Piotr Bręborowicz

Intracoronary infusion of bone marrow-derived selected CD34+CXCR4+ cells and non-selected mononuclear cells in patients with acute STEMI and reduced left ventricular ejection fraction: results of randomized, multicentre Myocardial Regeneration by Intracoronary Infusion of Selected Population of Stem Cells in Acute Myocardial Infarction (REGENT) Trial

AIMS Comparison of intracoronary infusion of bone marrow (BM)-derived unselected mononuclear cells (UNSEL) and selected CD34(+)CXCR4(+) cells (SEL) in patients with acute myocardial infarction (AMI) and reduced <40% left ventricular ejection fraction (LVEF). METHODS AND RESULTS Two hundred patients were randomized to intracoronary infusion of UNSEL (n = 80) or SEL (n = 80) BM cells or to the control (CTRL) group without BM cell treatment. Primary endpoint: change of LVEF and volumes measured by magnetic resonance imaging before and 6 months after the procedure. After 6 months, LVEF increased by 3% (P = 0.01) in patients treated with UNSEL, 3% in patients receiving SEL (P = 0.04) and remained unchanged in CTRL group (P = 0.73). There were no significant differences in absolute changes of LVEF between the groups. Absolute changes of left ventricular end-systolic volume and left ventricular end-diastolic volume were not significantly different in all groups. Significant increase of LVEF was observed only in patients treated with BM cells who had baseline LVEF < median (37%). Baseline LVEF < median and time from the onset of symptoms to primary percutaneous coronary intervention > or = median were predictors of LVEF improvement in patients receiving BM cells. There were no differences in major cardiovascular event (death, re-infarction, stroke, target vessel revascularization) between groups. CONCLUSION In patients with AMI and impaired LVEF, treatment with BM cells does not lead to a significant improvement of LVEF or volumes. There was however a trend in favour of cell therapy in patients with most severely impaired LVEF and longer delay between the symptoms and revascularization.

Influence of bone marrow stem cells on left ventricle perfusion and ejection fraction in patients with acute myocardial infarction of anterior wall: randomized clinical trial: Impact of bone marrow stem cell intracoronary infusion on improvement of microcirculation.

AIMS Randomized trial to assess change in left ventricle ejection fraction (LVEF) and myocardial perfusion in patients with acute myocardial infarction (AMI) of anterior wall treated with bone marrow stem cells (BMSCs), compared with control group-from baseline in the acute phase up to 12 months of follow-up. METHODS AND RESULTS Forty-five patients were randomized 2:1 to BMSC group (n= 31) or to control group (n = 14). Bone marrow stem cells were administered into infarct-related artery (IRA) at 4-6 day after primary PCI. Groups were followed up with Tc-99m-MIBI SPECT, radionuclide ventriculography (EF-RNV), echocardiography (ECHO), and spiroergometric stress test. Coronary angiography was repeated after 6 months. EF-RNV did not differ significantly in both groups, but trend towards increase in EF at 6 months and its maintenance after 12 months was noticed in the BMSC group. At rest study, perfusion index (PI) of region supplied with blood by IRA distal to its previous occlusion (PI-IRA) improved significantly in the BMSC group at 6 months: PI-IRA at 4-6 days vs. PI-IRA at 6 months (3.00 +/- 0.97 vs. 2.65 +/- 0.64; P = 0.017). At 12 months, PI-IRA at rest was 2.66 +/- 0.55; P = 0.07. The difference between BMSC and control groups at rest study in PI-IRA was not observed. At dipyridamole study (PI-dip), perfusion in the BMSC group was better compared with controls at 6 months (2.26 +/- 0.44 vs. 2.47 +/- 0.40; P = 0.033) and at 12 months (2.34 +/- 0.55 vs. 2.52 +/- 0.42; P = 0.014), also for region supplied with blood by IRA (PI-IRA-dip; at 6 months 2.63 +/- 0.77 vs. 3.06 +/- 0.46; P = 0.021 and at 12 months 2.71 +/- 0.63 vs. 3.15 +/- 0.51; P = 0.001). Results of LVEF, LVEDV, LVESV in ECHO and results of spiroergometric stress test did not differ significantly between groups. Major adverse cardiac events occurred more often in the control group (P = 0.027). CONCLUSION In our study, BMSC intracoronary transplantation in patients with anterior AMI did not result in increase in EF. Slight improvement of myocardial perfusion was noticed in the BMSC group. This finding may indicate better microcirculation enhanced by BMSCs, but small number of patients allow for hypothesis rather than final statement.

Evaluation of exercise capacity with cardiopulmonary exercise testing and BNP levels in adult patients with single or systemic right ventricles.

Introduction The aim of the study was to evaluate exercise capacity using cardiopulmonary exercise test (CpET) and serum B-type natriuretic peptide (BNP) levels in patients with single or systemic right ventricles. Material and methods The study group included 40 patients (16 males) – 17 with transposition of the great arteries after Senning operation, 13 with corrected transposition of the great arteries and 10 with single ventricle after Fontan operation, aged 19–55 years (mean 28.8 ±9.5 years). The control group included 22 healthy individuals (10 males) aged 23–49 years (mean 30.6 ±6.1 years). Results The majority of patients reported good exercise tolerance – accordingly 27 were classified in NYHA class I (67.5%), 12 (30%) in class II, and only 1 (0.5%) in class III. Cardiopulmonary exercise test revealed significantly lower exercise capacity in study patients than in control subjects. In the study vs. control group VO2max was 21.7 ±5.9 vs. 34.2 ±7.4 ml/kg/min (p = 0.00001), maximum heart rate at peak exercise (HRmax) 152.5 ±32.3 vs. 187.2 ±15.6 bpm (p = 0.00001), VE/VCO2 slope 34.8 ±7.1 vs. 25.7 ±3.2 (p = 0.00001), forced vital capacity (FVC) 3.7 ±0.9l vs. 4.6 ±0.3 (p = 0.03), forced expiratory volume in 1 s (FEV1) 3.0 ±0.7 vs. 3.7 ±0.9l (p = 0.0002) respectively. Serum BNP concentrations were higher in study patients than in control subjects; 71.8 ±74.4 vs. 10.7 ±8.1 (pg/ml) respectively (p = 0.00001). No significant correlations between BNP levels and CpET parameters were found. Conclusions Patients with a morphological right ventricle serving the systemic circulation and those with common ventricle physiology after Fontan operation show markedly reduced exercise capacity. They are also characterized by higher serum BNP concentrations, which do not however correlate with CpET parameters.

Exercise capacity, arrhythmic risk profile, and pulmonary function is not influenced by intracoronary injection of Bone Marrow Stem Cells in patients with acute myocardial infarction

OBJECTIVES To evaluate influence of Bone Marrow Stem Cells (BMSC) intracoronary infusion on exercise capacity, pulmonary function, heart rate recovery and SAECG in patients with AMI of anterior wall, compared to control group--from baseline in the acute phase during 12 months follow up. METHODS Forty five patients were randomized 2:1 to BMSC group (n = 31 pts) or to control group (n = 14 pts). BMSC were administered into infarct related artery (IRA) at 4-6 day after primary PCI. Patients were followed up with cardiopulmonary exercise testing. The QRS duration, QT and QTc interval were measured and signal averaged ECGs (SAECG) were performed to evaluate late potentials. RESULTS There were no significant differences between both groups neither at peak VO(2) (190.7 ± 7.4 at baseline; 24.2 ± 5.2 at 6 months; 22.2 ± 7.4 ml/kg/min at 12 months vs 18.4 ± 8.2 at baseline; 22.0 ± 7.2 at 6 months; 21.8 ± 6.2 ml/kg/min at 12 months; BMSC vs control group respectively; p = ns), nor VO(2) at anaerobic threshold, nor in VE/VCO(2) slope, RER, and systolic blood pressure at peak exercise at baseline and any time point of follow-up. There were no significant differences between groups concerning HR peak, HRR1 and HRR2 at any time point and also QRS, QT parameters, and SAEKG. There were no significant differences between both groups at any time point (baseline, 6 and 12 months) concerning FVC, FEV(1) and FVC/FEV(1) and % of their normal values. CONCLUSIONS We did not find that BMSC therapy in patients with anterior wall myocardial infarction influences exercise capacity. We did not confirm its potential proarrhythmogenic influence as assessed with SAECG and standard ECG analysis.

Huge pneumopericardium with irreversible dilatation of the pericardial sac after cardiac tamponade

An 86-year-old female patient was referred to the Department of Cardiology in order to drain a pericardial effusion (Fig. 1). The diagnosis had been made in a suburban general hospital by echocardiography confirmed by computed tomography (CT) (Fig. 2). The maximum thickness of fluid layer was 63 mm. On admission, our patient reported significant peripheral oedema and difficulty in swallowing associated with periodic vomiting for two years. For the past two months, she had suffered from breathlessness, even after slight effort or eating, which intensified in the evening. Those symptoms progressively worsened. Only oedema of the limbs decreased after pharmacological treatment for heart failure. On admission, the jugular veins were distended up to 1.5 cm. The manubrium and sternal angle were protuberant. The apex beat was diffuse, hyperdynamic and displaced laterally and inferiorly. Cardiac rhythm was irregular, average heart rate was 70/min and blood pressure was 167/52 mm Hg. Heart sounds were loud and muffled with a systolic-diastolic murmur over the aortic valve. The liver was enlarged to 4 cm below the costal arch. There was no swelling of the lower limbs. An electrocardiogram showed atrial fibrillation and features of left ventricular (LV) hypertrophy (despite massive pericardial effusion, the QRS complex amplitude was not diminished). On echocardiography, up to 40 mm of pericardial fluid was seen around the whole heart with features of right heart compression. Moreover, there was stenosis and insufficiency of the aortic valve, as well as cardiac hypertrophy of all walls, with the LV wall slightly enlarged. The inferior wall was hypokinetic and the ejection fraction was about 55%. We also observed ‘swinging heart’: features of right heart collapse, intermediate movement of the interventricular septum and moderate pulmonary hypertension. A pericardiocentesis was performed through a subxiphoid approach, removing 1,500 mL of serous fluid. Laboratory tests of the collected material excluded a bacterial (also TBC), viral or malignant aetiology. After ten hours, on physical examination, a splash was heard on auscultation and tympanic sounds on percussion. Echocardiography revealed numerous artefacts from the pericardium and swirly air bubbles in the pericardial fluid (up to 14 mm). Routine chest X-ray (Fig. 3) showed the presence of air and fluid in the pericardial sac, confirmed by CT (Fig. 4). Nonetheless, the patient’s condition significantly improved from the time of the pericardiocentesis. We noted an increasing volume of fluid without reduction of pericardial emphysema. The patient was still stable but in the absence of improvement, a pericardial suction drain 32 F was inserted by a cardiac surgeon. In cardiac magnetic resonance (CMR) imaging performed seven days after the operation, pericardial emphysema and 4–5 mm thick inflexible pericardium with symmetrical contrast enhancement was noted, possibly indicating long-term pericarditis. Amyloidosis was excluded. The heart moved to a posterior position, towards the area previously occupied by pericardial fluid. After CMR, drainage was removed. The patient was discharged in stable condition with a diagnosis of chronic exudative pericarditis and heart failure with a recommendation for further cardiac monitoring including echocardiography. X-ray performed on the day of discharge (Fig. 5).