Martin Malý

Bioresorbable vascular scaffolds in acute ST-segment elevation myocardial infarction: a prospective multicentre study ‘Prague 19’

Aims Bioresorbable vascular scaffolds (BVSs) have been studied in chronic coronary artery disease, but not in acute ST-segment elevation myocardial infarction (STEMI). This prospective multicentre study analysed the feasibility and safety of BVS implantation during primary percutaneous coronary intervention (p-PCI) in STEMI. Methods and results Bioresorbable vascular scaffold implantation became the default strategy for all consecutive STEMI patients between 15 December 2012 and 30 August 2013. A total of 142 patients underwent p-PCI; 41 of them (28.9%) fulfilled the inclusion/exclusion criteria for BVS implantation. The BVS device success was 98%, thrombolysis in myocardial infarction 3 flow was restored in 95% of patients, and acute scaffold recoil was 9.7%. An optical coherence tomography (OCT) substudy (21 patients) demonstrated excellent procedural results with only a 1.1% rate of scaffold strut malapposition. Edge dissections were present in a 38% of patients, but were small and clinically silent. Reference vessel diameter measured by quantitative coronary angiography was significantly lower than that measured by OCT by 0.29 (±0.56) mm, P = 0.028. Clinical outcomes were compared between BVS group and Control group; the latter was formed by patients who had implanted metallic stent and were in Killip Class I or II. Combined clinical endpoint was defined as death, myocardial infarction, or target vessel revascularization. Event-free survival was the same in both groups; 95% for BVS and 93% for Control group, P = 0.674. Conclusion Bioresorbable vascular scaffold implantation in acute STEMI is feasible and safe. The procedural results evaluated by angiography and OCT are excellent. The early clinical results are encouraging.

Effect of two-day atorvastatin pretreatment on the incidence of periprocedural myocardial infarction following elective percutaneous coronary intervention: a single-center, prospective, and randomized study.

Both randomized and observational studies have suggested that pretreatment with statins may reduce the incidence of periprocedural myocardial infarction (PMI) in patients with stable angina during elective percutaneous coronary intervention (PCI). The purpose of this randomized study (Clinical Trial Registration No. NCT00469326) was to investigate the effect of 2-day atorvastatin therapy on the incidence of PMI in patients with stable angina pectoris undergoing elective PCI. A total of 200 patients with stable angina pectoris who were not taking statins and who had been referred for PCI were enrolled and randomized (ratio 1:1) to a 2-day pretreatment regimen with atorvastatin 80 mg/day and subsequent PCI or immediate PCI. The serum concentration of creatine kinase-MB mass and troponin I were measured before and 16 to 24 hours after PCI. The incidence of PMI was assessed using established criteria. Of the patients, 10% in the atorvastatin group and 12% in the control group had a postprocedural creatine kinase-MB mass elevation > or =3 times the upper limit of normal (p = 0.65). The incidence of PMI as determined by the postinterventional release of troponin I > or =3 times the upper limit of normal was 17% in the atorvastatin group and 16% in the control group (p = 0.85). The median creatine kinase-MB mass peak after PCI was 1.46 ng/ml (interquartile range 0.83 to 2.52) in the atorvastatin group and 1.40 ng/ml (interquartile range 0.90 to 2.54) in the control group (p = 0.70). The median peak troponin I level after PCI was 0.100 ng/ml (0.096 to 0.385) in the atorvastatin group and 0.100 ng/ml (0.60 to 0.262) in the control group (p = 0.54). On multivariate analysis, the only independent predictor of PMI was patient age (odds ratio 1.09, 95% confidence interval 1.025 to 1.159, p = 0.006). In conclusion, in the present study 2-day pre-PCI therapy with atorvastatin did not reduce the occurrence of PMI in patients with stable angina pectoris undergoing elective PCI.

Antioxidants change platelet responses to various stimulating events

The role of platelets in hemostasis may be influenced by alteration of the platelet redox state-the presence of antioxidants and the formation of reactive oxygen and nitrogen species. We investigated the effects of two antioxidants, resveratrol and trolox, on platelet activation. Trolox and resveratrol inhibited aggregation of washed platelets and platelet-rich plasma activated by ADP, collagen, and thrombin receptor-activating peptide. Resveratrol was a more effective agent in reducing platelet static and dynamic adhesion in comparison with trolox. The antioxidant capacity of resveratrol was, however, the same as that of trolox. After incubation of platelets with antioxidants, the resveratrol intraplatelet concentration was about five times lower than the intracellular concentration of trolox. Although both antioxidants comparably lowered hydroxyl radical and malondialdehyde production in platelets stimulated with collagen, TxB(2) levels were decreased by resveratrol much more effectively than by trolox. Cyclooxygenase 1 was inhibited by resveratrol and not by trolox. Our data indicate that antioxidants, apart from nonspecific redox or radical-quenching mechanisms, inhibit platelet activation also by specific interaction with target proteins. The results also show the importance of studying platelet activation under conditions of real blood flow in contact with reactive surfaces, e.g., using dynamic adhesion experiments.

Plasma proteome changes in cardiovascular disease patients: novel isoforms of apolipoprotein A1

BackgroundThe aim of this proteomic study was to look for changes taking place in plasma proteomes of patients with acute myocardial infarction (AMI), unstable angina pectoris (UAP), and stable angina pectoris (SAP).MethodsDepleted plasma proteins were separated by 2D SDS-PAGE (pI 4-7), and proteomes were compared using Progenesis SameSpots statistical software. Proteins were identified by nanoLC-MS/MS. Proteins were quantified using commercial kits. Apolipoprotein A1 was studied using 1D and 2D SDS-PAGE, together with western blotting.ResultsReciprocal comparison revealed 46 unique, significantly different spots; proteins in 34 spots were successfully identified and corresponded to 38 different proteins. Discrete comparisons of patient groups showed 45, 41, and 8 significantly different spots when AMI, UAP, and SAP were compared with the control group. On the basis of our proteomic data, plasma levels of two of them, alpha-1 microglobulin and vitamin D-binding protein, were determined. The data, however, failed to prove the proteins to be suitable markers or risk factors in the studied groups. The plasma level and isoform representation of apolipoprotein A1 were also estimated. Using 1D and 2D SDS-PAGE, together with western blotting, we observed extra high-molecular weight apolipoprotein A1 fractions presented only in the patient groups, indicating that the novel high-molecular weight isoforms of apolipoprotein A1 may be potential new markers or possible risk factors of cardiovascular disease.ConclusionThe reported data show plasma proteome changes in patients with AMI, UAP, and SAP. We propose some apolipoprotein A1 fractions as a possible new disease-associated marker of cardiovascular disorders.

Feasibility, safety, and early outcomes of direct carotid artery stent implantation with use of the FilterWire EZ™ Embolic Protection System†

To report on early outcomes of prospective single‐center registry, which evaluated feasibility, safety, and effectiveness of direct carotid stenting using FilterWire EZ™ Embolic Protection System in high‐risk patients.

Effect of Two-Day Atorvastatin Pretreatment on Long-Term Outcome of Patients With Stable Angina Pectoris Undergoing Elective Percutaneous Coronary Intervention

Several randomized studies and meta-analyses have suggested that pretreatment with statins may decrease periprocedural myocardial infarction (MI) in patients undergoing percutaneous coronary intervention (PCI). The purpose of this randomized study was to investigate the effect of a 2-day atorvastatin therapy before PCI on long-term clinical outcome. Two hundred statin-naive patients with stable angina pectoris referred for PCI were enrolled and randomized (ratio 1:1) to 2-day pretreatment with atorvastatin 80 mg/day and subsequent PCI (atorvastatin group), or immediate PCI (control group). The registry group comprised 182 consecutive patients on long-term statin therapy referred for immediate PCI during the same period as randomized patients. We compared the first occurrence of MI or death during long-term follow-up. There were no significant differences in most clinical characteristics and early results among the 3 groups. Median follow-up was 45 months (1 to 59). Incidences of death/MI were 11.4%, 12.9%, and 13.8% in the atorvastatin, control, and registry groups, respectively. In the same groups, age-adjusted estimated 4-year freedom from death/MI was 0.78 versus 0.75 versus 0.80, respectively (p=0.882, log-rank test). In multivariate analysis, only age of patients (odds ratio 1.04, 95% confidence interval 1.02 to 1.07, p<0.001) was identified as a significant predictor of death or MI during follow-up. In conclusion, these results suggest that 2-day therapy with high-dose atorvastatin before PCI did not influence occurrence of periprocedural MI or long-term clinical outcomes.

Effect of seven-day atorvastatin pretreatment on the incidence of periprocedural myocardial infarction following percutaneous coronary intervention in patients receiving long-term statin therapy. A randomized study☆

BACKGROUND The aim of this randomized study was to investigate the effect of seven-day high-dose atorvastatin therapy on the incidence of peri-procedural myocardial infarction (PMI) in patients receiving long-term statin therapy. METHODS The patients with stable angina receiving statin therapy and referred for percutaneous coronary intervention (PCI) were randomized (ratio 1:1) to a 7-day pre-treatment with atorvastatin of 80 mg daily and subsequent PCI (Atorvastatin group), or immediate PCI (Control group). The incidence of PMI was based on serum concentration of creatine kinase myocardial band (CK-MB) mass and troponin I (TnI), which were measured prior to and between 16 and 24h post PCI. The values were considered as positive if they were elevated ≥ 3 times the upper limit normal. RESULTS We randomized 202 patients (male 67%, 65.5 ± 9.2 years; 100 vs. 102 pts.). There were no significant differences in the baseline characteristics among the randomized groups. The incidence of PMI, based on post-interventional release of TnI and/or CK-MB mass was 15% in the Atorvastatin group vs. 14% in the Control group (p=0.80). One patient (3%) in Atorvastatin group suffered from MI between randomization and PCI. CONCLUSIONS These results suggest that 7-day pre-PCI therapy with high-dose atorvastatin did not reduce the occurrence of PMI in patients receiving chronic statin therapy.

Two novel fibrinogen variants in the C-terminus of the Bβ-chain: fibrinogen Rokycany and fibrinogen Znojmo

Hereditary dysfibrinogenemia is a rare disorder wherein an inherited abnormality in fibrinogen structure may result in defective fibrin function and/or structure. Congenital hypofibrinogenemia is a rare autosomal bleeding disorder, either recessive or dominant, characterized by a low fibrinogen plasma level. A 28-year-old asymptomatic woman (fibrinogen Rokycany) and a 54-year-old man with thrombosis and pulmonary embolism (fibrinogen Znojmo) were investigated for a suspected fibrinogen mutation after abnormal coagulation tests results were obtained. DNA sequencing showed the heterozygous point mutation Bβ Asn351Lys in fibrinogen Rokycany and the heterozygous point mutation Bβ Arg237Ser in fibrinogen Znojmo, respectively. The kinetics of fibrinopeptide release was found to be normal in both cases. Fibrinolysis was impaired in the Znojmo variant. The average fibril diameters of Znojmo fibrin was slightly increased, but not differing significantly from normal; formed by less fibrils with abrupt fibril terminations. Rheological studies revealed a softer clot. Rokycany fibrin was formed by significantly narrower fibrils than normal fibrin; and the clot was denser than the control clot. Rheological studies revealed a stiffer clot. Impaired fibrinolysis and abnormal clot morphology may be the cause of thrombotic episodes in the patient with Znojmo mutation. New cases of hypofibrinogenemia and dysfibrinogenemia, found by routine coagulation testing, were genetically identified as a novel fibrinogen variants Bβ Asn351Lys (fibrinogen Rokycany) and Bβ Arg237Ser (fibrinogen Znojmo), respectively.

Long-term follow-up after bioresorbable vascular scaffold implantation in STEMI patients: PRAGUE-19 study update.

AIMS Early clinical results after implantation of bioresorbable vascular scaffolds (BVS) in ST-elevation myocardial infarction (STEMI) are encouraging, but long-term data are missing. This study evaluates long-term outcome in STEMI patients with implanted BVS. METHODS AND RESULTS The PRAGUE-19 study is an academic study enrolling consecutive STEMI patients with the intention to implant BVS. A total of 580 STEMI patients were screened between December 2012 and March 2015; 117 patients fulfilled entry criteria and BVS was successfully implanted in 114 (97%) of them. The primary combined clinical endpoint (death, reinfarction or target vessel revascularisation) occurred in 11.5% during the mean follow-up period of 730±275 days with overall mortality of 4.4%. Definite scaffold thrombosis occurred in two patients in the early phase after BVS implantation; there was no late thrombosis. Quantitative coronary angiography (10 patients) at three years demonstrated late lumen loss of 0.2±0.33 mm and optical coherence tomography showed minimal lumen area of 5.3±1.37 mm2 and neointimal hyperplasia area of 2.9±0.48 mm2. BVS struts were still visible at three years and 99.4% of them were well apposed and covered. CONCLUSIONS Encouraging clinical and imaging results after BVS implantation in STEMI patients persist during long-term follow-up.

Influence of concomitant heparin administration on pregnancy-associated plasma protein-A levels in acute coronary syndrome with ST segment elevation.

Introduction The time course of pregnancy-associated plasma protein-A (PAPP-A) levels was studied at admission, immediately after percutaneous coronary intervention (PCI) and 1, 2, 4, 6, 12, 24 and 48 h after PCI in acute coronary syndrome with ST segment elevation (ACS-STE) to determine the impact of PCI, concomitant clinical complications and heparin administration. Material and methods Pregnancy-associated plasma protein-A serum levels, examined by the KryptorTM system, were studied in 30 heparinized PCI ACS-STE patients, in 10 elective PCIs and 12 coronary angiographies with heparin, and in 5 patients with normal coronary angiogram without heparin. Results Heparin caused a high PAPP-A increase in ACS-STE patients, in all patients with heparin without ACS and angiographic signs of significant atherosclerosis. This increase was directly associated with heparin dosage and activated clotting time (ACT) (r = 0.71, p = 0.0001) and inversely with the interval between heparin applications and time of serum sampling. It was followed by a rapid decrease within 1 to 2 h and return to normal levels in 10 to 12 h. In ACS-STE patients the decrease was significantly slower than in heparinized elective PCI and angiography patients. The PAPP-A increase was not significantly dependent on the length of PCI. Persistent increase after 24 h was associated in 4/7 patients with concomitant clinical complications. Conclusions The diagnostic validity of PAPP-A can be verified only within the 1st h after clinical onset of ACS before heparin administration, the prognostic value in heparinized patients not earlier than 12 h after the last heparin application, if ACT is normal and serious clinical concomitant complications are eliminated.