Adam Witkowski

Altered Plasma Fibrin Clot Properties Are Associated With In-Stent Thrombosis

Objectives—We sought to investigate whether patients with in-stent thrombosis (IST) display altered plasma fibrin clot properties. Methods and Results—We studied 47 definite IST patients, including 15 with acute, 26 subacute and 6 late IST, and 48 controls matched for demographics, cardiovascular risk factors, concomitant treatment and angiographic/stent parameters. Plasma clot permeability (Ks), which indicates a pore size, turbidity (lag phase, indicating the rate of fibrin clot formation, &Dgr;Absmax, maximum absorbance of a fibrin gel, reflecting the fiber thickness), lysis time (t50%) and maximum rate of d-dimer release from clots (D-Drate) were determined 2 to 73 (median 14.7) months after IST. Patients with IST had 21% lower Ks, 14% higher &Dgr;Absmax, 11% lower D-Drate, 30% longer t50% (all P<0.0001) and 5% shorter lag phase compared to controls (P=0.042). There were no correlations between clot variables and the time of IST or that from IST to blood sampling. Multiple regression analysis showed that Ks (odds ratio=0.36 per 0.1 &mgr;m2, P<0.001), D-Drate (odds ratio=0.16 per 0.01 mg/L/min, P<0.001) and stent length (odds ratio=1.1 per 1 mm, P=0.043) were independent predictors of IST (R2=0.58, P<0.001). Conclusions—IST patients tend to form dense fibrin clots resistant to lysis, and altered plasma fibrin clot features might contribute to the occurrence of IST.

Effects of Ranolazine on Angina and Quality of Life After Percutaneous Coronary Intervention With Incomplete Revascularization: Results From the Ranolazine for Incomplete Vessel Revascularization (RIVER-PCI) Trial

Background— Angina often persists or returns in populations following percutaneous coronary intervention (PCI). We hypothesized that ranolazine would be effective in reducing angina and improving quality of life (QOL) in incomplete revascularization (ICR) post-PCI patients. Methods and Results— In RIVER-PCI, 2604 patients with a history of chronic angina who had ICR post-PCI were randomized 1:1 to oral ranolazine versus placebo; QOL analyses included 2389 randomized subjects. Angina and QOL questionnaires were collected at baseline and months 1, 6, and 12. Ranolazine patients were more likely than placebo to discontinue study drug by month 6 (20.4% versus 14.1%, P<0.001) and 12 (27.2% versus 21.3%, P<0.001). Following qualifying index PCI, the primary QOL outcome (Seattle Angina Questionnaire [SAQ] angina frequency score) improved markedly, but similarly, in the ranolazine and placebo groups, respectively, from baseline (67.3±24.5 versus 69.7±24.0, P=0.01) to month 1 (86.6±18.1 versus 85.8±18.5, P=0.27) and month 12 (88.4±17.8 versus 88.5±17.8, P=0.94). SAQ angina frequency repeated measures did not differ in adjusted analysis between groups post baseline (mean difference 1.0; 95% CI -0.2, 2.2; P=0.11). Improvement in SAQ angina frequency was observed with ranolazine at month 6 among diabetics (mean difference 3.3; 95% CI 0.6, 6.1; P=0.02) and those with more angina (baseline SAQ angina frequency ⩽60; mean difference 3.4; 95% CI 0.6, 6.2; P=0.02), but was not maintained at month 12. Conclusions— Despite ICR following PCI, there was no incremental benefit in angina or QOL measures by adding ranolazine in this angiographically-identified population. These measures markedly improved within 1 month of PCI and persisted up to 1 year in both treatment arms. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01442038.

D-dimer levels predict ischemic and hemorrhagic outcomes after acute myocardial infarction: a HORIZONS-AMI biomarker substudy

D-dimer is a product of cross linked fibrin degradation and is a measure of the amount of fibrin turnover. As such, D-dimer might be of utility in the prediction of both thrombotic and hemorrhagic events. Therefore, the aim of the present study was to evaluate whether elevated D-dimer levels on admission and at discharge could predict subsequent ischemic and hemorrhagic events in patients with acute myocardial infarction (AMI). D-dimer was measured on admission and at discharge in 461 out of a total of 3,602 patients in the HORIZONS-AMI trial, as part of the formal prespecified biomarker substudy. The predictive value for major adverse cardiovascular events (MACE) and non-CABG major bleeding after 3xa0year follow up was investigated by stratifying patients in groups of D-dimer level and comparing event rates using Kaplan–Meier and calculating hazard ratios using Cox proportional hazards models. D-dimer levelsxa0≥xa00.71xa0μg/mL on admission were associated with an adjusted hazard ratio of 2.58 for MACE (pxa0=xa00.0014) and 4.61 for major bleeding (pxa0=xa00.0018). A discharge D-dimer levelxa0≥xa01.26xa0μg/mL was associated with a higher risk for MACE by univariate analysis (HR 1.88, pxa0=xa00.037), but lost its significance after multivariate adjustment (HR 1.77, pxa0=xa00.070). High D-dimer levels on admission were associated with a higher risk of MACE and non-CABG major bleeding in STEMI patients undergoing pPCI.

Relationship between biomarkers and subsequent bleeding risk in ST-segment elevation myocardial infarction patients treated with paclitaxel-eluting stents: a HORIZONS-AMI substudy.

Major bleeding complications in STEMI patients result in significant mortality, morbidity and healthcare cost. Identification of patients at increased risk of bleeding is therefore essential. New biomarkers might be of incremental value to identify patients at risk for bleeding after primary PCI. A total of 26 biomarkers were measured at enrolment and analyzed at a central core laboratory in 464 STEMI patients in the HORIZONS-AMI trial. We investigated the relationship between tertiles of biomarker and in hospital non-CABG major bleeding. In hospital non-CABG major bleeding occurred in 3.7xa0% of patients (nxa0=xa017). Increasing levels of cystatin C and D-dimer at admission were associated with higher rates of in hospital major bleeding. After adjustment for a risk score for bleeding, the odds ratio for in hospital major bleeding was 3.13 for cystatin Cxa0>xa02.04xa0mg/L (pxa0=xa00.046) and 3.28 for ESAMxa0>xa034xa0ng/mL (pxa0=xa00.037). In this exploratory analysis of the HORIZONS-AMI biomarker substudy, high cystatin C and ESAM levels were associated with a higher risk of major bleeding. Larger studies are warranted to confirm the prognostic value of cystatin C and ESAM for major bleeding in STEMI patients.

Enhanced level of micronuclei in peripheral blood lymphocytes of patients treated for restenosis with 32P endovascular brachytherapy

BACKGROUNDnRestenosis is the complete occlusion of the blood vessel leading to such complications as ischemia/angina, myocardial infarction, and death. It can be managed by endovascular brachytherapy with both gamma and beta sources. Endovascular brachytherapy is performed worldwide on several thousands of cases per year. The gamma-emitter 192Ir as well as the beta-emitters 32P and 90Sr are mainly used. The dose to the occluded endothelial wall is 20 Gy. Interestingly, no information with respect to the dose absorbed by the blood during the course of the treatment exists. The aim of the present investigation was to verify if the micronucleus test is suitable to detect the dose absorbed by lymphocytes in the course of endovascular brachytherapy with 32P.nnnMATERIALS AND METHODSnBlood was drawn from 16 patients immediately before and 1 day after the treatment. Frequencies of micronuclei were assessed. In order to ensure that the micronuclei did not arise due to fluoroscopy or reperfusion, we analyzed lymphocytes of 16 control patients who underwent interventional cardiology with balloon angioplasty only.nnnRESULTS AND CONCLUSIONSnEnhanced frequencies of micronuclei were observed in lymphocytes of some donors following brachytherapy. No correlation could be detected between the level of induced micronuclei and the absorbed dose. Also, no effect of fluoroscopy or reperfusion was seen. Thus, although brachytherapy of restenosis with 32P leads to weak enhancement of the micronucleus frequency in lymphocytes, the effect was not seen in all patients; the reason for this heterogeneous response remains to be elucidated.