After rupture of an arteriosclerotic plaque in a coronary artery, platelets play a crucial role in the subsequent thrombus formation, leading to myocardial infarction. An increased mean platelet ...volume (MPV), as an indicator of larger, more reactive platelets, may represent a risk factor for myocardial infarction. However, this hypothesis is still controversial and most studies addressing the role of MPV were performed comparing patients suffering from myocardial infarction with healthy controls. We intended to identify patients at high risk of suffering myocardial infarction in a group of patients with known coronary artery disease. One hundred and eighty‐five consecutive patients with stable coronary artery disease were compared with 188 individuals who had suffered myocardial infarction. Patients within the highest quintile of MPV (≥ 11·6 fl) had a significantly higher risk of experiencing a myocardial infarction compared with patients within the lowest quintile (OR = 2·6, 95% CI 1·3–5·1) in a multivariate analysis that included sex, age, body mass index, hyperlipidaemia, hypertension, smoking and diabetes mellitus. Our results indicate that patients with pre‐existing coronary artery disease and an increased MPV (≥ 11·6 fl) are at higher risk of myocardial infarction. These patients can be easily identified during routine haematological analysis and could possibly benefit from preventive treatment.
We present the case of a 51-year-old male patient who received adjuvant chemotherapy consisting of oxaliplatin, bolus and continuous 5-fluorouracil (5-FU) and leucovorin after anterior resection ...because of locally advanced rectal cancer. Preoperative chemotherapy with capecitabine (an oral 5-FU prodrug) had been well tolerated. Two days after initiation of the first course of chemotherapy, the patient reported typical chest pain. The ECG showed ST elevations and prominent T waves in almost all leads. Due to suspicion of a high-risk acute coronary syndrome, an urgent cardiac catheterization was performed. It showed a generally reduced coronary flow with multiple significant stenoses (including the ostia of the left and right coronary artery), as well as a highly reduced left ventricular function with diffuse hypokinesia. Due to the meanwhile completely stable situation of the patient after medical acute coronary syndrome treatment, no ad hoc intervention was performed to allow further discussion of the optimal management. Thereafter, the patient remained clinically asymptomatic, without any rise in cardiac necrosis parameters; only NT-pro-BNP was significantly elevated. A control cardiac catheterization 2 days later revealed a restored normal coronary artery flow with only coronary calcifications without significant stenoses, as well as a normal left ventricular ejection fraction. Cardiovascular symptoms occurred on the second day of continuous 5-FU treatment. As cardiotoxic effects seem to appear more frequently under continuous application of 5-FU, compared to the earlier established 5-FU bolus regimens, treating medical oncologists should pay special attention to occurring cardiac symptoms and immediately interrupt 5-FU chemotherapy and start a cardiologic work-up.
While contributors to system delay in ST-elevation myocardial infarction (STEMI) are well described, predictors of patient-related delays are less clear. The aim of this study was to identify ...predictors that cause delayed diagnosis of STEMI in a metropolitan system of care (VIENNA STEMI network) and to investigate a possible association with long-term mortality.
The study population investigated consisted of 2366 patients treated for acute STEMI in the Vienna STEMI registry from 2003-2009. Multivariable regression modelling was performed for (a) onset of pain to first medical contact (FMC) as a categorical variable (pain-to-FMC⩽60 min versus >60 min: 'early presenters' versus 'late presenters'); and for (b) onset of pain-to-FMC (min) as a continuous variable.
After multivariable adjustment, female sex (odds ratio (OR) 1.348; 95% confidence interval (CI) 1.013-1.792; p=0.04) and diabetes mellitus (OR 1.355; 95% CI 1.001-1.835; p=0.05) were independently associated with late presentation in STEMI patients, whereas cardiogenic shock (OR 0.582; 95% CI 0.368-0.921; p=0.021) was a predictor of early diagnosis. When onset of pain-to-FMC was treated as a continuous variable, female sex ( p=0.003), anterior infarction ( p=0.004) and diabetes mellitus ( p=0.035) were independently associated with longer delay, while hyperlipidaemia ( p=0.002) and cardiogenic shock ( p=0.017) were strong predictors of short pain-to-FMC times. Three-year-all cause mortality was 9.6% and 11.3% ( p=0.289) for early and late presenters, respectively. After adjustment for clinical factors (sex, age, diabetes, current smoking, hypertension, hyperlipidaemia, cardiogenic shock and location of myocardial infarction) only a trend for increased risk of all-cause death was observed for longer pain-to-FMC times in a cox regression model (hazard ratio (HR) 1.012; 95% CI 0.999-1.025 for every 10 min of delay; p=0.061). Interestingly, early presentation within one hour of symptom onset was not associated with three-year mortality survival (HR 1.031; 95% CI 0.676-1.573; p=0.886).
In this all-comers study of STEMI patients in the VIENNA STEMI network, cardiogenic shock was the strongest predictor of short patient-related delays, whereas a history of diabetes and female sex were independent associated with late diagnosis in STEMI. After adjustment for clinical confounders, patient related delay did not significantly impact on long-term all-cause mortality.
Objective To evaluate the clinical utility of individualising dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in an all-comers population, including ST-elevation ...myocardial infarction (STEMI) patients. Setting Tertiary care single centre registry. Participants 1008 consecutive PCI patients with stent implantation, without exclusion criteria. Intervention Peri-interventional individualisation of DAPT, guided by multiple electrode aggregometry (MEA), to overcome high on-treatment platelet reactivity (HPR) to ADP-induced (≥50 U) and arachidonic acid (AA)-induced aggregation (>35 U). Outcome measures The primary efficacy end point was definite stent thrombosis (ST) at 30 days. The primary safety end point was thrombolysis in myocardial infarction (TIMI) major and minor bleeding. Secondary end points were probable ST, myocardial infarction, cardiovascular death and the combined end point: major cardiac adverse event (MACE). Results 53% of patients presented with acute coronary syndrome (9% STEMI, 44% non-ST-elevation). HPR to ADP after 600 mg clopidogrel loading occurred in 30% of patients (73±19 U vs 28±11 U; p<0.001) and was treated by prasugrel or ticagrelor (73%), or clopidogrel (27%) reloading (22±12 U; p<0.001). HPR to ADP after prasugrel loading occurred in 2% of patients (82±26 U vs 19±10 U; p<0.001) and was treated with ticagrelor (34±15 U; p=0.02). HPR to AA occurred in 9% of patients with a significant higher proportion in patients with HPR to ADP (22% vs 4%, p<0.001) and was treated with aspirin reloading. Definite ST occurred in 0.09% of patients (n=1); probable ST, myocardial infarction, cardiovascular death and MACE occurred in 0.19% (n=2), 0.09% (n=1) and 1.8% (n=18) of patients. TIMI major and minor bleeding did not differ between patients without HPR and individualised patients (2.6% for both). Conclusions Individualisation of DAPT with MEA minimises early thrombotic events in an all-comers PCI population to an unreported degree without increasing bleeding. A randomised multicentre trial utilising MEA seems warranted. Trial registration number http://www.clinicaltrials.gov; NCT01515345.
High factor VIII (FVIII) is a risk factor for venous thromboembolism (VTE). The pathomechanism by which high FVIII leads to an increased risk of VTE is unknown. Physical activity and infusion of ...adrenalin provoke a rise in FVIII, which can be blocked by a nonselective beta-blockade. We tested the hypothesis that in patients with a VTE beta-blockade decreases FVIII and inhibits coagulation activation. 17 male patients with high FVIII (> 170 IU/dL, n = 7) or low FVIII (<150 IU/dL, n = 10) and a history of VTE received 40 mg of propranolol thrice daily for 14 days. FVIII and vasopressin levels were measured before and during propranolol intake and 28 days thereafter. At the same time points, haemostatic system activation was investigated by measuring prothrombin fragment f1.2 (f1.2) and thrombin antithrombin complexes (TAT) in venous blood and in blood emerging from a skin incision (shed blood). The mean FVIII level before propranolol was 192 IU/dL and 115 IU/dL in patients with high and low FVIII, respectively. During and 28 days after propranolol, no significant change in FVIII was seen in both groups. Changes in f1.2 and TAT were not detectable in either venous blood or in shed blood. beta-receptor blockade did not lower FVIII or inhibit haemostatic system activation in patients with VTE and persistently high FVIII. Administration of propranolol cannot be recommended as secondary thromboprophylaxis in patients with high FVIII.
Primary pulmonary hypertension (PPH) is a rare disorder, with marked in-situ thrombosis of small pulmonary vessels occurring primarily in adult women. We investigated whether differences in the ...plasmin- and thrombin activation system are associated with the predominate affection of females. Plasma levels of plasminogen activator inhibitor type 1 (PAI-1), tissue-type plasminogen activator (t-PA), fibrinogen, thrombin-antithrombin (TAT) complexes, and prothrombin fragments (F1.2) were measured at baseline and after standardized venous occlusion (VO) in patients with PPH (24 female, 9 male). At baseline, females showed significant higher TAT levels (p = 0.05), higher t-PA antigen levels (p = 0.01) and higher fibrinogen levels (p = 0.03) with positive correlation to mean pulmonary artery pressure (mPAP), as well as nonsignificant lower t-PA activity, higher PAI-1 antigen and activity and F1.2 levels. After VO, females showed a significantly blunted increase in t-PA antigen (p = 0.01) and t-PA activity (p = 0.001), correlating with mPAP, as well as increased PAI-1 activity (p = 0.05). We hypothesize, that the observed presence of gender differences in the plasmin- and thrombin activation system in PPH leading to an antifibrinolytic/prothrombotic state might, in part, explain the female predominant incidence of this disease.
Percutaneous coronary interventions with stent-based restorations of vessel patency have become the gold standard in the treatment of acute coronary states. Bioresorbable vascular scaffolds (BVS) ...have been designed to combine the efficiency of drug-eluting stents (DES) at the time of implantation and the advantages of a lack of foreign body afterwards. Complete resolution of the scaffold was intended to enable the restoration of vasomotor function and reduce the risk of device thrombosis. While early reports demonstrated superiority of BVS over DES, larger-scale application and longer observation exposed major concerns about their use, including lower radial strength and higher risk of thrombosis resulting in higher rate of major adverse cardiac events. Further focus on procedural details and research on the second generation of BVS with novel properties did not allow to unequivocally challenge position of DES. Nevertheless, BVS still have a chance to present superiority in distinctive indications. This review presents an outlook on the available first and second generation BVS and a summary of results of clinical trials on their use. It discusses explanations for unfavorable outcomes, proposed enhancement techniques and a potential niche for the use of BVS.
Abstract Introduction Current guidelines still recommend the bolus and infusion administration of glycoprotein IIbIIIa inhibitors in patients with high-risk acute coronary syndrome undergoing ...percutaneous coronary intervention. We sought to evaluate the extent of platelet inhibition by a blocking and bridging strategy with intracoronary abciximab bolus-only administration and oral loading of adenosine diphosphate receptor antagonists. Patients and methods Fifty-six consecutive high-risk acute coronary syndrome patients with bolus-only abciximab administration (0.25 mg/kg i.c.) and loading with 600 mg clopidogrel (55%) or 60 mg prasugrel (45%) were included in this study. Platelet aggregation induced by thrombin receptor-activating peptide and adenosine diphosphate was measured by multiple electrode aggregometry up to 7 days. Results Thrombin receptor-activating peptide induced platelet aggregation was significantly suppressed for a minimum of 48 h (45 ± 17 U) and returned to a normal range (> 84 U) after 6 days (90 ± 26 U; p < 0.001). Co-medication with prasugrel significantly reduced adenosine diphosphate-induced (p = 0.002) and thrombin receptor-activating peptide-induced (p = 0.02) platelet aggregation compared with clopidogrel throughout the observation period. No stent thrombosis or repeat myocardial infarction occurred at 30-day follow-up. Conclusions Immediate blocking of platelet aggregation in high-risk acute coronary syndrome patients by intracoronary abciximab bolus-only administration and bridging to prolonged inhibition via oral blockade of ADP receptors effectively inhibited overall platelet reactivity for at least 48 h, questioning the value of continuous abciximab infusion. Co-medication with prasugrel vs. clopidogrel synergistically augmented platelet inhibition.
Methods The INVEST (INdependent OCT registry on VEry late bioresorbable Scaffold Thrombosis) registry is an independent international consortium investigating patients with VLScT after BRS ...implantation who underwent optical coherence tomography (OCT) at the time of VLScT. The putative mechanisms underlying VLScT were in descending order scaffold discontinuity (with luminal protrusion) (42.1%), malapposition (18.4%), neoatherosclerosis (18.4%), underexpansion or scaffold shrinkage (10.5%), uncovered struts (5.3%), edge related disease progression (2%), and undetermined cause (2.6%).
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