Cohort Profile: the European Unified Registries On Heart care Evaluation and Randomised Trials (EuroHeart) - Acute Coronary Syndrome and Percutaneous Coronary Intervention.

AIMS: The European Unified Registries On Heart care Evaluation And Randomized Trials (EuroHeart) aims to improve the quality of care and clinical outcomes for patients with cardiovascular disease. The collaboration of acute coronary syndrome/percutaneous coronary intervention (ACS/PCI) registries is operational in seven vanguard European Society of Cardiology member countries. METHODS AND RESULTS: Adults admitted to hospitals with ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) are included, and individual patient-level data collected and aligned according to the internationally agreed EuroHeart data standards for ACS/PCI. The registries provide up to 155 variables spanning patient demographics and clinical characteristics, in-hospital care, in-hospital outcomes, and discharge medications. After performing statistical analyses on patient data, participating countries transfer aggregated data to EuroHeart for international reporting.Between 1st January 2022 and 31st December 2022, 40 021 admissions (STEMI 46.7%, NSTEMI 53.3%) were recorded from 192 hospitals in the seven vanguard countries: Estonia, Hungary, Iceland, Portugal, Romania, Singapore, and Sweden. The mean age for the cohort was 67.9 (standard deviation 12.6) years, and it included 12 628 (31.6%) women. CONCLUSION: The EuroHeart collaboration of ACS/PCI registries prospectively collects and analyses individual data for ACS and PCI at a national level, after which aggregated results are transferred to the EuroHeart Data Science Centre. The collaboration will expand to other countries and provide continuous insights into the provision of clinical care and outcomes for patients with ACS and undergoing PCI. It will serve as a unique international platform for quality improvement, observational research, and registry-based clinical trials.

Major bleeding in patients with atrial fibrillation treated with apixaban versus warfarin in combination with amiodarone: nationwide cohort study.

BACKGROUND: Amiodarone is an established treatment for atrial fibrillation (AF) but might interfere with the metabolism of apixaban or warfarin. Therefore, the aim was to investigate the occurrence of major bleeding among patients with AF treated with amiodarone in combination with apixaban or warfarin. METHODS: Retrospective observational study using Swedish health registers. All patients with AF in the National Patient Register and the National Dispensed Drug Register with concomitant use of amiodarone and warfarin or apixaban between 1 June 2013 and 31 December 2018 were included. Propensity score matching was performed, and matched cohorts were compared using Cox proportional HRs. The primary outcome was major bleeding resulting in hospitalisation based on International Classification of Diseases (ICD)-10 codes. Secondary outcomes included intracranial bleeding, gastrointestinal bleeding and other bleeding. Exploratory outcomes included ischaemic stroke/systemic embolism and all-cause/cardiovascular (CV) mortality. RESULTS: A total of 12 103 patients met the inclusion criteria and 8686 patients were included after propensity score matching. Rates of major bleeding were similar in the apixaban (4.3/100 patient-years) and warfarin cohort (4.5/100 patient-years) (HR: 1.03; 95% CI: 0.76 to 1.39) during median follow-up of 4.4 months. Similar findings were observed for secondary outcomes including gastrointestinal bleeding and other bleeding, and exploratory outcomes including ischaemic stroke/systemic embolism and all-cause/CV mortality. CONCLUSIONS: Among patients treated with amiodarone in combination with apixaban or warfarin, major bleeding and thromboembolic events were rare and with no significant difference between the treatment groups. EUPAS REGISTRY NUMBER: EUPAS43681.

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.

European Society of Cardiology Quality indicators for the care and outcomes of adults undergoing transcatheter aortic valve implantation.

BACKGROUND AND AIMS: To develop a suite of quality indicators (QIs) for the evaluation of the care and outcomes for adults undergoing transcatheter aortic valve intervention (TAVI). METHODS: We followed the European Society of Cardiology (ESC) methodology for the development of QIs. Key domains were identified by constructing a conceptual framework for the delivery of TAVI care. A list of candidate QIs were developed by conducting a systematic review of the literature. A modified Delphi method was then used to select the final set of QIs. Finally, we mapped the QIs to the EuroHeart Data Standards for TAVI to ascertain the extent to which the EuroHeart TAVI registry captures information to calculate the QIs. RESULTS: We formed an international group of experts in quality improvement and TAVI, including representatives from the European Association of Percutaneous Cardiovascular Interventions, the European Association of Cardiovascular Imaging and the Association of Cardiovascular Nursing & Allied Professions. In total, 27 QIs were selected across eight domains of TAVI care, comprising 22 main (81%) and five secondary (19%) QIs. Of these, 19/27 (70%) are now being utilised in the EuroHeart TAVI registry. CONCLUSION: We present the 2023 ESC QIs for TAVI, developed using a standard methodology and in collaboration with ESC Associations. The EuroHeart TAVI registry allows calculation of the majority of the QIs, which may be used for benchmarking care and quality improvement initiatives.

Thromboembolic and bleeding events after valvular intervention in patients with atrial fibrillation.

AIM: To assess outcomes after cardiac surgery with biological valve replacement, valve repair or transcatheter aortic valve implantation (TAVI) in patients with atrial fibrillation (AF) in accordance with oral anticoagulant (OAC) treatment. METHODS: All patients in Sweden undergoing valvular intervention with AF were included. Associations between OAC exposure and cardiovascular (CV) events (composite of CV death, ischaemic stroke or systemic embolism) and major bleeding were investigated using Cox regression analysis. The analysis was separated in time periods of 0-3 and 3-12 months after discharge. RESULTS: 4730 patients were included in the first time period, 54.0% had received a surgical biological valve prosthesis, 23.8% valve repair and 22.2% TAVI. Exposure to warfarin (comparator) was 62.3%, to non-vitamin K antagonist oral anticoagulants (NOACs) 10.0% and to no OAC 27.7%. NOAC exposure was associated with similar risk of the composite CV outcome and major bleeding from 0 to 3 months. No OAC was associated with increased risk of the composite CV outcome (HR 1.71; 95% CI 1.26 to 2.32) and similar risk of major bleeding. Further analysis of the bioprosthetic valve replacement subgroup indicated increased risk of CV death when exposed to NOAC (HR 2.58; 95% CI 1.15 to 5.78) and no OAC (HR 2.82; 95% CI 1.65 to 4.82) compared with warfarin from 0 to 3 months. No differences were seen between 3 and 12 months. CONCLUSION: In this registry-based cohort study of patients with AF with severe valvular heart disease undergoing various valvular interventions, NOAC appears to be comparable with warfarin regarding efficacy and safety. Patients not receiving OAC had higher risk of CV events. NOAC was associated with increased CV death compared with warfarin in the surgical bioprosthetic valve replacement subgroup, illustrating the importance of being cautious when extrapolating data from one patient group to another. Further studies comparing NOAC and warfarin in the early postoperative phase are warranted, especially following surgical bioprosthetic valve replacement.

Clinical Outcomes in Patients With Atrial Fibrillation Treated With Non-Vitamin K Oral Anticoagulants Across Varying Body Mass Index.

Background There are conflicting data on outcomes in patients with atrial fibrillation treated with non-vitamin K oral anticoagulants across varying body mass index (BMI). We investigated cardiovascular and bleeding risk in patients with atrial fibrillation with varying BMI. Methods and Results Observational cohort study from the Swedish oral anticoagulation registry between August 2, 2011, and December 31, 2018. Primary outcomes were mortality, ischemic stroke/systemic embolism, and major bleeding. Baseline BMI (kg/m2) was analyzed continuously and categorized: underweight (<18.5 kg/m2), normal weight (18.5 to <25 kg/m2), preobesity (25 to <30 kg/m2), and obesity class I to III (30 to <35, 35 to <40, and ≥40 kg/m2). Adjusted Cox models and nonlinear relationships of BMI were modeled using restricted cubic splines. Non-vitamin K oral anticoagulant-treated patients with atrial fibrillation were included (n=26 047). At baseline, 602 (2.3%) were underweight, 9101 (34.9%) were normal weight, 9970 (38.3%) were preobese, 4280 (16.4%) were obese class I, 1486 (5.7%) were obese class II, and 608 (2.3%) were obese class III. Underweight and obesity class III were in adjusted continuous analysis associated with increased mortality and major bleeding, with lowest risk observed among preobese patients with BMI 28.2 and 26.2 kg/m2, respectively. In adjusted categorical analysis, underweight was associated with increased mortality (hazard ratio [HR], 1.77 [95% CI, 1.57-1.99]) and nonsignificant higher risk of major bleeding (HR, 1.23 [95% CI, 0.95-1.58]). Similarly, obesity class III was associated with increased mortality (HR, 1.67 [95% CI, 1.40-1.99]) and major bleeding (HR, 1.68 [95% CI, 1.29-2.17]). No significant association was observed between higher BMI and ischemic stroke/systemic embolism. Conclusions In non-vitamin K oral anticoagulant-treated patients with atrial fibrillation, there appears to be a U-shaped relationship between BMI and mortality and major bleeding.

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

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

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

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

Long-term antithrombotic therapy after coronary artery bypass grafting in patients with preoperative atrial fibrillation. A nationwide observational study from the SWEDEHEART registry.

AIMS: To provide data guiding long-term antithrombotic therapy after coronary artery by-pass grafting (CABG) in patients with preoperative atrial fibrillation (AF). METHODS AND RESULTS: From the SWEDEHEART registry, we included all patients, between January 2006 and September 2016, with preoperative AF and CHA2DS2-VASC score ≥2, undergoing CABG. Based on dispensed prescriptions 12 to 18 months after CABG, patients were divided in 3 groups: use of platelet inhibitors (PI) only, oral anticoagulant (OAC) only or a combination of OAC + PI. Outcomes were: Major adverse cardiac and cerebrovascular events (MACCE, [all-cause death, myocardial infarction, or stroke]), net adverse clinical events (NACE, [MACCE or bleeding]) and the individual components of NACE. Inverse probability of treatment weighting was used to adjust for the non-randomized study design. Among 2,564 patients, 1,040 (41%) were treated with PI alone, 1,064 (41%) with OAC alone, and 460 (18%) with PI + OAC. Treatment with PI alone was associated with higher risk for MACCE (adjusted HR 1.43, 95% CI 1.09-1.88), driven by higher risk for stroke and MI, compared with OAC alone. Treatment with PI + OAC, was associated with higher risk for NACE (adjusted HR 1.40, 95% CI 1.06-1.85), driven by higher risk for bleeds, compared with OAC alone. CONCLUSION: In this real-world observational study, a high proportion of patients with AF, undergoing CABG, did not receive a long-term OAC therapy. Treatment with OAC alone was associated with a net clinical benefit, compared with PI alone or PI + OAC.

Data standards for atrial fibrillation/flutter and catheter ablation: the European Unified Registries for Heart Care Evaluation and Randomized Trials (EuroHeart).

AIMS: Standardized data definitions are essential for monitoring and assessment of care and outcomes in observational studies and randomized controlled trials (RCTs). The European Unified Registries for Heart Care Evaluation and Randomized Trials (EuroHeart) project of the European Society of Cardiology aimed to develop contemporary data standards for atrial fibrillation/flutter (AF/AFL) and catheter ablation. METHODS AND RESULTS: We used the EuroHeart methodology for the development of data standards and formed a Working Group comprising 23 experts in AF/AFL and catheter ablation registries, as well as representatives from the European Heart Rhythm Association and EuroHeart. We conducted a systematic literature review of AF/AFL and catheter ablation registries and data standard documents to generate candidate variables. We used a modified Delphi method to reach a consensus on a final variable set. For each variable, the Working Group developed permissible values and definitions, and agreed as to whether the variable was mandatory (Level 1) or additional (Level 2). In total, 70 Level 1 and 92 Level 2 variables were selected and reviewed by a wider Reference Group of 42 experts from 24 countries. The Level 1 variables were implemented into the EuroHeart IT platform as the basis for continuous registration of individual patient data. CONCLUSION: By means of a structured process and working with international stakeholders, harmonized data standards for AF/AFL and catheter ablation for AF/AFL were developed. In the context of the EuroHeart project, this will facilitate country-level quality of care improvement, international observational research, registry-based RCTs, and post-marketing surveillance of devices and pharmacotherapies.

Reliability of estimating left ventricular ejection fraction in clinical routine: a validation study of the SWEDEHEART registry.

OBJECTIVE: Patients hospitalized with acute coronary syndrome (ACS) in Sweden routinely undergo an echocardiographic examination with assessment of left ventricular ejection fraction (LVEF). LVEF is a measurement widely used for outcome prediction and treatment guidance. The obtained LVEF is categorized as normal (> 50%) or mildly, moderately, or severely impaired (40-49, 30-39, and < 30%, respectively) and reported to the nationwide registry for ACS (SWEDEHEART). The purpose of this study was to determine the reliability of the reported LVEF values by validating them against an independent re-evaluation of LVEF. METHODS: A random sample of 130 patients from three hospitals were included. LVEF re-evaluation was performed by two independent reviewers using the modified biplane Simpson method and their mean LVEF was compared to the LVEF reported to SWEDEHEART. Agreement between reported and re-evaluated LVEF was assessed using Gwet's AC2 statistics. RESULTS: Analysis showed good agreement between reported and re-evaluated LVEF (AC2: 0.76 [95% CI 0.69-0.84]). The LVEF re-evaluations were in agreement with the registry reported LVEF categorization in 86 (66.0%) of the cases. In 33 (25.4%) of the cases the SWEDEHEART-reported LVEF was lower than re-evaluated LVEF. The opposite relation was found in 11 (8.5%) of the cases (p < 0.005). CONCLUSION: Independent validation of SWEDEHEART-reported LVEF shows an overall good agreement with the re-evaluated LVEF. However, a tendency towards underestimation of LVEF was observed, with the largest discrepancy between re-evaluated LVEF and registry LVEF in subjects with subnormal LV-function in whom the reported assessment of LVEF should be interpreted more cautiously.

Methodology for the development of international clinical data standards for common cardiovascular conditions: European Unified Registries for Heart Care Evaluation and Randomised Trials (EuroHeart).

AIMS: Data standards are consensual specifications for the representation of data arising from different sources. If provided with internationally harmonized variables, permissible values, and clinical definitions, they have the potential to enable reliable between- and within-country analysis of care and outcomes. The European Unified Registries for Heart Care Evaluation and Randomised Trials (EuroHeart) is a European Society of Cardiology project that allows participating countries to collect patient data to undertake quality improvement, observational studies, drug and device surveillance, and registry-based randomized controlled trials for cardiovascular conditions. This paper describes the methodology for development of harmonized data standards for EuroHeart. METHODS AND RESULTS: We adopted a five-step process for the development of harmonized data standards. The process includes (i) identification of clinical domains for data standard development by evaluating specific cardiovascular conditions with high prevalence and opportunities for quality improvement; (ii) construction of data standard specifications by systematic review of the literature; (iii) selection of variables by a domain-specific Working Group using a modified Delphi method; (iv) validation of data standards by a domain-specific Reference Group; and (v) implementation of the developed data standards into an IT platform. CONCLUSION: This paper describes the approach adopted by EuroHeart for the development of clinical data standards for cardiovascular disease. The methodology has been developed and is used by EuroHeart to create a suite of international data standards for cardiovascular diseases. The EuroHeart data standards may be used to systematically capture individual patient data about clinical care and for research.

Data standards for transcatheter aortic valve implantation: the European Unified Registries for Heart Care Evaluation and Randomised Trials (EuroHeart).

AIMS: Standardized data definitions are necessary for the quantification of quality of care and patient outcomes in observational studies and randomised controlled trials (RCTs). The European Unified Registries for Heart Care Evaluation and Randomised Trials (EuroHeart) project of the European Society of Cardiology (ESC) aims to create pan-European data standards for cardiovascular diseases and interventions, including transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS: We followed the EuroHeart methodology for cardiovascular data standard development. A Working Group of 29 members representing 12 countries was established and included a patient representative, as well as experts in the management of valvular heart disease from the European Association of Percutaneous Cardiovascular Interventions (EAPCI), the European Association of Cardiovascular Imaging (EACVI) and the Working Group on Cardiovascular Surgery. We conducted a systematic review of the literature and used a modified Delphi method to reach consensus on a final set of variables. For each variable, the Working Group provided a definition, permissible values, and categorized the variable as mandatory (Level 1) or additional (Level 2) based on its clinical importance and feasibility. In total, 93 Level 1 and 113 Level 2 variables were selected, with the level 1 variables providing the dataset for registration of patients undergoing TAVI on the EuroHeart IT platform. CONCLUSION: This document provides details of the EuroHeart data standards for TAVI processes of care and in-hospital outcomes. In the context of EuroHeart, this will facilitate quality improvement, observational research, registry-based RCTs and post-marketing surveillance of devices, and pharmacotherapies. ONE-SENTENCE SUMMARY: The EuroHeart data standards for transcatheter aortic valve implantation (TAVI) are a set of internationally agreed data variables and definitions that once implemented will facilitate improvement of quality of care and outcomes for patients receiving TAVI.

Association between heart failure quality of care and mortality: a population-based cohort study using nationwide registries.

AIMS: To evaluate the quality of heart failure (HF) care using the European Society of Cardiology (ESC) quality indicators (QIs) for HF and to assess whether better quality of care is associated with improved outcomes. METHODS AND RESULTS: We performed a nationwide cohort study using the Swedish HF registry, consisting of patients with any type of HF at their first outpatient visit or hospitalization. Independent participant data for quality of HF care was evaluated against the ESC QIs for HF, and association with mortality estimated using multivariable Cox regression. In total, 43 704 patients from 80 hospitals across Sweden enrolled between 2013-2019 were included, with median follow-up 23.6 months. Of the 16 QIs for HF, 13 could be measured and 5 were inversely associated with all-cause mortality during follow-up. Higher attainment (≥50% vs. <50% attainment) of the composite opportunity-based score (combination of QIs into a single score) for patients with reduced ejection fraction was associated with lower all-cause mortality (adjusted hazard ratio 0.81; 95% confidence interval 0.72-0.91). Attainment of the composite score was less in the outpatient than inpatient setting (adjusted odds ratio 0.85; 95% confidence interval 0.72-0.99). Quality of care varied across hospitals, with assessment of health-related quality of life being the indicator with the widest variation in attainment (interquartile range 61.7%). CONCLUSION: Quality of HF care may be measured using the ESC HF QIs. In Sweden, attainment of HF care evaluated using the QIs demonstrated between and within hospital variation, and many QIs were inversely associated with mortality.

Biomarker-Based Prediction of Recurrent Ischemic Events in Patients With Acute Coronary Syndromes.

BACKGROUND: In patients with acute coronary syndrome (ACS), there is residual and variable risk of recurrent ischemic events. OBJECTIVES: This study aimed to develop biomarker-based prediction models for 1-year risk of cardiovascular (CV) death and myocardial infarction (MI) in patients with ACS undergoing percutaneous coronary intervention. METHODS: We included 10,713 patients from the PLATO (A Comparison of Ticagrelor [AZD6140] and Clopidogrel in Patients With Acute Coronary Syndrome) trial in the development cohort and externally validated in 3,508 patients from the TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) trial. Variables contributing to risk of CV death/MI were assessed using Cox regression models, and a score was derived using subsets of variables approximating the full model. RESULTS: There were 632 and 190 episodes of CV death/MI in the development and validation cohorts. The most important predictors of CV death/MI were the biomarkers, growth differentiation factor 15, and N-terminal pro-B-type natriuretic peptide, which had greater prognostic value than all candidate variables. The final model included 8 items: age (A), biomarkers (B) (growth differentiation factor 15 and N-terminal pro-B-type natriuretic peptide), and clinical variables (C) (extent of coronary artery disease, previous vascular disease, Killip class, ACS type, P2Y12 inhibitor). The model, named ABC-ACS ischemia, was well calibrated and showed good discriminatory ability for 1-year risk of CV death/MI with C-indices of 0.71 and 0.72 in the development and validation cohorts, respectively. For CV death, the score performed better, with C-indices of 0.80 and 0.84 in the development and validation cohorts, respectively. CONCLUSIONS: An 8-item score for the prediction of CV death/MI was developed and validated for patients with ACS undergoing percutaneous coronary intervention. The ABC-ACS ischemia score showed good calibration and discrimination and might be useful for risk prediction and decision support in patients with ACS. (A Comparison of Ticagrelor [AZD6140] and Clopidogrel in Patients With Acute Coronary Syndrome [PLATO]; NCT00391872; Trial to Assess the Effects of Vorapaxar [SCH 530348; MK-5348] in Preventing Heart Attack and Stroke in Participants With Acute Coronary Syndrome [TRACER]; NCT00527943).

Oral anticoagulants, time in therapeutic range and renal function over time in real-life patients with atrial fibrillation and chronic kidney disease.

AIMS: To describe the use of warfarin and direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) and chronic kidney disease (CKD), to evaluate changes in renal function over time and predictors of rapid decline, and to describe time in therapeutic range (TTR) and predictors of poor TTR among patients on warfarin. METHODS AND RESULTS: Using data from AuriculA, the Swedish oral anticoagulation registry, patients with AF on warfarin or DOAC were identified between 2013 and 2018 (N=6567). Estimated glomerular filtration rate (eGFR) was calculated and categorised into normal (≥90 mL/min/1.73 m2), mild CKD (60-89 mL/min/1.73 m2), moderate CKD (30-59 mL/min/1.73 m2), severe CKD (15-29 mL/min/1.73 m2) and end-stage CKD (<15 mL/min/1.73 m2)/dialysis. TTR was estimated using international normalised ratio (INR) measurements. Predictors of eGFR decline over time and of poor TTR were estimated using regression analysis. Between 2013 and 2018, use of DOAC increased from 9.2% to 89.3%, with a corresponding decline in warfarin. A similar trend was observed in patients with mild to moderate CKD, while DOAC over warfarin increased slower among patients with severe to end-stage CKD/dialysis. In patients treated with warfarin, the median TTR was 77.1%. Worse TTR was observed among patients with severe CKD (70.0%) and end-stage CKD/dialysis (67.5%). A gradual annual decline in eGFR was observed (-1.1 mL/min/1.73 m2), with a more rapid decline among patients with older age, female sex, diabetes mellitus and/or heart failure. CONCLUSION: In patients with AF, use of DOAC has steadily increased across different CKD stages, but not in patients with severe to end-stage CKD/dialysis despite these patients having poor INR control. Patients with AF have a gradual decline in renal function, with a more rapid decline among a subgroup of patients.

Association of GDF-15, hs-cTnT and NT-proBNP with coronary artery disease in patients undergoing elective angiography.

Aim: This study investigated the association between plasma levels of GDF-15, hs-cTnT and NT-proBNP and the presence of coronary artery disease (CAD) in stable patients referred for elective coronary angiography. Methods: The outcome of CAD was defined as an ordinal variable with 3 levels. The association between each biomarker and the outcome was tested using the Winell and Lindbäck method. Results: In unadjusted analysis of 252 patients, GDF-15 and hs-cTnT were associated with the presence and extent of CAD. In multivariate regression analysis including traditional risk factors, this association was no longer significant. Conclusion: NT-proBNP, GDF-15 and hs-cTnT plasma levels do not seem to improve the predictive ability of traditional risk factors for CAD in stable patients referred for coronary angiography.

This study aimed to look at a possible association between blood levels of three molecules (GDF-15, hs-cTnT and N-terminal pro B-type natriuretic peptide [NT-proBNP]) and the presence of coronary artery disease (CAD) in stable patients referred for coronary angiography. Three CAD degrees of severity were identified: no CAD, 1- or 2-vessel CAD and 3-vessel or left main CAD. The association between each of the three blood molecules and CAD was studied using a specific statistical method. In the 252 consecutive patients enrolled, the two molecules GDF-15 and hs-cTnT were significantly associated with the presence and extent of CAD, while NT-proBNP was not. However, when the statistical analysis was adjusted for the traditional risk factors of CAD (age, gender, smoking, diabetes, etc.), the association of GDF-15 and hs-cTnT with CAD was no longer significant. NT-proBNP, GDF-15 and hs-cTnT blood levels do not seem to be independent predictive tools for CAD in stable patients referred for coronary angiography.

Data standards for acute coronary syndrome and percutaneous coronary intervention: the European Unified Registries for Heart Care Evaluation and Randomised Trials (EuroHeart).

Standardized data definitions are essential for monitoring and benchmarking the quality of care and patient outcomes in observational studies and randomized controlled trials. There are no contemporary pan-European data standards for the acute coronary syndrome (ACS) and percutaneous coronary intervention (PCI). The European Unified Registries for Heart Care Evaluation and Randomised Trials (EuroHeart) project of the European Society of Cardiology (ESC) aimed to develop such data standards for ACS and PCI. Following a systematic review of the literature on ACS and PCI data standards and evaluation of contemporary ACS and PCI registries, we undertook a modified Delphi process involving clinical and registry experts from 11 European countries, as well as representatives from relevant ESC Associations, including the European Association of Percutaneous Cardiovascular Interventions (EAPCI) and Acute CardioVascular Care (ACVC). This resulted in final sets of 68 and 84 'mandatory' variables and several catalogues of optional variables for ACS and PCI, respectively. Data definitions were provided for these variables, which have been programmed as the basis for continuous registration of individual patient data in the online EuroHeart IT platform. By means of a structured process and the interaction with major stakeholders, internationally harmonized data standards for ACS and PCI have been developed. In the context of the EuroHeart project, this will facilitate country-level quality of care improvement, international observational research, registry-based randomized trials, and post-marketing surveillance of devices and pharmacotherapies.

Data standards for heart failure: the European Unified Registries for Heart Care Evaluation and Randomized Trials (EuroHeart).

Standardized data definitions are essential for assessing the quality of care and patient outcomes in observational studies and randomized controlled trials. The European Unified Registries for Heart Care Evaluation and Randomized Trials (EuroHeart) project of the European Society of Cardiology (ESC) aims to create contemporary pan-European data standards for cardiovascular diseases, including heart failure (HF). We followed the EuroHeart methodology for cardiovascular data standard development. A Working Group including experts in HF registries, representatives from the Heart Failure Association of the ESC, and the EuroHeart was formed. Using Embase and Medline (2016-21), we conducted a systematic review of the literature on data standards, registries, and trials to identify variables pertinent to HF. A modified Delphi method was used to reach a consensus on the final set of variables. For each variable, the Working Group developed data definitions and agreed on whether it was mandatory (Level 1) or additional (Level 2). In total, 84 Level 1 and 79 Level 2 variables were selected for nine domains of HF care. These variables were reviewed by an international Reference Group with the Level 1 variables providing the dataset for registration of patients with HF on the EuroHeart IT platform. By means of a structured process and interaction with international stakeholders, harmonized data standards for HF have been developed. In the context of the EuroHeart, this will facilitate quality improvement, international observational research, registry-based randomized trials, and post-marketing surveillance of devices and pharmacotherapies across Europe.

Effects of early myocardial reperfusion and perfusion on myocardial necrosis/dysfunction and inflammation in patients with ST-segment and non-ST-segment elevation acute coronary syndrome: results from the PLATelet inhibition and patients Outcomes (PLATO) trial.

AIMS: Restoration of myocardial blood flow and perfusion during percutaneous coronary intervention (PCI) measured using Thrombolysis in Myocardial Infarction (TIMI) flow grade (TFG) and perfusion grade (TMPG) is associated with improved outcomes in acute coronary syndrome (ACS). Associations between TFG/TMPG and changes in biomarkers reflecting myocardial damage/dysfunction and inflammation is unknown. METHODS AND RESULTS: Among 2606 patients included, TFG was evaluated in 2198 and TMPG in 1874 with ST-segment elevation myocardial infarction (STEMI) or non-ST-segment ACS (NSTE-ACS). Biomarkers reflecting myocardial necrosis [troponin T (TnT)], myocardial dysfunction [N-terminal prohormone brain natriuretic peptide (NT-proBNP)], inflammation [interleukin-6 (IL-6) and C-reactive protein (CRP)], and oxidative stress/ageing/inflammation [growth differentiation factor-15 (GDF-15)] were measured at baseline, discharge, and 1- and 6-month post-randomization. Associations between TFG/TMPG and changes in biomarker levels were evaluated using the Mann-Whitney-Wilcoxon signed test. In total, 1423 (54.6%) patients had STEMI and 1183 (45.4%) NSTE-ACS. Complete reperfusion after PCI with TFG = 3 was achieved in 1110 (85.3%) with STEMI and in 793 (88.5%) with NSTE-ACS. Normal myocardial perfusion with TMPG = 3 was achieved in 475 (41.6%) with STEMI and in 396 (54.0%) with NSTE-ACS. Levels of TnT, NT-proBNP, IL-6, CRP, and GDF-15 were substantially lower at discharge in patients with complete vs. incomplete TFG and STEMI (P < 0.01). This pattern was not observed for patients with NSTE-ACS. Patients with normal vs. abnormal TMPG and NSTE-ACS had lower levels of NT-proBNP at discharge (P = 0.01). CONCLUSIONS: Successful restoration of epicardial blood flow in STEMI was associated with less myocardial necrosis/dysfunction and inflammation. Attainment of normal myocardial perfusion was associated with less myocardial dysfunction in NSTE-ACS.