Serum Adipokine Levels in Patients Considered for Lung Transplantation.

The aim of the study was to investigate serum concentration of visfatin, irisin, and omentin in patients diagnosed as having end-stage lung diseases who qualified for lung transplantation (LTx) and to find the relationship between adipokine levels and clinical status. MATERIAL AND METHODS: The study population consisted of 23 consecutive patients (10 patients diagnosed as having cystic fibrosis, 6 patients diagnosed as having chronic obstructive pulmonary disease, and 7 patients diagnosed as having idiopathic pulmonary fibrosis) who qualified for LTx. Patients performed pulmonary function tests; visfatin, irisin, and omentin serum levels were assessed using commercially available enzyme-linked immunosorbent assay kits. RESULTS: Mean visfatin serum level was 4.99 ± 3.83 pg/mL; mean irisin serum level was 2.82 ± 0.24 ng/mL; mean omentin serum level was 389.99 ± 320.85 ng/mL. Mean distance in 6-minute walk test (6MWT) was 310.62 ± 147.09 m. Average partial pressure of oxygen (pO2) was 55.79 ± 10.33 mm Hg, forced expiratory volume (FEV1) was 26.25 ± 22.38%, and forced vital capacity (FVC) was 56.95 ± 21.91% of a due value. There was no statistically significant correlation between adipokine levels and 6MWT, pO2, FEV1, and FVC in patients waiting for LTx, regardless of underlying lung disease. Significant difference between patients was noted only in 6MWT, FEV1, and pO2 in connection to lung disease. CONCLUSION: Our findings indicate that adipokines may not have a statistically significant effect on parameters of pulmonary function. Results require further investigation on a larger study group, especially comparison of adipokine serum levels between groups of overweight patients, obese patients, and patients with normal weight who qualify for LTx.

Immunosuppressive Treatment and Its Effect on the Occurrence of Pneumocystis jiroveci, Mycoplasma pneumoniae, Chlamydophila pnemoniae, and Legionella pneumophila Infections/Colonizations Among Lung Transplant Recipients.

BACKGROUND: The aim of the study was to assess the frequency of infections caused by Pneumocystis jiroveci, Chlamydophila pneumoniae, Legionella pneumophila, and Mycoplasma pneumoniae among lung transplant recipients in the context of immunosuppression. METHODS: The study group consisted of 94 patients (37 women and 57 men; mean age 42.03 years) transplanted between 2009 and 2016 at the Silesia Center for Heart Diseases (SCCS). Immunosuppressive treatment (induction and maintenance therapy) was assessed. The immunofluorescence methods were used to detect the P. jiroveci, L. pneumophila, C. pneumoniae, and M. pneumoniae antigens in samples obtained from the respiratory tract. RESULTS: Thirty-two of 94 graft recipients developed atypical or opportunistic infection. The median time of its occurrence was 178 days after transplantation. P. jiroveci was responsible for 84.38% of first infections. Five patients developed infection with P. jiroveci and C. pneumoniae. None of the infections occurred during induction of immunosuppression. An opportunistic or atypical infection developed in 19.35% of the patients treated with a tacrolimus-based regimen, and in 43.33% of patients on a cyclosporine-based regimen. CONCLUSION: Infection with P. jiroveci is a recognized problem after lung transplantation and should be monitored. The percentage of infected patients is higher in patients treated with a cyclosporine-based regimen in comparison to those treated with tacrolimus.

Nordic Walking in Pulmonary Rehabilitation of Patients Referred for Lung Transplantation.

BACKGROUND: Although the effectiveness of pulmonary rehabilitation in patients with chronic obstructive lung disease, cystic fibrosis, and interstitial lung disease is well documented, little is known about pulmonary rehabilitation in patients who are referred for lung transplantation. Nordic walking is a low-cost and accessible form of physical exercise with proven benefits. The purpose of this prospective study was to examine the effects of Nordic walking on lung function, perception of dyspnea, and health-related quality of life in patients referred for lung transplantation. METHODS: Twenty-two of 40 patients who was qualified for lung transplantation at the Department of Lung Diseases in Zabrze, Poland, completed a rehabilitation program consisting of 12 weeks of Nordic walking. Lung function tests, exercise tolerance, and perception of dyspnea and quality of life were assessed before and after completion of the program. RESULTS: No adverse events were observed during the rehabilitation program. After 12 weeks, there was a significant increase in mean 6-minute walk distance (374 meters vs 288 meters, P < .034) and a significant reduction in perception of dyspnea after completion of the rehabilitation program. Assessment of general health and quality of life showed significant improvement (P < .05). No significant changes in lung function tests were noted. CONCLUSION: Nordic walking is a safe and feasible physical activity for pulmonary rehabilitation in patients with end-stage lung disease who are referred for lung transplantation. This rehabilitation technique results in significant improvements in patient mobility and quality of life.

Bacterial Infections During Hospital Stay and Their Impact on Mortality After Lung Transplantation: A Single-Center Study.

INTRODUCTION: The aim of the study was to assess the impact of bacterial infection during hospital stay on long-term follow-up. MATERIALS AND METHODS: This was a retrospective single-center study of 97 recipients of lung transplantations performed between December 2004 and June 2016 at a single center. Information about age, sex, underlying lung disease, and date and type of procedure was gathered from patients' charts. Immunosuppressive treatment has been analyzed individually among the cohort. Microbiological evaluation included the presence of infection, bacterial species in recipients and donors, as well as type of biological material. RESULTS: During a mean hospitalization time of 57 days (range 4-398 days), 67 patients (69%) were diagnosed with bacterial infection. There were 120 episodes of infection caused by 32 species of bacteria. The most common were Pseudomonas aeruginosa (27%), Acinetobacter baumanii (21%), Klebsiella pneumoniae (10%) and Stenotrophomonas maltophilia (11%). Analysis revealed that 39 patients developed bronchiolitis obliterans syndrome (43%). Patients with A baumanii had a lower probability of survival than the rest of the population (P < .05). Patients treated with mammalian target of rapamycin inhibitors had a higher probability of survival. CONCLUSIONS: Infection with A baumanii affects lung transplant recipients' survival. Incorporating sirolimus could be beneficial for the lung transplant recipients' survival.

Usefulness of the Impulse Oscillometry System in Graft Function Monitoring in Lung Transplant Recipients.

BACKGROUND: After successful lung transplantation, patients are monitored for chronic lung allograft dysfunction. Pulmonary function tests and 6-minute-walk tests are commonly used for functional graft monitoring. As these methods require substantial effort, however, many patients are unable to complete testing fully. The impulse oscillometry system is a noninvasive method that requires minimal patient cooperation and is suitable for use for patients incapable of strenuous activity. We compared impulse oscillometry system with pulmonary function tests and 6-minute-walk tests to determine if impulse oscillometry system could serve as a substitute measure. METHODS: This prospective, observational study evaluated 25 consecutive patients (19 men, median age 54.5 years) admitted to a single institution from January to October 2016 (double-lung = 13, single-lung = 13). Patients were assessed using pulmonary function tests, impulse oscillometry system, and 6-minute-walk tests. RESULTS: Eighty-eight percent of patients reached high-resonance frequency (Fres) and, in 84% of patients, the value of Ax (area of reactance) increased above the norm (N < 0.33 kPa/L) indicating peripheral airways obstruction. High resistance of small airways, measured with an R5 - R20 difference, followed higher Ax values. The increase of resistance at 5 Hz in 31% of patients (R5 >150% predicted value) also indicated small airway obstruction. Airway obturation in patients with elevated Ax and R5 was confirmed by decreased FEV1 (<75% predictive value) and FEV1/FVC ratio in 38% of patients. CONCLUSIONS: Study results confirm the impulse oscillometry system method could be a substitute for pulmonary function tests in determining the occurrence of chronic lung allograft dysfunction. 6-minute-walk tests showed neither strong correlations regarding impulse oscillometry system and pulmonary function tests nor any base for differentiation of results regarding main factor codes.

Advanced glycation end products in the development of ischemic and dilated cardiomyopathy in patients with diabetes mellitus type 2.

INTRODUCTION: Hyperglycemia intensifies nonenzymatic glucose coupling to tissues, resulting in myocardial stiffness and formation of advanced glycation end products (AGE). The aim of this study was to assess seeking AGE in the myocardium from patients with type 2 diabetes (DM2) subjected to orthotopic heart transplantation (OHT), seeking to establish whether AGE play a role in the development of cardiomyopathies leading to OHT. MATERIAL: The 2 studied groups consisted of 11 hearts explanted from patients with ischemic cardiomyopathy+DM2 (ICM+DM2, 55 +/- 6.5 years) and 8 from dilated cardiomyopathy+DM2 (DCM+DM2, 49.6 +/- 4.5 years). Comparative subgroups were composed of nondiabetic explanted hearts, 41 with ICM (52.8 +/- 5.8 years) and 41 with DCM (52.7 +/- 4.2 years). All patients were males. METHODS: We examined immunohistochemical localization of AGE using a semiquantitative scale of reaction intensity in cardiomyocytes, fibroblasts, capillaries, arterioles, and arteries. Additionally, we calculated the scores for cardiocytes (AGE(Cardiocyte)) and all left ventricular components (AGE(LV)). RESULTS: The cytoplasmic AGE deposits in cardiomyocytes were predominantly diffuse-granular in DM2 groups, whereas nondiabetic groups showed a lack of a reaction or a diffuse pattern. There were no differences in the reaction intensity between the 2 studied groups, or 2 comparative groups. All myocardial constituents showed higher AGE intensity in DM2 than nondiabetic groups. Only in the ICM+DM2 group did the DM2 duration correlate with AGE staining in selected myocardial layers and with AGE(Cardiocyte) and AGE(LV). CONCLUSIONS: The presence of AGE in the hearts of patients requiring transplantation was related to the duration of DM2. The deposition of AGE in left ventricular myocardium was enhanced by DM2 particularly in patients with ICM.

Cardiocyte nuclear chromatin density correlates with transplanted heart left ventricular mass.

INTRODUCTION: Cardiocyte hypertrophy is accompanied by polyploidy, seen as a decrease in chromatin density in the enlarged nucleus. Repeated biopsies of a transplanted heart offer the possibility of a dynamic evaluation of these phenomena. The aim of this work was an evaluation of cardiocyte nuclear chromatin density in transplanted hearts during long-term follow-up. MATERIALS AND METHODS: The material encompassed myocardial biopsy specimens taken during the first week, first month, and then on an annual basis up to 10 years after surgery. Only biopsy specimens with no rejection were considered (grade "0" International Society for Heart and Lung Transplantation [ISHLT] 122 biopsy specimens). The control group consisted of 7 donor heart specimens. We evaluated the optical density-mean gray level-of cardiomyocyte nuclear chromatin. We determined correlations of this index with the nuclear area, and with left ventricle ultrasound measurements, using correlation analysis. RESULTS: The chromatin mean gray level decreased with time, correlating positively with interventricular septum thickness, left ventricle posterior wall diameter, and left ventricular mass. Analysis of individual periods showed a significant positive correlation of the mean grey level with the cardiocyte nuclear surface in year 3, 4, and 9 after transplantation, thereby suggesting the occurrence of polyploidy at those times. The significant negative correlation of these values (1 week and 1 year) indicated normalization of early cardiocyte hypertrophy. CONCLUSIONS: With the passage of time chromatin condenses, leading to pyknosis. The activity of cardiocyte chromatin correlated with left ventricular hypertrophy. Compensatory cardiomyocyte polyploidy is a periodical phenomenon.

Survival benefit in heart transplant recipients who have coronary artery disease confirmed using angiography and are receiving sirolimus.

INTRODUCTION: The aim of this study was to assess efficacy and safety of sirolimus (SIR) in heart transplant recipients to prevent further development of coronary artery disease (TxCAD) already confirmed by using coronary angiography. MATERIAL AND METHODS: We performed a retrospective case-control study involving all 60 heart transplant recipients receiving SIR in a number of combinations with other immunosuppressive drugs, and 60 matched individuals after heart transplantation treated without SIR. TxCAD was diagnosed using elective coronary angiography in 9 subjects in the study group (8 males and 1 female) of mean age 44 +/- 11 years, including ischemic cardiomyopathy in 4 members. The control group of 15 individuals 15 males of mean age 47 +/- 7 years, including ischemic cardiomyopathy in 8. We compared time to develop significant TxCAD and death caused by TxCAD, and all-cause deaths. Significance was assessed using log-rank and chi-square tests, when applicable. RESULTS: Significant TxCAD (critical coronary lesions, myocardial infarction or death) was observed in 5 (56%) patients receiving SIR and 11 (73%) without SIR (P = not significant [NS]). Time to develop significant TxCAD was comparable. There were 2 (22%) deaths in the SIR group and 8 (53%) in the control group (P = NS). Survival time was significantly longer among subjects receiving SIR (P = .02). None of deaths in the study group was caused by TxCAD compared with 6 (40%) deaths among controls (P = .09). Time of freedom from death caused by TxCAD was significantly longer in the study group (P = .023). CONCLUSION: SIR prolonged survival in heart transplant recipients with TxCAD confirmed using coronary angiography.

Remodeling of human transplanted myocardium in ten-year follow-up: a clinical pathology study.

UNLABELLED: Remodeling taking place in transplanted myocardium leads to a change in the number of cardiocytes. Ultrasound measurements and biopsy evaluation should reflect their loss and compensation. We sought to evaluate the morphology of the transplanted heart upon long-term follow-up. MATERIAL AND METHODS: Myocardial biopsies were obtained in the first week, first month, and then annually for 10 years from transplantation that did not show rejection (grade "0" ISHLT, 122 biopsies). The control group encompassed 7 donor heart fragments. Proliferation in biopsies was evaluated with Ki67 (M7240, DAKO), cardiocyte hypertrophy by measuring their diameter, the surface area of the nuclei, nuclear-sarcoplasmic index, and stromal fibrosis evaluated as the surface area fraction. Ultrasound measurements included diastolic thickness of the interventricular septum, posterior wall of the left ventricle, and left ventricular mass. The correlation of measurements with time from transplantation was evaluated using Spearman's test. RESULTS: A positive Ki67 reaction was observed in fibroblasts and endothelial cells. The increased cardiocyte nuclear area correlated with the time elapsed since transplantation (r = 0.2; P < .05) with a simultaneous decrease in cardiocyte thickness (r = -0.3; P < .05), without changes in the nuclear-cytoplasmic index (r = 0.02; P > .05). Stromal fibrosis also increased (r = 0.1; P < .05). Ultrasound measurements of the left ventricle showed a decreased tendency with the passage of time (r = -0.2 to -0.3; P < .05). CONCLUSION: A transplanted heart does not undergo hypertrophy but rather fibrous atrophy with apparent compensatory hypertrophy of the cardiomyocytes.

Transplanted heart cardiomyocytes reveal continuous expression of antiapoptotic Bcl-2 protein.

BACKGROUND: Apoptotic mechanisms take place in cardiocyte death during acute heart graft rejection and remodeling by the mitochondrial pathway. This process is suppressed by Bcl-2 protein. Besides that, knowledge about cardiocyte antiapoptotic responses after heart transplantation is scanty. We sought to estimate Bcl-2 expression in the absence of rejection. MATERIAL: The study group included endomyocardial biopsies taken at 1 week, 1 month, 1 through to 10 years after heart transplant, which showed rejection grade "0"; the control group were donor heart fragments. METHOD: Bcl-2 expression was determined immunohistochemically by NP030 antibody (DAKO) and Envision-DAB. The intensity of staining was assessed semiquantitatively. RESULTS: No Bcl-2 expression was seen in the controls; in the posttransplant groups, the significantly strongest sarcoplasmic reaction was observed at 1 week after heart transplant. Thereafter, the reaction decreased, and was weakest in the 3- and 5-year groups. From this time, Bcl-2 expression increased albeit without statistical significance. The intensity of the reaction showed no correlation with the time elapsed from heart transplant (Spearman r = 0.05; P > .05). CONCLUSION: The expression of antiapoptotic Bcl-2 protein occurs during the entire posttransplant period, being probably a preservative and adaptative response.

Cardiocyte nucleus shape as an indicator of heart graft aging.

UNLABELLED: Morphometric publications based on the measurement of cardiocyte nuclei indicated their progressive hypertrophy ignoring, however, their shape, which is a deciding factor for the microscopic-based diagnosis of hypertrophy. We sought was to demonstrate how the shapes of cardiocyte nuclei change over time and correlate them with the thickness of the interventricular septum, (IVS) the biopsy site. MATERIAL: We evaluated myocardial biopsies taken in the first week, first month, and then annually until posttransplant year 10. Only biopsies with no rejection were considered: grade "0" ISHLT (122 biopsies). The control group encompassed fragments from seven donor hearts. METHODS: Cardiomyocyte nuclei were evaluated morphometrically. We calculated the length, breadth, perimeter, roundness, elongation, and fullness factors for correlation with the IVS thickness, and selected indices. The relationships between karyometry and IVS thickness (measured by ultrasound) as well as time were calculated by Spearman's correlation test. RESULTS: Among the examined indices, only nuclear length did not correlate significantly with follow-up time. Among the remaining indices, the strongest correlations with time were observed with regard to breadth (r = 0.214), perimeter (r = 0.150), roundness (r = -0.06) and fullness (r = 0.06), and finally elongation (r = 0.02). The decreasing thickness of the interventricular septum (r = -0.31) showed a weak correlation only with the cardiocyte nuclear length (r = -0.05). CONCLUSION: Graft aging imitates hypertrophy inasmuch as cardiocyte nuclei become wider despite the decreased thickness of the interventricular septum. Therefore, karyometric measurements do not reflect myocardial morphology.

Use of sildenafil in heart transplant recipients with pulmonary hypertension may prevent right heart failure.

PURPOSE: We performed a short-term outcome analysis of orthotopic heart transplantation (OHT) in patients with pulmonary hypertension (PH) treated perioperatively with oral sildenafil. METHODS: PH (pulmonary vascular resistance > 2.5 Wood units, and/or transpulmonary gradient > 12 mmHg) was diagnosed in 6 of 25 (group A) heart transplant recipients operated in 2006. This group of patients underwent a modified medication protocol including perioperative administration of oral sildenafil: 50 mg before followed by 50 or 25 mg TID after heart transplantation. Sildenafil treatment was discontinued 10 to 14 days post OHT, after stepwise dose reduction. During the ICU stay all patients underwent circulatory monitoring of pulmonary and systemic pressures and resistance as well as transthoracic echocardiogram (TTE) evaluation. RESULTS: Perioperative oral sildenafil administration in PH patients undergoing OHT was associated with good short-term outcomes in the majority of transplanted patients (4/6). Sildenafil treatment reduced pulmonary resistance and pressures with a low rate of hemodynamic instability among OHT patients. CONCLUSIONS: Pharmacologic perioperative reduction of PH improves the short-term prognosis for successful OHT. One may speculate whether sildenafil treatment transplant recipients with PH would be associated with long-term improvement of pulmonary vascular status, therefore leading to extended life-expectancy and improved outcomes.

Effectiveness and safety of treatment with sildenafil for secondary pulmonary hypertension in heart transplant candidates.

BACKGROUND: Pulmonary hypertension (PH) is a predictor of early death risk owing to right heart insufficiency after orthotopic heart transplantation (OHT). The aim of this study was to evaluate the effectiveness and safety of sildenafil therapy to decrease pulmonary vascular resistance (PVR) in patients with heart failure requiring transplantation, who may otherwise have been excluded because of PH. MATERIAL AND METHODS: We analyzed the hemodynamic results of six men (aged 47 to 61) with well-grounded OHT indications and PH diagnosed by a transpulmonary gradient (TPG) > 12 mmHg and/or PVR > 2.5 Wood units. Patients underwent a PH reversibility test with sodium nitroprusside (NPS) to achieve normal TPG and PVR results without a drop in systolic arterial pressure <85 mmHg. Unresponsiveness to NPS was shown in all subjects, who were subsequently qualified for sildenafil therapy (50 mg bid). RESULTS: After 1 month of sildenafil, three subjects achieved normal TPG and PVR, and acceptable responsiveness of PH to NPS in two other patients, all of whom qualified for OHT. Therapy was unsuccessful in one patient, which was confirmed also by right heart catheterization after 3 months of sildenafil use. Therapy was well tolerated in all patients, namely, no significant drop in arterial pressure on angiotensin-converting enzyme inhibitors. CONCLUSIONS: Sildenafil may be effectively used for treatment of secondary, irreversible PH in potential heart transplant recipients.

Usefulness of stanford scale of intimal hyperplasia assessed by intravascular ultrasound to predict time of onset and severity of cardiac allograft vasculopathy.

BACKGROUND: The purpose of this study was to assess the prognostic value of a single IVUS result described by the Stanford scale to predict CAV development. METHODS: Inclusion criteria were heart transplantation (OHT) before 1997 and at least one IVUS performed before 1998. IVUS studies were performed in 37 patients at 37 +/- 26 months after OHT. Based on the Stanford scale, were divided patients into Four groups: group I (grade 0 or 1): n = 4, 42 +/- 19 years, 2 men/2 women; group II (grade 2): n = 10, 44 +/- 15 years, 9 men/1 woman; group III (grade 3): n = 11, 48 +/- 11 years, 11 men; and group IV (grade 4): n = 12, 46 +/- 8 years, 12 men. We compared the incidence and time of onset of clinically significant CAV, namely significant coronary lesions, myocardial infarction and death caused by CAV. RESULTS: There was no CAV diagnosed in group I. The rates of CAV in coronary angiograms in groups II, III and IV were: 80%, 36%, and 75%, respectively. Significant CAV was found in 30%, 9%, and 50% of patients, respectively. Average times of onset of any CAV in groups II, III and IV were 4.9, 5.6, and 3.3 years, and for significant CAV were 4.1, 3.6, and 5.5 years, respectively. Deaths in groups I to IV were 1, 4, 2, and 5, respectively. CAV was the reason for death in 1 patient from group III, and 3 patients from group IV. CONCLUSIONS: Extreme grades on the Stanford scale (0, 1, and 4) describing a single IVUS study in OHT recipients appear useful to stratify patients with the lowest versus the highest risk of CAV development.

Usefulness of pulmonary hypertension reversibility test with sodium nitroprusside in stratification of early death risk after orthotopic heart transplantation.

AIM: To assess the prognostic value of a PH reversibility test with NPS to predict early death risk after orthotopic heart transplantation (OHT). MATERIALS AND METHODS: We analyzed the results of 94 consecutive OHT procedures performed from 2002 to 2003. Pulmonary vascular resistance (PVR) and transpulmonary gradient (TPG) were assessed as part of the routine pre-OHT evaluation. PH was excluded in 57 patients (61%, group A); TPG > or = 12 mmHg and/or PVR > 2.5 Wood units were observed in 37 patients (39%). Sixteen patients underwent a PH reversibility test with NPS: 9 patients (group B) achieved normal TPG and PVR without a drop in systolic arterial pressure (BP(s) > 85 mmHg), while a marked decrease of BP(s) (< 85 mmHg) during NPS infusion was observed in 7 patients (group C). Then, 21 patients were selected for OHT despite PH without any reversibility test. We compared the number of early deaths after OHT among groups (chi-square test). RESULTS: The 30-day death rate was 7% in group A, 11% in group B, 71% in group C, and 29% in group D. (A vs C, P = .0001 and A vs D, P = .03). Right ventricle or biventricular failure was the cause of death in 1 patient in group A, 1 patient in group B, 5 patients in group C, and 6 patients in group D (A vs C, P < .0001 and A vs D, P = .0012). CONCLUSION: PH reversibility revealed with NPS does not increase the risk of early death after OHT unless there is an absence of marked fall in systemic pressure.