Robert Petr

Clopidogrel pre-treatment in stable angina: for all patients >6 h before elective coronary angiography or only for angiographically selected patients a few minutes before PCI? A randomized multicentre trial PRAGUE-8

Aims To compare two different clopidogrel regimens on the outcomes of patients undergoing elective coronary angiography (CAG)±ad hoc percutaneous coronary intervention (PCI). Methods and results Open-trial randomized 1028 patients with stable angina to group A (‘non-selective’—clopidogrel 600 mg >6 h before CAG; n = 513) or group B (‘selective’—clopidogrel 600 mg in the cath-lab after CAG, only in case of PCI; n = 515). Combined primary endpoint was death/periprocedural myocardial infarction (MI)/stroke/re-intervention within 7 days. Secondary endpoints were troponin elevation and bleeding complications. Primary endpoint occurred in 0.8% group A patients vs. 1% group B (P = 0.749; 90% CI for the percentage difference −1.2–0.8). Periprocedural troponin elevation (>3× ULN) was detected in 2.6% group A vs. 3.3% group B (P = 0.475; 90% CI −2.5–1.0). Bleeding complications occurred in 3.5% group A patients vs. 1.4% group B (P = 0.025). After adjustment for covariates and factors that may influence the bleeding risk, patients in group A were shown to have more likely bleeding complications when compared with group B (OR = 3.03; 95% CI 1.14–8.10; P = 0.027). Conclusion High (600 mg) loading dose of clopidogrel before elective CAG increased the risk of minor bleeding complications, while the benefit on periprocedural infarction was not significant. Clopidogrel can be given safely in the catheterization laboratory between CAG and PCI in chronic stable angina patients.

Primary angioplasty in acute myocardial infarction with right bundle branch block: should new onset right bundle branch block be added to future guidelines as an indication for reperfusion therapy?

Aims The current guidelines recommend reperfusion therapy in acute myocardial infarction (AMI) with ST-segment elevation or left bundle branch block (LBBB). Surprisingly, the right bundle branch block (RBBB) is not listed as an indication for reperfusion therapy. This study analysed patients with AMI presenting with RBBB [with or without left anterior hemiblock (LAH) or left posterior hemiblock (LPH)] and compared them with those presenting with LBBB or with other electrocardiographic (ECG) patterns. The aim was to describe angiographic patterns and primary angioplasty use in AMI patients with RBBB. Methods and results A cohort of 6742 patients with AMI admitted to eight participating hospitals was analysed. Baseline clinical characteristics, ECG patterns, coronary angiographic, and echocardiographic data were correlated with the reperfusion therapies used and with in-hospital outcomes. Right bundle branch block was present in 6.3% of AMI patients: 2.8% had RBBB alone, 3.2% had RBBB + LAH, and 0.3% had RBBB + LPH. TIMI flow 0 in the infarct-related artery was present in 51.7% of RBBB patients vs. 39.4% of LBBB patients (P = 0.023). Primary percutaneous coronary intervention (PCI) was performed in 80.1% of RBBB patients vs. 68.3% of LBBB patients (P< 0.001). In-hospital mortality of RBBB patients was similar to LBBB (14.3 vs. 13.1%, P = 0.661). Patients with new or presumably new blocks had the highest (LBBB 15.8% and RBBB 15.4%) incidence of cardiogenic shock from all ECG subgroups. Percutaneous coronary intervention was done more frequently (84.8%) in patients with new or presumably new RBBB when compared with other patients with blocks (old RBBB 66.0%, old LBBB 62.3%, new or presumably new LBBB 73.0%). In-hospital mortality was highest (18.8%) among patients presenting with new or presumably new RBBB, followed by new or presumably new LBBB (13.2%), old LBBB (10.1%), and old RBBB (6.4%). Among 35 patients with acute left main coronary artery occlusion, 26% presented with RBBB (mostly with LAH) on the admission ECG. Conclusion Acute myocardial infarction with RBBB is frequently caused by the complete occlusion of the infarct-related artery and is more frequently treated with primary PCI when compared with AMI + LBBB. In-hospital mortality of patients with AMI and RBBB is highest from all ECG presentations of AMI. Restoration of coronary flow by primary PCI may lead to resolution of the conduction delay on the discharge ECG. Right bundle branch block should strongly be considered for listing in future guidelines as a standard indication for reperfusion therapy, in the same way as LBBB.

Factors influencing clopidogrel efficacy in patients with stable coronary artery disease undergoing elective percutaneous coronary intervention: statin's advantage and the smoking "paradox".

Purpose: The aim was to identify factors that influence the efficacy of 600 mg of clopidogrel pretreatment in patients with stable coronary artery disease undergoing elective percutaneous coronary intervention. Methods: In a laboratory substudy of the PRAGUE-8 trial, the influences of nonmodifiable (age and sex) and modifiable (body mass index and tobacco smoke) factors, comorbidity (hypertension, hyperlipidemia, diabetes mellitus, and renal insufficiency) and cotherapy (statin, aspirin, and heparin), on the course of clopidogrel efficacy were investigated in 105 patients pretreated with clopidogrel ≥6 hours before coronary angiography ± percutaneous coronary intervention. Flow cytometric analysis of the vasodilator-stimulated phosphoprotein phosphorylation state was used. Independent predictors that influenced clopidogrel action were identified using linear regression. Results: There was no correlation between baseline platelet reactivity index (PRI) and severity of coronary atherosclerosis; mean index of platelet reactivity for a nonsignificant lesion was 72% ± 5.98% and for a significant lesion 70.08% ± 8.43%. The highest proportion of low responders was patients with diabetes (50% at 28 hours). Among tobacco smokers, the response to clopidogrel occurred quickly and 80% of smokers had effective inhibition of PRI, 12 hours after drug use. After adjustments, tobacco smoking was an independent predictor for the most robust drop of PRI 12 hours after clopidogrel (P = 0.027). The magnitude of total decrease of PRI at 28 hours was not significantly influenced by cigarette smoking (P = 0.12). Linear regression showed that patients on statin therapy had a better response to clopidogrel than those without statins-the mean decrease of PRI at 28 hours was significantly higher (P = 0.02) among these patients (40.0 vs. 27.6). Conclusions: In stable coronary artery disease, no correlation exists between baseline PRI and the severity and extent of coronary atherosclerosis. A high loading dose of clopidogrel does not satisfactorily suppress enhanced PRI in patients with diabetes. Cigarette smoking is independently associated with a prompt antiplatelet response to clopidogrel. Ongoing statin therapy is an independent determinant of more effective clopidogrel-mediated inhibition of platelet reactivity.

Platelet glycoprotein GP VI 13254C allele is an independent risk factor of premature myocardial infarction

AIM The purpose of this study was to asses the impact of haemostatic and platelet receptor gene polymorphisms as an inherited risk factor for premature onset of myocardial infarction (MI). METHODS Polymorphisms of platelet receptors - GP Ia (807C>T, rs1126643), GP VI (13254T>C, rs1613662), GP IIIa (HPA-1, rs5918), PAR -1 (IVS -14A>T; rs168753), P2Y(12) (34C>T, rs6785930 and H1/H2 haplotype, rs2046934), and genetic variations of the gene coding for cyclooxygenase-1 (COX-1) ( -842A>G, rs10306114 and 50C>T, rs3842787) were investigated. Mutations in the genes coding for coagulation factor V (Q506R (Leiden) mutation, rs6025) and factor II (prothrombin G20210A, rs1799963) were also determined. The prevalence of gene polymorphisms was investigated in 105 consecutive patients with premature MI. This was compared with the same gene polymorphism prevalence in a group of 132 patients in which coronary artery disease had been excluded. Genotyping was done using PCR, followed by melting curve analysis with specific fluorescent hybridization probes. RESULTS A significant association between GP VI 13254C allele carriers and premature MI was found (p=0.025). No other differences in prevalence of the investigated polymorphisms between the compared patient populations reached statistical significance. In a logistic regression, which took other cardiovascular risk factors into account, the significance of the GP VI 13254C allele and vascular risk was suggested (OR 1.888, 95% C.I. 1.029 to 3.464, p=0.040). In a binary logistic regression the positive relationship between the GP VI genotype and female gender was observed (0R 3.676; 95% C.I. 1.159 to 11.628; p=0.027). The frequencies of GP VI and GP Ia gene polymorphisms were independent of one another (p=0.836). CONCLUSION The presence of the GP VI 13254C allele is an independent predictor of premature MI.

The Insufficiency of Left Anterior Oblique and the Usefulness of Right Anterior Oblique Projection for Correct Localization of a Computed Tomography-Verified Right Ventricular Lead Into the Midseptum

Background—The aim of the study was to verify the correct anchoring location for the tip of the right ventricular lead using cardiac computed tomography and to assess the best fluoroscopic and ECG criteria associated with the correct location of the electrode into the midseptum. Methods and Results—Patients indicated to pacemaker implantation were prospectively enrolled. The right ventricular lead was implanted into the midseptum according to standard criteria in left anterior oblique 40 view. The cardiac shadow on the right anterior oblique 30 was divided into 4 quadrants perpendicular to the lateral cardiac silhouette and the position of the lead tip was analyzed. The exact position of the lead tip was assessed using computed tomography. Of 51 patients, the right ventricular lead was anchored midseptum in 21 (41.2%; MS group). In 30 patients (58.8%; non-MS group), the lead was anchored in the adjacent anterior wall. The angle between the lead and horizontal axis on the left anterior oblique was similar in both groups. The non-MS group was associated with shorter distances between the tip and the cardiac contours in the right anterior oblique 30 (96.7% of leads in the non-MS group were in the outer quadrant versus 9.6% in the MS group; P<0.001). The presence of the lead in the middle or inferior quadrants was independently associated with correct midseptum placement with positive predictive value of 94.7%. Conclusions—Despite the optimal shape of the left anterior oblique, substantial numbers of leads were not anchored in the midseptum. Knowing the right anterior oblique 30 lead position can ensure proper midseptal placement.

Platelet gene polymorphisms and risk of bleeding in patients undergoing elective coronary angiography: A genetic substudy of the PRAGUE-8 trial

AIM Utilization of cardiac catheterization has increased dramatically over time. Bleeding is a major prognostic predictor after percutaneous coronary catheterization procedures. This study aimed to assess the impact of eight polymorphisms of genes encoding platelet receptors and enzymes on the risk of bleeding in patients undergoing elective coronary angiography (CAG). METHODS Polymorphisms of platelet receptors, GP Ia (807C>T, rs1126643), GP VI (13254T>C, rs1613662), GP IIIa (HPA-1, rs5918), PAR-1 (IVS-14A>T, rs168753), P2Y(12) (34C>T, rs6785930 and H1/H2 haplotype, rs2046934), and genetic variations of the gene coding for cyclooxygenase-1 (COX-1) (-842A>G, rs10306114 and 50C>T, rs3842787) were studied. The frequencies of gene polymorphisms carriers were investigated in 696 patients undergoing elective CAG because of suspected or proven stable coronary artery disease. Genotyping was done using PCR, followed by melting curve analysis with specific fluorescent hybridization probes. RESULTS In patients undergoing elective CAG (without ad hoc percutaneous coronary intervention (PCI) and without clopidogrel pretreatment) a significant association was found between bleeding risk and variations in the gene coding for COX-1 (-842A>G and 50C>T) (both p=0.013). Six other investigated polymorphisms did not show any influence on bleeding complications. After controlling for potential bleeding confounders, the association between COX-1 gene polymorphisms (-842A>G and 50C>T) and bleeding risk remained statistically significant (both odds ratios 12.1, p=0.012). CONCLUSION Cyclooxygenase-1 -842G and 50T alleles significantly contribute to the risk of bleeding complications in patients undergoing elective CAG. Genetic testing is able to influence the safety of diagnostic cardiac catheterization in large numbers of low risk patients with borderline indications.

The Insufficiency of Left Anterior Oblique and the Usefulness of Right Anterior Oblique Projection for Correct Localization of a CT-Verified Right Ventricular Lead into the Midseptum

Background—The aim of the study was to verify the correct anchoring location for the tip of the right ventricular lead using cardiac computed tomography and to assess the best fluoroscopic and ECG criteria associated with the correct location of the electrode into the midseptum. Methods and Results—Patients indicated to pacemaker implantation were prospectively enrolled. The right ventricular lead was implanted into the midseptum according to standard criteria in left anterior oblique 40 view. The cardiac shadow on the right anterior oblique 30 was divided into 4 quadrants perpendicular to the lateral cardiac silhouette and the position of the lead tip was analyzed. The exact position of the lead tip was assessed using computed tomography. Of 51 patients, the right ventricular lead was anchored midseptum in 21 (41.2%; MS group). In 30 patients (58.8%; non-MS group), the lead was anchored in the adjacent anterior wall. The angle between the lead and horizontal axis on the left anterior oblique was similar in both groups. The non-MS group was associated with shorter distances between the tip and the cardiac contours in the right anterior oblique 30 (96.7% of leads in the non-MS group were in the outer quadrant versus 9.6% in the MS group; P<0.001). The presence of the lead in the middle or inferior quadrants was independently associated with correct midseptum placement with positive predictive value of 94.7%. Conclusions—Despite the optimal shape of the left anterior oblique, substantial numbers of leads were not anchored in the midseptum. Knowing the right anterior oblique 30 lead position can ensure proper midseptal placement.

Electrophysiological findings after surgical thoracoscopic atrial fibrillation ablation

BACKGROUND Hybrid ablation (a combination of thoracoscopic epicardial ablation and catheter ablation) has become a new technique for atrial fibrillation treatment. OBJECTIVE The goal of this study was to evaluate the success and electrophysiological follow-up after using the COBRA Fusion device to deliver a circumferential lesion set anterior to the pulmonary veins in an attempt to isolate the posterior left atrium (box isolation). METHODS Surgical ablation was carried out via a thoracoscopic approach using the COBRA Fusion radiofrequency catheter. An electrophysiology study was done 2-3 months later to verify box isolation (and to complete it, if needed) and to perform right-sided isthmus ablation. Fat thickness along the presumed box lesion line was measured using preprocedural computed tomography. RESULTS Thirty patients (mean age 60.0 ± 11.6 years; 22 men; 8 with long-standing persistent AF and 22 with persistent atrial fibrillation) were enrolled. The duration of the EP study was 216.3 ± 64.2 minutes. Box isolation, based on the EP study, was complete in 12 patients (40%) and incomplete in 18 patients (60%). Successful box isolation was achieved with catheter ablation in 16 of 18 patients (89%). A total of 39 gaps in these 16 patients were identified. Typical gap locations were the anterior-superior part of the superior pulmonary veins and the roofline. Fat thickness along the roofline was substantially higher than that along the inferior line (4.58 ± 1.61 mm vs 2.37 ± 0.76 mm; P < .001). CONCLUSION There is a relatively low rate of complete isolation using the COBRA catheter ablation system. The superior line and anterior parts of superior pulmonary veins have most conduction gaps.

Optimal pretreatment timing for high load dosing (600 mg) of clopidogrel before planned percutaneous coronary intervention for maximal antiplatelet effectiveness

BACKGROUND The optimal timing for 600 mg clopidogrel pre-treatment before planned PCI in patients with stable coronary artery disease has never been tested in a randomized trial. METHODS The time course of platelet inhibition was investigated in 105 patients pre-treated with clopidogrel ≥ 6 h before the planned procedure. Flow cytometric analysis of the vasodilator stimulated phosphoprotein (VASP) phosphorylation state was done and a Platelet Reactivity Index (PRI) was calculated prior to treatment (baseline) and at 12, 28, 36, 60, 84 and 108 h after the clopidogrel loading dose administration. RESULTS The maximal inhibition of platelet activation was seen at 28 h post administration (PRI mean 36 ± 23%), and 2/3 of patients had PRI value <50%. At 12 h 47% of patients had PRI value ≥ 50% (mean 45±21%). 600 mg of clopidogrel significantly suppressed platelet activation for 4 days. A correlation was between baseline PRI and its values by 28 h (r(S)=0.48, p<0.001), between 12 h-28 h the correlation was strong (r(S)=0.77, p<0.001). CONCLUSION The time curve of clopidogrel efficacy was dependent on baseline platelet reactivity. Among stable CAD patients, pre-treatment with 600 mg of clopidogrel resulted in maximal antiplatelet efficacy 1 day after drug administration.

One-Year Clinical and Computed Tomography Angiographic Outcomes After Bioresorbable Vascular Scaffold Implantation During Primary Percutaneous Coronary Intervention for ST-Segment–Elevation Myocardial Infarction: The PRAGUE-19 Study

Background—Bioresorbable vascular scaffolds (BVS) represent promising new technology, but data on their long-term outcomes in ST-segment–elevation myocardial infarction (STEMI) setting are missing. The aim was to analyze 1-year clinical and computed tomographic angiographic outcomes after BVS implantation in STEMI. Methods and Results—PRAGUE-19 is a prospective multicenter single-arm study enrolling consecutive STEMI patients undergoing primary percutaneous coronary intervention (pPCI) with intention-to-implant BVS. A total of 343 STEMI patients were screened during 15 months enrollment period, and 70 patients (mean age 58.6±10.3 and 74% males) fulfilled entry criteria and BVS was successfully implanted in 96% of them. All patients were invited for clinical and computed tomographic angiographic control 1 year after BVS implantation. Restenosis was defined as ≥75% area stenosis within the scaffolded segment. Three events were potentially related to BVS: 1 in-stent restenosis (treated 7 months after pPCI with drug-eluting balloon), 1 stent thrombosis (treated 2 weeks after pPCI by balloon dilatation—this patient stopped all medications after pPCI), and 1 sudden death at home 9 months after pPCI. Four other patients had events definitely unrelated to BVS. Overall, 1-year mortality was 2.9%. Computed tomographic angiography after 1 year was performed in 59 patients. All BVS were widely patent, and binary restenosis rate was 2% (the only restenosis mentioned above). Mean in-scaffold minimal luminal area was 7.8±2.6 mm2, area stenosis was 20.1±16.3%, minimal luminal diameter was 3.0±0.6 mm, and diameter stenosis was 12.8±11.1%. Conclusions—BVS implantation in STEMI is feasible and safe and offers excellent 1-year clinical and angiographic outcomes.