Stefan Grajek

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.

New Method of Intracoronary Adenosine Injection to Prevent Microvascular Reperfusion Injury in Patients With Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention

The aim of our study was to examine the role of a new, simple protocol of intracoronary adenosine administration performed during primary angioplasty on the immediate angiographic results and clinical course. A prospective, single-center, randomized, placebo-controlled trial of 70 consecutive patients (64 ± 14 years, 54 men) with acute myocardial infarction with ST-segment elevation undergoing primary percutaneous coronary intervention (PCI) was conducted. Patients were randomized to 2 groups. Group 1 (n = 35) received intracoronary adenosine (1 to 2 mg) with a hand injection through the guiding catheter 2 times: immediately after crossing the lesion of the infarct-related artery with guidewire and then after the first balloon inflation. Group 2 (n = 35) received placebo. The baseline clinical and angiographic characteristics of the 2 groups were similar. Percutaneous coronary intervention resulted in Thrombolysis In Myocardial Infarction grade 3 flow after PCI in 32 patients (91.4%) in the adenosine group and 27 patients (77.1%) in the placebo group (p = 0.059). Myocardial blush grade 3 was observed at the end of PCI in 23 patients (65.7%) in the adenosine group and 13 (37.1%) in the placebo group (p < 0.05). Resolution of ST-segment elevation (> 50%) was more frequently observed in the adenosine than in the placebo group: 27 (77%) versus 15 (43%), respectively (p < 0.01). In conclusion, intracoronary adenosine administration improved the angiographic and electrocardiographic results in patients with acute myocardial infarction with ST-segment elevation undergoing PCI. Adenosine administration seemed to be associated with a more favorable clinical course.

Six-month clinical follow-up of the Tryton side branch stent for the treatment of bifurcation lesions: A two center registry analysis

Background: Treatment of bifurcation lesions with the Tryton Sidebranch stent has been shown to be feasible with an acceptable clinical outcome and low side branch late loss in the first in man trial. Objective: To report acute procedural and six month clinical follow‐up after the use of the Tryton Sidebranch stent in an “all comer” registry. Methods: The first 100 coronary bifurcation lesions assigned for treatment with the Tryton stent were included in a prospective registry. Procedural and angiographic success rates were determined from patient charts and pre‐ and postprocedural quantitative coronary angiography. Results: Totally, 96 patients with 100 lesions were included in the study. Seventy‐two percent presented with stable angina, 25% with unstable angina/NSTEMI, and 3% STEMI. The bifurcation was located in the left main in 8%. Two lesions were chronic total occlusions. Sixty‐nine percent were true bifurcation lesions. One failure of stent delivery occurred. Acute gain in SB was 0.76 ± 0.64mm and three patients had residual stenosis of >30%. Angiographic success rate was 95%; procedural success rate reached 94%. Peri‐procedural MI occurred in two and there was one cardiac death during hospitalization. At a median six months follow‐up, TLR rate was 4%, MI 3%, and cardiac death 1%. The percentage MACE‐free survival at six months was 94%. No cases of definite stent thrombosis occurred. Conclusions: In a real world the use of the Tryton Sidebranch stent is associated with good procedural safety and angiographic success rate and acceptable outcome at six months of follow‐up.

The BNP concentrations and exercise capacity assessment with cardiopulmonary stress test in cyanotic adult patients with congenital heart diseases

Cyanosis is observed in patients with complex congenital heart disease (CHD) and pulmonary hypertension, heart failure represents an important clinical problem in such patients. The aim of this study was to evaluate the exercise capacity in patients with cyanotic CHDs using cardiopulmonary exercise test, measuring serum BNP levels as well as to seek correlation between BNP levels and cardiopulmonary exercise test parameters and identify the effects of blood oxygen desaturation and pulmonary hypertension on these indices. The study group consisted of 53 patients (21 males) at the mean age of 39.4 ± 14.3 years, of whom 19 were operated on at the mean age of 9.6 ± 8.6 years. Mean blood oxygen saturation (SO(2)) in patients was 81.2 ± 6.2%. Twenty four patients presented with Eisenmenger syndrome, 16--univentricular hearts, 4--transposition of the great arteries, 6--Fallots tetralogy, and 3--Ebstein anomaly. The control group comprised 32 healthy individuals (16 males) at the mean age of 40.7 ± 9.9 years. Cardiopulmonary stress test showed significantly lower exercise capacity in patients with cyanosis than in controls: maximal oxygen uptake (VO(2max)) 15.5 ± 4.9 vs. 31.6 ± 7.1 ml/kg/min (p=0.00001), maximum heart rate at peak exercise (HR max): 139.5 ± 22.5 bpm vs. 176.6 ± 12.1 (p=0.0001), VE/VCO(2) slope: 46.4 ± 10.1 vs. 27.3 ± 2.9 (p=0.00001), forced vital capacity FVC: 3.1 ± 1.1 l vs. 4.4 ± 0.8 l (p=0.00001). Subjects with the evidence of pulmonary hypertension (PH+) had lower exercise capacity than those without (PH-): VO(2max): 17.2 ± 4.2 vs. 12.8 ± 4.8 ml/kg/min (p=0.002), VE/VCO(2): 43.7 ± 11.1 vs. 50.9 ± 6.4 (p=0.01), FVC: 3.46 ± 1.05 l vs. 2.37 ± 0.91 l (p=0.0002). Plasma BNP levels in the study group were higher than in controls: 122.4 ± 106.7 vs. 21.1 ± 20.2 pg/ml p=0.00001 and did not differ between PH+ and PH- groups (115.7 ± 99.0 vs. 127.9 ± 114.1 pg/ml p=0.78). Negative correlations between BNP levels and VO(2max) (r=-0.389, p=0.006), FVC (r=-0.395 p=0.005), FEV1 (r=-0.386 p=0.006), SO(2) (r=-0.445 p=0.00001), and positive correlation between BNP level and VE/VCO(2) (r=0.369 p=0.009) were found.

Chronic infarct‐related artery occlusion is associated with a reduction in capillary density. Effects on infarct healing

To assess the relationship between infarct‐related artery (IRA) stenosis and capillary density and to assess its effect on scar formation in the human heart.

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.

Impact of Atrial Remodeling on Heart Rhythm After Radiofrequency Ablation and Mitral Valve Operations

BACKGROUND This study was conducted to determine the effect of left atrial structural remodeling on heart rhythm after radiofrequency ablation concomitant to mitral valve operation. METHODS Sixty-six consecutive patients with of atrial fibrillation (AF) and mitral valve disease underwent radiofrequency ablation and mitral valve operation. Heart rhythm was evaluated before and at 3, 6, and 12 months postoperatively. Biopsy specimens of the posterior wall of the left atrium were evaluated for the extent of fibrosis, myocyte diameter, intensity of inflammatory infiltrates, degree of myocytolysis, and capillary density. RESULTS Ten patients died and 1 patient was lost to follow-up. Heart rhythm at 12 months was used to divide the remaining 55 patients into two groups: group I, 34 with sinus rhythm; group II, 21 with AF. Paroxysmal AF preoperatively was more frequent among group I patients, and persistent/long-standing persistent AF in group II (p=0.0006). Groups I and II differed significantly in myocyte diameter (17.9±3.5 vs 20.3±4.6 μm, p=0.04), fibrosis percentage (38.7%±11.2% vs 47.6%±12.3%, p=0.009), inflammatory infiltrates (p=0.02), and preoperative left atrial diameter (5.03±0.7 vs 5.5±0.8 cm, p=0.04). No differences were found in capillary density (797.9±500.6 vs 946.0±373.7/mm2, p=0.3) and myocytolysis (p=0.4). Multivariate analysis showed myocyte diameter (p=0.047) and fibrosis (p=0.014) were independent predictors for an AF persistence at 12 months. CONCLUSIONS Left atrial structural remodeling strongly affects heart rhythm after concomitant radiofrequency ablation and mitral valve operation.

Postconditioning Reduces Enzymatic Infarct Size and Improves Microvascular Reperfusion in Patients with ST-Segment Elevation Myocardial Infarction

Objectives: Postconditioning has been reported to reduce infarct size in ST-segment myocardial infarction (STEMI). However, recently, few other studies did not show any effect of postconditioning and suggested that it may be even harmful. We sought to assess whether postconditioning could reduce infarct size and improve myocardial reperfusion in early presenters with STEMI. Methods: 72 STEMI patients treated with primary percutaneous coronary intervention (PCI) were randomly assigned to either the postconditioning (n = 35) or the standard PCI group (control group; n = 37). Blood samples were obtained for creatine kinase (CK) and its MB isoform (CK-MB) within 36 h. The angiographic (myocardial blush grade, MBG) and electrocardiographic (ST-segment resolution, STR) data were evaluated and compared between groups. Results: The areas under the curve of CK and CK-MB release were significantly reduced in the postconditioning group compared with the control group (38,612.91 ± 25,028.42 vs. 60,547.30 ± 25,264.63 for CK and 5,498.23 ± 3,787.91 vs. 7,443.12 ± 3,561.13 for CK-MB, p < 0.0001). MBG was significantly better in the postconditioning group than in the control group (MBG 3: 82.3 vs. 47.1%, p = 0.0023). In the postconditioning group, STR >70% was more often observed (97.1 vs. 64.1%, p = 0.0007). Conclusions: In patients with STEMI, postconditioning could significantly reduce enzymatic infarct size and improve myocardial reperfusion.

Cardiovascular safety of antihistamines.

Histamine is a mediator, which increases the permeability of capillaries during the early phase of allergic reaction, causes smooth muscle contraction of bronchi and stimulates mucous glands in the nasal cavity. Antihistamines are the basis of symptomatic treatment in the majority of allergic diseases, especially allergic rhinitis, allergic conjunctivitis, urticaria and anaphylaxis. The cardiotoxic effects of the two withdrawn drugs, terfenadine and astemizole, were manifested by prolonged QT intervals and triggering torsades de pointes (TdP) caused by blockade of the ‘rapid’ IKr potassium channels. These phenomena, however, are not a class effect. This review deals with a new generation of antihistamine drugs in the context of QT interval prolongation risk.