Radek Pudil

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.

Cytokines and adhesion molecules in the course of acute myocardial infarction

The plasma levels of interleukin 1 beta (IL 1beta), interleukin 6 (IL 6), interleukin 8 (IL 8), tumor necrosis factor alpha (TNF-alpha), E-selectin, ICAM 1 and C-reactive protein (CRP) have been studied in 24 patients with acute myocardial infarction in the course of 96 h. The plasma IL 1beta and IL 6 levels were continually elevated during the 96 h study period (the peak of plasma IL 1beta level was 22.2 pg/ml, S.D. 8.6, P < 0.001, normal values of IL 1beta are less than 10 pg/ml, the mean peak plasma concentration of IL 6 was 184.9 pg/ml, S.D. 134.7, vs. normal values of 15.57 pg/ml, S.D. 2.4, P < 0.001). The mean plasma IL 8 level was increased for the duration of the study, the mean plasma IL 8 level was 103.0 pg/ml, S.D. 23.4 (normal value was below 30 pg/l, S.D. 8.0) P < 0.001. The plasma TNF-alpha level was elevated throughout the time of observation without any significant peak. The mean plasma TNF-alpha concentration was 46.8 pg/ml, S.D. 2.13, vs. normal value 4.35 pg/ml, S.D. 1.23, P < 0.001. The plasma E-selectin level reached the mean level of 145.1 ng/ml, S.D. 75.4, vs. normal value 29.1-63.4 ng/ml, P < 0.001 at an interval of 15-42 h after the onset of the symptoms. The plasma ICAM 1 level showed only a slight significant increase during the first 36 h. The plasma CRP concentration increased later than IL 6, and reached a peak at 42 h after the onset of the symptoms (69.2 mg/l, S.D. 29.9, vs. 1.2 mg/l, S.D. 4.7, P < 0.0001). We conclude that cytokines and adhesion molecules can play an important role in the mechanisms of tissue injury in the process of ischemia and reperfusion.

The prognostic significance of intermediate QRS prolongation in acute myocardial infarction

Complete right and left bundle branch block and advanced atrioventricular block present on admission electrocardiograms of patients with acute myocardial infarction, are associated with poor short and long-term outcome. Little is known about the impact of intermediate QRS prolongation (0.09-0.11 s) on the prognosis of acute myocardial infarction. In this study, among 1100 consecutive patients with acute myocardial infarction treated with thrombolysis, the QRS duration on admission electrocardiogram was <0.09 s in 536 (48%) patients, between 0.09 and 0.11 s in 496 (45%) patients and >0.11 s in 78 (7%) patients. QRS duration was strongly associated with 7-day (0.6%, 6%,18%, P<0.001), 30-day (1%, 8%, 22%, P<0.001) and 1-year (3%, 11%, 26%, P<0.001) all-cause mortality. After adjustment for significant variables associated with 1-year mortality, including age, female gender, diabetes mellitus, systemic hypertension, previous myocardial infarction, anterior myocardial infarction and Killip class> or =2 on admission, both levels of QRS prolongation remained significant independent predictors of short and long-term all-cause mortality.

Routine upfront abciximab versus standard periprocedural therapy in patients undergoing primary percutaneous coronary intervention for cardiogenic shock: The PRAGUE-7 Study. An open randomized multicentre study

Background: The outcome of acute myocardial infarction (AMI) complicated with cardiogenic shock is poor. The aim of this study was to analyse, whether upfront abciximab administration could improve the outcomes of cardiogenic shock. Methods: This multicentre open trial randomized 80 patients with AMI complicated by cardiogenic shock expected to undergo primary PCI into group A (routine upfront—pre-procedural—abciximab bolus followed by 12-h abciximab infusion) and group B (standard therapy). The study primary objective was 30-day combined outcome (death/reinfarction/stroke/new severe renal failure). Results: PCI was technically successful in 90% (A) versus 87.5% (B) patients. Abciximab was used in 100% (A) versus 35% (B). The primary endpoint occurred in 17 group A patients (42.5%) and 11 group B patients (27.5%, P = 0.24). Ejection fraction among survivors after 30 days was 44 ± 11% (A) versus 41 ± 12% (B, P = 0.205). Major bleeding occurred in 17.5% (A) versus 7.5% (B, P = 0.310). No differences (A versus B) were found in TIMI-flow and MBG after PCI. Conclusions: This study did not show any benefit from routine pre-procedural abciximab when compared with a selective abciximab use during the intervention in patients with cardiogenic shock undergoing primary PCI. However, small sample size of the trial preclude any definitive conclusion, a larger prospective, randomized, multicentered trial is needed.

Cardiac troponin I seems to be superior to cardiac troponin T in the early detection of cardiac injury associated with anthracycline treatment.

Accessible online at: www.karger.com/onk Fax +49 761 4 52 07 14 Information@Karger.de www.karger.com liver and renal function during the study. Cardiac evaluation was performed at baseline (before CT), the day after the first CT with anthracyclines (mean cumulative dose 135.8 ± 28.5 mg/m2, median 150), the day after the last CT with anthracyclines (mean cumulative dose 472.1 ± 115.0 mg/m2, median 423), and approximately 6 months after completion of CT. Concentrations of cardiac troponins diagnostic for cardiotoxicity of oncology treatment have not yet been established. In our study, values above the reference range recommended by the manufacturer were considered elevated. The cut-off value for cTnT was 0.01 μg/l (Roche Diagnostics), and for cTnI 0.40 μg/l (Randox Laboratories Ltd.). Echocardiographic evaluation was performed on a Hewlett Packard Image Point machine by an experienced echocardiographer who was blinded to the cardiac troponin data. Parameters of systolic and diastolic left ventricular (LV) function were assessed. Systolic LV dysfunction was defined as LV ejection fraction (LVEF) ≤ 55%. Diastolic LV dysfunction was defined as E/A inversion and a E wave deceleration time above 220 ms on the transmitral Doppler curve (impaired relaxation). Statistical analysis was performed with Statistica for Windows, version 5.0 (StatSoft, Tulsa, OK, USA). Analysis of variance test was used. Correlations were evaluated with normal and Spearman correlation tests. The values are expressed as mean ± standard deviation (SD). Probability values (p) of < 0.01 were considered statistically significant. The results are summarized in table 1. Of the cardiac troponins, only cTnI became positive on the days after the first and last CT with anthracyclines, which was observed in a total of 4 (17.4%) patients. Positivity of cTnI correlated with systolic and diastolic LV dysfunction on echocardiography: r = 0.712; p < 0.00001 and r = 0.591; p < 0.0001, Cardiac toxicity is among the undesirable side effects of oncology treatment. Of the cytostatics, anthracyclines represent the greatest risk for development of cardiotoxicity [1]. Various methods have been recommended for monitoring cardiotoxicity in oncology [2, 3]. Echocardiography and electrocardiography are routinely used, and recently, the applicability of cardiac troponins in the detection of cancer therapy-induced cardiotoxicity has been investigated [4]. In some studies, administration of anthracyclines did not cause any elevation of cardiac troponins [5–7]. In other studies, cardiac troponins became positive after anthracycline treatment, correlated with disease severity, and were suggested as predictors of subsequent major cardiac events during follow-up [8–10]. The results of clinical studies are inconsistent, and cardiac troponins have not been established in clinical practice for monitoring cardiotoxicity in oncology. The aim of our study was to evaluate acute and chronic cardiotoxicity of anthracyclines with cardiac troponins. We used current immunoassays for cardiac troponin T (cTnT; Roche Diagnostics, Mannheim, Germany) and cardiac troponin I (cTnI; Randox Laboratories Ltd., Crumlin, Co. Antrim, UK), and correlated the results with echocardiography findings. A total of 23 patients (mean age 47.0 ± 11.1 years; 14 males, 9 females) with acute leukemia were studied. The patients were treated with 3–6 cycles of conventional chemotherapy (CT) containing anthracyclines at a total cumulative dose of 472.1 ± 115.0 mg/m2; to calculate the total cumulative anthracycline dose, we applied conversion factors derived from the maximum recommended cumulative doses for the individual agents used (idarubicin, daunorubicin, mitoxantrone). Six patients were treated for arterial hypertension; other patients had no history of cardiovascular disease. All patients had normal Cardiac Troponin I Seems to Be Superior to Cardiac Troponin T in the Early Detection of Cardiac Injury Associated with Anthracycline Treatment

Use of the biochip microarray system in detection of myocardial injury caused by radiofrequency catheter ablation.

Abstract Background: In a prospective study, we measured plasma markers of myocardial damage induced by radiofrequency catheter ablation (RFA) with the protein biochip microarray system. Methods: A total of 32 consecutive patients undergoing RFA for atrioventricular nodal re-entry tachycardia (AVNRT), right atrial flutter (AFL) and atrial fibrillation (AF) were included in the study. Cardiac troponin I (cTnI), creatine kinase isoenzyme MB (CK-MB), heart-type fatty acid binding protein (hFABP) and glycogen phosphorylase BB (GPBB) were measured using biochip array technology at baseline and 24 h after the procedure. Results: Values for all markers increased 24 h after RFA (cTnI: 0.92±0.49 μg/L vs. 0.33±0.06 μg/L, p<0.001; CK-MB: 3.79±2.04 μg/L vs. 1.85±0.55 μg/L, p<0.001; hFABP: 2.82±0.95 μg/L vs. 2.00±0.95 μg/L, p<0.001; GPBB: 9.07±5.83 μg/L vs. 4.70±2.50 μg/L, p<0.001). The correlations between plasma marker levels and RFA time were cTnI: r=0.63, p<0.01; CK-MB: r=0.75, p<0.01; hFABP: r=0.55, p<0.05, GPBB: r=0.51, p<0.05; the correlation between RFA time and number of RF applications was significant (r=0.81, p<0.001). Patients with RFA due to AF or flutter had elevated cTnI, CK-MB and hFABP levels compared to patients with AVNRT (cTnI: 1.14± 0.49 μg/L vs. 0.59±0.25 μg/L, p<0.05; CK-MB: 4.46± 2.07 μg/L vs. 2.81±1.54 μg/L, p<0.05; hFABP: 3.21± 0.98 μg/L vs. 2.25±0.54 μg/L, p<0.01). Conclusions: Myocardial injury induced by RFA can be detected by cTnI, CK-MB, hFABP and GPBB. Plasma cTnI, CK-MB and hFABP levels significantly increased in patients with AFL and AF compared to patients with AVNRT. The increase of cTnI, CK-MB and GPBB levels correlates with the total duration of RFA. Clin Chem Lab Med 2008;46:1726–8.

High-sensitivity troponin T as a marker of myocardial injury after radiofrequency catheter ablation.

Background The aim of our study was to monitor radiofrequency catheter ablation-induced myocardial damage by measuring high-sensitivity cardiac troponin T (hs-cTnT). Methods Serum concentrations of hs-cTnT (Elecsys 2010 system, Roche) were measured in 73 healthy blood donors and serially in 27 patients who had samples taken both before and 24 h after radiofrequency ablation (RFA) for atrioventricular nodal re-entry tachycardia (AVNRT), atrial fibrillation (AF) or right atrial flutter (AFL). Results Significant increases of hs-cTnT were seen in patients after RFA (AVNRT: P = 0.0115, AF: P = 0.0011, AFL: P = 0.0009). Postprocedural serum hs-cTnT correlated with the number of radiofrequency applications and with the duration of RFA procedure. Spearmans coefficient of rank correlation (r) were as follows: hs-cTnT versus RFA duration: r = 0.771 (P < 0.001); hs-cTnT versus number of pulses: r = 0.708 (P < 0.001). Patients with the diagnosis of AVNRT had lower serum hs-cTnT concentration after RFA compared with AFL (P < 0.0001) and AF (P < 0.0001) patients. Conclusions Our data indicate that RFA causes a significant increase of serum hs-cTnT concentration that could be used to monitor myocardial injury.

PLASMA INTERLEUKIN-6 LEVEL IS ASSOCIATED WITH NT-PROBNP LEVEL AND PREDICTS SHORT- AND LONG TERM MORTALITY IN PATIENTS WITH ACUTE HEART FAILURE

OBJECTIVES Interleukin 6 plays an important role in chronic heart failure (HF), but little is known about its involvement in acute decompensated heart failure (ADHF). The aim of our study is to evaluate the prognostic role of interleukin 6 (IL-6) in the patients with ADHF. METHODS Plasma levels of interleukin IL-6, N-terminal pro brain natriuretic peptide levels, and clinical covariates were measured in 92 patients with ADHF. Survival was followed up to 12 months, and prognostic factors were evaluated. RESULTS Elevated plasma IL-6 levels were increased in nonsurvivors and were associated with 1-year mortality (p < 0.01). Plasma IL-6 levels were associated with plasma NT-proBNP levels. In multivariate analysis, increased plasma IL-6 and NT-proBNP levels remained strong independent predictors of 1-year mortality. CONCLUSIONS Plasma IL-6 levels provide important prognostic information in the patients with ADHF. Measurement combining plasma IL-6 and NT-proBNP should serve as a powerful prognostic tool of multimarker strategy in patients with acute decompensated heart failure.

Application of the DETECT algorithm for detection of risk of pulmonary arterial hypertension in systemic sclerosis: data from a Czech tertiary centre

OBJECTIVE The early, simple and reliable detection of pulmonary arterial hypertension (PAH) in SSc (DETECT) study described a new algorithm for early detection of PAH in patients with SSc. The aim of this retrospective, single-centre, cross-sectional study was to apply a modified DETECT calculator in patients with SSc in the East Bohemian region, Czech Republic, to assess the risk of PAH and to compare these results with PAH screening based on the European Society of Cardiology/European Respiratory Society (ESC/ERS) 2009 guidelines. METHODS Sixty patients were recruited with a diagnosis of SSc (according to ACR criteria), aged 27-78 years. A modified DETECT algorithm using the modified parameter of (1.4 × right ventricle diameter)(2) in place of right atrium area was applied to all patients. Right heart catheterization (RHC) was performed in all patients with an estimated (by echocardiography) increased systolic pulmonary artery pressure ≥50 mm Hg in accordance with the ESC/ERS guidelines; however, RHC was not performed in patients solely recommended for RHC using the modified DETECT algorithm. RESULTS Using the modified DETECT calculator, 24/58 (41.4%) patients were recommended for RHC, compared with 14/58 (24.1%) when applying the ESC/ERS 2009 guidelines. PAH was diagnosed in 7/58 (12.1%) patients. During follow-up, PAH was diagnosed in six patients. Of these, four were modified DETECT score-positive for 2 years and all for 1 year before PAH diagnosis. CONCLUSION The modified DETECT algorithm detects all patients with PAH diagnosed according to ECS/ERS 2009 guidelines and RHC. Data of the 2-year follow-up indicate a possible positive predictive role for the modified DETECT calculator.

Biomarkers for the early detection of anthracycline-induced cardiotoxicity: current status

BACKGROUND Cardiotoxicity is a well-known and potentially serious complication of anticancer therapy. Anthracycline-based chemotherapy represents the greatest risk. Early detection of cardiotoxicity is crucial for applying preventive and supportive therapeutic strategies. METHODS AND RESULTS Various methods have been recommended for monitoring of cardiotoxicity. In our conditions, echocardiography and electrocardiography are routinely used. However, this approach shows low sensitivity for the early prediction of cardiomyopathy when the possibilities of appropriate management could still improve the patients outcome. Recently, biomarkers of cardiac injury have been investigated in the assessment of chemotherapy-induced cardiotoxicity. Cardiospecific biomarkers, such as cardiac troponins, show high diagnostic efficacy in the early subclinical phase of the disease before the clinical onset of cardiomyopathy. Increase in their concentrations correlates with disease severity. As for natriuretic peptides, some studies, including ours, have shown promising results. Definitive evidence of their diagnostic and prognostic role in this context is still lacking and natriuretic peptides have not been routinely used for monitoring of cardiotoxicity in clinical practice. Other perspective biomarkers of cardiotoxicity in oncology are under study, especially heart-type fatty acid-binding protein (H-FABP) and glycogen phosphorylase BB (GPBB). Our studies using GPBB have provided encouraging results. However, the available data are limited and their practical use in this context cannot be recommended until their clinical efficacy is clearly defined. CONCLUSIONS This review covers the current status of biomarkers for the early detection of anthracycline-induced cardiotoxicity. The authors present in brief, their own experience with multiple biomarkers in the detection of cardiotoxicity.