive pulmonary disease (COPD, 89,221 [14.9%]), cerebrovascular disease (51,883 [8.6%]), chronic heart failure (33,813 [5.6%]), chronic renal failure (31,029 [5.0%]) and peripheral vascular disease (27,627 [4.6%]). Receipt of optimal care was associated with greatest survival benefit for patients without comorbidities (HR 0.53, 95% CI 0.51-0.56) followed by patients with hypertension (HR 0.60, 95% CI 0.58-0.62), diabetes (HR 0.83, 95% CI 0.80-0.87), peripheral vascular disease (HR 0.85, 95% CI 0.79-0.91), renal failure (HR 0.89, 95% CI 0.84-0.94) and COPD (HR 0.90, 95% CI 0.87-0.94). For patients with heart failure and cerebrovascular disease, optimal care for AMI was not associated with improved survival. CONCLUSIONS: Overall, guideline-indicated care was associated with improved long-term survival. However, this was not the case in AMI patients with concomitant heart failure or cerebrovascular disease. There is therefore a need for novel treatments to improve outcomes for AMI patients with pre-existing heart failure or cerebrovascular disease.

Association of cardiac rehabilitation and health-related quality of life following acute myocardial infarction.

OBJECTIVE: To study the association of cardiac rehabilitation and physical activity with temporal changes in health-related quality of life (HRQoL) following acute myocardial infarction (AMI). METHODS: Evaluation of the Methods and Management of Acute Coronary Events-3 is a nationwide longitudinal prospective cohort study of 4570 patients admitted with an AMI between 1 November 2011 and 17 September 2013. HRQoL was estimated using EuroQol 5-Dimension-3 Level Questionnaire at hospitalisation, 30 days, and 6 and 12 months following hospital discharge. The association of cardiac rehabilitation and self-reported physical activity on temporal changes in HRQoL was quantified using inverse probability of treatment weighting propensity score and multilevel regression analyses. RESULTS: Cardiac rehabilitation attendees had higher HRQoL scores than non-attendees at 30 days (mean EuroQol 5-Visual Analogue Scale (EQ-VAS) scores: 71.0 (SD 16.8) vs 68.6 (SD 19.8)), 6 months (76.0 (SD 16.4) vs 70.2 (SD 19.0)) and 12 months (76.9 (SD 16.8) vs 70.4 (SD 20.4)). Attendees who were physically active ≥150 min/week had higher HRQoL scores compared with those who only attended cardiac rehabilitation at 30 days (mean EQ-VAS scores: 79.3 (SD 14.6) vs 70.2 (SD 17.0)), 6 months (82.2 (SD 13.9) vs 74.9 (SD 16.7)) and 12 months (84.1 (SD 12.1) vs 75.6 (SD 17.0)). Cardiac rehabilitation and self-reported physical activity of ≥150 min/week were each positively associated with temporal improvements in HRQoL (coefficient: 2.12 (95% CI 0.68 to 3.55) and 4.75 (95% CI 3.16 to 6.34), respectively). CONCLUSIONS: Cardiac rehabilitation was independently associated with temporal improvements in HRQoL at up to 12 months following hospitalisation, with such changes further improved in patients who were physically active.

Quality of life trajectories in survivors of acute myocardial infarction: a national longitudinal study.

AIM: To define trajectories of perceived health-related quality of life (HRQoL) among survivors of acute myocardial infarction (AMI) and identify factors associated with trajectories. METHODS: Data on HRQoL among 9566 survivors of AMI were collected from 77 National Health Service hospitals in England between 1 November 2011 and 24 June 2015. Longitudinal HRQoL was collected using the EuroQol five-dimension questionnaire measured at hospitalisation, 1, 6 and 12 months post-AMI. Trajectories of perceived HRQoL post-MI were determined using multilevel regression analysis and latent class growth analysis (LCGA). RESULTS: One or more percieved health problems in mobility, self-care, usual activities, pain/discomfort and anxiety/depression was reported by 69.1% (6607/9566) at hospitalisation and 59.7% (3011/5047) at 12 months. Reduced HRQoL was associated with women (-4.07, 95% CI -4.88 to -3.25), diabetes (-2.87, 95% CI -3.87 to -1.88), previous AMI (-1.60, 95% CI -2.72 to -0.48), previous angina (-1.72, 95% CI -2.77 to -0.67), chronic renal failure (-2.96, 95% CI -5.08 to -0.84; -3.10, 95% CI -5.72 to -0.49), chronic obstructive pulmonary disease (-3.89, 95% CI -5.07 to -2.72) and cerebrovascular disease (-2.60, 95% CI -4.24 to -0.96). LCGA identified three subgroups of HRQoL which we labelled: improvers (68.1%), non-improvers (22.1%) and dis-improvers (9.8%). Non-improvers and dis-improvers were more likely to be women, non-ST-elevation myocardial infarction (NSTEMI) and have long-term health conditions, compared with improvers. CONCLUSIONS: Quality of life improves for the majority of survivors of AMI but is significantly worse and more likely to decline for women, NSTEMI and those with long-term health conditions. Assessing HRQoL both in hospital and postdischarge may be important in determining which patients could benefit from tailored interventions. TRIAL REGISTRATION: NCT01808027 and NCT01819103.

A nationwide causal mediation analysis of survival following ST-elevation myocardial infarction.

OBJECTIVE: International studies report a decline in mortality following ST-elevation myocardial infarction (STEMI). The extent to which the observed improvements in STEMI survival are explained by temporal changes in patient characteristics and utilisation of treatments is unknown. METHODS: Cohort study using national registry data from the Myocardial Ischaemia National Audit Project between first January 2004 and 30th June 2013. 232 353 survivors of hospitalisation with STEMI as recorded in 247 hospitals in England and Wales. Flexible parametric survival modelling and causal mediation analysis were used to estimate the relative contribution of temporal changes in treatments and patient characteristics on improved STEMI survival. RESULTS: Over the study period, unadjusted survival at 6 months and 1 year improved by 0.9% and 1.0% on average per year (HR: 0.991, 95% CI: 0.988 to 0.994 and HR: 0.990, 95% CI: 0.987 to 0.993, respectively). The uptake of primary percutaneous coronary intervention (PCI) (HR: 1.025, 95% CI: 1.021 to 1.028) and increased prescription of P2Y12 inhibitors (HR: 1.035, 95% CI: 1.031 to 1.039) were significantly associated with improvements in 1-year survival. Primary PCI explained 16.8% (95% CI: 10.8% to 31.6%) and 13.2% (9.2% to 21.9%) of the temporal survival improvements at 6 months and 1 year, respectively, whereas P2Y12 inhibitor prescription explained 5.3% (3.6% to 8.8%) of the temporal improvements at 6 months but not at 1 year. CONCLUSIONS: For STEMI in England and Wales, improvements in survival between 2004 and 2013 were significantly explained by the uptake of primary PCI and increased use of P2Y12 inhibitors at 6 months and primary PCI only at 1 year. TRIAL REGISTRATION NUMBER: NCT03749694.

Development and Validation of a Novel Risk Score for In-Hospital Major Bleeding in Acute Myocardial Infarction:-The SWEDEHEART Score.

Background Bleeding risk stratification in acute coronary syndrome is of highest clinical interest but current risk scores have limitations. We sought to develop and validate a new in-hospital bleeding risk score for patients with acute myocardial infarction. Methods and Results From the nationwide SWEDEHEART (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) register, 97,597 patients with acute myocardial infarction enrolled from 2009 until 2014 were selected. A full model with 23 predictor variables and 8 interaction terms was fitted using logistic regression. The full model was approximated by a model with 5 predictors and 1 interaction term. Calibration, discrimination, and clinical utility was evaluated and compared with the ACTION (Acute Coronary Treatment and Intervention Outcomes Network) and CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Ad verse Outcomes With Early Implementation of the ACC /AHA Guidelines) scores. Internal and temporal validity was assessed. In-hospital major bleeding, defined as fatal, intracranial, or requiring surgery or blood transfusion, occurred in 1356 patients (1.4%). The 5 predictors in the approximate model that constituted the SWEDEHEART score were hemoglobin, age, sex, creatinine, and C-reactive protein. The ACTION and CRUSADE scores were poorly calibrated in the derivation cohort and therefore were recalibrated. The SWEDEHEART score showed higher discriminative ability than both recalibrated scores, overall ( C-index 0.80 versus 0.73/0.72) and in all predefined subgroups. Decision curve analysis demonstrated consistently positive and higher net benefit for the SWEDEHEART score compared with both recalibrated scores across all clinically relevant decision thresholds. The original ACTION and CRUSADE scores showed negative net benefit. Conclusions The 5-item SWEDEHEART score discriminates in-hospital major bleeding in patients with acute myocardial infarction and has superior model performance compared with the recalibrated ACTION and CRUSADE scores.

International comparison of acute myocardial infarction care and outcomes using quality indicators.

OBJECTIVE: To compare temporal changes in European Society of Cardiology (ESC) acute myocardial infarction (AMI) quality indicator (QI) attainment in the UK and Israel. METHODS: Data cross-walking using information from the Myocardial Ischaemia National Audit Project and the Acute Coronary Syndrome in Israel Survey for matching 2-month periods in 2006, 2010 and 2013 was used to compare country-specific attainment of 14 ESC AMI QIs. RESULTS: Patients in the UK (n=17 068) compared with Israel (n=5647) were older, more likely to be women, and had less diabetes, dyslipidaemia and heart failure. Baseline ischaemic risk was lower in Israel than the UK (Global Registry of Acute Coronary Events (GRACE) risk, 110.5 vs 121.0). Overall, rates of coronary angiography (87.6% vs 64.8%) and percutaneous coronary intervention (70.3% vs 41.0%) were higher in Israel compared with the UK. Composite QI performance increased more in the UK (1.0%-86.0%) than Israel (70.2%-78.0%). Mortality rates at 30 days declined in each country, with lower rates in Israel in 2013 (4.2% vs 7.6%). Composite QI adherence adjusted for GRACE risk score was inversely associated with 30-day mortality (OR 0.95; CI 0.95 to 0.97, p<0.001). CONCLUSIONS: International comparisons of guideline recommended AMI care and outcomes can be quantified using the ESC AMI QIs. International implementation of the ESC AMI QIs may reveal country-specific opportunities for improved healthcare delivery.

Association between time of hospitalization with acute myocardial infarction and in-hospital mortality.

AIMS: To study the association between time of hospitalization and in-hospital mortality for acute myocardial infarction (AMI). METHODS AND RESULTS: Patients admitted with ST-elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) across 243 hospitals in England and Wales between 1 January 2004 and 31 March 2013 were included. The outcome measure was in-hospital mortality. Adjusted odds ratios (ORs) for in-hospital mortality were estimated across six 4-hourly time periods over the 24-h clock using multilevel logistic regression, inverse-probability weighting propensity score, and instrumental variable analysis. Among 615 035 patients [median age 70.0 years, interquartile range 59.0-80.0 years; 406 519 (66.0%) men], there were 52 777 (8.8%) in-hospital deaths. At night, patients with NSTEMI were more frequently comorbid, and for STEMI had longer symptom-onset-to-reperfusion times. For STEMI, unadjusted in-hospital mortality was highest between 20:00 and 23:59 [4-h period range 8.4-9.9%; OR compared with 00:00-03:59 reference 1.13, 95% confidence interval (CI) 1.07-1.20], and for NSTEMI highest between 12:00 and 15:59 (8.0-8.8%; OR compared with 00:00-03:59 reference 1.07, 95% CI 1.03-1.12). However, these differences were only apparent in the earlier years of the study, and were attenuated by adjustment for demographics, comorbidities, and clinical presentation. Differences were not statistically significant after adjustment for acute clinical treatment provided. CONCLUSION: There is little evidence to support an association between time of hospitalization and in-hospital mortality for AMI; variation in in-hospital mortality may be explained by case mix and the use of treatments.

Relative survival and excess mortality following primary percutaneous coronary intervention for ST-elevation myocardial infarction.

BACKGROUND:: High survival rates are commonly reported following primary percutaneous coronary intervention for ST-elevation myocardial infarction, with most contemporary studies reporting overall survival. AIMS:: The aim of this study was to describe survival following primary percutaneous coronary intervention for ST-elevation myocardial infarction corrected for non-cardiovascular deaths by reporting relative survival and investigate clinically significant factors associated with poor long-term outcomes. METHODS AND RESULTS:: Using the prospective UK Percutaneous Coronary Intervention registry, primary percutaneous coronary intervention cases ( n=88,188; 2005-2013) were matched to mortality data for the UK populace. Crude five-year relative survival was 87.1% for the patients undergoing primary percutaneous coronary intervention and 94.7% for patients <55 years. Increasing age was associated with excess mortality up to four years following primary percutaneous coronary intervention (56-65 years: excess mortality rate ratio 1.61, 95% confidence interval 1.46-1.79; 66-75 years: 2.49, 2.26-2.75; >75 years: 4.69, 4.27-5.16). After four years, there was no excess mortality for ages 56-65 years (excess mortality rate ratio 1.27, 0.95-1.70), but persisting excess mortality for older groups (66-75 years: excess mortality rate ratio 1.72, 1.30-2.27; >75 years: 1.66, 1.15-2.41). Excess mortality was associated with cardiogenic shock (excess mortality rate ratio 6.10, 5.72-6.50), renal failure (2.52, 2.27-2.81), left main stem stenosis (1.67, 1.54-1.81), diabetes (1.58, 1.47-1.69), previous myocardial infarction (1.52, 1.40-1.65) and female sex (1.33, 1.26-1.41); whereas stent deployment (0.46, 0.42-0.50) especially drug eluting stents (0.27, 0.45-0.55), radial access (0.70, 0.63-0.71) and previous percutaneous coronary intervention (0.67, 0.60-0.75) were protective. CONCLUSIONS:: Following primary percutaneous coronary intervention for ST-elevation myocardial infarction, long-term cardiovascular survival is excellent. Failure to account for non-cardiovascular death may result in an underestimation of the efficacy of primary percutaneous coronary intervention.

Effect of oral ß-blocker treatment on mortality in contemporary post-myocardial infarction patients: a systematic review and meta-analysis.

Aims: Guidelines concerning ß-blocker treatment following acute myocardial infarction (AMI) are based on studies undertaken before the implementation of reperfusion and secondary prevention therapies. We aimed to estimate the effect of oral ß-blockers on mortality in contemporary post-AMI patients with low prevalence of heart failure and/or reduced left ventricular ejection fraction. Methods and results: A random effects model was used to synthetize results of 16 observational studies published between 1 January 2000 and 30 October 2017. Publication bias was evaluated, and heterogeneity between studies examined by subgroup and random effects meta-regression analyses considering patient-related and study-level variables. The pooled estimate showed that ß-blocker treatment [among 164 408 (86.8%) patients, with median follow-up time of 2.7 years] was associated with a 26% reduction in all-cause mortality [rate ratio (RR) 0.74, 95% confidence interval (CI) 0.64-0.85] with moderate heterogeneity (I2 = 67.4%). The patient-level variable mean age of the cohort explained 31.5% of between study heterogeneity. There was presence of publication bias, or small study effect, and when controlling for bias by the trim and fill simulation method, the effect disappeared (adjusted RR 0.90, 95% CI 0.77-1.04). Also, small study effect was demonstrated by a cumulative meta-analysis starting with the largest study showing no effect, with increasing effect as the smaller studies were accumulated. Conclusion: Evidence from this study suggests that there is no association between ß-blockers and all-cause mortality. A possible beneficial effect in AMI survivors needs to be tested by large randomized clinical trials.

Sex differences in quality indicator attainment for myocardial infarction: a nationwide cohort study.

AIM: To investigate sex differences in acute myocardial infarction (AMI) guideline-indicated care as defined by the European Society of Cardiology (ESC) Acute Cardiovascular Care Association (ACCA) quality indicators. METHODS: Nationwide cohort study comprising 691 290 AMI hospitalisations in England and Wales (n=233 hospitals) from the Myocardial Ischaemia National Audit Project between 1 January 2003 and 30 June 2013. RESULTS: There were 34.5% (n=238 489) women (median age 76.7 (IQR 66.3-84.0) years; 33.9% (n=80 884) ST-elevation myocardial infarction (STEMI)) and 65.5% (n=452 801) men (median age 67.1 (IQR 56.9-77.2) years; 42.5% (n=192 229) STEMI). Women less frequently received 13 of the 16 quality indicators compared with men, including timely reperfusion therapy for STEMI (76.8% vs 78.9%; p<0.001), timely coronary angiography for non-STEMI (24.2% vs 36.7%; p<0.001), dual antiplatelet therapy (75.4% vs 78.7%) and secondary prevention therapies (87.2% vs 89.6% for statins, 82.5% vs 85.6% for ACE inhibitor/angiotensin receptor blockers and 62.6% vs 67.6% for beta-blockers; all p<0.001). Median 30-day Global Registry of Acute Coronary Events risk score adjusted mortality was higher for women than men (median: 5.2% (IQR 1.8%-13.1%) vs 2.3% (IQR 0.8%-7.1%), p<0.001). An estimated 8243 (95% CI 8111 to 8375) deaths among women could have been prevented over the study period if their quality indicator attainment had been equal to that attained by men. CONCLUSION: According to the ESC ACCA AMI quality indicators, women in England and Wales less frequently received guideline-indicated care and had significantly higher mortality than men. Greater attention to the delivery of recommended AMI treatments for women has the potential to reduce the sex-AMI mortality gap.

Multimorbidity and survival for patients with acute myocardial infarction in England and Wales: Latent class analysis of a nationwide population-based cohort.

BACKGROUND: There is limited knowledge of the scale and impact of multimorbidity for patients who have had an acute myocardial infarction (AMI). Therefore, this study aimed to determine the extent to which multimorbidity is associated with long-term survival following AMI. METHODS AND FINDINGS: This national observational study included 693,388 patients (median age 70.7 years, 452,896 [65.5%] male) from the Myocardial Ischaemia National Audit Project (England and Wales) who were admitted with AMI between 1 January 2003 and 30 June 2013. There were 412,809 (59.5%) patients with multimorbidity at the time of admission with AMI, i.e., having at least 1 of the following long-term health conditions: diabetes, chronic obstructive pulmonary disease or asthma, heart failure, renal failure, cerebrovascular disease, peripheral vascular disease, or hypertension. Those with heart failure, renal failure, or cerebrovascular disease had the worst outcomes (39.5 [95% CI 39.0-40.0], 38.2 [27.7-26.8], and 26.6 [25.2-26.4] deaths per 100 person-years, respectively). Latent class analysis revealed 3 multimorbidity phenotype clusters: (1) a high multimorbidity class, with concomitant heart failure, peripheral vascular disease, and hypertension, (2) a medium multimorbidity class, with peripheral vascular disease and hypertension, and (3) a low multimorbidity class. Patients in class 1 were less likely to receive pharmacological therapies compared with class 2 and 3 patients (including aspirin, 83.8% versus 87.3% and 87.2%, respectively; ß-blockers, 74.0% versus 80.9% and 81.4%; and statins, 80.6% versus 85.9% and 85.2%). Flexible parametric survival modelling indicated that patients in class 1 and class 2 had a 2.4-fold (95% CI 2.3-2.5) and 1.5-fold (95% CI 1.4-1.5) increased risk of death and a loss in life expectancy of 2.89 and 1.52 years, respectively, compared with those in class 3 over the 8.4-year follow-up period. The study was limited to all-cause mortality due to the lack of available cause-specific mortality data. However, we isolated the disease-specific association with mortality by providing the loss in life expectancy following AMI according to multimorbidity phenotype cluster compared with the general age-, sex-, and year-matched population. CONCLUSIONS: Multimorbidity among patients with AMI was common, and conferred an accumulative increased risk of death. Three multimorbidity phenotype clusters that were significantly associated with loss in life expectancy were identified and should be a concomitant treatment target to improve cardiovascular outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT03037255.

Editor's Choice - Impact of initial hospital diagnosis on mortality for acute myocardial infarction: A national cohort study.

AIMS: Early and accurate diagnosis of acute myocardial infarction is central to successful treatment and improved outcomes. We aimed to investigate the impact of the initial hospital diagnosis on mortality for patients with acute myocardial infarction. METHODS AND RESULTS: Cohort study using data from the Myocardial Ischaemia National Audit Project of patients discharged with a final diagnosis of ST-elevation myocardial infarction (STEMI, n=221,635) and non-STEMI (NSTEMI, n=342,777) between 1 April 2004 and 31 March 2013 in all acute hospitals ( n = 243) in England and Wales. Overall, 168,534 (29.9%) patients had an initial diagnosis which was not the same as their final diagnosis. After multivariable adjustment, for STEMI a change from an initial diagnosis of NSTEMI (time ratio 0.97, 95% confidence interval 0.92-1.01) and chest pain of uncertain cause (0.98, 0.89-1.07) was not associated with a significant reduction in time to death, whereas for other initial diagnoses the time to death was significantly reduced by 21% (0.78, 0.74-0.83). For NSTEMI, after multivariable adjustment, a change from an initial diagnosis of STEMI was associated with a reduction in time to death of 10% (time ratio 0.90, 95% confidence interval 0.83-0.97), but not for chest pain of uncertain cause (0.99, 0.96-1.02). Patients with NSTEMI who had other initial diagnoses had a significant 14% reduction in their time to death (time ratio 0.86, 95% confidence interval 0.84-0.88). STEMI and NSTEMI with other initial diagnoses had low rates of pre-hospital electrocardiograph (24.3% and 21.5%), aspirin on hospitalisation (61.6% and 48.5%), care by a cardiologist (60.0% and 51.5%), invasive coronary procedures (38.8 % and 29.2%), cardiac rehabilitation (68.9% and 62.6%) and guideline indicated medications at time of discharge from hospital. Had the 3.3% of patients with STEMI and 17.9% of NSTEMI who were admitted with other initial diagnoses received an initial diagnosis of STEMI and NSTEMI, then 33 and 218 deaths per year might have been prevented, respectively. CONCLUSION: Nearly one in three patients with acute myocardial infarction had other diagnoses at first medical contact, who less frequently received guideline indicated care and had significantly higher mortality rates. There is substantial potential, greater for NSTEMI than STEMI, to improve outcomes through earlier and more accurate diagnosis of acute myocardial infarction.

ß-Blockers and Mortality After Acute Myocardial Infarction in Patients Without Heart Failure or Ventricular Dysfunction.

BACKGROUND: For acute myocardial infarction (AMI) without heart failure (HF), it is unclear if ß-blockers are associated with reduced mortality. OBJECTIVES: The goal of this study was to determine the association between ß-blocker use and mortality in patients with AMI without HF or left ventricular systolic dysfunction (LVSD). METHODS: This cohort study used national English and Welsh registry data from the Myocardial Ischaemia National Audit Project. A total of 179,810 survivors of hospitalization with AMI without HF or LVSD, between January 1, 2007, and June 30, 2013 (final follow-up: December 31, 2013), were assessed. Survival-time inverse probability weighting propensity scores and instrumental variable analyses were used to investigate the association between the use of ß-blockers and 1-year mortality. RESULTS: Of 91,895 patients with ST-segment elevation myocardial infarction and 87,915 patients with non-ST-segment elevation myocardial infarction, 88,542 (96.4%) and 81,933 (93.2%) received ß-blockers, respectively. For the entire cohort, with >163,772 person-years of observation, there were 9,373 deaths (5.2%). Unadjusted 1-year mortality was lower for patients who received ß-blockers compared with those who did not (4.9% vs. 11.2%; p < 0.001). However, after weighting and adjustment, there was no significant difference in mortality between those with and without ß-blocker use (average treatment effect [ATE] coefficient: 0.07; 95% confidence interval [CI]: -0.60 to 0.75; p = 0.827). Findings were similar for ST-segment elevation myocardial infarction (ATE coefficient: 0.30; 95% CI: -0.98 to 1.58; p = 0.637) and non-ST-segment elevation myocardial infarction (ATE coefficient: -0.07; 95% CI: -0.68 to 0.54; p = 0.819). CONCLUSIONS: Among survivors of hospitalization with AMI who did not have HF or LVSD as recorded in the hospital, the use of ß-blockers was not associated with a lower risk of death at any time point up to 1 year. (ß-Blocker Use and Mortality in Hospital Survivors of Acute Myocardial Infarction Without Heart Failure; NCT02786654).