Acute Coronary Syndrome Subphenotypes Based on Repeated Biomarker Measurements in Relation to Long-Term Mortality Risk.

BACKGROUND: We aimed to identify patients with subphenotypes of postacute coronary syndrome (ACS) using repeated measurements of high-sensitivity cardiac troponin T, N-terminal pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, and growth differentiation factor 15 in the year after the index admission, and to investigate their association with long-term mortality risk. METHODS AND RESULTS: BIOMArCS (BIOMarker Study to Identify the Acute Risk of a Coronary Syndrome) was an observational study of patients with ACS, who underwent high-frequency blood sampling for 1 year. Biomarkers were measured in a median of 16 repeated samples per individual. Cluster analysis was performed to identify biomarker-based subphenotypes in 723 patients without a repeat ACS in the first year. Patients with a repeat ACS (N=36) were considered a separate cluster. Differences in all-cause death were evaluated using accelerated failure time models (median follow-up, 9.1 years; 141 deaths). Three biomarker-based clusters were identified: cluster 1 showed low and stable biomarker concentrations, cluster 2 had elevated concentrations that subsequently decreased, and cluster 3 showed persistently elevated concentrations. The temporal biomarker patterns of patients in cluster 3 were similar to those with a repeat ACS during the first year. Clusters 1 and 2 had a similar and favorable long-term mortality risk. Cluster 3 had the highest mortality risk. The adjusted survival time ratio was 0.64 (95% CI, 0.44-0.93; P=0.018) compared with cluster 1, and 0.71 (95% CI, 0.39-1.32; P=0.281) compared with patients with a repeat ACS. CONCLUSIONS: Patients with subphenotypes of post-ACS with different all-cause mortality risks during long-term follow-up can be identified on the basis of repeatedly measured cardiovascular biomarkers. Patients with persistently elevated biomarkers have the worst outcomes, regardless of whether they experienced a repeat ACS in the first year.

Bifurcation PCI with a hybrid strategy with drug- eluting balloons versus a stepwise provisional two- stent strategy: Rationale and design of the hybrid DEB study.

The optimal treatment strategy for coronary bifurcation lesions by percutaneous coronary intervention (PCI) is complex and remains a subject of debate. Current guidelines advise a stepwise provisional approach with optional two-stent strategy. However, a two-stent strategy, both upfront and stepwise provisional, is technically demanding. Therefore, there is increasing interest in the use of drug-eluting balloons (DEB) in bifurcation lesions, mainly after a provisional approach with unsatisfactory result of the side branch. Some small pilot studies already showed that the use of DEB in bifurcation lesions is safe and feasible. However, a randomized comparison of this hybrid DEB strategy with a two-stent strategy is currently lacking. TRIAL DESIGN: The Hybrid DEB study is a prospective, multicenter, randomized controlled trial investigating noninferiority of a hybrid DEB approach, using a combination of a drug-eluting stent (DES) in the main vessel and DEB in the side branch, compared to stepwise provisional two-stent strategy in patients with true bifurcation lesions. A total of 500 patients with de novo true coronary bifurcation lesions, treated with a stepwise provisional approach and an unsatisfactory result of the side branch after main vessel stenting (≥ 70% stenosis and/or < thrombolysis in myocardial infarction III flow), will be randomized in a 1:1 ratio to receive either treatment with a DEB or with a DES in the side branch. The primary endpoint is a composite endpoint of the occurrence of all-cause death, periprocedural or spontaneous myocardial infarction and/or target vessel revascularization at the anticipated median 2-year follow-up. CONCLUSION: The Hybrid DEB study will compare in a multicenter, randomized fashion a hybrid DEB approach with a stepwise provisional two-stent strategy in patients with true bifurcation lesions. TRIAL REGISTRATION: ClinicalTrials.gov no. NCT05731687.

Comparison of Supraflex Cruz 60 µm Versus Ultimaster Tansei 80 µm Stent Struts in High Bleeding Risk PCI Patients: Study design and Rational of Compare 60/80 HBR trial.

Up to 45% of patients who underwent percutaneous coronary intervention (PCI) may have a high bleeding risk (HBR), depending on the bleeding risk definition.1 This condition is often associated with an enhanced risk of thrombotic events with a negative impact on short- and long-term outcomes,2-8 making the choice of an appropriate antithrombotic regimen after PCI particularly challenging. Advances in stent technologies, in which the introduction of newer generations of thinner strut drug-eluting stents (DES), have significantly reduced the rate of thrombotic complications and may justify a shorter dual antiplatelet therapy (DAPT) duration. Both in vitro and in vivo studies have shown that local hemodynamic factors may critically affect the natural history of atherosclerosis. Strut thickness correlates with flow disturbances and endothelial shear stress. Flow separation within struts determines areas of recirculation with low endothelial shear stress which promotes local concentration of activated platelets.9 By mitigating inflammation, vessel injury, and neointimal proliferation, thin and streamlined struts have been associated with faster vascular healing and re-endothelization and have resulted in lower rates of thrombotic events after PCI.10,11 The use of thin strut and ultra-thin strut stents may lead to a favorable trade-off in bleeding and ischemic events in patients with HBR. However, dedicated studies evaluating the performance of thin strut versus ultrathin strut stents in patients with HBR are lacking.

Fractional Flow Reserve-Negative High-Risk Plaques and Clinical Outcomes After Myocardial Infarction.

Importance: Even after fractional flow reserve (FFR)-guided complete revascularization, patients with myocardial infarction (MI) have high rates of recurrent major adverse cardiovascular events (MACE). These recurrences may be caused by FFR-negative high-risk nonculprit lesions. Objective: To assess the association between optical coherence tomography (OCT)-identified high-risk plaques of FFR-negative nonculprit lesions and occurrence of MACE in patients with MI. Design, Setting, and Participants: PECTUS-obs (Identification of Risk Factors for Acute Coronary Events by OCT After STEMI [ST-segment elevation MI] and NSTEMI [non-STEMI] in Patients With Residual Non-flow Limiting Lesions) is an international, multicenter, prospective, observational cohort study. In patients presenting with MI, OCT was performed on all FFR-negative (FFR > 0.80) nonculprit lesions. A high-risk plaque was defined containing at least 2 of the following prespecified criteria: (1) a lipid arc at least 90°, (2) a fibrous cap thickness less than 65 µm, and (3) either plaque rupture or thrombus presence. Patients were enrolled from December 14, 2018, to September 15, 2020. Data were analyzed from December 2, 2022, to June 28, 2023. Main Outcome and Measure: The primary end point of MACE, a composite of all-cause mortality, nonfatal MI, or unplanned revascularization, at 2-year follow-up was compared in patients with and without a high-risk plaque. Results: A total of 438 patients were enrolled, and OCT findings were analyzable in 420. Among included patients, mean (SD) age was 63 (10) years, 340 (81.0) were men, and STEMI and non-STEMI were equally represented (217 [51.7%] and 203 [48.3%]). A mean (SD) of 1.17 (0.42) nonculprit lesions per patient was imaged. Analysis of OCT images revealed at least 1 high-risk plaque in 143 patients (34.0%). The primary end point occurred in 22 patients (15.4%) with a high-risk plaque and 23 of 277 patients (8.3%) without a high-risk plaque (hazard ratio, 1.93 [95% CI, 1.08-3.47]; P = .02), primarily driven by more unplanned revascularizations in patients with a high-risk plaque (14 of 143 [9.8%] vs 12 of 277 [4.3%]; P = .02). Conclusions and Relevance: Among patients with MI and FFR-negative nonculprit lesions, the presence of a high-risk plaque is associated with a worse clinical outcome, which is mainly driven by a higher number of unplanned revascularizations. In a population with a high recurrent event rate despite physiology-guided complete revascularization, these results call for research on additional pharmacological or focal treatment strategies in patients harboring high-risk plaques.

Serially measured high-sensitivity cardiac troponin T, N-terminal-pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, and growth differentiation factor 15 for risk assessment after acute coronary syndrome: the BIOMArCS cohort.

AIMS: Evidence regarding the role of serial measurements of biomarkers for risk assessment in post-acute coronary syndrome (ACS) patients is limited. The aim was to explore the prognostic value of four, serially measured biomarkers in a large, real-world cohort of post-ACS patients. METHODS AND RESULTS: BIOMArCS is a prospective, multi-centre, observational study in 844 post-ACS patients in whom 12 218 blood samples (median 17 per patient) were obtained during 1-year follow-up. The longitudinal patterns of high-sensitivity cardiac troponin T (hs-cTnT), N-terminal-pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), and growth differentiation factor 15 (GDF-15) were analysed in relation to the primary endpoint (PE) of cardiovascular mortality and recurrent ACS using multivariable joint models. Median age was 63 years, 78% were men and the PE was reached by 45 patients. The average biomarker levels were systematically higher in PE compared with PE-free patients. After adjustment for 6-month post-discharge Global Registry of Acute Coronary Events score, 1 standard deviation increase in log[hs-cTnT] was associated with a 61% increased risk of the PE [hazard ratio (HR) 1.61, 95% confidence interval (CI) 1.02-2.44, P = 0.045], while for log[GDF-15] this was 81% (HR 1.81, 95% CI 1.28-2.70, P = 0.001). These associations remained significant after multivariable adjustment, while NT-proBNP and hs-CRP were not. Furthermore, GDF-15 level showed an increasing trend prior to the PE (Structured Graphical Abstract). CONCLUSION: Longitudinally measured hs-cTnT and GDF-15 concentrations provide prognostic value in the risk assessment of clinically stabilized patients post-ACS. CLINICAL TRIAL REGISTRATION: The Netherlands Trial Register. Currently available at URL https://trialsearch.who.int/; Unique Identifiers: NTR1698 and NTR1106.

Impact of multisite artery disease on clinical outcomes after percutaneous coronary intervention: an analysis from the e-Ultimaster registry.

BACKGROUND: Multisite artery disease is considered a 'malignant' type of atherosclerotic disease associated with an increased cardiovascular risk, but the impact of multisite artery disease on clinical outcomes after percutaneous coronary intervention (PCI) is unknown. METHODS: Patients enrolled in the large, prospective e-Ultimaster study were grouped into (1) those without known prior vascular disease, (2) those with known single-territory vascular disease, and (3) those with known two to three territories (i.e coronary, cerebrovascular, or peripheral) vascular disease (multisite artery disease). The primary outcome was coronary target lesion failure (TLF), defined as the composite of cardiac death, target vessel-related myocardial infarction, and clinically driven target lesion revascularization at 1-year. Inverse propensity score weighted (IPSW) analysis was performed to address differences in baseline patient and lesion characteristics. RESULTS: Of the 37 198 patients included in the study, 62.3% had no prior known vascular disease, 32.6% had single-territory vascular disease, and 5.1% had multisite artery disease. Patients with known vascular disease were older and were more likely to be men and to have more co-morbidities. After IPSW, the TLF rate incrementally increased with the number of diseased vascular beds (3.16%, 4.44%, and 6.42% for no, single, and multisite artery disease, respectively, P < 0.01 for all comparisons). This was also true for all-cause death (2.22%, 3.28%, and 5.29%, P < 0.01 for all comparisons) and cardiac mortality (1.26%, 1.91%, and 3.62%, P ≤ 0.01 for all comparisons). CONCLUSIONS: Patients with previously known vascular disease experienced an increased risk of adverse cardiovascular events and mortality post-PCI. This risk is highest among patients with multisite artery disease.Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02188355.

Prognostic value of syntax score, intravascular ultrasound and near-infrared spectroscopy to identify low-risk patients with coronary artery disease 5-year results from the ATHEROREMO and IBIS-3 cohorts.

The prognostic value of SYNTAX score (SS), intravascular ultrasound (IVUS)-derived plaque burden (PB) and near-infrared spectroscopy (NIRS)-derived lipid core burden index(LCBI) for identification of high-risk patients for major adverse cardiovascular events (MACE) has been proven in previous studies. The majority of patients presenting in the cathlab however do not endure MACE over time, and identification of low-risk groups has remained underexposed. This study evaluates the combined prognostic value of SS, PB and LCBI in identifying patients with low MACE risk. This post-hoc analysis combines the ATHEROREMO and IBIS-3 studies and included 798 patients undergoing coronary angiography. Anatomical SS was calculated (N = 617) and ≥40mm non-stenotic segment of a non-target vessel was investigated with IVUS (N = 645) and NIRS (N = 273) to determine PB and maximum 4mm LCBI (LCBI4mm). During five-year follow-up, 191 MACE were observed. Patients with PB ≤70%, LCBI4mm ≤227 (median), or SS ≤8 (median) had lower MACE incidence than their counterparts with higher values. Combined into one model, LCBI4mm ≤227 (adjusted hazard ratio [aHR] 0.49, 95% confidence interval [CI] 0.30-0.78; p-value = 0.003) and SS ≤8 (aHR 0.67, 95%CI 0.48-0.96, p-value = 0.027) were independently associated with (lower) MACE rate, but PB was not. Additionally, negative predictive value (NPV) of this model was high (SS<8: 0.80, PB<70%: 0.77, LCBI4mm<227: 0.79). In this cohort, SS and LCBI4mm proved to be independent predictors of MACE-free survival during five-year follow-up. Combination of SS and LCBI4mm is useful to identify a low-risk population. Furthermore, NPV of SS, PB and LCBI4mm for prediction of MACE is high.

Clinical Outcomes of Percutaneous Coronary Intervention for Bifurcation Lesions According to Medina Classification.

Background Coronary bifurcation lesions (CBLs) are frequently encountered in clinical practice and are associated with worse outcomes after percutaneous coronary intervention. However, there are limited data around the prognostic impact of different CBL distributions. Methods and Results All CBL percutaneous coronary intervention procedures from the prospective e-Ultimaster (Prospective, Single-Arm, Multi Centre Observations Ultimaster Des Registry) multicenter international registry were analyzed according to CBL distribution as defined by the Medina classification. Cox proportional hazards models were used to compare the hazard ratio (HR) of the primary outcome, 1-year target lesion failure (composite of cardiac death, target vessel-related myocardial infarction, and clinically driven target lesion revascularization), and its individual components between Medina subtypes using Medina 1.0.0 as the reference category. A total of 4003 CBL procedures were included. The most prevalent Medina subtypes were 1.1.1 (35.5%) and 1.1.0 (26.8%), whereas the least prevalent was 0.0.1 (3.5%). Overall, there were no significant differences in patient and procedural characteristics among Medina subtypes. Only Medina 1.1.1 and 0.0.1 subtypes were associated with increased target lesion failure (HR, 2.6 [95% CI, 1.3-5.5] and HR, 4.0 [95% CI, 1.6-9.0], respectively) at 1 year, compared with Medina 1.0.0, prompted by clinically driven target lesion revascularization (HR, 3.1 [95% CI, 1.1-8.6] and HR, 4.6 [95% CI, 1.3-16.0], respectively) as well as cardiac death in Medina 0.0.1 (HR, 4.7 [95% CI, 1.0-21.6]). No differences in secondary outcomes were observed between Medina subtypes. Conclusions In a large multicenter registry analysis of coronary bifurcation percutaneous coronary intervention procedures, we demonstrate prognostic differences in 1-year outcomes between different CBL distributions, with Medina 1.1.1 and 0.0.1 subtypes associated with an increased risk of target lesion failure.

Clinical Performance of a Paclitaxel Drug-Coated Balloon in Real-World Percutaneous Coronary Intervention Practice: The PEARL Registry.

BACKGROUND: Randomized controlled trials for in-stent restenosis (ISR) and de novo lesions in small-diameter vessels have shown promising results, but data on DCB use in real-world practice are still scarce. The aim of the PEARL (Paclitaxel-Eluting Angioplasty Balloon in the Real-World) registry was to evaluate the safety and efficacy of a paclitaxel DCB in real-world percutaneous coronary intervention (PCI) practice. METHODS: Between 2014 and 2019, a total of 513 patients treated with the Protégé paclitaxel DCB (Wellinq) were prospectively included at 4 hospitals in the Netherlands. The primary endpoint was 2-year major adverse cardiac event (MACE), defined as cardiac death, target-vessel myocardial infarction, or target-lesion revascularization (TLR). RESULTS: DCB was used for ISR in 382 patients and for de novo lesions in 131 patients. Acute coronary syndrome was the reason for presentation in 58.9% of patients. At lesion level, 34.1% of lesions were classified as type B2 and 36.1% as type C. Predilation was performed in 62.2% and noncompliant DCB was used in 40.7% of lesions. DCB-related procedural complications were infrequent (3.3%, mostly coronary dissection [2.3%]). Bailout stenting was required in 3.1%. MACE during 2-year follow-up occurred in 17.1% of patients treated for ISR and 9.7% of patients treated for de novo lesions. The incidence of TLR was 11.7% of ISR patients and 2.9% of de novo patients. History of coronary artery bypass grafting and lesion length were predictors of MACE in patients treated for ISR. CONCLUSION: The use of Protégé paclitaxel DCB for PCI of ISR and de novo lesions is safe and effective during 2-year follow-up.

Relation of Iron Status to Prognosis After Acute Coronary Syndrome.

Iron deficiency has been extensively researched and is associated with adverse outcomes in heart failure. However, to our knowledge, the temporal evolution of iron status has not been previously investigated in patients with acute coronary syndrome (ACS). Therefore, we aimed to explore the temporal pattern of repeatedly measured iron, ferritin, transferrin, and transferrin saturation (TSAT) in relation to prognosis post-ACS. BIOMArCS (BIOMarker study to identify the Acute risk of a Coronary Syndrome) is a prospective, multicenter, observational cohort study conducted in The Netherlands between 2008 and 2015. A total of 844 patients with post-ACS were enrolled and underwent high-frequency (median 17) blood sampling during 1 year follow-up. Biomarkers of iron status were measured batchwise in a central laboratory. We analyzed 3 patient subsets, including the case-cohort (n = 187). The primary endpoint (PE) was a composite of cardiovascular mortality and repeat nonfatal ACS, including unstable angina pectoris requiring revascularization. The association between iron status and the PE was analyzed using multivariable joint models. Mean age was 63 years; 78% were men, and >50% had iron deficiency at first sample in the case-cohort. After adjustment for a broad range of clinical variables, 1 SD decrease in log-iron was associated with a 2.2-fold greater risk of the PE (hazard ratio 2.19, 95% confidence interval 1.34 to 3.54, p = 0.002). Similarly, 1 SD decrease in log-TSAT was associated with a 78% increased risk of the PE (hazard ratio 1.78, 95% confidence interval 1.17 to 2.65, p = 0.006). Ferritin and transferrin were not associated with the PE. Repeated measurements of iron and TSAT predict risk of adverse outcomes in patients with post-ACS during 1 year follow-up. Trial Registration: The Netherlands Trial Register. Unique identifiers: NTR1698 and NTR1106. Registered at https://www.trialregister.nl/trial/1614 and https://www.trialregister.nl/trial/1073.

Identification of anatomic risk factors for acute coronary events by optical coherence tomography in patients with myocardial infarction and residual nonflow limiting lesions: rationale and design of the PECTUS-obs study.

INTRODUCTION: In patients with myocardial infarction, the decision to treat a nonculprit lesion is generally based on its physiological significance. However, deferral of revascularisation based on nonischaemic fractional flow reserve (FFR) values in these patients results in less favourable outcomes compared with patients with stable coronary artery disease, potentially caused by vulnerable nonculprit lesions. Intravascular optical coherence tomography (OCT) imaging allows for in vivo morphological assessment of plaque 'vulnerability' and might aid in the detection of FFR-negative lesions at high risk for recurrent events. METHODS AND ANALYSIS: The PECTUS-obs study is an international multicentre prospective observational study that aims to relate OCT-derived vulnerable plaque characteristics of nonflow limiting, nonculprit lesions to clinical outcome in patients with myocardial infarction. A total of 438 patients presenting with myocardial infarction (ST-elevation myocardial infarction and non-ST-elevation myocardial infarction) will undergo OCT-imaging of any FFR-negative nonculprit lesion for detection of plaque vulnerability. The primary study endpoint is a composite of major adverse cardiovascular events (all-cause mortality, nonfatal myocardial infarction or unplanned revascularisation) at 2-year follow-up. Secondary endpoints will be the same composite at 1-year and 5-year follow-up, target vessel failure, target vessel revascularisation, target lesion failure and target lesion revascularisation. ETHICS AND DISSEMINATION: This study has been approved by the Medical Ethics Committee of the region Arnhem-Nijmegen. The results of this study will be disseminated in a main paper and additional papers with subgroup analyses. TRIAL REGISTRATION NUMBER: NCT03857971.

Temporal Evolution of Serum Concentrations of High-Sensitivity Cardiac Troponin During 1 Year After Acute Coronary Syndrome Admission.

Background Detailed insights in temporal evolution of high-sensitivity cardiac troponin following acute coronary syndrome (ACS) are currently missing. We aimed to describe and compare the post-ACS kinetics of high-sensitivity cardiac troponin I (hs-cTnI) and high-sensitivity cardiac troponin T (hs-cTnT), and to determine their intra- and interindividual variation in clinically stable patients. Methods and Results We determined hs-cTnI (Abbott) and hs-cTnT (Roche) in 1507 repeated blood samples, derived from 191 patients with ACS (median, 8/patient) who remained free from adverse cardiac events during 1-year follow-up. Post-ACS kinetics were studied by linear mixed-effect models. Using the samples collected in the 6- to 12-month post-ACS time frame, patients were then considered to have chronic coronary syndrome. We determined (differences between) the average hs-cTnI and average hs-cTnT concentration, and the intra- and interindividual variation for both biomarkers. Compared with hs-cTnT, hs-cTnI peaked higher (median 3506 ng/L versus 494 ng/L; P<0.001) and was quicker below the biomarker-specific upper reference limit (16 versus 19 days; P<0.001). In the post-6-month samples, hs-cTnI and hs-cTnT showed modest correlation (rspearman=0.60), whereas the average hs-cTnT concentration was 5 times more likely to be above the upper reference limit than hs-cTnI. The intraindividual variations of hs-cTnI and hs-cTnT were 14.0% and 18.1%, while the interindividual variations were 94.1% and 75.9%. Conclusions Hs-cTnI peaked higher after ACS and was quicker below the upper reference limit. In the post-6-month samples, hs-cTnI and hs-cTnT were clearly not interchangeable, and average hs-cTnT concentrations were much more often above the upper reference limit than hs-cTnI. For both markers, the within-patient variation fell largely below beween-patient variation. Registration URL: https://www.trialregister.nl; unique identifiers: NTR1698 and NTR1106.

One-year performance of thin-strut cobalt chromium sirolimus-eluting stent versus thicker strut stainless steel biolimus-eluting coronary stent: a propensity-matched analysis of two international all-comers registries.

OBJECTIVES: Recent improvements in coronary stent design have focussed on thinner struts, different alloys and architecture, more biocompatible polymers, and shorter drug absorption times. This study evaluates safety and efficacy of a newer generation thin-strut cobalt chromium sirolimus-eluting coronary stent (SES, Ultimaster) in comparison with a second-generation thicker strut stainless steel biolimus-eluting stent (BES, Nobori) in percutaneous coronary intervention (PCI) practice. METHODS: A propensity score analysis was performed to adjust for differences in baseline characteristics of 8137 SES patients and 2738 BES patients of two PCI registries (e-Ultimaster and NOBORI 2). An independent clinical event committee adjudicated all endpoint-related adverse events. RESULTS: The use of SES, as compared with BES was associated with a significantly lower rate of myocardial infarction (MI) (1.2% vs 2.2%; P = 0.0006) and target vessel-related MI (1.1% vs 1.8%; P = 0.002) at 1 year. One-year composite endpoints of all predefined endpoints were lower in patients undergoing SES implantation (target lesion failure: 3.2% vs 4.1%; P = 0.03, target vessel failure: 3.7% vs 5.0%; P = 0.003, patient-oriented composite endpoint 5.7% vs 6.8%; P = 0.03). No significant differences between SES and BES were observed in all-cause death (2.0% vs 1.6%; P = 0.19), cardiac death (1.2% vs 1.2%; P = 0.76) or stent thrombosis (0.6% vs 0.8%; P = 0.43). CONCLUSIONS: These findings suggest an improved clinical safety and efficacy of a newer generation thin-strut SES as compared with a second-generation thicker strut BES.

Stabilization patterns and variability of hs-CRP, NT-proBNP and ST2 during 1 year after acute coronary syndrome admission: results of the BIOMArCS study.

Objectives Details of the biological variability of high-sensitivity C-reactive protein (hs-CRP), N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and ST2 are currently lacking in patients with acute coronary syndrome (ACS) but are crucial knowledge when aiming to use these biomarkers for personalized risk prediction. In the current study, we report post-ACS kinetics and the variability of the hs-CRP, NT-proBNP and ST2. Methods BIOMArCS is a prospective, observational study with high frequency blood sampling during 1 year post-ACS. Using 1507 blood samples from 191 patients that remained free from adverse cardiac events, we investigated post-ACS kinetics of hs-CRP, NT-proBNP and ST2. Biological variability was studied using the samples collected between 6 and 12 months after the index ACS, when patients were considered to have stable coronary artery disease. Results On average, hs-CRP rose peaked at day 2 and rose well above the reference value. ST2 peaked immediately after the ACS but never rose above the reference value. NT-proBNP level rose on average during the first 2 days post-ACS and slowly declined afterwards. The within-subject variation and relative change value (RCV) of ST2 were relatively small (13.8%, RCV 39.7%), while hs-CRP (41.9%, lognormal RCV 206.1/-67.3%) and NT-proBNP (39.0%, lognormal RCV 185.2/-64.9%) showed a considerable variation. Conclusions Variability of hs-CRP and NT-proBNP within asymptomatic and clinically stable post-ACS patients is considerable. In contrast, within-patient variability of ST2 is low. Given the low within-subject variation, ST2 might be the most useful biomarker for personalizing risk prediction in stable post-ACS patients.

High-frequency metabolite profiling and the incidence of recurrent cardiac events in patients with post-acute coronary syndrome.

Purpose: The aim of this study was to study temporal changes in metabolite profiles in patients with post-acute coronary syndrome (ACS), in particular prior to the development of recurrent ACS (reACS).Methods: BIOMArCS (BIOMarker study to identify the Acute risk of a Coronary Syndrome) is a prospective study including patients admitted for ACS, who underwent high-frequency blood sampling during 1-year follow-up. Within BIOMArCS, we performed a nested case-cohort analysis of 158 patients (28 cases of reACS). We determined 151 metabolites by nuclear magnetic resonance in seven (median) blood samples per patient. Temporal evolution of the metabolites and their relation with reACS was assessed by joint modelling. Results are reported as adjusted (for clinical factors) hazard ratios (aHRs).Results: Median age was 64 (25th-75th percentiles; 56-72) years and 78% were men. After multiple testing correction (p < 0.001), high concentrations of extremely large very low density lipoprotein (VLDL) particles (aHR 1.60/SD increase; 95%CI 1.25-2.08), very large VLDL particles (aHR 1.60/SD increase; 95%CI 1.25-2.08) and large VLDL particles (aHR 1.56/SD increase; 95%CI 1.22-2.05) were significantly associated with reACS. Moreover, these longitudinal particle concentrations showed a steady increase over time prior to reACS. Among the other metabolites, no significant associations were observed.Conclusion: Post-ACS patients with persistent high concentrations of extremely large, very large and large VLDL particles have increased risk of reACS within 1 year.

Details on high frequency blood collection, data analysis, available material and patient characteristics in BIOMArCS.

The Biomarker Study to Identify the Acute Risk of a Coronary Syndrome (BIOMArCS) is a prospective, observational study that has been designed to study the evolution of blood biomarkers in post-acute coronary syndrome (ACS) patients. In our recently published study "Temporal evolution of Myeloperoxidase and Galectin 3 during 1 year after acute coronary syndrome admission" [1] in the American Heart Journal, we demonstrated that repeatedly measuring MPO and Galectin-3 does not aid to differentiate between patients with and without adverse cardiac events during 1-year follow-up. In this Data-In-Brief article, we present further details on data collections and data analysis. In addition, a detailed description of baseline characteristics and the distribution of blood sampling moments is provided. The BIOMArCS dataset contains clinical information and follow-up data on all enrolled 844 patients. These patients underwent a median of 17 (25th -75th percentile 12-20) repeated blood samples in the first year after the index ACS. Blood samples were stored at -80 °C within a median of 82 (25th-75th percentile 58-117) minutes after withdrawal. We collected whole blood, citrate plasma, EDTA plasma, serum and DNA. The dataset used for the analysis in the accompanying research paper has been made available online. We welcome collaborations for further use of our data, whether or not in combination with other biobanks.

Temporal evolution of myeloperoxidase and galectin 3 during 1 year after acute coronary syndrome admission.

Prior studies reported that Myeloperoxidase and Galectin-3, which are biomarkers of coronary plaque vulnerability, are elevated in acute coronary syndrome (ACS) patients. We studied the temporal evolution of these biomarkers early after ACS admission and prior to a recurrent ACS event during 1 year follow-up.

Temporal Pattern of Growth Differentiation Factor-15 Protein After Acute Coronary Syndrome (From the BIOMArCS Study).

Growth differentiation factor-15 (GDF-15) has appeared as a promising biomarker with strong predictive abilities in acute coronary syndrome (ACS). However, studies are solely based on single measurements in the acute phase of an ACS event. The way GDF-15 patterns in post-ACS patients behave on the long term is largely unknown. We conducted a nested case-control study within our multicenter, prospective, observational biomarker study (BIOMArCS) of 844 ACS patients. Following an index ACS event, high-frequency blood sampling was performed during 1-year of follow-up. GDF-15 was determined batchwise by electrochemiluminescence immunoassays in 37 cases with a recurrent event during 1-year follow-up, and in 74 event-free controls. Cases and controls had a mean ± standard deviation age of 66.9 ± 11.3 years and 81% were men. From 30 days onwards, patients showed stable levels, which were on average 333 (95% confidence interval 68 to 647) pg/mL higher in cases than controls (1704 vs 1371 pg/mL; p value 0.013). Additionally, in the post 30-day period, GDF-15 showed low within-individual variability in both cases and controls. In conclusion, post-ACS patients experiencing a recurrent event had stable and systematically higher GDF-15 levels during 30-day to 1-year follow-up than their event-free counterparts with otherwise similar clinical characteristics. Thus, postdischarge blood sampling might be used throughout the course of 1 year to improve prognostication, whereas, in view of the low within-individual variation, the number of repeated sampling moments might be limited.

SYNTAX score in relation to intravascular ultrasound and near-infrared spectroscopy for the assessment of atherosclerotic burden in patients with coronary artery disease.

AIMS: The aim of this study was to examine the relationship between the anatomical SYNTAX score (SXscore), derived from all three coronary arteries, and coronary wall pathology measured by radiofrequency intravascular ultrasound (RF-IVUS) and near-infrared spectroscopy (NIRS) in a single non-culprit segment. METHODS AND RESULTS: In patients referred for coronary angiography (N=88) or PCI (N=592) for stable angina or acute coronary syndrome, the SYNTAX score calculator (www.syntaxscore.com) was used to determine the SXscore before PCI, if applicable. RF-IVUS and/or NIRS were performed in a non-stenotic 40 mm study segment following the clinically indicated angiography/PCI. After adjustment for multiple confounders, a higher SXscore was associated with higher segmental plaque volume in the study segment (2.21 mm3 per SXscore point, 95% CI: 0.92-3.50, p-value 0.001), as well as with higher volume of fibrous (0.93 mm3 per point) and fibro-fatty tissue (0.29 mm3 per point). A higher SXscore was also associated with a higher NIRS-derived lipid core burden index (LCBI) in the full study segment (1.35 units per SXscore point, 95% CI: 0.22-2.47, p-value 0.019). Importantly, SXscore correlated with the fatty/fibro-fatty and LCBI signals despite adjusting for plaque burden. CONCLUSIONS: In patients with CAD, higher SXscores are associated with higher atherosclerotic burden as assessed by RF-IVUS and NIRS in a single non-stenotic coronary artery segment.