Coronary intravascular lithotripsy and rotational atherectomy for severely calcified stenosis: Results from the ROTA.shock trial.

BACKGROUND: Severely calcified coronary lesions present a particular challenge for percutaneous coronary intervention. AIMS: The aim of this randomized study was to determine whether coronary intravascular lithotripsy (IVL) is non-inferior to rotational atherectomy (RA) regarding minimal stent area (MSA). METHODS: The randomized, prospective non-inferiority ROTA.shock trial enrolled 70 patients between July 2019 and November 2021. Patients were randomly (1:1) assigned to undergo either IVL or RA before percutaneous coronary intervention of severely calcified coronary lesions. Optical coherence tomography was performed at the end of the procedure for primary endpoint analysis. RESULTS: The primary endpoint MSA was lower but non-inferior after IVL (mean: 6.10 mm2 , 95% confidence interval [95% CI]: 5.32-6.87 mm2 ) versus RA (6.60 mm2 , 95% CI: 5.66-7.54 mm2 ; difference in MSA: -0.50 mm2 , 95% CI: -1.52-0.52 mm2 ; non-inferiority margin: -1.60 mm2 ). Stent expansion was similar (RA: 0.83 ± 0.10 vs. IVL: 0.82 ± 0.11; p = 0.79). There were no significant differences regarding contrast media consumption (RA: 183.1 ± 68.8 vs. IVL: 163.3 ± 55.0 mL; p = 0.47), radiation dose (RA: 7269 ± 11288 vs. IVL: 5010 ± 4140 cGy cm2 ; p = 0.68), and procedure time (RA: 79.5 ± 34.5 vs. IVL: 66.0 ± 19.4 min; p = 0.18). CONCLUSION: IVL is non-inferior regarding MSA and results in a similar stent expansion in a random comparison with RA. Procedure time, contrast volume, and dose-area product do not differ significantly.

Instant rule-out of suspected non-ST-segment elevation myocardial infarction using high-sensitivity cardiac troponin T with Copeptin versus a single low high-sensitivity cardiac troponin T: findings from a large pooled individual data analysis on 10,329 patients.

BACKGROUND: Evidence is sparse and inconsistent on the role of a dual marker strategy (DMS) combining Copeptin with cardiac troponin T (cTnT) for instant rule-out of a non-ST-segment myocardial infarction (NSTEMI) when high sensitivity cardiac troponin T (hs-cTnT) is used. METHODS: Data on 10,329 patients from 5 trials were pooled to evaluate initial Copeptin in combination with hs-cTnT against a single marker strategy (SMS) based on hs-cTnT < limit of detection. Endpoints were sensitivities and negative predictive values (NPV) for rule-out of NSTEMI, 30-day all-cause mortality and rates of applicability for DMS or SMS. RESULTS: NPV for rule-out of NSTEMI was high, exceeding 99.0% for the lower limits of the 95% confidence intervals (99.0% vs 99.2%) for DMS and SMS, and NPV for all cause death at 30 days was similar with very low mortality after rule-out [0.07% (0.0-0.4%) vs 0.0% (0.0-1.2%), p = 1.0], but applicability was 2.4-fold higher [64.6% (63.0-66.2%) vs 27.9% (26.2%-29.7%), p < 0.001] with DMS than SMS. In a secondary analysis on DMS after inclusion of high risk patients, performance and applicability were similar. CONCLUSION: Findings corroborate the 2015 European Society of Cardiology recommendation to use dual marker strategy for instant rule-out of NSTEMI, extending evidence to hs-cTnT. Novel data demonstrate a comparably safe and effective instant rule-out with Copeptin in combination with hs-cTnT versus a single marker strategy based on very low hs-cTnT but a more than twofold higher applicability of the dual marker strategy without the need to exclude very early presenters or other important subgroups. Dual marker strategy using hs-cTnT at 99th percentile and Copeptin versus ESC 0-h immediate rule-out based on hs-cTnT < limit of detection.

Everolimus- vs. novolimus-eluting bioresorbable scaffolds in patients with acute coronary syndrome.

BACKGROUND: Limited data exist on bioresorbable scaffolds (BRS) in patients with acute coronary syndrome (ACS). The aim of the present study was to evaluate novolimus-eluting BRS (DESolve) as interventional treatment for patients with ACS, and to compare its 12-month outcomes with the everolimus-eluting bioresorbable scaffolds (Absorb). METHODS: In this retrospective study, patients with ACS (including unstable angina pectoris, ST-segment elevation myocardial infarction, or non-ST-segment elevation myocardial infarction) treated with either the Absorb or the DESolve BRS were evaluated in a 1:1 matched-pair analysis. Major adverse cardiac events (MACE), including death, myocardial infarction, and target lesion revascularization, were evaluated as a major endpoint. The occurrence of scaffold thrombosis was also assessed. RESULTS: A total of 102 patients were eligible for this analysis. The rate of MACE at 12 months was comparable between the Absorb and the DESolve group (8.3% vs. 6.8%, p = 0.738). The occurrence of target lesion revascularization (6.2% vs. 4.7%; p = 0.700) and scaffold thrombosis (4.1% vs. 2.1%; p = 0.580) was comparable as well. All instances of scaffold thrombosis occurred within 30 days of the index procedure. CONCLUSION: In this study, similar 12-month event rates were observed for both BRS types after implantation for the treatment of ACS.

[Prehospital management of acute coronary syndrome in patients on long-term direct oral anticoagulant treatment]. / Prähospitale Behandlung des akuten Koronarsyndroms unter DOAK-Dauertherapie.

BACKGROUND: Despite an increasing incidence of patients suffering from acute coronary syndrome (ACS) under simultaneous treatment with direct oral anticoagulants (DOAC), neither sufficient scientific data nor uniform guidelines for the anticoagulation treatment of these patients are currently available. OBJECTIVE: The aim of this study was to determine the current practice of preclinical treatment of ACS in patients under DOAC treatment. MATERIAL AND METHODS: An internet and paper-based survey of emergency physicians, specialists of internal medicine, anesthesiologists, emergency and intensive care physicians was performed concerning the prehospital treatment of ACS in patients under long-term DOAC treatment. RESULTS: Overall, 284 questionnaires were answered. Substantial differences in the current treatment of ACS under long-term DOAC therapy were identified. While 39% of the respondents stated that they administer a combination treatment of heparin and acetylsalicylic acid (ASA), 36% renounced the administration of heparin. If a dose reduction was performed, 71% answered that they reduce the heparin dosage. Also, in cases of ST-segment elevation myocardial infarction 48% of the physicians renounced the administration of heparin. CONCLUSION: In Germany there is currently a heterogeneous practice of emergency treatment of ACS patients under DOAC therapy with respect to the administration of heparin and ASA. Therefore, guidelines of the specialist medical societies should address the prehospital emergency anticoagulation management of ACS in patients under therapy with DOAC, which correspond to the needs of patients and emergency physicians.

[MINOCA-myocardial infarction with non-obstructive coronary arteries]. / MINOCA ­ Myokardinfarkt ohne obstruktive Koronarerkrankung.

In recent years it has been observed with increasing interest that there is a group of patients with electrocardiographic and laboratory features of myocardial infarction (MI) but no obstructive coronary artery disease (<50% diameter stenosis). For this entity the term myocardial infarction with non-obstructive coronary arteries (MINOCA) has been coined. The prevalence of MINOCA is estimated to be 6-9% among patients diagnosed with MI and it is more common in women than men as well as in patients presenting with NSTEMI than in those presenting with STEMI. The MINOCA is a working diagnosis that requires a further diagnostic work-up by invasive techniques, such as intravascular ultrasound (IVUS) and optical coherence tomography (OCT) or non-invasive imaging with cardiac magnetic resonance imaging (CMRI). When it is ascertained that obstructive coronary artery disease has not been inadvertently overlooked, other coronary disorders, such as plaque rupture or erosion, thrombosis, dissection, spasms or microvascular dysfunction should be evaluated. Furthermore, myocarditis or tako-tsubo cardiomyopathy should be excluded by CMRI as non-coronary causes. The further treatment and prognosis of patients with MINOCA depend on the underlying cause and the final diagnosis.

[Patent foramen ovale-intervention or pharmaceutical treatment]. / Persistierendes Foramen ovale ­ Intervention oder Arzneitherapie.

BACKGROUND: Approximately 40-50% of patients with cryptogenic stroke have a patent foramen ovale (PFO). A concomitant atrial septal aneurysm aggravates the risk of recurrent stroke. OBJECTIVE: The most important changes regarding the evidence for interventional closure of a PFO in patients with cryptogenic stroke are described. This includes the prerequisites for making a diagnosis and the indications for interventional treatment. The article also provides an overview about platelet aggregation inhibitor treatment with and without oral anticoagulation. CURRENT DATA: The balance between benefits and risks of interventional versus pharmaceutical treatment in patients with cryptogenic stroke and PFO has so far not been sufficiently proven. In 2017 two prospective randomized trials (CLOSE and REDUCE) and the long-term follow-up results of the RESPECT study were published, followed by the results of the DEFENSE-PFO study in 2018. A better assessment of the weighing up of the treatment options can now be made. All four studies showed that the interventional treatment of PFO is superior to pharmaceutical treatment alone for patients with cryptogenic stroke under 60 years of age. CONCLUSION: There was a significant reduction in the incidence of recurrent stroke in patients with interventional PFO closure compared with pharmaceutical treatment. The complication rate of PFO closure is very low and younger patients (<60 years) in particular benefit from PFO closure.

Early changes in N-terminal pro-B-type natriuretic peptide levels after transcatheter aortic valve replacement and its impact on long-term mortality.

BACKGROUND: N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) levels correlate with higher peri-procedural mortality after transcatheter aortic valve replacement (TAVR). The long-term prognostic value of NT-proBNP within the first days after TAVR, however, remains unclear. This study examined early changes in NT-proBNP prior to and within 6 days after TAVR, the diagnostic value of this biomarker regarding aortic regurgitation (AR), and its prognostic value regarding one-year mortality. METHODS AND RESULTS: NT-proBNP concentrations were measured in 504 consecutive patients undergoing transapical (TA) or transfemoral (TF) TAVR before and directly after TAVR as well as 4 h and 1, 2, 3, and 6 days after TAVR. The follow-up period was 1 year. NT-proBNP was elevated in all patients at baseline (median 2141 ng/L [IQR 1021-5319 ng/L]). NT-proBNP changes in the first 6 days after TAVR showed significant differences depending on the approach, with a greater and more prolonged rise evident in TA-TAVR patients. NT-proBNP was an independent predictor of mortality in TA patients with AR, with an AUC of 0.794 (95% CI 0.663-0.925; P = 0.003) when measured on day 3 after TAVR. For TF patients with AR and reduced left ventricular systolic function, the AUC for prediction of mortality was 0.897 (95% CI 0.778-1.0; P = 0.004) on day 2. CONCLUSIONS: The prognostic information of early post-procedural NT-proBNP concentrations is superior to pre-procedural values regarding all-cause mortality within 1 year. Post-procedural NT-proBNP must be interpreted in relation to the TAVR approach. NT-proBNP predicts mortality in TF-TAVR patients with AR and reduced left ventricular function.

Application of the Bogossian formula for evaluation of the QT interval in pacemaker patients with stimulated left bundle branch block.

BACKGROUND: The presence of left bundle branch block (LBBB) represents a particular challenge in properly measuring the QT interval. Here we demonstrate the applicability of the "Bogossian formula" in pacemaker patients with LBBB due to apical or nonapical right ventricular (RV) pacing and preserved left ventricular function. METHODS: A total of 163 patients with a cardiac one- or two-chamber pacemaker were included in this prospective, multicentre observational study. Twelve-lead ECG recordings were obtained during both intrinsic rhythm and RV pacing with induced LBBB. The QT interval measured during LBBB was corrected using the Bogossian formula to obtain the "modified QT" (QTm). The QTmc interval was calculated with the Bazett formula, and this was compared with the QTc interval during intrinsic rhythm. RESULTS: Eighty-three patients (78 ± 9 years; male n = 83) with apical and eighty patients (71 ± 13 years; male n = 80) with non-apical RV pacing were included in this study. In the apical group the QTmc was determined to be 444 ± 39 ms in paced rhythm and the QTc interval 413 ± 36 ms in intrinsic rhythm. In the non-apical group these values were 430 ± 34 ms in paced and 416 ± 32 ms in intrinsic rhythm. CONCLUSION: The Bogossian formula is a reliable tool for QTc interval evaluation in pacemaker patients with LBBB due to apical or non-apical RV pacing. However, an overestimation of 30 ms should be included in the calculation.

[Management of acute coronary syndrome without ST-segment elevation]. / Management des akuten Koronarsyndroms ohne ST-Strecken-Hebung.

Acute coronary syndrome without persistent ST-segment elevation (non-ST segment elevation myocardial infarction and instable angina pectoris NSTEMI-ACS) is common and is associated with a high mortality. In addition to 12-channel echocardiograph (ECG) assessment, measurement of cardiac troponins I and T are important for risk stratification and diagnosis. The introduction of high-sensitivity cardiac troponin assays and their implementation into clinical practice has influenced risk stratification and treatment of these patients. Additional diagnostic validation must supplement routine clinical chemistry testing following the initial measurement to distinguish between different possible causes of troponin elevation above the 99th percentile. The time point for the additional troponin measurement depends on the different protocols and troponin assays and is stipulated in the current guidelines. The use of both 1­hour and 3­hour protocols together with the clinical presentation and work-up of possible differential diagnoses provide optimal care of patients. Patients who test positive for troponin dynamics should undergo invasive diagnostics and treatment within 24 h of presentation and within 2 h is recommended for unstable patients. Clopidogrel is indicated only in patients requiring oral anticoagulation.

[Computed tomography in patients with chronic stable angina : Fractional flow reserve measurement]. / Computertomographie bei Patienten mit stabiler Angina Pectoris : Messung der fraktionellen Flussreserve.

Coronary computed tomography angiography (cCTA) has been established for the non-invasive diagnosis of coronary artery disease (CAD). Previous studies demonstrated the high diagnostic accuracy of cCTA, particularly for ruling out CAD. As a known limitation of cCTA a large number of visually significant coronary stenoses are found to be hemodynamically not relevant by invasive fractional flow reserve (FFR). CT-based FFR (CT-FFR) builds on recent advances in computational fluid dynamics and image simulation techniques. Along with CT myocardial perfusion imaging, CT-FFR is a promising approach towards a more accurate estimation of the hemodynamic relevance of coronary artery stenoses. CT-FFR is derived from regular CT datasets without additional image acquisitions, contrast material, or medication. Two CT-FFR techniques can be differentiated. The initial method requires external use of supercomputers and has gained approval for clinical use in the USA. Furthermore, a prototype-software has been introduced which is less computationally demanding via integration of reduced-order models for on-site calculation of CT-FFR. The present article reviews these methods in the context of available study results and meta-analyses. Furthermore, limitations and future concepts of CT-FFR are discussed.

Clinical experience with contact-force and flexible-tip ablation catheter designs.

PURPOSE: Lesion formation is a critical determinant of technical and clinical success of pulmonary vein isolation. Different catheter designs aim to enhance tissue contact during ablation to enable optimized lesion formation. We analyzed procedural characteristics and predictors of clinical success in patients ablated with three different contemporary ablation catheters. METHODS: Two hundred sixty-eight sequentially included patients receiving pulmonary vein isolation (PVI) with conventional (n = 122), contact-force (n = 96) and flexible-tip (n = 60) catheters were followed for a median of 14.1 months with 7d-Holter-monitoring and TTE at 3, 6, 12, and 24 months. Baseline characteristics and follow-up times were homogeneous across all groups. RESULTS: Multivariable Cox proportional hazard regression for arrhythmia recurrence demonstrated a favorable hazard ratio for contact-force and flexible-tip catheters vs. conventional open irrigation catheters. Procedure time and fluoroscopy time were shorter for contact-force and flexible-tip catheters versus conventional catheters, but equal between. Linear lesions were applied in 58 % of contact-force and 66 % of flexible-tip cases, and CFAEs were targeted in 26 % of either. CONCLUSIONS: Our non-randomized prospectively collected data do not show a difference in observed procedure characteristics and in clinical outcome for flexible-tip versus contact-force catheter designs, while both display improved performance against conventional open irrigated-tip catheters. Linear lesions and CFAEs ablation were not associated with improved arrhythmia-free survival.

[Interventional therapy of aortic valve stenosis in Germany]. / Interventionelle Therapie der Aortenklappenstenose in Deutschland.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has gained importance in recent years for the treatment of symptomatic aortic stenosis in Germany. OBJECTIVE: This article discusses the indications, the procedure itself and safety issues in TAVI. MATERIAL AND METHODS: Randomized controlled trials, registry studies, guidelines and expert recommendations are discussed. RESULTS: Inoperable patients as well as patients ≥ 75 years with a high perioperative risk and patients ≥ 85 years should primarily be treated by TAVI. The decision must be made following discussions in a heart team. If no contraindications are detected the TAVI procedure should be performed via the transfemoral approach with the patient under conscious sedation. In recent years there has been a significant reduction in complication rates. CONCLUSION: In Germany TAVI is the standard of care for surgical high-risk and inoperable patients with aortic valve stenosis.

Development of a novel in vivo corneal fibrosis model in the dog.

The aim of this study was to develop a novel in vivo corneal model of fibrosis in dogs utilizing alkali burn and determine the ability of suberanilohydroxamic acid (SAHA) to inhibit corneal fibrosis using this large animal model. To accomplish this, we used seven research Beagle dogs. An axial corneal alkali burn in dogs was created using 1 N NaOH topically. Six dogs were randomly and equally assigned into 2 groups: A) vehicle (DMSO, 2 µL/mL); B) anti-fibrotic treatment (50 µM SAHA). The degree of corneal opacity, ocular health, and anti-fibrotic effects of SAHA were determined utilizing the Fantes grading scale, modified McDonald-Shadduck (mMS) scoring system, optical coherence tomography (OCT), corneal histopathology, immunohistochemistry (IHC), and transmission electron microscopy (TEM). The used alkali burn dose to produce corneal fibrosis was well tolerated as no significant difference in mMS scores between control and treatment groups (p = 0.89) were detected. The corneas of alkali burned dogs showed significantly greater levels of α-smooth muscle actin, the fibrotic marker, than the controls (p = 0.018). Total corneal thickness of all dogs post-burn was significantly greater than baseline OCT images irrespective of treatment (p = 0.004); TEM showed that alkali burned corneas had significantly greater minimum and maximum interfibrillar distances than the controls (p = 0.026, p = 0.018). The tested topical corneal alkali burn dose generated significant opacity and fibrosis in dog corneas without damaging the limbus as evidenced by histopathology, IHC, TEM, and OCT findings, and represents a viable large animal corneal fibrosis in vivo model. Additional in vivo SAHA dosing studies with larger sample size are warranted.

Ventricular tachycardias in patients with pulmonary hypertension: an underestimated prevalence? A prospective clinical study.

BACKGROUND: Sudden cardiac death (SCD) accounts for approximately 30 % in patients with pulmonary arterial hypertension (PAH). The exact circumference for SCD in this patient population is still unclear. Malignant cardiac arrhythmias are reported to be rarely present. There are no systematic data concerning long-term electrocardiographic (ECG) recording in patients with PAH. OBJECTIVES: We sought to investigate the rate of potentially relevant arrhythmias in patients with pulmonary hypertension (PH). METHODS: Consecutive patients without diagnosis of known cardiac arrhythmias followed in our outpatient clinic for PH were enrolled in the study. All patients underwent a 72-h Holter ECG. Clinical data, 6-min walk distance, laboratory values, and echocardiography were collected/performed. RESULTS: Ninety-two consecutive patients (New York Heart Association class (NYHA) III/IV: 65.2 %/5.4 %, PH Group 1: 35.9 %, Group 3: 10.9 %, Group 4: 28.3 %, Group 5: 2.2 %) were investigated. Relevant arrhythmias were newly detected in 17 patients: non-sustained ventricular tachycardia (n = 12), intermittent second-degree heart block (n = 1), intermittent third-degree heart block (n= 3), and atrial flutter (n = 1). Echocardiographic systolic pulmonary pressure and diameter of the right heart were elevated in patients with relevant arrhythmias. Right heart catheterization revealed higher pulmonary vascular resistance (672 vs. 542 dyn · s · cm(-5), p = 0.247) and lower cardiac index (2.46 vs. 2.82 l/min/m(2), p = 0.184). CONCLUSIONS: Ventricular tachycardias occur more often in PH patients than previously reported. However, the prognostic relevance of non-sustained ventricular tachycardias in this cohort remains unclear. As a large number of PH patients die from SCD, closer monitoring, e.g., using implantable event recorders, might be useful to identify patients at high risk.

[ESC/EACTS guidelines on myocardial revascularization : Amendments 2014]. / ESC/EACTS-Leitlinie zur Revaskularisation des Myokards : Veränderungen 2014.

One of the most important treatment principles in interventional cardiology relies on myocardial revascularization by percutaneous coronary intervention (PCI) or surgical placement of coronary artery bypass grafts (CABG). However, in order to apply these principles effectively, it is important to identify patients who require revascularization. Consequently, the appropriate method has to be selected to effectively restore blood flow. Patients will only benefit from the interventional or surgical procedures when those revascularization measures that can cause more harm than good are avoided. In the new European Society of Cardiology and European Association for Cardio-Thoracic Surgery (ESC/EACTS) guidelines on myocardial revascularization some new aspects will be addressed.

[Procedural aspects in primary PCI: arterial access, stent selection, thrombectomy and treatment of non-culprit lesions]. / Prozedurale Aspekte im Rahmen der primären PCI: Arterieller Zugang, Stentselektion, Thrombektomie, Behandlung der Non-culprit-Läsionen.

Acute myocardial infarction was one of the most common causes of death in Germany in 2011. According to the guidelines of the European Society for Cardiology, systemic fibrinolysis and primary percutaneous coronary intervention (PCI) are the methods of choice for acute treatment. Primary PCI should be given priority due to its superiority. The transradial access should be preferred due to the lower bleeding complication rate. In the selection of stents the new generation of drug-eluting stents (DES) are superior to the first generation of bare metal stents (BMS). It has now been demonstrated that the incident rates of DES (e.g. mortality, target vessel revascularization, early and late stent thrombosis and myocardial infarction) are significantly lower. For bioresorbable scaffolds (BRS) long-term results for the use in treatment of ST-elevation myocardial infarction (STEMI) are not yet available but initial results are very promising. However, the selection of a stent needs to be done on an individual basis in order to do justice to all aspects. Data with respect to thrombectomy in acute treatment are heterogeneous. Currently, a thorough consideration of all aspects is necessary because thrombus aspiration can also be associated with an increased rate of incidents. In a state of hemodynamic stability only so-called culprit lesions should currently be treated with a stent. Elective interventions on further stenoses should be carried out after consideration of individual factors and if necessary evaluation of the hemodynamic relevance.

The temporal and spatial distribution of macrophage subpopulations during arteriogenesis.

Chronic arterial occlusion leads to growth of collaterals - a process termed arteriogenesis, in which macrophages play a prominent role in remodelling and growth. However, a detailed analysis which of distinct macrophage subpopulations involved in arteriogenesis has never been performed. In the present study the temporal and spatial distribution of macrophage subtypes during arteriogenesis in a rat model with chronically elevated fluid shear stress (FSS) is investigated. Local macrophage subpopulations were histologically immuno-phenotyped using CD68 (a ubiquitous macrophage marker) and CD163, a specific M2 macrophage marker. Without occlusion few M2-macrophages reside in the perivascular space. Early after occlusion (12h) the number of M2 macrophages increases strongly and M1 macrophages begin emerging into the collateral. After 3 days they appear in the perivascular space. Both macrophage subtypes increase until 28d after treatment, whereas M2 macrophages dominate at the site of collateral growth. The local distribution of the subpopulations changes during the arteriogenic process. Whereas M1 macrophages are detected directly adjacent to the media, M2 macrophages are present in the most outer perivascular region of the growing collateral vessel. Systemic alterations of blood leucocytes in mice after femoral artery ligature (FAL) were investigated by FACS analysis of serial blood samples. During collateral remodelling histological changes were not reflected in circulating monocytes in the peripheral blood. The activation state of macrophages in mice with FAL was modulated by injections of either dexamethasone or the interleukins IL10 or IL3/IL14. The arteriogenic response was assessed by hind limb perfusion with laser Doppler measurements after 3, 7 and 14d. Suppressing inflammatory monocyte subtypes (M1) with dexamethasone led to impaired perfusion recovery after FAL in mice, whereas IL10 or IL4/IL13 application significantly increased perfusion recovery. This investigation demonstrates that a forced shift towards M2 macrophages improves the arteriogenic response. The distinct early increase and spatial distribution of M2 macrophages support the idea that this subtype plays a predominant role during collateral remodelling.

Multimarker risk model containing troponin-T, interleukin 10, myeloperoxidase and placental growth factor predicts long-term cardiovascular risk after non-ST-segment elevation acute coronary syndrome.

OBJECTIVE: To evaluate the predictive value of seven biomarkers, which individually have been shown to be independent predictors, for use in a combined multimarker model for long-term cardiovascular outcome after non-ST-segment elevation acute coronary syndrome (NSTEACS). DESIGN AND SETTING: Levels of high-sensitivity C-reactive protein (hsCRP), myeloperoxidase, pregnancy-associated plasma protein A, placental growth factor (PlGF), soluble CD40 ligand (sCD40L), interleukin 10 (IL-10) and troponin-T (TnT) were determined in patients enrolled in the CAPTURE trial. Cox proportional hazard regression analyses were applied to evaluate the relation between biomarkers and the occurrence of all-cause mortality or non-fatal myocardial infarction (MI). PATIENTS: 1090 patients with NSTEACS. MAIN OUTCOME MEASURE: All-cause mortality and non-fatal MI during a median follow-up of 4 years. RESULTS: The composite endpoint was reached by 15.3% of patients. Admission levels of TnT >0.01 µg/l (adjusted HR 1.8), IL-10 <3.5 ng/l (1.7), myeloperoxidase >350 µg/l (1.5) and PlGF >27 ng/l (1.9) remained significant predictors for the incidence of all-cause mortality or non-fatal MI after multivariable adjustment for other biomarkers and clinical characteristics, whereas hsCRP, pregnancy-associated plasma protein A and sCD40L were only associated with the endpoint in univariate analysis. A multimarker model consisting of TnT, IL-10, myeloperoxidase and PlGF predicted 4-year event rates that varied between 6.0% (all markers normal) and 35.8% (three or more biomarkers abnormal). CONCLUSION: In patients with NSTEACS, biomarkers characterising distinct aspects of the underlying atherosclerotic process and myocardial damage of the initial cardiac event can assist in predicting long-term adverse cardiac outcomes. The use of combinations of selected biomarkers adds incremental predictive value to further risk stratification in an otherwise seemingly homogeneous NSTEACS population.