Dynamic nature of nonculprit coronary artery lesion morphology in STEMI: a serial IVUS analysis from the HORIZONS-AMI trial.

OBJECTIVES: The authors sought to report the temporal stability of an untreated, nonculprit lesion phenotype in patients presenting with ST-segment elevation myocardial infarction (STEMI). BACKGROUND: The temporal stability of the untreated, nonculprit lesion phenotype has been studied using intravascular ultrasound-virtual histology (IVUS) in patients with stable ischemic heart disease, but not in STEMI patients. METHODS: As part of a formal substudy of the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial, baseline and 13-month follow-up IVUS was performed in 99 untreated nonculprit lesions in 63 STEMI patients. Lesions were classified as pathological intimal thickening (PIT), IVUS-derived thin-cap fibroatheroma (TCFA), thick-cap fibroatheroma (ThCFA), fibrotic plaque, or fibrocalcific plaque. RESULTS: The frequency of TCFA increased from 41% at baseline to 54% at follow-up, whereas ThCFAs decreased from 41% to 34% and PIT decreased from 16% to 8%. Among the 41 lesions classified at baseline as TCFA, at follow-up, 32 (78%) were still classified as TCFA, whereas 9 (22%) were classified as ThCFAs or fibrotic plaques. An additional 21 lesions at follow-up were newly classified as TCFA, developing from either PIT or ThCFA. TCFA at baseline that evolved into non-TCFAs trended toward a more distal location than TCFA that did not change (p = 0.12). In lesions classified as TCFA, the minimum lumen area (MLA) decreased from 8.1 (interquartile range [IQR]: 7.4 to 8.8) mm(2) at baseline to 7.8 (IQR: 7.2 to 8.4) mm(2) at follow-up, p < 0.05; this was associated with an increase in percent necrotic core at the MLA site (14% [IQR: 12 to 16] to 19% [IQR: 17 to 22], p < 0.0001) and over the entire length of the lesion (14% [IQR: 12 to 16] to 18% [IQR: 17 to 20], p < 0.0001). CONCLUSIONS: Untreated nonculprit lesions in STEMI patients frequently have TCFA morphology that does not change during 13-month follow-up and is accompanied by a decrease in MLA and an increase in necrotic core. (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction [HORIZONS-AMI]; NCT00433966).

Bivalirudin inhibits periprocedural platelet function and tissue factor expression of human smooth muscle cells.

AIM: A major concern of stent implantation after percutaneous coronary intervention (PCI) is acute stent thrombosis. Effective inhibition of periprocedural platelet function in patients with coronary artery disease (CAD) leads to an improved outcome. In this study, we examined the periprocedural platelet reactivity after administrating bivalirudin during PCI compared to unfractionated heparin (UFH) administration. Further, the effect of bivalirudin on induced tissue factor (TF) expression in smooth muscle cells (SMC) was determined. METHODS: Patients with CAD (n = 58) and double antithrombotic medication were treated intraprocedural with UFH (n = 30) or bivalirudin (n = 28). Platelet activation markers were flow cytometrically measured before and after stenting. The expression of TF in SMC was determined by real-time PCR and Western blotting. The thrombogenicity of platelet-derived microparticles and SMC was assessed via a TF activity assay. RESULTS: Bivalirudin significantly diminished the agonist-induced platelet reactivity post-PCI. Compared to UFH treatment, the adenosine diphosphate (ADP) and thrombin receptor-activating peptide (TRAP)-induced thrombospondin expression post-PCI was reduced when bivalirudin was administrated during intervention. In contrast to UFH, bivalirudin reduced the P-selectin expression of unstimulated and ADP-induced platelets post-PCI. Moreover, bivalirudin inhibited the thrombin-, but not FVIIa- or FVIIa/FX-induced TF expression and pro-coagulant TF activity of SMC. Moreover, bivalirudin reduced the TF activity of platelet-derived microparticles postinduction with TRAP or ADP. CONCLUSIONS: Bivalirudin is better than UFH in reducing periprocedural platelet activation. Moreover, thrombin-induced TF expression is inhibited by bivalirudin. Thus, bivalirudin seems to be a better anticoagulant during PCI than UFH.

Impact of telemedical care and monitoring on morbidity in mild to moderate chronic heart failure.

OBJECTIVE: We investigated in a pilot study whether telemedicine is beneficial in mild to moderate chronic heart failure. METHODS: A total of 128 patients with an ejection fraction < or =60% and NYHA class II or III chronic heart failure were evaluated. Thirty-two patients were enrolled prospectively in a staged telemedical service program. Ninety-six controls were matched 3:1 to each telemedicine patient. RESULTS: Median follow-up was 307 days (range 104-459). All-cause hospitalization duration [317 vs. 693 days/100 patient years; relative risk (RR) 0.46; 95% confidence interval (CI) 0.37-0.58; p < 0.0001) and rate (38 vs. 77/100 patient years; RR 0.49; 95% CI 0.25-0.95; p = 0.034) as well as cardiac hospitalization duration (49 vs. 379 days/100 patient years; RR 0.13; 95% CI 0.08-0.23; p < 0.0001] were significantly lower, cardiac hospitalization rate (11 vs. 35/100 patient years; RR 0.31; 95% CI 0.11-1.02; p = 0.058) tended to be lower in the telemedicine compared with the control group. CONCLUSION: These preliminary data suggest that telemedical care and monitoring may reduce morbidity in patients with NYHA class II and III chronic heart failure.

The amount of fibrinogen-positive platelets predicts the occurrence of in-stent restenosis.

AIMS: To determine the value of fibrinogen-positive platelet-analysis in predicting restenosis after stent implantation in acute myocardial infarction patients. METHODS AND RESULTS: Our patient population comprised 50 patients who underwent intravascular ultrasound (IVUS) guided stent implantation for acute myocardial infarction. In all cases, IVUS confirmed a deep vessel wall injury due to a ruptured plaque within the culprit lesion. Flow cytometry quantified the amount of platelets with surface-bound fibrinogen and thrombospondin before and immediately after the intervention. After 5 months, IVUS was repeated to assess the long-term results. In-stent restenosis - defined as a percent diameter stenosis of >50% - was detected in 11 of 45 patients who attended follow-up angiography. The amount of fibrinogen-positive platelets was significantly higher among patients who subsequently developed in-stent restenosis (50.5+/-6.8% fibrinogen-positive platelets immediately after intervention) than among those who did not (39.7+/-12.3% fibrinogen-positive platelets, p<0.005). Receiver operating characteristic curve revealed a 40% cut-off for fibrinogen-positive platelets immediately after the intervention to predict restenosis (p<0.05, sensitivity: 90.9%, specificity: 47.1%). CONCLUSION: The amount of fibrinogen-positive platelets immediately after stent implantation predicts the occurrence of in-stent restenosis, as confirmed by IVUS in acute myocardial infarction patients.

Treatment with ezetimibe plus low-dose atorvastatin compared with higher-dose atorvastatin alone: is sufficient cholesterol-lowering enough to inhibit platelets?

OBJECTIVES: We sought to test the platelet inhibitory and anti-inflammatory effects of a higher statin dosage compared with combined treatment with ezetimibe plus a low statin dose. BACKGROUND: Reducing the level of low-density lipoprotein cholesterol (LDL-C) with statins induces important pleiotropic effects such as platelet inhibition. An insufficient LDL-C reduction often is treated with ezetimibe, an intestinal cholesterol absorption inhibitor, in combination with a low statin dose. It is not known whether this combination therapy has the same pleiotropic effects as a statin monotherapy. METHODS: Fifty-six patients with coronary artery disease were assigned randomly to receive either 40 mg/day of atorvastatin or 10 mg/day of ezetimibe plus 10 mg/day of atorvastatin for 4 weeks. The levels of LDL-C, platelet activation markers after stimulation, platelet aggregation, and plasma chemokine levels (i.e., regulated on activation normally T-cell expressed and secreted [RANTES]) were measured before and after changing lipid-lowering medication. RESULTS: Platelet activation markers (P-selectin) after stimulation (adenosine diphosphate) were reduced by 40 mg/day of atorvastatin (-5.2 +/- 1.6 arbitrary units) but not by ezetimibe plus low-dose atorvastatin (2.1 +/- 1.8 arbitrary units; p < 0.005) despite a similar reduction of LDL-C (atorvastatin -1.01 +/- 0.18 mmol/l vs. ezetimibe plus atorvastatin -1.36 +/- 0.22 mmol/l, p = NS). Thrombin receptor-activating peptide-induced platelet aggregation as well as plasma RANTES levels were reduced by 40 mg/day of atorvastatin but not by ezetimibe plus low-dose atorvastatin. CONCLUSIONS: Platelet reactivity and a proinflammatory chemokine were reduced more by the higher atorvastatin dose than by ezetimibe plus low-dose atorvastatin. In patients with coronary artery disease, it might be important to combine ezetimibe with higher statin dosages to benefit from cholesterol-independent pleiotropic effects.

Abciximab therapy is associated with increased platelet activation and decreased heparin dosage in patients with acute myocardial infarction.

The inhibition of the glycoprotein (GP) IIb/IIIa receptor for reducing periprocedural ischemic events in patients undergoing coronary intervention is known to influence platelet reactivity. Suboptimal doses of GP IIb/IIIa antagonists have been suggested to be prothrombotic and proinflammatory. This study was performed to observe platelet activation markers, whole blood aggregation and the dosage of unfractionated heparin (UFH) in the presence or absence of the GP IIb/IIIa inhibitor abciximab. Patients with acute myocardial infarction undergoing percutaneous coronary intervention were treated with (n = 15) or without (n = 15) abciximab. Platelet activation markers were flow cytometrically measured before and after PCI. Whole blood platelet aggregation was tested by a platelet function assay. The patients with abciximab showed a significant increase in platelet activation markers (P-selectin: 7.12 +/- 0.36 AU vs 11.05 +/- 0.79 AU) and a lower requirement of UFH to prolong aPTT > 60 sec during the infusion. 12 hours after infusion P-selectin level decreased (7.20 +/- 0.58 AU), whereas whole blood aggregation was increasing again. After stopping abciximab, requirement of UFH to prolong aPTT increased in the treated group to a greater extent to a level similar to the untreated group even when most of the platelets were still inhibited. The increased platelet activation found at the end of abciximab treatment points to a procoaguable condition that should be carefully monitored and treated by adapting anticoagulation and antiplatelet drugs.

Randomized comparison of platelet-leukocyte aggregates and platelet activation in blood: heparin-coated coiled wire stent implantation versus balloon angioplasty in acute myocardial infarction.

INTRODUCTION: Stent implantation has been shown to be superior to balloon angioplasty in patients with acute myocardial infarction (AMI). Newer trials indicate that platelet-leukocyte aggregates are a more sensitive marker for platelet activation than platelet surface marker. Our study examined platelet activation and platelet-leukocyte interaction in blood in patients with AMI randomized to heparin-coated stent implantation versus balloon angioplasty. MATERIALS AND METHODS: Forty-seven patients with AMI were included into our study. Patients were randomized to heparin-coated stent implantation (n=31) or balloon angioplasty (n=16). Platelet activation, total platelet-leukocyte aggregates and aggregate composition in blood were assessed by flow cytometry before, immediately after and 24 h after intervention. RESULTS: No differences in platelet activation, total platelet-leukocyte aggregates and aggregate composition were found between both groups before intervention. Immediately after intervention, platelet activation was comparably increased in both groups. Patients treated with heparin-coated stent showed a decrease in total platelet-leukocyte aggregates 24 h after intervention (3.9% [2.8; 4.7] versus 3.2% [2.4; 4.1]; p<0.01). Platelet-monocyte conjugates decreased 24 h after heparin-coated stent implantation compared to balloon angioplasty alone (0.28% [0.17; 0.42] versus 0.49% [0.45; 0.79]; p<0.05). No difference in total platelet-leukocyte aggregates was found in patients treated with balloon angioplasty alone. CONCLUSIONS: An inhibitory effect of heparin-coated stent implantation on total platelet-leukocyte aggregates and platelet-monocyte conjugates in blood was demonstrated in patients with AMI. This reflects heparin-coated stent implantation to be less thrombogenic than balloon angioplasty alone.