Empagliflozin after Acute Myocardial Infarction.

BACKGROUND: Empagliflozin improves cardiovascular outcomes in patients with heart failure, patients with type 2 diabetes who are at high cardiovascular risk, and patients with chronic kidney disease. The safety and efficacy of empagliflozin in patients who have had acute myocardial infarction are unknown. METHODS: In this event-driven, double-blind, randomized, placebo-controlled trial, we assigned, in a 1:1 ratio, patients who had been hospitalized for acute myocardial infarction and were at risk for heart failure to receive empagliflozin at a dose of 10 mg daily or placebo in addition to standard care within 14 days after admission. The primary end point was a composite of hospitalization for heart failure or death from any cause as assessed in a time-to-first-event analysis. RESULTS: A total of 3260 patients were assigned to receive empagliflozin and 3262 to receive placebo. During a median follow-up of 17.9 months, a first hospitalization for heart failure or death from any cause occurred in 267 patients (8.2%) in the empagliflozin group and in 298 patients (9.1%) in the placebo group, with incidence rates of 5.9 and 6.6 events, respectively, per 100 patient-years (hazard ratio, 0.90; 95% confidence interval [CI], 0.76 to 1.06; P = 0.21). With respect to the individual components of the primary end point, a first hospitalization for heart failure occurred in 118 patients (3.6%) in the empagliflozin group and in 153 patients (4.7%) in the placebo group (hazard ratio, 0.77; 95% CI, 0.60 to 0.98), and death from any cause occurred in 169 (5.2%) and 178 (5.5%), respectively (hazard ratio, 0.96; 95% CI, 0.78 to 1.19). Adverse events were consistent with the known safety profile of empagliflozin and were similar in the two trial groups. CONCLUSIONS: Among patients at increased risk for heart failure after acute myocardial infarction, treatment with empagliflozin did not lead to a significantly lower risk of a first hospitalization for heart failure or death from any cause than placebo. (Funded by Boehringer Ingelheim and Eli Lilly; EMPACT-MI ClinicalTrials.gov number, NCT04509674.).

Empagliflozin in Patients with Chronic Kidney Disease.

BACKGROUND: The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients. METHODS: We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m2 of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m2 with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to <10 ml per minute per 1.73 m2, a sustained decrease in eGFR of ≥40% from baseline, or death from renal causes) or death from cardiovascular causes. RESULTS: A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; P<0.001). Results were consistent among patients with or without diabetes and across subgroups defined according to eGFR ranges. The rate of hospitalization from any cause was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.86; 95% CI, 0.78 to 0.95; P = 0.003), but there were no significant between-group differences with respect to the composite outcome of hospitalization for heart failure or death from cardiovascular causes (which occurred in 4.0% in the empagliflozin group and 4.6% in the placebo group) or death from any cause (in 4.5% and 5.1%, respectively). The rates of serious adverse events were similar in the two groups. CONCLUSIONS: Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo. (Funded by Boehringer Ingelheim and others; EMPA-KIDNEY ClinicalTrials.gov number, NCT03594110; EudraCT number, 2017-002971-24.).

Effect of Empagliflozin on Heart Failure Outcomes After Acute Myocardial Infarction: Insights From the EMPACT-MI Trial.

BACKGROUND: Empagliflozin reduces the risk of heart failure (HF) events in patients with type 2 diabetes at high cardiovascular risk, chronic kidney disease, or prevalent HF irrespective of ejection fraction. Whereas the EMPACT-MI trial (Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients With Acute Myocardial Infarction) showed that empagliflozin does not reduce the risk of the composite of hospitalization for HF and all-cause death, the effect of empagliflozin on first and recurrent HF events after myocardial infarction is unknown. METHODS: EMPACT-MI was a double-blind, randomized, placebo-controlled, event-driven trial that randomized 6522 patients hospitalized for acute myocardial infarction at risk for HF on the basis of newly developed left ventricular ejection fraction of <45% or signs or symptoms of congestion to receive empagliflozin 10 mg daily or placebo within 14 days of admission. In prespecified secondary analyses, treatment groups were analyzed for HF outcomes. RESULTS: Over a median follow-up of 17.9 months, the risk for first HF hospitalization and total HF hospitalizations was significantly lower in the empagliflozin compared with the placebo group (118 [3.6%] versus 153 [4.7%] patients with events; hazard ratio, 0.77 [95% CI, 0.60, 0.98]; P=0.031, for first HF hospitalization; 148 versus 207 events; rate ratio, 0.67 [95% CI, 0.51, 0.89]; P=0.006, for total HF hospitalizations). Subgroup analysis showed consistency of empagliflozin benefit across clinically relevant patient subgroups for first and total HF hospitalizations. The need for new use of diuretics, renin-angiotensin modulators, or mineralocorticoid receptor antagonists after discharge was less in patients randomized to empagliflozin versus placebo (all P<0.05). CONCLUSIONS: Empagliflozin reduced the risk of HF in patients with left ventricular dysfunction or congestion after acute myocardial infarction. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04509674.

Subclinical atherosclerosis and accelerated epigenetic age mediated by inflammation: a multi-omics study.

AIMS: Epigenetic age is emerging as a personalized and accurate predictor of biological age. The aim of this article is to assess the association of subclinical atherosclerosis with accelerated epigenetic age and to investigate the underlying mechanisms mediating this association. METHODS AND RESULTS: Whole blood methylomics, transcriptomics, and plasma proteomics were obtained for 391 participants of the Progression of Early Subclinical Atherosclerosis study. Epigenetic age was calculated from methylomics data for each participant. Its divergence from chronological age is termed epigenetic age acceleration. Subclinical atherosclerosis burden was estimated by multi-territory 2D/3D vascular ultrasound and by coronary artery calcification. In healthy individuals, the presence, extension, and progression of subclinical atherosclerosis were associated with a significant acceleration of the Grim epigenetic age, a predictor of health and lifespan, regardless of traditional cardiovascular risk factors. Individuals with an accelerated Grim epigenetic age were characterized by an increased systemic inflammation and associated with a score of low-grade, chronic inflammation. Mediation analysis using transcriptomics and proteomics data revealed key pro-inflammatory pathways (IL6, Inflammasome, and IL10) and genes (IL1B, OSM, TLR5, and CD14) mediating the association between subclinical atherosclerosis and epigenetic age acceleration. CONCLUSION: The presence, extension, and progression of subclinical atherosclerosis in middle-aged asymptomatic individuals are associated with an acceleration in the Grim epigenetic age. Mediation analysis using transcriptomics and proteomics data suggests a key role of systemic inflammation in this association, reinforcing the relevance of interventions on inflammation to prevent cardiovascular disease.

Impact of standard modifiable cardiovascular risk factors on 2-year all-cause mortality: Insights from an international cohort of 23,489 patients with acute coronary syndrome.

BACKGROUND: Controversial findings have been reported in the literature regarding the impact of the absence of standard modifiable cardiovascular risk factors (SMuRFs) on long-term mortality risk in patients with acute coronary syndrome (ACS). While the prognostic additive value of SMuRFs has been well described, the prognostic role of prior cardiovascular disease (CVD) by sex is less well-known in patients with and without SMuRFs. METHODS: EPICOR and EPICOR Asia are prospective, observational registries conducted between 2010 and 2014, which enrolled ACS patients in 28 countries across Europe, Latin America, and Asia. Association between SMuRFs (diabetes, dyslipidaemia, hypertension, and smoking) and 2-year postdischarge mortality was evaluated using adjusted Cox models stratified by geographical region. RESULTS: Among 23,489 patients, the mean age was 60.9 ± 11.9 years, 24.3% were women, 4,582 (20.1%) presented without SMuRFs, and 16,055 (69.5%) without prior CVD. Patients with SMuRFs had a higher crude 2-year postdischarge mortality (HR 1.86; 95% CI, 1.56-2.22; P < .001), compared to those without SMuRFs. After adjustment for potential confounding, the association between SMuRFs and 2-year mortality risk was substantially attenuated (HR 1.17, 95% CI 0.98-1.41; P = .087), regardless of the type of ACS. The risk conferred by prior CVD was added to the underlying risk of SMuRFs to provide risk-specific phenotypes (eg, women with SMuRFs and with prior CVD were at higher risk of dying than women without SMuRFs and without CVD; HR 1.67, 95% CI 1.34-2.06). CONCLUSIONS: In this large-scale international ACS cohort the absence of SMuRFs was not associated with a lower adjusted 2-year postdischarge mortality risk. Patients with both SMuRFs and prior CVD had a higher mortality irrespective of their sex.

Bone marrow activation in response to metabolic syndrome and early atherosclerosis.

AIMS: Experimental studies suggest that increased bone marrow (BM) activity is involved in the association between cardiovascular risk factors and inflammation in atherosclerosis. However, human data to support this association are sparse. The purpose was to study the association between cardiovascular risk factors, BM activation, and subclinical atherosclerosis. METHODS AND RESULTS: Whole body vascular 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI) was performed in 745 apparently healthy individuals [median age 50.5 (46.8-53.6) years, 83.8% men] from the Progression of Early Subclinical Atherosclerosis (PESA) study. Bone marrow activation (defined as BM 18F-FDG uptake above the median maximal standardized uptake value) was assessed in the lumbar vertebrae (L3-L4). Systemic inflammation was indexed from circulating biomarkers. Early atherosclerosis was evaluated by arterial metabolic activity by 18F-FDG uptake in five vascular territories. Late atherosclerosis was evaluated by fully formed plaques on MRI. Subjects with BM activation were more frequently men (87.6 vs. 80.0%, P = 0.005) and more frequently had metabolic syndrome (MetS) (22.2 vs. 6.7%, P < 0.001). Bone marrow activation was significantly associated with all MetS components. Bone marrow activation was also associated with increased haematopoiesis-characterized by significantly elevated leucocyte (mainly neutrophil and monocytes) and erythrocyte counts-and with markers of systemic inflammation including high-sensitivity C-reactive protein, ferritin, fibrinogen, P-selectin, and vascular cell adhesion molecule-1. The associations between BM activation and MetS (and its components) and increased erythropoiesis were maintained in the subgroup of participants with no systemic inflammation. Bone marrow activation was significantly associated with high arterial metabolic activity (18F-FDG uptake). The co-occurrence of BM activation and arterial 18F-FDG uptake was associated with more advanced atherosclerosis (i.e. plaque presence and burden). CONCLUSION: In apparently healthy individuals, BM 18F-FDG uptake is associated with MetS and its components, even in the absence of systemic inflammation, and with elevated counts of circulating leucocytes. Bone marrow activation is associated with early atherosclerosis, characterized by high arterial metabolic activity. Bone marrow activation appears to be an early phenomenon in atherosclerosis development.[Progression of Early Subclinical Atherosclerosis (PESA); NCT01410318].

Effects of a comprehensive lifestyle intervention on cardiovascular health: the TANSNIP-PESA trial.

AIMS: To investigate the effectiveness of a 3-year worksite lifestyle intervention on cardiovascular metrics and to study whether outcomes are influenced by baseline subclinical atherosclerosis (SA) by non-invasive imaging. METHODS AND RESULTS: A randomized controlled trial was performed to compare a lifestyle intervention with standard of care in asymptomatic middle-aged subjects, stratified by SA. The intervention consisted of nine motivational interviews during the first year, followed by three further sessions between Years 1 and 3. The primary outcome was the change in a pre-specified adaptation of the Fuster-BEWAT score (Blood pressure, Exercise, Weight, Alimentation, and Tobacco) between baseline and follow-up Years 1-3. A total of 1020 participants (mean age 50 ± 4 years) were enrolled, of whom 510 were randomly assigned to the intervention and 510 to the control group. The baseline adapted Fuster-BEWAT score was 16.2 ± 3.7 points in the intervention group and 16.5 ± 3.5 points in the control group. At Year 1, the score improved significantly in intervention participants compared with controls [estimate 0.83 (95% CI 0.52-1.15) points]. However, intervention effectiveness decreased to non-significant levels at Year 3 [0.24 (95% CI -0.10 to 0.59) points]. Over the 3-year period, the intervention was effective in participants having low baseline SA [0.61 (95% CI 0.30-0.93) points] but not in those with high baseline SA [0.19 (95% CI -0.26 to 0.64) points]. CONCLUSION: In middle-aged asymptomatic adults, a lifestyle intervention was associated with a significant improvement in cardiovascular health and behavioural metrics. The effect attenuated after 1 year as the intensity of the intervention was reduced. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02561065).

Amphilimus- vs. zotarolimus-eluting stents in patients with diabetes mellitus and coronary artery disease: the SUGAR trial.

AIM: Patients with diabetes mellitus are at high risk of adverse events after percutaneous revascularization, with no differences in outcomes between most contemporary drug-eluting stents. The Cre8 EVO stent releases a formulation of sirolimus with an amphiphilic carrier from laser-dug wells, and has shown clinical benefits in diabetes. We aimed to compare Cre8 EVO stents to Resolute Onyx stents (a contemporary polymer-based zotarolimus-eluting stent) in patients with diabetes. METHODS AND RESULTS: We did an investigator-initiated, randomized, controlled, assessor-blinded trial at 23 sites in Spain. Eligible patients had diabetes and required percutaneous coronary intervention. A total of 1175 patients were randomly assigned (1:1) to receive Cre8 EVO or Resolute Onyx stents. The primary endpoint was target-lesion failure, defined as a composite of cardiac death, target-vessel myocardial infarction, and clinically indicated target-lesion revascularization at 1-year follow-up. The trial had a non-inferiority design with a 4% margin for the primary endpoint. A superiority analysis was planned if non-inferiority was confirmed. There were 106 primary events, 42 (7.2%) in the Cre8 EVO group and 64 (10.9%) in the Resolute Onyx group [hazard ratio (HR): 0.65, 95% confidence interval (CI): 0.44-0.96; Pnon-inferiority < 0.001; Psuperiority = 0.030]. Among the secondary endpoints, Cre8 EVO stents had significantly lower rate than Resolute Onyx stents of target-vessel failure (7.5% vs. 11.1%, HR: 0.67, 95% CI: 0.46-0.99; P = 0.042). Probable or definite stent thrombosis and all-cause death were not significantly different between groups. CONCLUSION: In patients with diabetes, Cre8 EVO stents were non-inferior to Resolute Onyx stents with regard to target-lesion failure composite outcome. An exploratory analysis for superiority at 1 year suggests that the Cre8 EVO stents might be superior to Resolute Onyx stents with regard to the same outcome. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT03321032.

Impact of the MEESSI-AHF tool to guide disposition decision-making in patients with acute heart failure in the emergency department: a before-and-after study.

OBJECTIVES: To determine the impact of risk stratification using the MEESSI-AHF (Multiple Estimation of risk based on the Emergency department Spanish Score In patients with acute heart failure) scale to guide disposition decision-making on the outcomes of ED patients with acute heart failure (AHF), and assess the adherence of emergency physicians to risk stratification recommendations. METHODS: This was a prospective quasi-experimental study (before/after design) conducted in eight Spanish EDs which consecutively enrolled adult patients with AHF. In the pre-implementation stage, the admit/discharge decision was performed entirely based on emergency physician judgement. During the post-implementation phase, emergency physicians were advised to 'discharge' patients classified by the MEESSI-AHF scale as low risk and 'admit' patients classified as increased risk. Nonetheless, the final decision was left to treating emergency physicians. The primary outcome was 30-day all-cause mortality. Secondary outcomes were days alive and out of hospital, in-hospital mortality and 30-day post-discharge combined adverse event (ED revisit, hospitalisation or death). RESULTS: The pre-implementation and post-implementation cohorts included 1589 and 1575 patients, respectively (median age 85 years, 56% females) with similar characteristics, and 30-day all-cause mortality was 9.4% and 9.7%, respectively (post-implementation HR=1.03, 95% CI=0.82 to 1.29). There were no differences in secondary outcomes or in the percentage of patients entirely managed in the ED without hospitalisation (direct discharge from the ED, 23.5% vs 24.4%, OR=1.05, 95% CI=0.89 to 1.24). Adjusted models did not change these results. Emergency physicians followed the MEESSI-AHF-based recommendation on patient disposition in 70.9% of cases (recommendation over-ruling: 29.1%). Physicians were more likely to over-rule the recommendation when 'discharge' was recommended (56.4%; main reason: need for hospitalisation for a second diagnosis) than when 'admit' was recommended (12.8%; main reason: no appreciation of severity of AHF decompensation by emergency physician), with an OR for over-ruling the 'discharge' compared with the 'admit' recommendation of 8.78 (95% CI=6.84 to 11.3). CONCLUSIONS: Implementing the MEESSI-AHF risk stratification tool in the ED to guide disposition decision-making did not improve patient outcomes.

Increased production of functional small extracellular vesicles in senescent endothelial cells.

Small extracellular vesicles (EVs) are novel players in vascular biology. However, a thorough understanding of their production and function remains elusive. Endothelial senescence is a key feature of vascular ageing and thus, is an attractive therapeutic target for the treatment of vascular disease. In this study, we sought to characterize the EV production of senescent endothelial cells. To achieve this, Human Umbilical Vascular Endothelial Cells (HUVECs) were replicated until they reached senescence, as determined by measurement of Senescence-Associated ß-Galactosidase activity via microscopy and flow cytometry. Expression of the endosomal marker Rab7 and the EV marker CD63 was determined by immunofluorescence. Small EVs were isolated by ultracentrifugation and characterized using electron microscopy, nanoparticle tracking analysis and immunoassays to assess morphology, size, concentration and expression of exosome markers CD9 and CD81. Migration of HUVECs in response to EVs was studied using a transwell assay. The results showed that senescent endothelial cells express higher levels of Rab7 and CD63. Moreover, senescent endothelial cells produced higher levels of CD9- and CD81-positive EVs. Additionally, small EVs from both young and senescent endothelial cells promoted HUVEC migration. Overall, senescent endothelial cells produce an increased number of functional small EVs, which may have a role in vascular physiology and disease.

Metoprolol blunts the time-dependent progression of infarct size.

Early metoprolol administration protects against myocardial ischemia-reperfusion injury, but its effect on infarct size progression (ischemic injury) is unknown. Eight groups of pigs (total n = 122) underwent coronary artery occlusion of varying duration (20, 25, 30, 35, 40, 45, 50, or 60 min) followed by reperfusion. In each group, pigs were randomized to i.v. metoprolol (0.75 mg/kg) or vehicle (saline) 20 min after ischemia onset. The primary outcome measure was infarct size (IS) on day7 cardiac magnetic resonance (CMR) normalized to area at risk (AAR, measured by perfusion computed tomography [CT] during ischemia). Metoprolol treatment reduced overall mortality (10% vs 26%, p = 0.03) and the incidence and number of primary ventricular fibrillations during infarct induction. In controls, IS after 20-min ischemia was ≈ 5% of the area AAR. Thereafter, IS progressed exponentially, occupying almost all the AAR after 35 min of ischemia. Metoprolol injection significantly reduced the slope of IS progression (p = 0.004 for final IS). Head-to-head comparison (metoprolol treated vs vehicle treated) showed statistically significant reductions in IS at 30, 35, 40, and 50-min reperfusion. At 60-min reperfusion, IS was 100% of AAR in both groups. Despite more prolonged ischemia, metoprolol-treated pigs reperfused at 50 min had smaller infarcts than control pigs undergoing ischemia for 40 or 45 min and similar-sized infarcts to those undergoing 35-min ischemia. Day-45 LVEF was higher in metoprolol-treated vs vehicle-treated pigs (41.6% vs 36.5%, p = 0.008). In summary, metoprolol administration early during ischemia attenuates IS progression and reduces the incidence of primary ventricular fibrillation. These data identify metoprolol as an intervention ideally suited to the treatment of STEMI patients identified early in the course of infarction and requiring long transport times before primary angioplasty.

Impact of malnutrition in the embolic-haemorrhagic trade-off of elderly patients with atrial fibrillation.

AIMS: Nutrition is an important determinant of health above the age of 80 years. Malnutrition in the elderly is often underdiagnosed. The aim of this study was to report the prevalence and prognostic value of malnutrition in patients ≥80 years old with atrial fibrillation (AF) with and without anticoagulant therapy. METHODS AND RESULTS: We assessed the nutritional status of 4724 octogenarian patients with diagnoses of AF in a single centre from Spain between 2014 and 2017 with the CONUT score. Malnutrition was confirmed in 2036 patients (43.1%). Anticoagulation prescription was more frequent in patients with good nutrition than in those malnourished (79.5% vs. 71.7%, P < 0.001). The impact of malnutrition on mortality was evaluated by Cox regression, whereas its association with ischaemic stroke and major bleeding was studied through competing risk analysis. After multivariate adjusting, malnutrition was associated with mortality [hazard ratio (HR) 1.36, 95% confidence interval (CI) 1.24-1.49], stroke [sub-distribution HR (sHR) 1.37, 95% CI 1.10-1.69], and major bleeding (sHR 1.29, 95% CI 1.02-1.64). In anticoagulated patients, the embolic-haemorrhagic trade-off event was virtually neutral for those who had normal nutritional status [average daily rates (ADRs) for stroke and bleeding: 4.70 and 4.69 per 100 000 patients/day, respectively; difference = +0.01 per 100 000 patients/day; P = 0.99] and negative for those with malnutrition (ADR for stroke and bleeding: 5.38 and 7.61 per 100 000 patients/day, respectively; difference = -2.23 per 100 000 patients/day; P = 0.07). CONCLUSION: Malnutrition is very common in octogenarian patients with AF, being a clinical predictor for poor prognosis. For anticoagulated patients, malnutrition was associated with a negative embolic-haemorrhagic balance.

External Validation of the MEESSI Acute Heart Failure Risk Score: A Cohort Study.

Background: The MEESSI-AHF (Multiple Estimation of risk based on the Emergency department Spanish Score In patients with AHF) score was developed to predict 30-day mortality in patients presenting with acute heart failure (AHF) to emergency departments (EDs) in Spain. Whether it performs well in other countries is unknown. Objective: To externally validate the MEESSI-AHF score in another country. Design: Prospective cohort study. (ClinicalTrials.gov: NCT01831115). Setting: Multicenter recruitment of dyspneic patients presenting to the ED. Participants: The external validation cohort included 1572 patients with AHF. Measurements: Calculation of the MEESSI-AHF score using an established model containing 12 independent risk factors. Results: Among 1572 patients with adjudicated AHF, 1247 had complete data that allowed calculation of the MEESSI-AHF score. Of these, 102 (8.2%) died within 30 days. The score predicted 30-day mortality with excellent discrimination (c-statistic, 0.80). Assessment of cumulative mortality showed a steep gradient in 30-day mortality over 6 predefined risk groups (0 patients in the lowest-risk group vs. 35 [28.5%] in the highest-risk group). Risk was overestimated in the high-risk groups, resulting in a Hosmer-Lemeshow P value of 0.022. However, after adjustment of the intercept, the model showed good concordance between predicted risks and observed outcomes (P = 0.23). Findings were confirmed in sensitivity analyses that used multiple imputation for missing values in the overall cohort of 1572 patients. Limitations: External validation was done using a reduced model. Findings are specific to patients with AHF who present to the ED and are clinically stable enough to provide informed consent. Performance in patients with terminal kidney failure who are receiving long-term dialysis cannot be commented on. Conclusion: External validation of the MEESSI-AHF risk score showed excellent discrimination. Recalibration may be needed when the score is introduced to new populations. Primary Funding Source: The European Union, the Swiss National Science Foundation, the Swiss Heart Foundation, the Cardiovascular Research Foundation Basel, the University of Basel, and University Hospital Basel.

Prognostic value of a new semiquantitative score system for adenosine stress myocardial perfusion by CMR.

OBJECTIVES: Cardiovascular magnetic resonance (CMR) provides information on myocardial ischemia through stress perfusion studies. In clinical practice, the grading of induced perfusion defects is performed by visual estimation of their extension. The aim of our study is to devise a score of the degree of ischemia and to test its prognostic value. METHODS: Between 2009 and 2011, patients with diagnosed or suspected coronary artery disease underwent stress perfusion CMR. A score of ischemic burden was calculated on the basis of (1) stress-induced perfusion defect, (2) persistence, (3) transmurality, and (4) stress-induced contractile defect. Follow-up was censored after 4 years and primary end-point was defined by a composite of death, heart failure episode, acute coronary syndrome, and ventricular arrhythmias. Univariate and multivariate logistic regressions were used to assess the strength of the association between the CMR ischemic variables, and the composite outcome. RESULTS: Forty-four of the 128 patients (34%) presented with adverse events, while 84 (66%) did not. Sixty-one patients (48%) had negative perfusion studies while 67 (52%) showed perfusion defect. Patients with positive perfusion studies and adverse events (n = 39) had higher number of segments with persistent defect (3.3 vs 1.3, p = 0.001) and highest score (19.6 vs 13.3 p = 0.012) than patients with positive perfusion studies and absence of events (n = 28). The number of segments with persistent defect showed the strongest predictive value of adverse events (OR 1.54; CI 1.19-2.00; p < 0.001). CONCLUSIONS: The score of ischemic burden proposed herein has prognostic value. Persistence of a perfusion defect has the strongest impact on prognosis. KEY POINTS: • Cardiovascular magnetic resonance provides information on myocardial ischemia by visual estimation of the presence of perfusion defects induced by stress. • There is not a standardized method for grading perfusion defects which, in practice, is performed by visual estimation of their extension. • As proven in this study, the integration of several parameters of perfusion defects (in addition to extension) into a semiquantitative score has prognostic value.

Effect of Barthel Index on the Risk of Thirty-Day Mortality in Patients With Acute Heart Failure Attending the Emergency Department: A Cohort Study of Nine Thousand Ninety-Eight Patients From the Epidemiology of Acute Heart Failure in Emergency Departments Registry.

STUDY OBJECTIVE: We assess the value of the Barthel Index (BI) in predicting 30-day mortality risk among patients with acute heart failure who are attending the emergency department (ED). METHODS: We selected 9,098 acute heart failure patients from the Acute Heart Failure in Emergency Departments registry who had BI score available both at baseline and the ED visit. Patients' data were collected from 41 Spanish hospitals during four 1- to 2-month periods between 2009 and 2016. Unadjusted and adjusted logistic regression models were used to assess the association between 30-day mortality and BI score. c Statistics were used to estimate their prognostic value. RESULTS: The mean baseline BI score was 79.4 (SD 24.6) and the mean ED BI score was 65.3 (SD 29.1). Acute functional decline (≥5-point decrease between baseline BI and ED BI score) was observed in 5,771 patients (53.4%). Within 30 days of the ED visit, 905 patients (9.9%) died. There was a steep inverse gradient in 30-day mortality risk for baseline BI and ED BI score. For instance, compared with BI score=100, a BI score of 50 to 55 doubled the mortality risk both at baseline and the ED visit. At the ED visit, a BI score of 0 to 5 carried a 5-fold increase in risk after adjustment for other risk predictors. In comparison with baseline BI score, ED BI score consistently provided greater discrimination. Neither baseline BI score nor the change in BI score from baseline to the ED visit added further prognostic value to the ED BI score. CONCLUSION: Functional status assessed by the BI score at the ED visit is a strong predictor of 30-day mortality in acute heart failure patients, with higher predictive value than baseline BI score and acute functional decline. Routine recording of BI score at the ED visit may help in decisionmaking and health care planning.

Analysis of How Emergency Physicians' Decisions to Hospitalize or Discharge Patients With Acute Heart Failure Match the Clinical Risk Categories of the MEESSI-AHF Scale.

STUDY OBJECTIVE: The Multiple Estimation of Risk Based on the Emergency Department Spanish Score in Patients With Acute Heart Failure (MEESSI-AHF) is a validated clinical decision tool that characterizes risk of mortality in emergency department (ED) acute heart failure patients. The objective of this study is to compare the distribution of risk categories between hospitalized and discharged ED patients with acute heart failure. METHODS: We included consecutive acute heart failure patients from 34 Spanish EDs. Patients were retrospectively classified according to MEESSI-AHF risk categories. We calculated the odds of hospitalization (versus direct discharge from the ED) across MEESSI-AHF risk categories. Next, we assessed the following 30-day postdischarge outcomes: ED revisit, hospitalization, death, and their combination. We used Cox hazards models to determine the adjusted association between ED disposition decision and the outcomes among patients who were stratified into low- and increased-risk categories. RESULTS: We included 7,930 patients (80.5 years [SD 10.1 years]; women 54.7%; hospitalized 75.3%). Compared with that for low-risk MEESSI-AHF patients, odds ratios for hospitalization of patients in intermediate-, high-, and very-high-risk categories were 1.83 (95% confidence interval [CI] 1.64 to 2.05), 3.05 (95% CI 2.48 to 3.76), and 3.98 (95% CI 3.13 to 5.05), respectively. However, almost half (47.6%) of all discharged patients were categorized as being at increased risk by MEESSI-AHF, and 19.0% of all the increased-risk patients were discharged from the ED. Among the low-risk MEESSI-AHF patients, the 30-day postdischarge mortality did not differ by ED disposition (hazard ratio [HR] for discharged patients with respect to hospitalized ones 0.65; 95% CI 0.70 to 1.11), nor did it differ in the increased-risk group (HR 0.88; 95% CI 0.63 to 1.23). The discharged low-risk MEESSI-AHF patients had higher risks of 30-day ED revisit and hospitalization (HR 1.86, 95% CI 1.57 to 2.20; and HR 1.92, 95% CI 1.54 to 2.40, respectively) compared with the admitted patients, as did the discharged patients in the increased-risk group (HR 1.62, 95% CI 1.39 to 1.89; and HR 1.40, 95% CI 1.16 to 1.68, respectively), with similar results for the combined endpoint. CONCLUSION: The disposition decisions made in current clinical practice for ED acute heart failure patients calibrate with MEESSI-AHF risk categories, but nearly half of the patients currently discharged from the ED fall into increased-risk MEESSI-AHF categories.