Prospective benchmarking of an observational analysis in the SWEDEHEART registry against the REDUCE-AMI randomized trial.

Prospective benchmarking of an observational analysis against a randomized trial increases confidence in the benchmarking process as it relies exclusively on aligning the protocol of the trial and the observational analysis, while the trials findings are unavailable. The Randomized Evaluation of Decreased Usage of Betablockers After Myocardial Infarction (REDUCE-AMI, ClinicalTrials.gov ID: NCT03278509) trial started recruitment in September 2017 and results are expected in 2024. REDUCE-AMI aimed to estimate the effect of long-term use of beta blockers on the risk of death and myocardial following a myocardial infarction with preserved left ventricular systolic ejection fraction. We specified the protocol of a target trial as similar as possible to that of REDUCE-AMI, then emulated the target trial using observational data from Swedish healthcare registries. Had everyone followed the treatment strategy as specified in the target trial protocol, the observational analysis estimated a reduction in the 5-year risk of death or myocardial infarction of 0.8 percentage points for beta blockers compared with no beta blockers; effects ranging from an absolute reduction of 4.5 percentage points to an increase of 2.8 percentage points in the risk of death or myocardial infarction were compatible with our data under conventional statistical criteria. Once results of REDUCE-AMI are published, we will compare the results of our observational analysis against those from the trial. If this prospective benchmarking is successful, it supports the credibility of additional analyses using these observational data, which can rapidly deliver answers to questions that could not be answered by the initial trial. If benchmarking proves unsuccessful, we will conduct a "postmortem" analysis to identify the reasons for the discrepancy. Prospective benchmarking shifts the investigator focus away from an endeavour to use observational data to obtain similar results as a completed randomized trial, to a systematic attempt to align the design and analysis of the trial and the observational analysis.

Beta-Blockers after Myocardial Infarction and Preserved Ejection Fraction.

BACKGROUND: Most trials that have shown a benefit of beta-blocker treatment after myocardial infarction included patients with large myocardial infarctions and were conducted in an era before modern biomarker-based diagnosis of myocardial infarction and treatment with percutaneous coronary intervention, antithrombotic agents, high-intensity statins, and renin-angiotensin-aldosterone system antagonists. METHODS: In a parallel-group, open-label trial performed at 45 centers in Sweden, Estonia, and New Zealand, we randomly assigned patients with an acute myocardial infarction who had undergone coronary angiography and had a left ventricular ejection fraction of at least 50% to receive either long-term treatment with a beta-blocker (metoprolol or bisoprolol) or no beta-blocker treatment. The primary end point was a composite of death from any cause or new myocardial infarction. RESULTS: From September 2017 through May 2023, a total of 5020 patients were enrolled (95.4% of whom were from Sweden). The median follow-up was 3.5 years (interquartile range, 2.2 to 4.7). A primary end-point event occurred in 199 of 2508 patients (7.9%) in the beta-blocker group and in 208 of 2512 patients (8.3%) in the no-beta-blocker group (hazard ratio, 0.96; 95% confidence interval, 0.79 to 1.16; P = 0.64). Beta-blocker treatment did not appear to lead to a lower cumulative incidence of the secondary end points (death from any cause, 3.9% in the beta-blocker group and 4.1% in the no-beta-blocker group; death from cardiovascular causes, 1.5% and 1.3%, respectively; myocardial infarction, 4.5% and 4.7%; hospitalization for atrial fibrillation, 1.1% and 1.4%; and hospitalization for heart failure, 0.8% and 0.9%). With regard to safety end points, hospitalization for bradycardia, second- or third-degree atrioventricular block, hypotension, syncope, or implantation of a pacemaker occurred in 3.4% of the patients in the beta-blocker group and in 3.2% of those in the no-beta-blocker group; hospitalization for asthma or chronic obstructive pulmonary disease in 0.6% and 0.6%, respectively; and hospitalization for stroke in 1.4% and 1.8%. CONCLUSIONS: Among patients with acute myocardial infarction who underwent early coronary angiography and had a preserved left ventricular ejection fraction (≥50%), long-term beta-blocker treatment did not lead to a lower risk of the composite primary end point of death from any cause or new myocardial infarction than no beta-blocker use. (Funded by the Swedish Research Council and others; REDUCE-AMI ClinicalTrials.gov number, NCT03278509.).

A Single High-Sensitivity Cardiac Troponin T Strategy for Ruling Out Myocardial Infarction.

Background: Ruling out acute myocardial infarction (AMI) in the emergency department (ED) is challenging. Studies have shown that a high-sensitivity cardiac troponin T (hs-cTnT) <5 ng/L or <6 ng/L at presentation (0 h) can be used to rule out AMI. The objective of this study was to identify whether an even higher hs-cTnT threshold can be used for a safe rule out of AMI in the ED. Methods: The derivation cohort consisted of 24,973 ED patients with a primary complaint of chest pain. In this cohort, we identified the highest concentration of 0 h hs-cTnT that corresponded to a negative predictive value (NPV) of ≥99.5% for the primary endpoint of AMI/all-cause death within 30 days and the secondary endpoint of all-cause death within one year. The results were validated in two cohorts consisting of 132,021 and 1167 ED chest pain patients. Results: The 0 h hs-cTnT threshold corresponding to a NPV of ≥99.5% for the primary endpoint was <9 ng/L (NPV: 99.6% and 95% CI: 99.5-99.7). This cutoff provided a sensitivity of 96.2% (95% CI: 95.2-97.1) and identified 59.7% of the patients as low risk compared to 35.8% and 43.9% with a 0 h hs-cTnT <5 ng/L and <6 ng/L, respectively. The results were similar in the validation cohorts and seemed to perform even better in patients where the 0 h hs-cTnT was measured >3 h after symptom onset and in those with a nonischemic ECG and nonhigh risk history. Conclusions: A 0 h hs-cTnT cutoff of <9 ng/L safely rules out AMI/death within 30 days in a majority of chest pain patients and is a more effective strategy than the currently recommended <5 ng/L and <6 ng/L cutoffs. This trial is registered with NCT03421873.

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

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

Associations between inflammatory and angiogenic proteomic biomarkers, and cardiovascular events and mortality in relation to kidney function.

Background: The links between chronic kidney disease (CKD) and the high burden of cardiovascular disease remain unclear. We aimed to explore the association between selected inflammatory and angiogenic biomarkers, kidney function and long-term outcome in patients with an acute coronary syndrome (ACS) and to test the hypothesis that CKD status modifies this association. Methods: A total of 1293 ACS patients hospitalized between 2008 and 2015 were followed until 31 December 2017. Plasma was collected on days 1-3 after admission. A total of 13 biomarkers were a priori identified and analysed with two proteomic methods, proximity extension assay or multiple reaction monitoring mass spectrometry. Boxplots and multiple linear regression models were used to study associations between biomarkers and kidney function and adjusted standardized Cox regression with an interaction term for CKD was used to assess whether CKD modified the association between biomarkers and major adverse cardiovascular events and death (MACE+). Results: The concentrations of nine biomarkers-endothelial cell-specific molecule-1 (ESM-1), fibroblast growth factor 23 (FGF-23), fractalkine (CX3CL1), interleukin-1 receptor antagonist (IL-1RA), interleukin-18 (IL-18), monocyte chemotactic protein-1 (MCP-1), placenta growth factor (PlGF), transmembrane immunoglobulin 1 (TIM-1) and vascular endothelial growth factor A (VEGFA)-were inversely associated with kidney function. ESM-1, FGF-23 and TIM-1 showed associations with MACE+. Only FGF23 remained independently associated after adjustment for the other biomarkers (hazard ratio per standard deviation increase 1.34; 95% Bonferroni corrected confidence interval 1.19-1.50). None of the biomarkers showed an interaction with CKD. Conclusions: The concentrations of 9 of the 13 prespecified inflammatory and angiogenic proteomic biomarkers increased when kidney function declined. Only FGF-23 demonstrated an independent association with MACE+, and this association was not modified by CKD status. These findings further support FGF-23 as an independent prognostic marker in ACS patients with and without CKD.

Global longitudinal strain in long-term risk prediction after acute coronary syndrome: an investigation of added prognostic value to ejection fraction.

AIMS: This study aimed to investigate the additional value of global longitudinal strain (GLS) on top of left ventricular ejection fraction (LVEF) in long-term risk prediction of combined death and heart failure (HF) re-hospitalization after acute coronary syndrome (ACS). METHOD AND RESULTS: This retrospective study included patients admitted with ACS between 2008 and 2014 from the three participating university hospitals. LVEF and GLS were assessed at a core lab from images acquired during the index hospital stay. Their prognostic value was studied with the Cox proportional hazards model (median follow-up 6.2 years). A nested model comparison was performed with C-statistics. A total of 941 patients qualified for multivariable analysis after multiple imputation of missing baseline covariables. The combined outcome was reached in 17.7% of the cases. Both GLS and LVEF were independent predictors of the combined outcome, hazard ratio (HR) 1.068 (95% CI 1.017-1.121) and HR 0.980 (95% CI 0.962-0.998), respectively. The C-statistic increased from 0.742 (95% CI 0.702-0.783) to 0.749 (95% CI 0.709-0.789) (P = 0.693) when GLS entered the model with clinical data and LVEF. CONCLUSION: GLS emerged as an independent long-term risk predictor of all-cause death and HF re-hospitalization. However, there was no significant incremental predictive value of GLS when LVEF was already known.

Type 2 Myocardial Infarction-Poorly Understood, Underevaluated, and Too Often Ignored.

This Viewpoint discusses diagnosis of type 2 myocardial infarction.

Biomarkers associated with cardiovascular disease in women with spontaneous preterm birth: A case-control study.

INTRODUCTION: Women with spontaneous preterm birth have an increased risk of cardiovascular disease later in life. Studies suggest potential pathophysiological mechanisms in common, but whether these could be identified by measurement of soluble circulating protein biomarkers in women with spontaneous preterm birth is unknown. The aim of this study was to determine if protein biomarkers associated with cardiovascular disease distinguish women with spontaneous preterm birth from healthy controls, both at pregnancy and at follow up. MATERIAL AND METHODS: Study participants were identified in the population-based Uppsala biobank of pregnant women in Sweden, where plasma samples were collected in mid-pregnancy. In a first screening phase, we identified participants who subsequently experienced spontaneous preterm birth (<37 weeks) in the index pregnancy (N = 13) and controls (N = 6). In these samples, differences in protein expression were examined by comparative mass spectrometry. In a second validation phase, we invited 100 cases with previous spontaneous preterm birth in the index pregnancy and 100 controls (matched for age, body mass index, and year of delivery) from the same source population, to a follow-up visit 4-15 years after pregnancy. At follow up, we collected plasma samples and data on cardiovascular risk factors. We measured concentrations of selected biomarkers identified in the screening phase, as well as lipid profiles in samples both from pregnancy (biobank) and follow up. CLINICALTRIALS: gov registration NCT05693285. RESULTS: In the screening phase, fibrinogen, cadherin-5, complement C5, factor XII, plasma kallikrein, apolipoprotein M, and vitamin D-binding protein differed significantly at pregnancy. In the validation phase, 65 women agreed to participate (35 cases and 30 controls), with a median follow-up time of 11.8 years since pregnancy. The concentration of fibrinogen (p = 0.02) and triglycerides (p = 0.03) were slightly higher in cases compared with matched controls at follow up. CONCLUSIONS: Compared with women without preterm birth, those with spontaneous preterm birth had slightly higher concentrations of fibrinogen, both at mid-pregnancy and a decade after pregnancy. Additionally, we found slightly higher concentration of triglycerides at follow up in women with previous spontaneous preterm birth. The relevance of this finding is uncertain but might indicate potential pathophysiological mechanisms in common between spontaneous preterm birth and cardiovascular disease.

Temporal biomarker concentration patterns during the early course of acute coronary syndrome.

OBJECTIVES: Biomarker concentrations and their changes during acute coronary syndrome (ACS) provide clinically useful information on pathophysiological processes, e.g. myocardial necrosis, hemodynamic stress and inflammation. However, current evidence on temporal biomarker patterns early during ACS is limited, and studies investigating multiple biomarkers are lacking. METHODS: We measured concentrations of high-sensitivity cardiac troponin T (hs-cTnT) and I (hs-cTnI), NT-terminal pro-B-type natriuretic peptide, C-reactive protein, and growth-differentiation factor-15 (GDF-15) in plasma samples obtained at randomization in ACS patients from the PLATelet inhibition and patient Outcomes (PLATO) trial. Linear regressions with interaction analyses were used to investigate the associations of biomarker concentrations with the time from symptom onset and to model temporal biomarker concentration patterns. RESULTS: The study population consisted of 16,944 patients (median age 62 years; 71.3 % males) with 6,853 (40.3 %) having ST-elevation myocardial infarction (STEMI) and 10,141 (59.7 %) having non-ST-elevation ACS (NSTE-ACS). Concentrations of all biomarkers were associated with time from symptom onset (pinteraction<0.001), apart for GDF-15 (pinteraction=0.092). Concentration increases were more pronounced in STEMI compared to NSTE-ACS. Temporal biomarker patterns for hs-cTnT and hs-cTnI were different depending on sex whereas biomarker patterns for the other biomarkers were similar in cohorts defined by age and sex. CONCLUSIONS: Temporal concentration patterns differ for various biomarkers early during ACS, reflecting the variability in the activation and duration of different pathophysiological processes, and the amount of injured myocardium. Our data emphasize that the time elapsed from symptom onset should be considered for the interpretation of biomarker results in ACS.

Prognostic significance of chronic myocardial injury diagnosed by three different cardiac troponin assays in patients admitted with suspected acute coronary syndrome.

OBJECTIVES: Chronic myocardial injury (CMI) is defined as stable concentrations of cardiac troponin T or I (cTnT or cTnI) above the assay-specific 99th percentile upper reference limit (URL) and signals poor outcome. The clinical implications of diagnosing CMI are unclear. We aimed to assess prevalence and association of CMI with long-term prognosis using three different high-sensitivity cTn (hs-cTn) assays. METHODS: A total of 1,292 hospitalized patients without acute myocardial injury had cTn concentrations quantified by hs-cTn assays by Roche Diagnostics, Abbott Diagnostics and Siemens Healthineers. The median follow-up time was 4.1 years. The prevalence of CMI and hazard ratios for mortality and cardiovascular (CV) events were calculated based on the URL provided by the manufacturers and compared to the prognostic accuracy when lower percentiles of cTn (97.5, 95 or 90), limit of detection or the estimated bioequivalent concentrations between assays were used as cutoff values. RESULTS: There was no major difference in prognostic accuracy between cTnT and cTnI analyzed as continuous variables. The correlation between cTnT and cTnI was high (r=0.724-0.785), but the cTnT assay diagnosed 3.9-4.5 times more patients with having CMI based on the sex-specific URLs (TnT, n=207; TnI Abbott, n=46, TnI Siemens, n=53) and had higher clinical sensitivity and AUC at the URL. CONCLUSIONS: The prevalence of CMI is highly assay-dependent. cTnT and cTnI have similar prognostic accuracy for mortality or CV events when measured as continuous variables. However, a CMI diagnosis according to cTnT has higher prognostic accuracy compared to a CMI diagnosis according to cTnI.

Chest Pain in Cancer Patients: Prevalence of Myocardial Infarction and Performance of High-Sensitivity Cardiac Troponins.

Background: Little is known about patients with cancer presenting with acute chest discomfort to the emergency department (ED). Objectives: The aim of this study was to assess the prevalence of acute myocardial infarction (AMI), outcomes, and the diagnostic utility of recommended diagnostic tools in this population. Methods: Patients presenting with chest pain to the ED were prospectively enrolled in an international multicenter diagnostic study with central adjudication. Cancer status was assessed prospectively and additional cancer details retrospectively. Findings were externally validated in an independent multicenter cohort. Results: Among 8,267 patients, 711 (8.6%) had cancer. Patients with cancer had a higher burden of cardiovascular risk factors and pre-existing cardiac disease. Total length of stay in the ED (5.2 hours vs 4.3 hours) and hospitalization rate (49.8% vs 34.3%) were both increased in patients with cancer (P < 0.001 for both). Among 8,093 patients eligible for the AMI analyses, those with cancer more often had final diagnoses of AMI (184 of 686 with cancer [26.8%] vs 1,561 of 7,407 without cancer [21.1%]; P < 0.001). In patients with cancer, high-sensitivity cardiac troponin T (hs-cTnT) but not high sensitivity cardiac troponin I (hs-cTnI) concentration had lower diagnostic accuracy for non-ST-segment elevation myocardial infarction (for hs-cTnT, area under the curve: 0.89 [95% CI: 0.86-0.92] vs 0.94 [95% CI: 0.93-0.94] [P < 0.001]; for hs-cTnI, area under the curve: 0.93 [95% CI: 0.91-0.95] vs 0.95 [95% CI: 0.94-0.95] [P = 0.10]). In patients with cancer, the European Society of Cardiology 0/1-hour hs-cTnT and hs-cTnI algorithms maintained very high safety but had lower efficacy, with twice the number of patients remaining in the observe zone. Similar findings were obtained in the external validation cohort. Conclusions: Patients with cancer have a substantially higher prevalence of AMI as the cause of chest pain. Length of ED stay and hospitalization rates are increased. The diagnostic performance of hs-cTnT and the efficacy of both the European Society of Cardiology 0/1-hour hs-cTnT and hs-cTnI algorithms is reduced. (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE] Study; NCT00470587).

Cohort profile: Data standards for cardiac rehabilitation structure and processes for the SWEDEHEART cardiac rehabilitation (SWEDEHEART-CR) registry.

Data standards for quality registries should be evidence-based and follow guideline recommendations. To optimally monitor quality of care, not only patient-level variables, but also centre-level variables need to be included. Here we describe the development of variables to audit the structure and processes in cardiac rehabilitation for patients after myocardial infarction, and the resulting data standards to be implemented in the Swedish quality registry for cardiac disease, SWEDEHEART. The methodology used for the development of international clinical data standards for the European Unified Registries for Heart Care Evaluation and Randomised Trials (EuroHeart) was followed. Based on national guidelines for secondary prevention, candidate variables were prepared, after which a multiprofessional expert group on cardiac rehabilitation selected key variables and assured face validity. An external reference group had the role of peer reviewing, ascertaining content validity and test-retest reliability. The process has resulted in 30 data standards to be introduced into the SWEDEHEART cardiac rehabilitation registry and administered on centre-level biannually. The data standards include measures of human resources, centre requirements and process-based metrics. Including registry variables which audit centre-level structure and processes is essential to improve benchmarking and standardize monitoring of quality of care, covering both services provided and patient outcomes.

HEART-score can be simplified without loss of discriminatory power in patients with chest pain - Introducing the HET-score.

BACKGROUND: The History, Electrocardiogram (ECG), Age, Risk factors and Troponin, (HEART) score is useful for early risk stratification in chest pain patients. The aim was to validate previous findings that a simplified score using history, ECG and troponin (HET-score) has similar ability to stratify risk. METHODS: Patients presenting with chest pain with duration of ≥10 min and an onset of last episode ≤12 h but without ST-segment elevation on ECG at 6 emergency departments were eligible for inclusion. The HEART-score and the simplified HET-score were calculated. The endpoint was a composite of myocardial infarction (MI) as index diagnosis, readmission due to new MI or death within 30 days. RESULTS: HEART-score identified 32% as low risk (0-2p), 47% as intermediate risk (3-5p), and 20% as high risk (6-10p) patients. The endpoint occurred in 0.5%, 7.3% and 35.7%, respectively. HET-score identified 39%, 42% and 19% as low- (0p), intermediate- (1-2p) and high-risk (3-6p) patients, with the endpoint occurring in 0.6%, 6.2% and 43.2%, respectively. When all variables included in the HEART-score were included in a multivariable logistic regression analysis, only History (OR, CI [95%]): 2.97(2.16-4.09), ECG (1.61[1.14-2.28]) and troponin level (5.21[3.91-6.95]) were significantly associated with cardiovascular events. When HEART- and HET-score were compared in a ROC-analysis, HET-score had a significantly larger AUC (0.887 vs 0.853, p < 0.001). CONCLUSIONS: Compared with HEART-score, HET-score is simpler and appears to have similar ability to discriminate between chest pain patients with and without cardiovascular event.

Helicobacter pylori and Pro-Inflammatory Protein Biomarkers in Myocardial Infarction with and without Obstructive Coronary Artery Disease.

Myocardial infarction (MI) with obstructive coronary artery disease (MI-CAD) and MI in the absence of obstructive coronary artery disease (MINOCA) affect different populations and may have separate pathophysiological mechanisms, with greater inflammatory activity in MINOCA compared to MI-CAD. Helicobacter pylori (Hp) can cause systemic inflammation and has been associated with cardiovascular disease (CVD). We aimed to investigate whether Hp infection is associated with concentrations of protein biomarkers of inflammation and CVD. In a case-control study, patients with MINOCA (n = 99) in Sweden were included, complemented by matched subjects with MI-CAD (n = 99) and controls (n = 100). Protein biomarkers were measured with a proximity extension assay in plasma samples collected 3 months after MI. The seroprevalence of Hp and cytotoxin-associated gene A (CagA) was determined using ELISA. The associations between protein levels and Hp status were studied with linear regression. The prevalence of Hp was 20.2%, 19.2%, and 16.0% for MINOCA, MI-CAD, and controls, respectively (p = 0.73). Seven proteins were associated with Hp in an adjusted model: tissue plasminogen activator (tPA), interleukin-6 (IL-6), myeloperoxidase (MPO), TNF-related activation-induced cytokine (TRANCE), pappalysin-1 (PAPPA), soluble urokinase plasminogen activator receptor (suPAR), and P-selectin glycoprotein ligand 1 (PSGL-1). Hp infection was present in one in five patients with MI, irrespective of the presence of obstructive CAD. Inflammatory proteins were elevated in Hp-positive subjects, thus not ruling out that Hp may promote an inflammatory response and potentially contribute to the development of CVD.

Entrustable professional activities (EPAs) for undergraduate medical education - development and exploration of social validity.

BACKGROUND: The development of entrustable professional activities (EPAs) as a framework for work-based training and assessment in undergraduate medical education has become popular. EPAs are defined as units of a professional activity requiring adequate knowledge, skills, and attitudes, with a recognized output of professional labor, independently executable within a time frame, observable and measurable in its process and outcome, and reflecting one or more competencies. Before a new framework is implemented in a specific context, it is valuable to explore social validity, that is, the acceptability by relevant stakeholders. AIM: The aim of our work was to define Core EPAs for undergraduate medical education and further explore the social validity of the constructs. METHOD AND MATERIAL: In a nationwide collaboration, EPAs were developed using a modified Delphi procedure and validated according to EQual by a group consisting of teachers nominated from each of the seven Swedish medical schools, two student representatives, and an educational developer (n = 16). In the next step, social validity was explored in a nationwide survey. The survey introduced the suggested EPAs. For each EPA, the importance of the EPA was rated, as was the rater's perception of the present graduates' required level of supervision when performing the activity. Free-text comments were also included and analyzed. RESULTS: Ten Core EPAs were defined and validated. The validation scores for EQual ranged from 4.1 to 4.9. The nationwide survey had 473 responders. All activities were rated as "important" by most responders, ranging from 54 to 96%. When asked how independent current graduates were in performing the ten activities, 6 to 35% reported "independent". The three themes of the free text comments were: 'relevant target areas and content'; 'definition of the activities'; and 'clinical practice and learning'. CONCLUSION: Ten Core EPAs were defined and assessed as relevant for Swedish undergraduate medical education. There was a consistent gap between the perceived importance and the certainty that the students could perform these professional activities independently at the time of graduation. These results indicate that the ten EPAs may have a role in undergraduate education by creating clarity for all stakeholders.

A new clinical classification of acute myocardial infarction.

The existence of a universal definition of myocardial infarction-which involves classification into multiple subtypes-has promoted the use of standard diagnostic criteria across the world. However, this classification has not been applied consistently in practice and is perceived by some as too complicated. Where there is diagnostic uncertainty, patients have worse outcomes. This uncertainty has also impacted on the validity of the diagnosis of myocardial infarction in clinical trials. To address these issues and to encourage clinicians to recognize that different mechanisms of myocardial infarction have differing treatment implications, we propose an alternative clinical classification for consideration; one that recognizes that myocardial infarction can arise spontaneously, secondary to another condition, or as a complication of a cardiac procedure. This classification is aligned with clinical practice and proposes more objective and specific diagnostic criteria that, if agreed by international consensus, could reduce diagnostic uncertainty in practice and research.

Associations of Inflammatory Biomarkers With the Risk of Morbidity and Mortality After Cardiac Surgery: A Systematic Review and Meta-analysis.

BACKGROUND: Although inflammatory biomarkers have been associated with cardiovascular events in nonsurgical settings, these associations have not been systematically addressed in patients undergoing cardiac surgery. This review aimed to evaluate the relationships of inflammatory markers with mortality and adverse cardiovascular events in patients undergoing cardiac surgery. METHODS: Medline, Embase, and Central databases were systematically searched for studies reporting pre- or postoperative levels of inflammatory biomarkers in patients undergoing cardiac surgery. Outcomes of interest were postoperative mortality, nonfatal myocardial infarction, stroke, congestive heart failure, and major adverse cardiovascular events (MACE). Studies reporting multivariable adjusted risk estimates were included. Risk estimates were pooled with the use of random-effects models and reported as summary odds ratios (ORs). RESULTS: Among 14,465 citations identified, 29 studies including 29,401 participants met the eligibility criteria. The average follow-up time after surgery was 31 months. Preoperative C-reactive protein (CRP) levels were associated with an increased risk of all-cause mortality (OR 1.88, 95% CI 1.60-2.20; I2 = 19%; 11 studies) and MACE (OR 1.73, 95% CI 1.34-2.24; I2 = 0%; 3 studies). CRP levels measured on postoperative day 6 (OR 7.4, 95% CI 2.90-18.88, 1 study) and day 10 (OR 11.8, 95% CI 3.50-39.78, 1 study) were associated with a higher risk of all-cause mortality. Less, but overall similar, information was available for other inflammatory biomarkers. CONCLUSIONS: In this large meta-analysis, inflammatory biomarkers measured before or after cardiac surgery were associated with mortality and adverse cardiovascular outcomes in patients undergoing cardiac surgery.

Comparison between ticagrelor and clopidogrel in myocardial infarction patients with high bleeding risk.

AIMS: Ticagrelor is associated with a lower risk of ischemic events than clopidogrel. However, it is uncertain whether the benefits of more intensive anti-ischemic therapy outweigh the risks of major bleeding in patients who have a high bleeding risk (HBR). Therefore, this study compared ticagrelor and clopidogrel in myocardial infarction (MI) patients with HBR. METHODS AND RESULTS: This study included all patients enrolled in the SWEDEHEART registry who were discharged with dual antiplatelet therapy using ticagrelor or clopidogrel following MI between 2010 and 2017. High bleeding risk was defined as a PRECISE-DAPT score ≥25. Information on ischemic events, major bleeding, and mortality was obtained from national registries, with 365 days of follow-up. Additional outcomes include major adverse cardiovascular events (MACE), a composite of MI, stroke and all-cause mortality, and net adverse clinical events (NACE), a composite of MACE and bleeding. This study included 25 042 HBR patients, of whom 11 848 were treated with ticagrelor. Ticagrelor was associated with a lower risk of MI, stroke, and MACE, but a higher risk of bleeding compared to clopidogrel. There were no significant differences in mortality and NACE. Additionally, when examining the relationship between antiplatelet therapy and bleeding risk in 69 040 MI patients, we found no statistically significant interactions between the PRECISE-DAPT score and treatment effect. CONCLUSIONS: We observed no difference in NACE when comparing ticagrelor and clopidogrel in HBR patients. Moreover, we found no statistically significant interactions between bleeding risk and the comparative effectiveness of clopidogrel and ticagrelor in a larger population of MI patients.

Temporal trends in cardiovascular risk factors, lifestyle and secondary preventive medication for patients with myocardial infarction attending cardiac rehabilitation in Sweden 2006-2019: a registry-based cohort study.

OBJECTIVES: Registries have been highlighted as means to improve quality of care. Here, we describe temporal trends in risk factors, lifestyle and preventive medication for patients after myocardial infarction (MI) registered in the quality registry Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART). DESIGN: A registry-based cohort study. SETTING: All coronary care units and cardiac rehabilitation (CR) centres in Sweden. PARTICIPANTS: Patients attending a CR visit at 1-year post-MI 2006-2019 were included (n=81 363, 18-74 years, 74.7% men). OUTCOME MEASURES: Outcome measures at 1-year follow-up included blood pressure (BP) <140/90 mm Hg, low-density lipoprotein-cholesterol (LDL-C)<1.8 mmol/L, persistent smoking, overweight/obesity, central obesity, diabetes prevalence, inadequate physical activity, and prescription of secondary preventive medication. Descriptive statistics and testing for trends were applied. RESULTS: The proportion of patients attaining the targets for BP<140/90 mmHg increased from 65.2% (2006) to 86.0% (2019), and LDL-C<1.8 mmol/L from 29.8% (2006) to 66.9% (2019, p<0.0001 both). While smoking at the time of MI decreased (32.0% to 26.5%, p<0.0001), persistent smoking at 1 year was unchanged (42.8% to 43.2%, p=0.672) as was the prevalence of overweight/obesity (71.9% to 72.9%, p=0.559). Central obesity (50.5% to 57.0%), diabetes (18.2% to 27.2%) and patients reporting inadequate levels of physical activity (57.0% to 61.5%) increased (p<0.0001 for all). From 2007, >90.0% of patients were prescribed statins and approximately 98% antiplatelet and/or anticoagulant therapy. Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker prescription increased from 68.7% (2006) to 80.2% (2019, p<0.0001). CONCLUSIONS: While little change was observed for persistent smoking and overweight/obesity, large improvements were observed for LDL-C and BP target achievements and prescription of preventive medication for Swedish patients after MI 2006-2019. Compared with published results from patients with coronary artery disease in Europe during the same period, these improvements were considerably larger. Continuous auditing and open comparisons of CR outcomes might possibly explain some of the observed improvements and differences.

Elevated low-density lipoprotein cholesterol: An inverse marker of morbidity and mortality in patients with myocardial infarction.

BACKGROUND: The incidence of atherosclerotic cardiovascular disease increases with levels of low-density lipoprotein cholesterol (LDL-C). Yet, a paradox may exist where lower LDL-C levels at myocardial infarction (MI) are associated with poorer prognoses. OBJECTIVE: To assess the association between LDL-C levels at MI with risk factor burden and cause-specific outcomes. METHODS: Statin-naive patients hospitalized for a first MI and registered in SWEDEHEART were included. Data were linked to Swedish registers. Primary outcomes were all-cause mortality and nonfatal MI. Associations between LDL-C and outcomes were assessed using adjusted proportional hazards models. RESULTS: Among 63,168 patients (median age, 66 years), the median LDL-C level was 3.0 mmol/L (interquartile range 2.4-3.6). Patient age and comorbidities increased as LDL-C decreased. During a median follow-up of 4.5 years, 10,236 patients died, and 4973 had nonfatal MI. Patients with the highest LDL-C had a lower risk of mortality (hazard ratio [HR] 0.75; 95% confidence interval [CI] 0.71-0.80). The risk of hospitalization for pneumonia, hip fracture, chronic obstructive pulmonary disease, and new cancer diagnosis was lower with higher LDL-C (HR range, 0.40-0.81). Patients with the highest LDL-C had a greater risk of recurrent MI (HR 1.16; 95% CI 1.07-1.26). CONCLUSIONS: Patients with the highest LDL-C levels at MI had the lowest incidence of mortality and morbidity. This seems to reflect lower age at MI, less underlying morbidities, paired with the modifiability of LDL-C. However, supporting the causal association between LDL-C and ischemic heart disease, elevated LDL-C was simultaneously associated with an increased risk of nonfatal MI.