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: NCT0374969

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 Adverse 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

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, NCT0181910

Association of multimorbidity and changes in health-related quality of life following myocardial infarction: a UK multicentre longitudinal patient-reported outcomes study

Background Multimorbidity is prevalent for people with myocardial infarction (MI), yet previous studies investigated single-health conditions in isolation. We identified patterns of multimorbidity in MI survivors and their associations with changes in HRQoL. Methods In this national longitudinal cohort study, we analysed data from 9566 admissions with MI from 77 National Health Service hospitals in England between 2011 and 2015. HRQoL was measured using EuroQol 5 dimension (EQ5D) instrument and visual analogue scale (EQVAS) at hospitalisation, 6, and 12 months following MI. Latent class analysis (LCA) of pre-existing long-term health conditions at baseline was used to identify clusters of multimorbidity and associations with changes in HRQoL quantified using mixed effects regression analysis. Results Of 9566 admissions with MI (mean age of 64.1 years [SD 11.9], 7154 [75%] men), over half (5119 [53.5%] had multimorbidities. LCA identified 3 multimorbidity clusters which were severe multimorbidity (591; 6.5%) with low HRQoL at baseline (EQVAS 59.39 and EQ5D 0.62) which did not improve significantly at 6 months (EQVAS 59.92, EQ5D 0.60); moderate multimorbidity (4301; 47.6%) with medium HRQoL at baseline (EQVAS 63.08, EQ5D 0.71) and who improved at 6 months (EQVAS 71.38, EQ5D 0.76); and mild multimorbidity (4147, 45.9%) at baseline (EQVAS 64.57, EQ5D 0.75) and improved at 6 months (EQVAS 76.39, EQ5D 0.82). Patients in the severe and moderate groups were more likely to be older, women, and presented with NSTEMI. Compared with the mild group, increased multimorbidity was associated with lower EQ-VAS scores (adjusted coefficient: −5.12 [95% CI −7.04 to −3.19] and −0.98 [−1.93 to −0.04] for severe and moderate multimorbidity, respectively. The severe class was more likely than the mild class to report problems in mobility, OR 9.62 (95% confidence interval: 6.44 to 14.36), self-care 7.87 (4.78 to 12.97), activities 2.41 (1.79 to 3.26), pain 2.04 (1.50 to 2.77), and anxiety/depression 1.97 (1.42 to 2.74). Conclusions Among MI survivors, multimorbidity clustered into three distinct patterns and was inversely associated with HRQoL. The identified multimorbidity patterns and HRQoL domains that are mostly affected may help to identify patients at risk of poor HRQoL for which clinical interventions could be beneficial to improve the HRQoL of MI survivors. Trial registration ClinicalTrials.gov NCT01808027 and NCT0181910

Morganella morganii septicemia and concurrent renal crassicaudiasis in a Cuvier’s beaked whale (Ziphius cavirostris) stranded in Italy

Information regarding bacterial diseases in Cuvier's beaked whale (CBW, Ziphius cavirostris) is scattered and mostly incomplete. This report describes a case of septicemia by Morganella morganii in a juvenile male CBW with concurrent renal crassicaudiasis. The animal stranded along the Ligurian coastline (Italy) and underwent a systematic post-mortem examination to determine the cause of death. Histopathology showed lesions consistent with a septicemic infection, severe meningoencephalitis, and renal crassicaudiasis. An M. morganii alpha-hemolytic strain was isolated in pure culture from liver, lung, prescapular lymph node, spleen, hepatic and renal abscesses, and central nervous system (CNS). The antimicrobial susceptibility profile of the strain was evaluated with the minimum inhibitory concentrations (MICs) method and reduced susceptibility to Trimethoprim-Sulfamethoxazole is reported. Crassicauda sp. nematodes were retrieved from both kidneys. No other pathogens were detected by immunohistochemistry, serology, or biomolecular analyses. Toxicological investigations detected high concentrations of immunosuppressant pollutants in the blubber. The chronic parasitic infestation and the toxic effects of xenobiotics likely compromised the animal's health, predisposing it to an opportunistic bacterial infection. To our knowledge, this is the first description of M. morganii septicemia with CNS involvement in a wild cetacean

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; β-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