Implementation of an extracorporeal resuscitation (ECPR) program for out-of-hospital cardiac arrest in Stockholm, Sweden: Feasibility, safety, and outcome.

Background: The aim of this study was to evaluate the implementation of a novel extra corporeal cardiopulmonary (ECPR) program in the greater Stockholm area with focus on feasibility, safety aspects and clinical outcomes. Methods: Prospective observational study of ECPR program including patients with OHCA from January 2020 to December 2022, fulfilling ECPR criteria: age 18-65 years, initial shockable rhythm or pulseless electrical activity, witnessed arrest, bystander cardiopulmonary resuscitation and refractory arrest after three cycles of advance cardiac life support. The predefined time threshold from collapse to extracorporeal membrane oxygenation (ECMO) initiation was set at 60 min. Results: We included 95 patients. Of these, 22/95 (23%) had return of spontaneous circulation before ECMO initiation, 39/95 (41%) were excluded for ECMO and 34/95 (36%) had ECMO initiated out of which 23 patients were admitted alive to the ICU. ECMO-initiation within 60 min was met in 9%. In 6 patients vascular access was complicated, 2 patients had severe bleeding at access site requiring intervention. Survival to discharge among all cases was 25% (24/95). Among patients admitted to ICU on ECMO 39% (9/23) survived to discharge, of these 78% had cerebral performance category scale score 1-2 within 12 months. 8 out of 9 survivors had time from OHCA to ECMO-initiation >60 min. Conclusion: The implementation of an ECPR protocol was feasible without any major, unexpected safety aspects but did not meet the intended target time intervals. Despite this, survival rates were similar to previous studies although most survivors had >60 min to ECMO-initiation.

Sex differences in the association between insulin resistance and non-fatal myocardial infarction across glycaemic states.

BACKGROUND: Females are generally less prone to cardiovascular (CV) events than males, but this protection is trumped by diabetes. The mechanism behind the increased relative risk in females with diabetes is not fully understood. Insulin resistance (IR) is suggested to be a more important contributor to CV morbidity in females than in males. We aim to investigate differences in the association between IR indexes (Homeostatic Model Assessment of IR - HOMA-IR, visceral adiposity index - VAI, and triglycerides/high-density lipoprotein-cholesterol - TG/HDL-C index), and a first non-fatal myocardial infarction (MI) across different glycaemic states. METHODS: IR indexes were calculated in a population with (n = 696) and without (n = 707) a first non-fatal MI, free from known diabetes. MI cases were investigated at least six weeks after the event. All participants were categorized by an oral glucose tolerance test as having normal glucose tolerance, impaired fasting glucose, impaired glucose tolerance, or newly diagnosed diabetes. Comparison of proportion of glycaemic states by sex was tested by chi-square test. The associations between sex, a first non-fatal MI, IR indexes, and traditional CV risk factors were analysed by multivariate logistic regression models. Continuous variables were logarithmically transformed. RESULTS: Of the total population 19% were females and 81% males, out of whom 47% and 50% had a first non-fatal MI, respectively. Compared with males, females were older, less often smokers, with lower body mass index and higher total cholesterol and high-density lipoprotein cholesterol levels. The proportion of glycaemic states did not differ between the sexes (p = 0.06). Females were less insulin resistant than males, especially among cases and with normal glucose tolerance. In logistic regression models adjusted for major CV risk factors including sex, the associations between VAI and TG/HDL-C index and a first non-fatal MI remained significant only in females (odds ratios and 95% confidence intervals: 1.7, 1.0-2.9, and 1.9, 1.1-3.4 respectively). CONCLUSIONS: These results support the assumption that IR indexes based on anthropometrics and lipid panel, i.e., VAI and TG/HDL-C, could be a better measure of IR and CV-predictor for non-fatal MI in females, even without glycaemic perturbations.

Implantable cardioverter defibrillator and cardiac resynchronization treatment in people with type 2 diabetes: a comparison with age- and sex matched controls from the general population.

BACKGROUND: Increased risk of severe tachyarrhythmias is reported in patients with type 2 diabetes mellitus (T2DM). The aim of this study was to explore if treatment with cardiac implantable electronic device (CIED) such as implantable cardioverter defibrillator (ICD), cardiac resynchronization therapy- pacemaker and -defibrillator (CRT-P/CRT-D) differed in patients with vs. without T2DM. A secondary aim was to identify patient characteristics indicating an increased CIED treatment. METHOD: 416 162 adult patients with T2DM from the Swedish National Diabetes Registry and 2 081 087 controls from the Swedish population, matched for age, sex and living area, were included between 1/1/1998 and 31/12/2012 and followed until 31/12/2013. They were compared regarding prevalence of ventricular tachycardia (VT) at baseline and the risk of receiving a CIED during follow-up. Multivariable Cox regression analysis was performed to estimate the risk of CIED-treatment and factors identifying patients with such risk. RESULTS: Ventricular fibrillation (VF) (0.1% vs 0.0004%) and (VT) (0.2% vs. 0.1%) were more frequent among patients with T2DM compared to controls. CIED-treatment was significantly increased in patients with T2DM both in unadjusted and adjusted analyses. HR and 95% CI, after adjustment for sex, age, marital status, income, education, country of birth, coronary artery disease and congestive heart failure, were 1.32 [1.21-1.45] for ICD, 1.74 [1.55-1.95] for CRT-P and 1.69 [1.43-1.99] for CRT-D. Blood-pressure and lipid lowering therapies were independent risk factors associated to receiving CIED, while female sex was protective. CONCLUSIONS: Although the proportion of VT/VF was low, patients with T2DM had a higher prevalence of these conditions and increased risk for treatment with CIED compared to controls. This underlines the importance of recognizing that T2DM patients have an increased need of CIED.

High Mannose Correlates With Surrogate Indexes of Insulin Resistance and Is Associated With an Increased Risk of Cardiovascular Events Independently of Glycemic Status and Traditional Risk Factors.

OBJECTIVE: To explore the associations among mannose, indexes of insulin resistance (IR) and secretion, and long-term cardiovascular outcomes. RESEARCH DESIGN AND METHODS: Fasting mannose was assayed in 1,403 participants, one-half of which had a first myocardial infarction (MI) with either normal glucose tolerance (n = 1,045) or newly detected dysglycemia (i.e., impaired glucose tolerance or type 2 diabetes; n = 358). Regression models were used to explore mannose associations with surrogate indexes of IR/insulin secretion. Multivariate Cox models were used to investigate the independent association between high (higher quartile) versus low (lower three quartiles) mannose and major adverse cardiac events (MACE) (n = 163) during the 10-year follow-up. RESULTS: Mannose was independently associated with IR indexes (all P ≤ 0.001). High versus low mannose was independently associated with MACE (hazard ratio 1.54, 95% CI 1.07-2.20) in the overall population. CONCLUSIONS: Mannose might represent a new biomarker able to track early, potentially detrimental glucometabolic alterations independently of glycemic state.

Effect of semaglutide on major adverse cardiovascular events by baseline kidney parameters in participants with type 2 diabetes and at high risk of cardiovascular disease: SUSTAIN 6 and PIONEER 6 post hoc pooled analysis.

BACKGROUND: Semaglutide is a glucose-lowering treatment for type 2 diabetes (T2D) with demonstrated cardiovascular benefits; semaglutide may also have kidney-protective effects. This post hoc analysis investigated the association between major adverse cardiovascular events (MACE) and baseline kidney parameters and whether the effect of semaglutide on MACE risk was impacted by baseline kidney parameters in people with T2D at high cardiovascular risk. METHODS: Participants from the SUSTAIN 6 and PIONEER 6 trials, receiving semaglutide or placebo, were categorised according to baseline kidney function (estimated glomerular filtration rate [eGFR] < 45 and ≥ 45-<60 versus ≥ 60 mL/min/1.73 m2) or damage (urine albumin:creatinine ratio [UACR] ≥ 30-≤300 and > 300 versus < 30 mg/g). Relative risk of first MACE by baseline kidney parameters was evaluated using a Cox proportional hazards model. The same model, adjusted with inverse probability weighting, and a quadratic spline regression were applied to evaluate the effect of semaglutide on risk and event rate of first MACE across subgroups. The semaglutide effects on glycated haemoglobin (HbA1c), body weight (BW) and serious adverse events (SAEs) across subgroups were also evaluated. RESULTS: Independently of treatment, participants with reduced kidney function (eGFR ≥ 45-<60 and < 45 mL/min/1.73 m2: hazard ratio [95% confidence interval]; 1.36 [1.04;1.76] and 1.52 [1.15;1.99]) and increased albuminuria (UACR ≥ 30-≤300 and > 300 mg/g: 1.53 [1.14;2.04] and 2.52 [1.84;3.42]) had an increased MACE risk versus those without. Semaglutide consistently reduced MACE risk versus placebo across all eGFR and UACR subgroups (interaction p value [pINT] > 0.05). Semaglutide reduced HbA1c regardless of baseline eGFR and UACR (pINT>0.05); reductions in BW were affected by baseline eGFR (pINT<0.001) but not UACR (pINT>0.05). More participants in the lower eGFR or higher UACR subgroups experienced SAEs versus participants in reference groups; the number of SAEs was similar between semaglutide and placebo arms in each subgroup. CONCLUSIONS: MACE risk was greater for participants with kidney impairment or damage than for those without. Semaglutide consistently reduced MACE risk across eGFR and UACR subgroups, indicating that semaglutide provides cardiovascular benefits in people with T2D and at high cardiovascular risk across a broad spectrum of kidney function and damage. TRIAL REGISTRATIONS: NCT01720446; NCT02692716.

Empagliflozin improves insulin sensitivity in patients with recent acute coronary syndrome and newly detected dysglycaemia : Experiences from the randomized, controlled SOCOGAMI trial.

BACKGROUND: Empagliflozin reduces the risk of cardiovascular disease (CVD) in patients with type 2 diabetes (T2DM) and high cardiovascular risk via mechanisms which have not been fully explained. The mechanisms of such benefit have not been fully understood, and whether empagliflozin can be safely administered as first-line treatment in patients with CVD at the initial stages of glycaemic perturbations remains to be established. We investigated the effects of empagliflozin on insulin resistance, insulin sensitivity and ß-cell function indexes in patients with a recent acute coronary event and newly detected dysglycaemia, i.e., impaired glucose tolerance (IGT) or T2DM. METHODS: Forty-two patients (mean age 67.5 years, 19% females) with a recent myocardial infarction (n = 36) or unstable angina (n = 6) and newly detected dysglycaemia were randomized to either empagliflozin 25 mg daily (n = 20) or placebo (n = 22). Patients were investigated with stress-perfusion cardiac magnetic resonance imaging before randomization, 7 months after the start of study drug and 3 months following its cessation. Indexes of insulin resistance, sensitivity and ß-cell function were calculated based on glucose and insulin values from 2-hour oral glucose tolerance tests (OGTT) and fasting C-peptide. The differences in glucose, insulin, C-peptide, mannose levels and indexes between the two groups were computed by repeated measures ANOVA including an interaction term between the treatment allocation and the time of visit. RESULTS: After 7 months, empagliflozin significantly decreased glucose and insulin values during the OGTT, whereas C-peptide, mannose and HbA1c did not differ. Empagliflozin significantly improved insulin sensitivity indexes but did not impact insulin resistance and ß-cell function. After cessation of the drug, all indexes returned to initial levels. Insulin sensitivity indexes were inversely correlated with left ventricular mass at baseline. CONCLUSIONS: Empagliflozin improved insulin sensitivity indexes in patients with a recent coronary event and drug naïve dysglycaemia. These findings support the safe use of empagliflozin as first-line glucose-lowering treatment in patients at very high cardiovascular risk with newly diagnosed dysglycaemia. TRIAL REGISTRATION NUMBER: EudraCT number 2015-004571-73.

Greater Combined Reductions of HbA1c ≥ 1.0% and Body Weight Loss ≥ 5.0% or ≥ 10.0% with Orally Administered Semaglutide Versus Comparators.

INTRODUCTION: A post hoc analysis of the PIONEER 1-5 and 8 trials assessed the clinically relevant composite endpoints of HbA1c (glycated haemoglobin) reduction ≥ 1% and body weight loss of ≥ 5% or ≥ 10% with orally administered semaglutide versus comparators. METHODS: In the PIONEER trials, people with type 2 diabetes were randomised to orally administered semaglutide versus placebo (PIONEER 1, 4, 5 and 8), empagliflozin (PIONEER 2), sitagliptin (PIONEER 3) and liraglutide (PIONEER 4) for 26-78 weeks. This analysis assessed the proportion of people achieving an HbA1c reduction of ≥ 1% and body weight loss of ≥ 5% at week 26 and at end of treatment, and the proportion of people achieving an HbA1c reduction of ≥ 1% and body weight loss of ≥ 10% at end of treatment. RESULTS: Overall, 3506 people in PIONEER 1-5 and 8 were included. At week 26 and at end of treatment, odds of achieving the composite endpoint of an HbA1c reduction of ≥ 1% and body weight loss of ≥ 5% were significantly greater with orally administered semaglutide 14 mg than with placebo (PIONEER 1, 4, 5 and 8; all p < 0.0001), empagliflozin 25 mg (PIONEER 2, p < 0.0001), sitagliptin 100 mg (PIONEER 3, p < 0.0001) and liraglutide 1.8 mg (PIONEER 4, p < 0.0001). Odds of achieving the composite endpoint of HbA1c reduction of ≥ 1% and body weight loss of ≥ 10% at end of treatment were also significantly greater with orally administered semaglutide versus comparators. CONCLUSION: In PIONEER 1-5 and 8, odds of achieving clinically relevant reductions in both HbA1c and body weight were significantly greater with orally administered semaglutide versus comparators.

Enhanced External Counterpulsation for Management of Postacute Sequelae of SARS-CoV-2 Associated Microvascular Angina and Fatigue: An Interventional Pilot Study.

Background: Postacute sequelae of SARS-CoV-2 infection (PASC) are a novel clinical syndrome characterized in part by endothelial dysfunction. Enhanced external counterpulsation (EECP) produces pulsatile shear stress, which has been associated with improvements in systemic endothelial function. Objective: To explore the effects of EECP on symptom burden, physical capacity, mental health, and health-related quality of life (HRQoL) in patients with PASC-associated angina and microvascular dysfunction (MVD). Methods: An interventional pilot study was performed, including 10 patients (male = 5, mean age 50.3 years) recruited from a tertiary specialized PASC clinic. Patients with angina and MVD, defined as index of microcirculatory resistance (IMR) ≥25 and/or diagnosed through stress perfusion cardiac magnetic resonance imaging, were included. Patients underwent one modified EECP course (15 one-hour sessions over five weeks). Symptom burden, six-minute walk test, and validated generic self-reported instruments for measuring psychological distress and HRQoL were assessed before and one month after treatment. Results: At baseline, most commonly reported PASC symptoms were angina (100%), fatigue (80%), and dyspnea (80%). Other symptoms included palpitations (50%), concentration impairment (50%), muscle pain (30%), and brain fog (30%). Mean IMR was 63.6. After EECP, 6MWD increased (mean 29.5 m, median 21 m) and angina and fatigue improved. Mean depression scores showed reduced symptoms (-0.8). Mean HRQoL scores improved in seven out of eight subscales (+0.2 to 10.5). Conclusions: Patients with PASC-associated angina and evidence of MVD experienced subjective and objective benefits from EECP. The treatment was well-tolerated. These findings warrant controlled studies in a larger cohort.

SOdium-glucose CO-transporter inhibition in patients with newly detected Glucose Abnormalities and a recent Myocardial Infarction (SOCOGAMI).

AIMS/HYPOTHESIS: Established dysglycaemia (impaired glucose tolerance [IGT] or type 2 diabetes [T2DM]) is a risk factor for further cardiovascular events in patients with coronary artery disease. Sodium-glucose cotransporter 2 inhibitors reduce this risk. The aim of the present investigation was to test the hypothesis that empagliflozin exerts beneficial effects on myocardial function in patients with a recent acute coronary syndrome and newly detected dysglycaemia. METHODS: Forty-two patients (mean age 67.5 years, 81 % male) with recent myocardial infarction (n = 36) or unstable angina (n = 6) and newly detected IGT (n = 27) or T2DM (n = 15) were randomised to 25 mg of empagliflozin daily (n = 20) or placebo (n = 22) on top of ongoing therapy. They were investigated with oral glucose tolerance tests, stress-perfusion cardiac magnetic resonance imaging (CMR) and echocardiography at three occasions: before randomisation, after seven months on study drug and three months following cessation of such drug. Primary outcome was a change in left ventricular (LV) end-diastolic volume (LVEDV) and secondary outcomes were a change in a) systolic and diastolic LV function; b) coronary flow reserve; c) myocardial extracellular volume (ECV) in non-infarcted myocardium; d) aortic pulse wave velocity. RESULTS: Empagliflozin induced a significant decrease in fasting and post load glucose (p < 0.05) and body weight (p < 0.01). Empagliflozin did not influence LVEDV, LV systolic or mass indexes, coronary flow reserve, ECV or aortic pulse wave velocity. Echocardiographic indices of LV diastolic function (E/e' and mitral E/A ratio) were not influenced. No safety concerns were identified. CONCLUSIONS/INTERPRETATION: Empagliflozin had predicted effects on the dysglycaemia but did not influence variables expressing LV function, coronary flow reserve and ECV. An explanation may be that the LV function of the patients was within the normal range.

Plasma mannose as a novel marker of myocardial infarction across different glycaemic states: a case control study.

BACKGROUND: Plasma mannose, an emerging novel biomarker of insulin resistance, is associated with both diabetes mellitus and coronary atherosclerosis, but the relationship between mannose concentrations and myocardial infarction (MI) across different glycaemic states remains to be elucidated. The aim of this study was to investigate the independent association between mannose and a first MI in a group of subjects characterized according to their glycaemic state. METHODS: Fasting plasma mannose concentrations were analysed in 777 patients 6-10 weeks after a first myocardial infarction and in 770 matched controls by means of high-performance liquid chromatography coupled to tandem mass spectrometry. Participants without known diabetes mellitus were categorized by an oral glucose tolerance test (OGTT) as having normal glucose tolerance (NGT, n = 1045), impaired glucose tolerance (IGT, n = 246) or newly detected type 2 diabetes (T2DM, n = 112). The association between mannose and MI was investigated across these glycaemic states by logistic regression. RESULTS: Mannose levels increased across the glycaemic states (p < 0.0001) and were significantly associated with a first MI in the whole study population (odds ratio, OR: 2.2; 95% CI 1.4 to - 3.5). Considering the different subgroups separately, the association persisted only in subjects with NGT (adjusted OR: 2.0; 95% CI 1.2-3.6), but not in subgroups with glucose perturbations (adjusted OR: 1.8, 95% CI 0.8-3.7). CONCLUSIONS: Mannose concentrations increased across worsening levels of glucose perturbations but were independently associated with a first MI only in NGT individuals. Thus, mannose might be a novel, independent risk marker for MI, possibly targeted for the early management of previously unidentified patients at high cardiovascular risk.

Sitagliptin reduces FAP-activity and increases intact FGF21 levels in patients with newly detected glucose abnormalities.

INTRODUCTION: Fibroblast growth factor 21 (FGF21), a hormone with pleiotropic metabolic effects, is inactivated by fibroblast activation protein (FAP), a member of the dipeptidyl peptidase-IV (DPP-IV) family. We investigate if sitagliptin (DPP-IV inhibitor) inhibits FAP-activity and increases intact FGF21. METHODS: Patients with impaired glucose metabolism were randomized to 100 mg sitagliptin (n = 34) or placebo (n = 37) treatment for 12 weeks. Plasma samples obtained at study entry and at 12-weeks were analysed for FAP-activity, FAP, total FGF21 and intact FGF21. RESULTS: Sitagliptin significantly inhibited FAP-activity (497 ± 553 vs. 48 ± 712 RFU/min, p < 0.01) and correspondingly increased intact FGF21 (253 ± 182 vs 141 ± 80 ng/L, p < 0.01) compared to placebo in plasma. Sitagliptin dose-dependently inhibited the FAP-activity in vitro. Intact FGF21 was higher in patients obtaining a normal glucose tolerance regardless of treatment (p = 0.03). CONCLUSION: A sitagliptin-induced increase of intact FGF21 may contribute to an improved metabolic effect in patients with impaired glucose metabolism.

Mannose-binding lectin does not explain the dismal prognosis after an acute coronary event in dysglycaemic patients. A report from the GAMI cohort.

BACKGROUND: Mannose binding lectin (MBL) has been suggested to be associated with an impaired cardiovascular prognosis in dysglycaemic conditions, but results are still contrasting. Our aims are (i) to examine whether MBL levels differ between patients with an acute myocardial infarction (MI) and healthy controls and between subgroups with different glucose tolerance status, and (ii) to investigate the relation between MBL and future cardiovascular events. METHODS: MBL levels were assessed at discharge and after 3 months in 161 AMI patients without any previously known glucose perturbations and in 183 age- and gender-matched controls from the Glucose metabolism in patients with Acute Myocardial Infarction (GAMI) study. Participants were classified as having dysglycaemia, i.e. type 2 diabetes or impaired glucose tolerance, or not by an oral glucose tolerance test. The primary outcome was a composite of cardiovascular events comprising cardiovascular death, AMI, stroke or severe heart failure during 11 years of follow-up. Total and cardiovascular mortality served as secondary outcomes. RESULTS: At hospital discharge patients had higher MBL levels (median 1246 µg/L) than three months later (median 575 µg/L; p < 0.01), the latter did not significantly differ from those in the controls (801 µg/L; p = 0.47). MBL levels were not affected by dysglycaemia either in patients or controls. Independent of glycaemic state, increasing MBL levels did not predict any of the studied outcomes in patients. In unadjusted analyses increasing MBL levels predicted cardiovascular events (hazard ratio HR: 1.67, 95% confidence interval CI 1.06-2.64) and total mortality (HR 1.53, 95% CI 1.12-2.10) in the control group. However, this did not remain in adjusted analyses. CONCLUSIONS: Patients had higher MBL levels than controls during the hospital phase of AMI, supporting the assumption that elevated MBL reflects acute stress. MBL was not found to be independently associated with cardiovascular prognosis in patients with AMI regardless of glucose state.

Measures of Insulin Resistance as a Screening Tool for Dysglycemia in Patients With Coronary Artery Disease: A Report From the EUROASPIRE V Population.

OBJECTIVE: The optimal screening strategy for dysglycemia (including type 2 diabetes and impaired glucose tolerance) in patients with coronary artery disease (CAD) is debated. We tested the hypothesis that measures of insulin resistance by HOMA indexes may constitute good screening methods. RESEARCH DESIGN AND METHODS: Insulin, C-peptide, glycated hemoglobin A1c, and an oral glucose tolerance test (OGTT) were centrally assessed in 3,534 patients with CAD without known dysglycemia from the fifth European Survey of Cardiovascular Disease Prevention and Diabetes (EUROASPIRE V). Three different HOMA indexes were calculated: HOMA of insulin resistance (HOMA-IR), HOMA2 based on insulin (HOMA2-ins), and HOMA2 based on C-peptide (HOMA2-Cpep). Dysglycemia was diagnosed based on the 2-h postload glucose value obtained from the OGTT. Information on study participants was obtained by standardized interviews. The optimal thresholds of the three HOMA indexes for dysglycemia diagnosis were obtained by the maximum value of Youden's J statistic on receiver operator characteristic curves. Their correlation with clinical parameters was assessed by Spearman coefficients. RESULTS: Of 3,534 patients with CAD (mean age 63 years; 25% women), 41% had dysglycemia. Mean insulin, C-peptide, and HOMA indexes were significantly higher in patients with versus without newly detected dysglycemia (all P < 0.0001). Sensitivity and specificity of the three HOMA indexes for the diagnosis of dysglycemia were low, but their correlation with BMI and waist circumference was strong. CONCLUSIONS: Screening for dysglycemia in patients with CAD by HOMA-IR, HOMA2-ins, and HOMA2-Cpep had insufficient diagnostic performance to detect dysglycemia with reference to the yield of an OGTT, which should still be prioritized despite its practical drawbacks.

Eligibility for Dapagliflozin and Empagliflozin in a Real-world Heart Failure Population.

BACKGROUND: We investigated eligibility for dapagliflozin and empagliflozin in a real-world heart failure (HF) cohort based on selection criteria of DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure), DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure), and EMPEROR (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Reduced Ejection Fraction and Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with APreserved Ejection Fraction) trials. METHODS AND RESULTS: Selection criteria were applied to the Swedish HF registry outpatient population according to 3 scenarios: (i) a "trial scenario" applying all selection criteria; (ii) a "pragmatic scenario" applying the most clinically relevant criteria; and (iii) a "label scenario" following the regulatory agencies labels. Of the 49,317 patients, 55% had an ejection fraction of less than 40% and were assessed for eligibility based on DAPA-HF and EMPEROR-Reduced, 45% had ejection fraction of 40% or greater and were assessed based on EMPEROR-Preserved and DELIVER. Eligibility using trial, pragmatic, and label scenarios was 35%, 61%, and 80% for DAPA-HF; 31%, 55%, and 81% for EMPEROR-Reduced; 30%, 61%, and 74% for DELIVER; and 32%, 59%, and 75% for EMPEROR-Preserved, respectively. The main selection criteria limiting eligibility were HF duration and N-terminal pro-B type natriuretic peptide levels. Eligible patients had more severe HF, more comorbidities, higher use of HF treatments and higher mortality and morbidity.Clinical Highlights: Large clinical trials for the approval of new drugs in heart failure often apply numerous selection criteria, limiting the generalizability of trial findings to real-world populations. We assessed eligibility for dapagliflozin and empagliflozin according to trial criteria, the more practical criteria usually applied in daily practice for treatment selection, and the criteria mandated by regulatory agencies, in a real-word heart failure population. Our results from the Swedish Heart Failure Registry show that a great number of patients with heart failure might be candidates for these therapies, which have been shown to significantly decrease morbidity and mortality; therefore, their use should be implemented in clinical practice. LAY SUMMARY: When strictly applying selection criteria used in clinical trials, only one-third of a real-world heart failure population is eligible for treatment with empagliflozin and dapagliflozin. Adopting approaches that consider the most meaningful criteria, that is, those most clinically relevant or those mandated by regulatory agencies, significantly broadened eligibility. These results might contribute to future trial design taking into consideration the characteristics of real-world populations, feasibility, and potential cost benefits. CONCLUSIONS: In a real-world HF setting, eligibility for sodium glucose co-transporter-2 inhibitors was similar whether selection criteria from DAPA-HF or EMPEROR-Reduced were applied in HFrEF, or EMPEROR-Preserved or DELIVER in HFpEF. These data might help stakeholders assessing the consequences of future trial eligibility.

Clinical Frailty Scale classes are independently associated with 6-month mortality for patients after acute myocardial infarction.

AIMS: Data on the prognostic value of frailty to guide clinical decision-making for patients with myocardial infarction (MI) are scarce. To analyse the association between frailty classification, treatment patterns, in-hospital outcomes, and 6-month mortality in a large population of patients with MI. METHODS AND RESULTS: An observational, multicentre study with a retrospective analysis of prospectively collected data using the SWEDEHEART registry. In total, 3381 MI patients with a level of frailty assessed using the Clinical Frailty Scale (CFS-9) were included. Of these patients, 2509 (74.2%) were classified as non-vulnerable non-frail (CFS 1-3), 446 (13.2%) were vulnerable non-frail (CFS 4), and 426 (12.6%) were frail (CFS 5-9). Frailty and non-frail vulnerability were associated with worse in-hospital outcomes compared with non-frailty, i.e. higher rates of mortality (13.4% vs. 4.0% vs. 1.8%), cardiogenic shock (4.7% vs. 2.5% vs. 1.9%), and major bleeding (4.5% vs. 2.7% vs. 1.1%) (all P < 0.001), and less frequent use of evidence-based therapies. In Cox regression analyses, frailty was strongly and independently associated with 6-month mortality compared with non-frailty, after adjustment for age, sex, the GRACE risk score components, and other potential risk factors [hazard ratio (HR) 3.32, 95% confidence interval (CI) 2.30-4.79]. A similar pattern was seen for vulnerable non-frail patients (fully adjusted HR 2.07, 95% CI 1.41-3.02). CONCLUSION: Frailty assessed with the CFS was independently and strongly associated with all-cause 6-month mortality, also after comprehensive adjustment for baseline differences in other risk factors. Similarly, non-frail vulnerability was independently associated with higher mortality compared with those with preserved functional ability.