Ewa Straburzyńska-Migaj

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.

Bone mineral density and bone turnover in male masters athletes aged 40-64.

We evaluated areal bone mineral density (aBMD), bone mineral content (BMC), and markers of bone turnover in male competitive masters athletes representing different training profile in the past and at present, aged 40–64 (14 endurance runners, and 12 speed-power athletes), and non-sport controls (n = 13). Dual-energy X-ray absorptiometry measurements of total body and regional aBMD, BMC and soft tissue composition were acquired. Serum concentrations of osteocalcin (OC), C-terminal crosslinking telopeptide of type I collagen (CTX), tumour necrosis factor-α (TNF-α), total testosterone (TT), free testosterone (FT) and insulin like growth factor-1 (IGF-1) were measured. Adjusted total and regional aBMD and BMC (covariates: body mass, body height and age) were significantly greater in all measured regions in speed-power athletes than in endurance athletes and control subjects, but adjusted aBMD and BMC values were not significantly different between endurance athletes and controls. No differences in bone formation (OC), bone resorption (CTX), and serum concentrations of TNF-α, TT, FT and IGF-1 were noted. This suggests that weight-bearing exercise in young age and the training continuation in later life may be an important contributor to the aBMD and BMC in the middle age and in the elderly. It seems also that training-related bone differences in men are not caused by present alterations in bone turn-over or somatotropic effects. However, conclusions must be drawn with caution due to a large variability of biochemical markers.

Characteristics, treatments and 1-year prognosis of hospitalized and ambulatory heart failure patients with chronic obstructive pulmonary disease in the European Society of Cardiology Heart Failure Long-Term Registry

To describe the characteristics and assess the 1‐year outcomes of hospitalized (HHF) and chronic (CHF) heart failure patients with chronic obstructive pulmonary disease (COPD) enrolled in a large European registry between May 2011 and April 2013.

Does the influence of obesity on prognosis differ in men and women? A study of obesity paradox in patients with acute coronary syndrome

BACKGROUND Recent studies have reported the existence of obesity paradox in acute coronary syndromes (ACS). However, the occurrence of obesity paradox in men and women has not yet been thoroughly investigated, even though both genders differ in patterns and incidence of obesity. AIM Therefore, the aim of this study was to investigate whether obesity influence on outcomes of patients with ACS varies by gender. METHODS This retrospective study included 341 patients admitted to hospital for treatment due to ACS in 2012. They were classified according to the World Health Organisation with use of body mass index (BMI) as normal weight, overweight, and obese. All patients received standard discharge medication. All-cause mortality was assessed during a mean follow-up time of 212 ± 121 days. RESULTS There were 82 (24%) normal weight, 160 (47%) overweight, and 99 (29%) obese patients. There were 252 (73.9%) men. All-cause mortality was lower in the obese and overweight vs. normal weight male patients (1.4% vs. 3.3% vs. 13.1%, respectively, p = 0.009). There was a trend favouring the normal weight and obese vs. overweight women (4.8% vs. 3.6% vs. 17.5%, respectively, p = 0.103). In the general population, after adjustment, BMI increase by one reduced risk by 15.6% (p = 0.015), and obesity reduced risk by 50.8% (p = 0.056). Obesity reduced risk for men by 69.4% (p = 0.015), and BMI increase by one reduced risk for men by 22% (p = 0.002). BMI and obesity were independent prognostic factors in men, whereas no such phenomenon was observed in women. CONCLUSIONS Only male patients seem to contribute to the obesity paradox observed in patients with ACS. The obesity paradox does not occur in female patients when considered separately. Obesity seems to have a different influence on outcomes in both genders, and this might be worthy of further studies.

Safety, feasibility and effectiveness of first in‐human administration of muscle‐derived stem/progenitor cells modified with connexin‐43 gene for treatment of advanced chronic heart failure

To assess the safety and efficacy of transendocardial delivery of muscle‐derived stem/progenitor cells with connexin‐43 overexpression (Cx‐43‐MDS/PC) in advanced heart failure (HF).

Patients with heart failure and concomitant chronic obstructive pulmonary disease participating in the Heart Failure Pilot Survey (ESC-HF Pilot) – Polish population

Introduction There is an increasing interest in comorbidities in heart failure patients. Data about chronic obstructive pulmonary disease (COPD) in the Polish population of heart failure (HF) patients are scarce. The aim of this study was to investigate the clinical characteristics, treatment differences and outcome according to COPD occurrence in the Polish population of patients participating in the ESC-HF Pilot Survey Registry. Material and methods We analyzed the data of 891 patients with HF recruited in 2009–2011 in Poland: 648 (72.7%) hospitalized patients and 243 (27.3%) patients included as outpatients. Results The COPD was documented in 110 (12.3%) patients with HF in the analyzed population. Patients with – compared to those without COPD were older, more often smokers, had higher NYHA class, and higher prevalence of hypertension. Ejection fraction (EF) was higher in hospitalized patients with COPD compared to patients without COPD (40.5 ±14.6% vs. 37.2 ±13.7%, p < 0.04), without a significant difference in the outpatient group. There was a significant difference in β-blocker use between patients with and without COPD (81.8% vs. 94.7%, p < 0.0001). Most patients received them below target doses. At the end of the 12-month follow-up, there was no significant difference in mortality between COPD and no-COPD patients (10.9% vs. 11.1%, p = 0.66). Conclusions The findings from the Polish part of the ESC-HF registry indicate that COPD in patients with HF is associated with older age, smoker status, hypertension and higher NYHA class. The use of β-blockers was significantly lower in patients with than without COPD. There were no significant differences in mortality between groups.

Sustained Improvement of Clinical Status and Pulmonary Hypertension in Patients with Severe Heart Failure Treated with Sildenafil

BACKGROUND Sildenafil, a phosphodiesterase-5 inhibitor, has been shown to decrease pulmonary vascular resistance (PVR) in patients with heart failure. The purpose of the study was to evaluate the effect of sildenafil on clinical status and pulmonary vascular reactivity in patients with congestive heart failure. MATERIAL AND METHODS We enrolled 20 patients (18 men and 2 women, mean age 51 ± 12 years, diagnosed with congestive heart failure and pulmonary hypertension. This was a prospective, single-center study. Patients were treated with sildenafil 25 mg TDS for 12 months. Protocol included NYHA evaluation and repeated echocardiography, cardiac pulmonary stress tests, and right- sided catheterization. RESULTS Initially, there were 16 (80%) patients in III NYHA status and 4 (20%) patients in II NYHA. After 12 months, 8 patients were in NYHA III (40%) status and 12 patients in NYHA II (60%). Peak oxygen consumption increased from 12 ± 3 ml/kg/min to 19 ± 4 ml/kg/min after 1-year therapy (p<0.001). The cardiac index increased from 3.1 ± 0.6 L/min/m2 to 3.6 ± 0.4 L/min/m2 (p<0.05). Pulmonary vasculature resistance decreased after 1-year therapy (4.7 ± 1 vs. 1.6 ± 0.5 Woods units (p<0.005) comparing to initials. Mean pulmonary artery pressure decreased to 23 ± 6 mmHg from 42 ± 5 mmHg (p<0.001) after 1-year therapy. CONCLUSIONS One-year sildenafil therapy effectively improved clinical status and pulmonary vascular resistance in patients diagnosed with congestive heart failure.

Comparison of conventional tacrolimus versus prolong release formula as initial therapy in heart transplantation.

BACKGROUND A new formulation of tacrolimus that is characterized by prolonged release has been developed to facilitate treatment and patient compliance. Initial therapy with prolonged release formula in heart transplantation is not widely accepted. MATERIAL AND METHODS We enrolled 19 patients into a randomized analysis divided into 2 groups with different initial regimens. There were 8 patients with a mean age of 44 ± 13 years treated by Advagraf, and 11 patients with a mean age of 41 ± 9 years treated by Prograf. Serum concentration of immunosuppressive drug was followed by its oral dosage and endomyocardial biopsy results. Arterial hypertension, kidney function, and incidence of diabetes mellitus were recorded. RESULTS There were no perioperative deaths. The risk of acute rejection within 6 months following surgery was 1 (2%) in the Advagraf group and 1 (1.5%) in the Prograf group. Although the serum tacrolimus results were comparable between groups, the drugs daily dosages were different after 6 months of therapy (3 ± 1 mg in the Advagraf group and 6 ± 2 mg in the Prograf group (p<0.05). The low rate of adverse effects throughout the study was noted. CONCLUSIONS Prolonged-release tacrolimus formula is an efficient immunosuppressant in heart transplantation. Its initial application after surgery has low risk of adverse effects with similar results to conventional formula.

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.

Induction therapy, tacrolimus plasma concentration, and duration if intensive care unit stay are risk factors for peripheral leucopenia following heart transplantation.

BACKGROUND Although survival among heart recipients has increased, a limiting factor is chronic adverse effects of immunosuppression therapy. MATERIAL AND METHODS We performed a retrospective analysis of 22 patients (19 men and 3 women) with a mean age of 48 ± 12 years who underwent orthotropic heart transplantation. There were 20 (91%) patients who received induction therapy (basiliximab, Simulect, Novartis Europharm Limited). All patients were treated with standard triple immunosuppressive regimen (tacrolimus, mycophenolate mofetil, and steroids). RESULTS Patients were divided into 2 groups according to postoperative peripheral cytopenia diagnosis. There were 16 (73%) in the cytopenic group and 6 (27%) in the non-cytopenic group. Mean time of peripheral leucopenia detection was 65 ± 13 days following surgery. The blood leucocyte count was 0.98 ± 0.2 × 10(3)/mm(3) vs. 5.85 ± 0.9 × 10(3)/mm(3) in patients with peripheral cytopenia compared to non-cytopenic patients (p<0.01). There was a statistically important difference in duration of intensive care unit stay between the 2 groups (p<0.01). A correlation between tacrolimus serum concentration and risk for leucopenia was also detected (p<0.05). CONCLUSIONS Basiliximab administration as induction therapy, tacrolimus serum concentration, and duration of intensive care unit stay are risk factors for leucopenia.