Radoslav Romanovic

Autologous bone marrow-derived progenitor cell transplantation for myocardial regeneration after acute infarction.

BACKGROUND Experimental and first clinical studies suggest that the transplantation of bone marrow derived, or circulating blood progenitor cells, may beneficially affect postinfarction remodelling processes after acute myocardial infarction. AIM This pilot trial reports investigation of safety and feasibility of autologous bone marrow-derived progenitor cell therapy for faster regeneration of the myocardium after infarction. METHODS AND RESULTS Four male patients (age range 47-68 years) with the first extensive anterior, ST elevation, acute myocardial infarction (AMI), were treated by primary angioplasty. Bone marrow mononuclear cells were administered by intracoronary infusion 3-5 days after the infarction. Bone marrow was harvested by multiple aspirations from posterior cristae iliacae under general anesthesia, and under aseptic conditions. After that, cells were filtered through stainless steel mesh, centrifuged and resuspended in serum-free culture medium, and 3 hours later infused through the catheter into the infarct-related artery in 8 equal boluses of 20 ml. Myocardial viability in the infarcted area was confirmed by dobutamine stress echocardiography testing and single-photon emission computed tomography (SPECT) 10-14 days after infarction. One patient had early stent thrombosis immediately before cell transplantation, and was treated successfully with second angioplasty. Single average ECG revealed one positive finding at discharge, and 24-hour Holter ECG showed only isolated ventricular ectopic beats during the follow-up period. Early findings in two patients showed significant improvement of left ventricular systolic function 3 months after the infarction. There were no major cardiac events after the transplantation during further follow-up period (30-120 days after infarction). Control SPECT for the detection of ischemia showed significant improvement in myocardial perfusion in two patients 4 months after the infarction. Echocardiographic assessment in these two patients also showed significant improvement of systolic function three months after the infarction. CONCLUSION Preliminary results of the study showed that the transplantation of bone marrow-derived progenitor cells into the infarcted area was safe, and feasible, and might improve myocardial function. Further follow-up will show if this treatment is effective in preventing negative remodeling of the left ventricle and reveal potential late adverse events (arrhythmogenicity and propensity for restenosis).

THERAPEUTIC APPROACH IN PATIENTS WITH A FLOATING THROMBUS IN THE RIGHT HEART

BACKGROUND The occurrence of a floating thrombus in the right heart, although rare, is a life-threatening condition requiring a specific approach. In most cases, these thrombi are a result of embolization from deep venous thrombosis, and have lodged temporarily in the right heart. The management of this condition is variable, depending on whether or not there is a thrombus entrapped within a foramen ovale (FO). OBJECTIVES To present the management of 2 patients with a free-floating thrombus in the right heart, and a third patient with an entrapped thrombus in the FO. CASE REPORTS Two patients with a free-floating thrombus in the right atrium who were treated with thrombolytic therapy had an immediate excellent outcome. The patient with a thrombus entrapped within the FO was scheduled for surgical removal of the thrombus due to an unacceptable risk of systemic embolization if treated with thrombolytic and anticoagulant therapy. Unfortunately, he developed an ischemic stroke on the fifth day of presentation, just a few hours before the scheduled surgery, despite meticulous monitoring of continuous heparin infusion with activated partial thromboplastin time. CONCLUSION Thrombolytic therapy is recommended in patients with a free-floating thrombus in the right heart. However, in patients with a thrombus entrapped within an FO, delaying surgical removal of the thrombus may be deleterious due to unpredictable systemic embolization.

Relationship between QT dispersion and reperfusion in the acute myocardial infarction

BACKGROUND: QT dispersion (QTd) represents the parameter of the expanded heterogeneity of myocard of ventricles. The aim of this study was to examine the dynamics of changes of QTd during the first 5 days of the acute myocardial infarction (AMI) in dependence to noninvasively estimated success of thrombolytic therapy. METHODS: Thirty six patients with AMI were included in the study. All patients were treated with alteplaze according to rapid protocol. QTd (QTc max-QTc min) was measured immediately after the reception (0 min), after the thrombolytic therapy (90 min) and since the 2nd to the 5th day of the hospitalization. Reperfusion was estimated on the basis of electrocardiographic and biohumoral parameters. RESULTS: In the group of 36 patients, 22 male and 11 female, both parameters of the reperfusion were not compatible in 3 patients. The other 23 patients had the reperfusion, while 10 patients did not have it. At the reception there was no significant difference of QTd between the group with reperfusion (79 +/- 34 ms) and the group without reperfusion (65 +/- 19 ms). After receiving alteplase, the average QTd in the group with reperfusion was 67 +/- 31 ms, which was not shorter in relation to the group without reperfusion (70 +/- 23 ms). Since the 2nd day of AMI, significantly smaller QTd in pa-patients with reperfusion was not registered compared with the patients without the reperfusion (54 +/- 17 vs. 73 +/- 20 ms), whereas since the 3rd day the difference became significant (46 +/- 16 vs. 87 +/- 24 ms). On the 4th day it was 43 +/- 12 vs. 78 +/- 21 ms, and on the 5th day it was 38 +/- 11 vs. 62 +/- 23 ms. On the 1st day significant difference of QTd between the groups with and without reperfusion was not registered in the group of patients with anterior AMI (0 min: 97 +/- 47 vs. 72 +/- 16; 90 min: 68 +/- 47 vs. 72 +/- 20) whereas on the 2nd day it became statistically significant (51 +/- 15 vs. 74 +/- 20 on the 2nd day, 51 +/- 20 vs. 88 +/- 24 on the 3rd day, 46 +/- 10 vs. 81 +/- 19 on the 4th day and 40 +/- 8 vs. 69 +/- 22 ms on the 5th day. In the group of patients with inferolateral AMI, only on the 3rd day significant difference of QTd between the group with and the group without reperfusion was registered (43 +/- 14 vs. 69 +/- 29 ms), while in all other measuring it was not registered (0 min: 69 +/- 22 vs. 42 +/- 9; 90 min: 67 +/- 20 vs. 67 +/- 41; 55 +/- 19 vs. 60 +/- 25 on the 2nd day; 41 +/- 14 vs. 51 +/- 6 on the 4th day and 51 +/- 12 vs. 37 +/- 8 ms on the 5th day). CONCLUSION: Qt dispersion was of significantly shorter duration in patients with the successfully performed reperfusion in relation to the patients without the reperfusion. In patients with the anterior AMI, QTd was significantly different in patients with in relation to the patients without the reperfusion in distinction with the patients with inferolateral AMI.

Lower plasma protein C activity is associated with early myocardial necrosis and no-reflow phenomenon in patients with ST elevation myocardial infarction

Abstract Background: Activity of protein C has important role in the development of early necrosis and no-reflow phenomenon in patients with ST-segment elevation myocardial infarction (STEMI) after successful primary percutaneous coronary intervention (pPCI). Methods: We examined association between plasma activity of protein C, antithrombin, coagulation factors II, VII, VIII and fibrinogen to early formation of new Q-waves (myocardial necrosis) before pPCI and early ST-segment resolution (microcirculatory reperfusion) after pPCI in patients with acute STEMI. According to ischaemic time, patients were considered as early or late presenters. 12-lead ECG was analysed for the presence of new Q-wave at admission and for significant ST-segment resolution 60 minutes after primary PCI. Results: In early presenters’ group, protein C activity was significantly lower in patients who did not achieve significant ST-segment resolution after pPCI compared to patients who did (1.11 IU/L vs. 0.99 IU/L, p = .006) and in patients who had new Q-waves compared to group who had not (1.04 UI/l vs. 1.11 IU/L, p = .038). There was significant negative correlation between protein C activity and maximal CK-MB levels (R2 = 0.06, p = .009) and BNP levels (R2 = 0.109, p = .003) and significant positive correlation between protein C activity with LVEF (R2 = 0.065, constant = 33.940, b = 11.968, p = .007) in early STEMI presenters. There were no differences between the activity of other examined haemostasis factors. Conclusion: Therefore we concluded that STEMI patients with early myocardial necrosis and no-reflow phenomenon after pPCI have lower activity of plasma protein C levels.

Association between serum concentration of parathyroid hormone and left ventricle ejection fraction, and markers of heart failure and inflammation in ST elevation myocardial infarction patients treated with primary percutaneous coronary intervention

Background/Aim. Previous studies have shown increased serum concentration of parathyroid hormone (PTH) in acute myocardial infarction and heart failure. In this study we examined the relationships between parathyroid hormone status and biochemical markers of myocardial injury and heart failure, as well as electrocardiographic (ECG) and echocardiographic indicators of infarction size and heart failure. Methods. In 390 consecutive patients with ST segment elevation myocardial infarction (STEMI), average age 62 ± 12 years, laboratory analysis of serum concentrations of creatine kinase MB isoenzyme (CK-MB), C-reactive protein (CRP) and intact PTH and plasma concentration of brain natriuretic peptide (BNP) were done during the first three days after admission. All patients were treated with primary percutaneous coronary intervention (PCI). Exclusion criterion was severe renal insufficiency (glomerular filtration rate ≤ 30 mL/min). Serum concentration of PTH was measured on the 1st, 2nd and, in some cases, on the 3rd morning after admission and maximum level of PTH was taken for analysis. Patient cohort was divided into four groups according to quartiles of PTH maximum serum concentration (I ≤ 4.4 pmol/L; II > 4.4 pmol/L and < 6.3 pmol/L; III ≥ 6.3 pmol/L and < 9.2 pmol/L; IV ≥ 9.2 pmol/L). Selvester’s ECG score, left ventricle ejection fraction and wall motion index (WMSI) were determined at discharge between 5–14 days after admission. Results. We found that LVEF at discharge significantly decreased (p < 0.001) and WMSI at discharge and ECG Selvester ́s score significantly increased across the quartiles of PTH max. level (p < 0.001 for both parameters). BNP, CRP and CK-MB isoenzyme level significantly increased across the quartiles of PTH max. level (p < 0.001; p < 0.001 and p = 0.004, retrospectively). Conclusion. The patients in the 4th quartile of PTH had significantly lower LVEF and higher WMSI and Selvester’s ECG score at discharge. This group of patients also had higher levels of BNP, CRP and CK-MB in blood in the early course of STEMI.

INFLAMMATORY RESPONSE AND INFARCTION SIZE ARE DECREASED WITH TICAGRELOR COMPARED TO CLOPIDOGREL IN PRIMARY PERCUTANEOUS CORONARY INTERVENTION

Background: It is unknown whether ticagrelor treatment before and after primary percutaneous coronary intervention (pPCI) can reduce the inflammatory response and infarction size compared to clopidogrel. Methods: Four hundred and sixty consecutive patients with ST-segment elevation myocardial

Forearm Approach for Percutaneous Coronary Procedures

This article gives contemporary review on the forearm approach for percutaneous diagnostic and interventional coronary procedures. Advantages and disadvantages as well as practical issues and current controversies regarding both radial and ulnar artery approach are discussed throughout the paper. Having in mind advantages of forearm approach in terms of safety and comfort over the traditional femoral approach, as well as the rapid development of invasive technology in the past years, it will probably become the default vascular approach for all percutaneous coronary procedures in the near future.

Effects of reperfusion on late potentials of the QRS complex in acute myocardial infarction

INTRODUCTION Cardiac rhythm disorders are common in patients after myocardial infarction. They play an important role in the course and in prognosis of this illness. Signal-averaged electrocardiogram (SAECG) is a non-invasive diagnostic method for the induction of sustained monomorphic ventricular tachycardia. Early opening of the infarct-related artery decreases occurrence of ventricular disorders in these patients. The aim of this study was to establish the connection between the late potentials of the QRS complex (SAECG) and unsuccessful reperfusion in patients with acute myocardial infarction (AMI). MATERIAL AND METHODS After myocardial infarction, presence of SAECG was examined in patients receiving reperfusion therapy in order to establish the treatment outcome. Late potentials in SAECG were determined by computer measurements in regard to criteria for its positivity. RESULTS The study group consisted of 33 patients. Out of 23 patients with successful reperfusion, only 6 (26.1%) had late potentials, in contrast to the group without reperfusion, 8 (80%) out of 10 patients had late potentials. CONCLUSION Based on our results, we can conclude that there is a significant association between the presence of late ORS-complex potentials (SAECG) and unsuccessful reperfusion. Also, we can conclude that presence of late potentials is an independent predictor of infarct-related artery patency in patients with AMI treated with thrombolytic therapy.