Role of Pro-Brain Natriuretic Peptide Serum Concentration in the Detection of Pulmonary Hypertension in Patients With End-Stage Lung Diseases Referred for Lung Transplantation.

BACKGROUND: Serum N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration is elevated in patients with pulmonary hypertension (PH); however, its role in the detection of PH associated with lung disease is not well established. AIM: The aim of this study was to assess the value of NT-proBNP in the detection of PH in patients with end-stage lung disease (esLD) referred for lung transplantation. MATERIALS AND METHODS: The study population consisted of 65 patients: 37 with idiopathic pulmonary fibrosis (IPF), 20 with chronic obstructive pulmonary disease, and 8 patients with other interstitial lung diseases (75% men, mean age 53.3 ± 9.5 years). Serum concentration of NT-proBNP was assessed with an immunoradiometric assay kit. The mean pulmonary artery pressure (mPAP) was measured using a Swan-Ganz catheter. PH was defined as mPAP ≥ 25 mm Hg. RESULTS: Median NT-proBNP concentrations were significantly higher in patients with PH than in patients without PH: 139 (49-1236) pg/mL vs 67 (38-116) pg/mL, respectively; P = .016. Receiver operating characteristic (ROC) analysis revealed that NT-proBNP concentration higher than 131.5 pg/mL was a predictor of PH with good specificity (81%) and positive predictive value (78.9%) but low sensitivity (55.6%) and negative predictive value (58.6%). The area under the ROC curve of serum NT-proBNP concentration for PH was 0.71 (95% confidence interval 0.57-0.85, P = .039). CONCLUSION: Serum concentration of NT-proBNP may be useful in the diagnosis of PH in patients with esLD referred for lung transplantation.

Prognostic Value of Mean, Diastolic, and Systolic Pulmonary Artery Pressure in Patients With End-stage Lung Disease Referred for Lung Transplantation.

BACKGROUND: Pulmonary hypertension (PH) is a common complication in end-stage lung disease (esLD). The aim of this study was to establish the best threshold values for mean, systolic, and diastolic artery pressure (mPAP, dPAP, and sPAP, respectively) to identify patients with esLD referred for lung transplantation and to predict 1-year prognosis. METHODS: Sixty-five patients were enrolled in the study (75% men) with a mean age of 53.3 ± 9.5 years; 31% had chronic obstructive pulmonary disease (COPD), 57% had idiopathic pulmonary fibrosis (IPF), and 12% had interstitial lung diseases (ILDs). The mean period of observation was 14.4 ± 5 months. We assessed invasively mPAP, dPAP, and sPAP, as well as pulmonary capillary wedge pressure (PCWP), using a Swan-Ganz catheter. Receiver-operating characteristic (ROC) curves were constructed to identify the best cutoff points for mPAP, dPAP, and sPAP to predict survival. The study endpoint was defined as 1-year mortality before transplantation. Survival analysis was completed according to the Kaplan-Meier method. RESULTS: During follow-up, 30 (46.1%) patients died and 19 (29%) underwent lung transplantation. Based on ROC curve analysis, we estimated mPAP ≥30 mm Hg, dPAP ≥20 mm Hg, and sPAP ≥44 mm Hg as the best threshold values with the highest sensitivity (70%, 70%, and 73%, respectively) and specificity (76%, 69%, and 72%, respectively) and the acceptable area under curve (0.67, 0.68, and 0.72, respectively). The negative predictive values for mPAP, dPAP, and sPAP were higher than the positive predictive values (79%, 77%, and 81% vs 67%, 61%, and 64%, respectively). We also constructed Kaplan-Meier curves for mPAP, dPAP, and sPAP threshold values. There were significant differences in 1-year survival between patients with and without PH for mPAP, dPAP, and sPAP threshold values (P = .005, P = .035, and P < .001; respectively). CONCLUSION: Elevated mPAP, dPAP, and sPAP are related to worse prognosis in patients with esLD referred for lung transplantation.

Predictive Value of Models for End-Stage Liver Disease Score in Patients With Pulsatile Flow POLVAD MEV Left Ventricular Assist Device Support.

BACKGROUND: Model for End-Stage Liver Disease (MELD) score predicts multisystem dysfunction and death in patients with heart failure (HF). Left ventricular assist devices (LVADs) have been used for the treatment of end-stage HF. AIM OF THE STUDY: We evaluated the prognostic values of MELD, MELD-XI, and MELD-Na scores in patients with POLVAD MEV LVAD. MATERIALS AND METHODS: We retrospectively analyzed data of 25 consecutive pulsatile flow POLVAD MEV LVAD patients (22 men and 3 women) divided in 2 groups: Group S (survivors), 20 patients (18 men and 2 women), and Group NS (nonsurvivors), 5 patients (4 men and 1 woman). Patients were qualified in INTERMACS class 1 (7 patients) and class 2 (18 patients). Clinical data and laboratory parameters for MELD, MELD-XI, and MELD-Na score calculation were obtained on postoperative days 1, 2, and 3. Study endpoints were mortality or 30 days survival. MELD scores and complications were compared between Groups S and NS. RESULTS: 20 patients survived, and 5 (4 men and 1 woman) died during observation. Demographics did not differ. MELD scores were insignificantly higher in patients who died (Group 2). Values were as follows: 1. MELD preoperatively (21.71 vs 15.28, P = .225) in day 1 (22.03 vs 17.14, P = .126), day 2 (20.52 vs 17.03, P = .296); 2. MELD-XI preoperatively (19.28 vs 16.39, P = .48), day 1 (21.55 vs 18.14, P = .2662), day 2 (20.45 vs 17.2, P = .461); and 3. MELD-Na preoperatively (20.78 vs 18.7, P = .46), day 1 23.68 vs 18.12, P = .083), day 2 (22.00 vs 19.19, P = .295) consecutively. CONCLUSIONS: The MELD scores do not identify patients with pulsatile LVAD at high risk for mortality in our series. Further investigation is needed.

Left Ventricular Assist Device Implantation in Patients With Optimal and Borderline Echocardiographic Assessment of Right Ventricle Function.

BACKGROUND: Left ventricular assist devices (LVADs) are used for treatment of end-stage heart failure. Outcomes are dependent on right ventricle (RV) function. Prediction of RV function after LVAD implantation is crucial for device selection and patient outcome. The aim of our study was to compare early LVAD course in patients with optimal and borderline echocardiographic parameters of RV function. MATERIAL AND METHODS: We retrospectively reviewed 24 male patients with LVAD implantation. The following echocardiographic data of RV function were collected: FAC (fractional area change) with optimal value > 20%, tricuspid annulus plane systolic excursion >15 mm, RV diameter < 50mm, and right-to-left ventricle ratio < 0.57 (RV/LV). Patients were divided into group 1 (12 patients) with transthoracic echocardiography parameters in optimal ranges and group 2 (12 patients) with suboptimal transthoracic echocardiography findings. Study endpoints were mortality, discharge from the intensive care unit, and RV dysfunction. Demographics, postoperative clinical outcomes, comorbidities, complications, and results in a 30-day period were analyzed between groups. RESULTS: Echocardiography parameters differed significantly between groups 1 and 2 according to FAC (31.8% vs 24.08%; P = .005), RV4 (45.08 mm vs 51.69 mm; P = .02), and RV/LV ratio (0.6 vs 0.7; P = .009). Patients did not differ according to course of disease, comorbidities before implantation, or complications. One patient from each group died. Patients in group 2 experienced more pulmonary hypertension, required increased doses of catecholamines, and stayed in the intensive care unit longer. No RV dysfunction was noted. CONCLUSIONS: Borderline FAC, tricuspid annulus plane systolic excursion, and RV4 add RV/LV ratio prolonged recovery after LVAD implantation even with no RV failure. Parameters chosen for qualification are in safe ranges.

Speckle-Tracking Echocardiography for Monitoring Acute Rejection in Transplanted Heart.

BACKGROUND: The diagnosis of acute cellular rejection (ACR) is a major objective in the management of heart transplant recipients. The aim of this study was to assess the utility of speckle-tracking derived parameters in identifying patients at risk of graft rejection. METHODS: A prospective, single-center study was carried out involving 45 consecutive heart transplant patients who underwent a total of 220 routine endomyocardial biopsies (EMBs) with correlative echocardiographic examination. RESULTS: No significant ACR (grade 0-1R) was seen in 190 biopsies (81.2% of the ACR-free group), and moderate ACR requiring specific treatment (grade 2R) was detected in 30 biopsies (13.6% of the ACR group). Grade 3R was not observed. All longitudinal left ventricular (LV) and right ventricular (RV) strain parameters were greater in the ACR-free group than in patients with ACR, while no differences were observed between radial and circumferential strain parameters. In our analysis, we selected RV free wall longitudinal strain (RV FW) ≤ 16.8% and 4-chamber longitudinal strain (4CH LS) ≤ 13.8%, which related to the presence of ACR requiring treatment. We assigned 1 point for each parameter (minimum 0, maximum 2 points) and derived a new echocardiographic index, the Strain Rejection Score (SRS). Our proposed approach-a combination of the 2 abovementioned indices-for screening patients at risk of ACR ≥ 2R, when expressed by a score 2 points, showed good specificity, strong negative predictive value, and the highest area under the curve. CONCLUSIONS: Our study demonstrated that combination of 4CH LS and RV FW as a new echocardiographic index, the Strain Rejection Score, can be useful as a noninvasive assessment of ACR during the first year of follow-up after heart transplant.

Red Blood Cell Distribution Width in End-Stage Heart Failure Patients Is Independently Associated With All-Cause Mortality After Orthotopic Heart Transplantation.

BACKGROUND: Red blood cell markers (RBCM) have been found to be predictors of mortality in various populations. However, there is no information regarding the association between the values of RBCM and long-term outcomes after orthotopic heart transplantation (OHT). The aim of this study was to assess whether the values of inflammatory markers and RBCM obtained directly before OHT are associated with mortality in patients diagnosed as having end-stage heart failure undergoing OHT. METHODS: We retrospectively analyzed data of 173 nonanemic adult patients diagnosed as having end-stage heart failure undergoing primary OHT between 2007 and 2014. Clinical and laboratory data were obtained at the time of admission for the OHT. RBCM were analyzed using an automated blood counter (Sysmex XS-1000i and XE-2100, Sysmex Corporation, Kobe, Japan). RESULTS: Mean age of the patients was 54 (41-59) and 72% of them were male. During the observation period, the mortality rate was 32%. Multivariable analysis of Cox proportional hazard confirmed that elevated pretransplantation red blood cell distribution width value (hazard ratio [HR], 1.38 [1.25-1.48], P < .001) was the sole independent predictor of death during long-term follow-up. Other red blood cell distribution width such as mean corpuscular volume, mean corpuscular hemoglobin concentration, and mean corpuscular hemoglobin (HR, 0.88 [0.84-0.91]; P < .001; HR, 0.75 [0.53-1.05]; P < .05; HR, 0.78 [0.64-0.96]; P < .05, respectively) had predictive value in univariable analysis. CONCLUSIONS: In summary, we have demonstrated that elevated red blood cell distribution width immediately before OHT is an independent predictor of all-cause mortality in heart transplant recipients. Other factors associated with posttransplantation mortality include lower values of mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration.

Predictive Value of the Model for End-Stage Liver Disease Score Excluding International Normalized Ratio One Year After Orthotopic Heart Transplantation.

BACKGROUND: The Model for End-Stage Liver Disease (MELD) scoring system incorporating a combination of hepatic and renal laboratory parameters does not adequately reflect the degree of multi-organ dysfunction in patients with heart failure, who need oral anticoagulation. In order to exclude the impact of oral anticoagulation on the international normalized ratio (INR), we used the MELD excluding INR (MELD-XI) score. The aims of the study were to calculate the individual preoperative MELD-XI score and its ability to predict 1-year mortality after heart transplantation and to identify other preoperative laboratory prognostic parameters. METHODS: We retrospectively analysed data of 87 consecutive adults undergoing heart transplantation between 2011 and 2014. Clinical data and laboratory parameters for the calculation of the MELD-XI score were obtained at the time of admission for the heart transplantation. RESULTS: The average age of the patients was 48.8 ± 13.3 years and 68.9% of them were male. During the observation period, the mortality rate was 18.4%. Multivariate analysis of Cox proportional hazard confirmed that the pretransplantation MELD-XI score (hazard ratio [HR] = 1.625 [1.286-2.053]; P < .001), sodium serum concentration (HR = 0.824 [0.677-1.001]; P < .05) and highly sensitive C-reactive protein (hs-CRP) serum concentration (HR = 1.045 [1.008-1.083]; P < .02) were independent predictors of death during the first year after heart transplantation. Area under the receiver operating characteristic (ROC) curve (AUC) indicated a good discriminatory power of MELD-XI (AUC 0.997; P < .04) and plasma sodium concentration (AUC 0.901; P < .01) in death prediction. CONCLUSIONS: Our study confirms that the pretransplantation MELD-XI score, as well as serum sodium and hsCRP concentrations, may be used to estimate postoperative risk in heart transplant recipients during a 1-year follow-up.

BRCA1 Reflects Myocardial Adverse Remodeling in Idiopathic Dilated Cardiomyopathy.

BACKGROUND: The role of BRCA1 in chronic ischemic episodes seems to be pivotal for adverse remodeling and development of ischemic cardiomyopathy, because of its role in DNA repair and apoptosis. The aim of this study was to investigate the role of BRCA-1 in idiopathic dilated cardiomyopathy (IDCM). MATERIAL AND METHODS: The study group (IDCM) comprised myocardial samples from hearts explanted before transplantation owing to IDCM in 10 males (age 44 ± 5.3 years) without clinical symptoms of ischemic heart disease. The control group consisted myocardial fragments taken from 10 male heart valve and pulmonary artery donors with diagnosed cerebral death (age 40 ± 2.3 years). BRCA1 was detected immunohistochemically with rabbit anti-BRCA1 polyclonal antibody. The intensity of BRCA1 expression was semiquantitatively assessed for cardiocytes, small vessels including capillaries, and interstitial cells. The significances between groups were estimated using the Mann-Whitney U test. RESULTS: All IDCM cases were positive and presented nonuniform BRCA1 expression: hypertrophied cardiocytes showed very intense staining and typical cardiomyopathic cardiocytes were stained weakly forming mosaic. Control cases showed weak-to-moderate uniform staining. Intensity of staining was significantly higher in IDCM cardiocytes, whereas small vessels and interstitial were stained similarly in both groups. CONCLUSIONS: IDCM adverse remodeling results in more intense but nonuniform BRCA1 expression. This phenomenon seems to reflect IDCM biology: lower BRCA1 expression in myocytes with lower anti-apoptotic and DNA damage repair activity, with the opposite in hypertrophied myofibers.

Perioperative Risk Factors of Cardiac Allograft Vasculopathy in the Long-Term Follow-up.

BACKGROUND: Cardiac allograft vasculopathy (CAV) still remains to be one of the most important limiting factors for heart transplant recipients' long-term survival. The aim of our study was to identify the perioperative risk factors impacting the occurrence of CAV during the long-term follow-up. METHODS: We retrospectively analysed the data from 198 consecutive adult patients, who underwent heart transplantation between 2007 and 2012, in whom at least one routine coronarography (CAG) was performed. CAV onset was defined as any lesion seen at least at one routine CAG. RESULTS: The average follow-up was 63.6 ± 14.7 months. The frequency of CAV in the analysed population was 36 (18.1%). Multivariate stepwise logistic regression analysis confirmed that NT-proBNP plasma concentration directly before heart transplant [logNT-proBNP OR = 16.455 (4.587-31.036), P < .0001], fibrinogen plasma concentration a month after heart transplant [OR = 1.022 (1.009-1.035), P < .001] and occurrence of diabetes [OR = 12.355 (1.417-35.750), P < .001], were independent predictors of CAV. Area under the ROC curves (AUC) indicated a well discriminatory power of plasma fibrinogen [AUC 0.9278, P < .001] and plasma NTproBNP concentration [AUC 0.9514, P < .001] in CAV prediction. The optimal cut-off value of fibrinogen was 509 mg/dL, and of NT-proBNP was 10080 pg/mL. CONCLUSIONS: Our data show that NT-proBNP and fibrinogen plasma concentrations as well as occurence of diabetes, both preexisting and new onset after heart transplant can be used to identify patients at risk of developing CAV.

Predictive Value of Hepatic and Renal Dysfunction Based on the Models for End-Stage Liver Disease in Patients With Heart Failure Evaluated for Heart Transplant.

BACKGROUND: The evaluation of prognosis and determination of a long-term treatment strategy is an important element of management in patients with heart failure (HF). METHODS: The aim of the study was to determine the prognostic value of the Model for End-Stage Liver Disease (MELD) and its modifications, MELD and serum sodium (MELD-Na) and MELD excluding the international normalized ratio (MELD-XI), as well as other independent risk factors for death during a 4-year follow-up. We analyzed retrospectively 143 patients with advanced HF, evaluated for heart transplant between 2009 and 2011. Patients using warfarin were excluded from the study. The long-term follow-up data were obtained during follow-up visits and/or phone contact with the patients or their families. RESULTS: The age of the patients was 54 (48-59) years and 88.1% of patients were male. Mortality rate during the follow-up period was 49%. The MELD scores (hazard ratio [HR], 1.12; P < .001), as well as serum high-sensitivity C-reactive protein (hs-CRP; HR, 1.01; P < .01) and N-terminal pro-brain natriuretic peptide (NT-proBNP; HR, 1.01; P < .05) levels, were independent risk factors for death. Receiver operator characteristic analysis indicated that a MELD cutoff of 10 (area under the curve [AUC], 0.756; P < .0001], MELD-XI cutoff of 13.0 (AUC, 0.720; P < .0001), MELD-Na cutoff of 13.0 (AUC, 0.813; P < .0001), hs-CRP cutoff of 4.02 (AUC, 0.686; P < .001), and NT-proBNP cutoff of 1055 (AUC, 0.722; P < .001) were the best predictive values as predictors of death. CONCLUSIONS: MELD, MELD-Na, and MELD-XI scores are prognostic factors for death during a 4-year follow-up. A high MELD score is an independent prognostic factor for death. NT-proBNP and hs-CRP serum concentrations are other independent factors influencing death.

Comparison of Mechanical Circulatory Support by the Use of Pulsatile Left Ventricular Assist Devices Polvad MEV and Continuous Flow Heart Ware and Heart Mate II in a Single-Center Experience.

BACKGROUND: Mechanical circulatory support is increasingly used in patients with heart failure as a bridge to transplant or recovery. Results of use the Polish POLVAD MEV pulsatile circulatory support system and its comparison with novel devices never was done. We compared the course of patients with left ventricular circulatory support (left ventricular assist device [LVAD]) supported by POLVAD MEV or continuous flow devices Heart Mate II (HM II) and Heart Ware (HW) in single-center cohort. METHODS: We retrospectively reviewed 44 patients who underwent Polvad Mev (group P; n = 24 [21M/3F]) or HW or HM II (group C; n = 20 [20M/0F]) implantation between April 2007 and February 2014. Patients were in INTERMACS 1 (6 in group P and 1 in group C) or 2. Preimplant demographics, and perioperative and postoperative clinical outcomes were reviewed between groups. We analyzed baseline signs of heart failure, comorbidities, complications, and the 30- and 90-day results. RESULTS: Among the groups, age, gender, weight, and cause of heart failure were comparable. Patients in group C suffered more frequently from hypercholesterolemia preoperatively. Patients in group P had more pulmonary complications (7 vs 0) after LVAD implantation and stay longer on intensive care unit than patients in group C (17.61 ± 16.96 vs 9.56 ± 9.42; P = .047). After exclusion, INTERMACS 1 patients it was not significant (14.8 ± 10.8 vs 9.8 ± 9.6 days; P = .065), the 30- and 90-day mortality was comparable. CONCLUSIONS: Implantation of pulsatile POLVAD MEV and continuous flow devices as LVAD support provides comparable results. A greater number of complications in group P can cause increased mortality over a longer observation period.

Effects of Left Ventricular Assist Device Support on End-Organ Function in Patients With Heart Failure: Comparison of Pulsatile- and Continuous-Flow Support in a Single-Center Experience.

BACKGROUND: Limited data exist about the effects of continuous-flow versus pulsatile-flow left ventricular assist devices (LVADs) on end-organ function. We hypothesized that a pulsatile Polvad MEV (PM) would result in outcomes similar to those of similarly ill patients implanted with a continuous-flow LVAD (Heartware [HW] or Heartmate II [HMII]). We aimed to compare renal, hepatic, and hematologic functions in the 1st 30 days of support. METHODS: We retrospectively reviewed patients with 24 PM (21 M, 3 F; group P) and 15 HW and 5 HMII (20 M, 0 F); group C LVAD implantations from April 2007 to February 2014. Creatinine, bilirubin, aspartate (AST) and alanine (ALT) transaminases, hematocrit, platelet count, international normalized ratio (INR), and activated partial thromboplastin time (APTT) parameters were analyzed before implantation and during 30 days of support. Demographic parameters were similar. RESULTS: No significant differences were found between the groups regarding baseline renal, hepatic, or hematologic function. Baseline INR and APTT were significantly higher in group P. Levels of creatinine were similar between groups. They increased from baseline to postoperative day (POD) 1 and then decreased. Bilirubin levels were insignificantly higher in group P. Transaminases were significantly higher in group P (AST in PODs 3-6, ALT in PODs 3-7). INR values were significantly higher at baseline and in POD 0. APTT values were insignificantly higher in group P. CONCLUSIONS: The use of LVAD improved renal and hepatic function in our series. Patients in group P had more decreased hepatic function and presented slower regeneration.

Right Ventricular Function in Patients With Left Ventricular Assist Device Support by Pulsatile Polvad MEV and Continuous-Flow Pumps Heartware and Heartmate II.

BACKGROUND: Left ventricular assist device (LVAD) support is increasingly used in patients with heart failure. The right ventricle (RV) plays a main role in LVAD support. Little is known about the effects of pulsatile Polvad MEV devices or continuouseconds flow pumps on RV function. We compared hemodynamic parameters of RV in patients after implantation of Polvad MEV (PM) and Heartware (HW) or Heartmate II (HMII) LVADs. METHODS: Forty-four patients were retrospectively reviewed after implantation of PM (group P; n = 24 [21 M, 3 F]) or HW or HMII (group C; n = 20 [20 M, 0 F]) LVADs from April 2007 to February 2014. Hemodynamic data-mean pulmonary pressure (mPAP), central venous pressure (CVP), cardiac output (CO), and cardiac index (CI)-were collected before surgery, after surgery, and every 2 hours in the intensive care unit, with the time points numbered from 1 to 120. Right ventricular work (RVW) was calculated according to the equation: RCW = CO × (mPAP - CVP) × 0.0144 (g·m). RESULTS: Baseline characteristic of the patients were similar. mPAP values were similar between groups. CVP values were higher in group P, significantly at time points 5 and 7-33. CO values were higher in group C, significantly from point 3 and almost all the time to point 43. CI reached significance at point 9, 12-14, 16-19, and 30-41. RCW was higher in group P before implantation. Post-implantation RCW values were higher in group C, significantly at time points 19, 20, 32-34, 51-53, and 55-57. CONCLUSIONS: Continuous-flow pumps more effectively optimize RV function than pulsatile LVADs, which can result in more effective prevention of RV failure or insuffiency in that group.

Renal Artery Denervation in Patient After Heart and Kidney Transplantation With Refractory Hypertension.

We describe the case of a 54-year-old patient after renal and heart transplantation in whom uncontrolled hypertension was diagnosed. Despite combined antihypertensive therapy, no significant therapeutic effect was achieved. Clinical assessment of ambulatory blood pressure monitoring (ABPM) revealed the ineffectiveness of a bisoprolol, nitrendypin, klonidyn, ramipryl, furosemide, and doxasosine combination used at high doses. High blood pressure levels with their effect on a hypertrophic transplanted heart (left ventricular mass 254 g) and poor renal graft function (39 mL/kg/min) posed an extremely high risk of future cardiovascular complications, and were the reason to perform a native renal arteries denervation. The procedure was carried out through the right femoral artery with the use of a 6F guiding catheter. During a 1-year observation, significant decreases in ABPM systolic and diastolic blood pressures were observed after the procedure (168/88 mm Hg vs 154/77 mm Hg, respectively). Moreover a significant regression of left ventricular mass (215 g/m(2)) and stable renal graft function were noted. The presented case shows that native renal arteries denervation may be successful and safe in kidney and heart transplant recipients. Moreover, during the 1-year follow-up, the reduction in blood pressure was followed by a reduction in transplanted heart hypertrophy, both leading to regression of cardiovascular risk for the patient.

Fractal analysis of heart graft acute rejection microscopic images.

BACKGROUND: Endomyocardial biopsy to evaluate rejection in the transplanted heart is accepted at the "gold standard." The complexity of microscopic images suggested using digital methods for precise evaluating of acute rejection episodes with numerical representation. The aim of the present was study to characterize digitally acute rejection of the transplanted heart using complexity/fractal image analysis. MATERIAL AND METHODS: Biopsy samples harvested form 40 adult recipients after orthotropic heart transplantation were collected and rejection grade was evaluated according to the International Society for Heart and Lung Transplantation (0, 1a, 1b, or 3a) at transverse and longitudinal sections. Fifteen representative digital microscope images from each grade were collected and analyzed after Sobel edge detection and binarization. RESULTS: Only mean fractal dimension showed a progressive and significant increase and correlation based on rejection grade using longitudinal sections. Lacunarity and number of foreground pixels showed unequivocal results. CONCLUSION: Mean fractal diameter could serve as auxiliary digital parameter for grading of acute rejection in the transplanted heart.

Maternal allergy as a potential source of variability of exhaled nitric oxide in children non-sensitized to common domestic allergens.

The goal of the study is to evaluate the importance of maternal atopy as a potential biological source of variability of exhaled FeNO values in healthy children who were non-asthmatic and non-sensitized to common domestic allergens. The study sample consisted of 61 seven-year old children. Fractional exhaled nitric oxide (FeNO) has been measured by NObreath (Bedfont portable device). Children with reported maternal atopy had significantly higher mean FeNO values (geometric mean =10.7 ppb; 95%CI: 6.7-17.1 ppb) than those who denied it (geometric mean =5.2 ppb 95%CI: 3.9-6.9 ppb) (p=0.010). Neither the correlation between FeNO values and gender, respiratory and eczema symptoms, nor ETS exposure in the prenatal and postnatal period or body mass of children were significant. We also found no significant association of FeNO values with the amount of common domestic allergens measured in the households. The results of the ROC analysis suggested 11 ppb as the cut-off point for FeNO to distinguish groups of healthy children with and without maternal atopy. In conclusion, our study provided some evidence suggesting that maternal atopy may affect FeNO level in children independently of asthma and sensitization status to common domestic allergens. The data should be considered in the interpretation of FeNO levels in clinical practice and setting up FeNO screening criteria for identification of eosinophilic airway inflammation.

Paradox of advanced glycation end-products in late cardiac biopsies of heart transplant recipients.

BACKGROUND: A pilot study of orthotopic heart transplant (OHT) recipients showed that advanced glycation end-product (AGE) deposits were related to acute rejection episodes among subjects with diabetes mellitus (DM); in contrast, among non-DM patients it was associated with prolonged freedom from coronary artery vasculopathy (CAV). However the number of observations in non-diabetic subjects was low. The aim of the current study was to establish the role of AGEs in late endomyocardial biopsies (EMBs) among a larger group of non-diabetic patients. MATERIAL AND METHODS: Elective EMBs were performed at 3 years post OHT in 62 subjects with DM, namely, 57 males and 5 females of overall mean age of 50±8 years versus 92 free of DM, including 79 males and 13 females of mean age 51±13 years. We localized AGEs in myocardial paraffin sections using monoclonal mouse anti-AGE antibodies. The presence of AGEs in cardiomyocytes, stromal cells, capillaries, and arterioles was described with a semiquantitative scale. RESULTS: All-cause deaths, CAV, and CAV-related events were observed in 28% versus 23%, 27% versus 29%, and 15% versus 19% of non-DM versus DM patients (P=NS). The occurrence of AGEs was significantly more frequent among non-DM than DM subjects: cardiocytes, 100% versus 69% (P<.0001); stroma, 54% versus 31% (P=.0037); capillaries, 67% versus 31% (P<.0001); and arterioles, 26% versus 3% (P=.0002; chi-square). Among the DM group, mean EMB score correlated with AGE presence in cardiomyocytes (n=0.29; P<.05, Spearman test) AGE presence had no impact on survival or CAV development. CONCLUSION: AGE presence was more common in late EMB from non-diabetic than diabetic OHT recipients; they had no impact on survival or CAV in non-diabetic patients.

Lymphocyte subtypes CD3+, CD19+, CD16+CD56+, CD4+, CD8+, and CD3+HLA-DR+ in peripheral blood obtained from patients after thoracic organ transplantation.

INTRODUCTION: The aim of this study was to assess peripheral blood lymphocyte subtypes (CD3+, CD19+, CD16+CD56+, CD4+, CD8+, and CD3+HLA-DR+) obtained from thoracic organ recipients at various periods after transplantation. MATERIAL AND METHODS: Seventeen patients after lung transplantation (LT) and 5 patients after heart transplantation (HT) included 13 males (76.5%) and 4 females (23.5%) of overall mean age at the time of transplantation of 46.7±11.55 years and mean body mass index of 21.1±4. Lymphocyte phenotypes were estimated using Simultest IMK Plus. RESULTS: A significant decrease in lymphocytes of the majority of subtypes was observed at 1 year posttransplantation compared with normal ranges: CD19+ B lymphocytes in 56% of patients, CD8+ T cells among 48% and CD16+CD56+ natural killer elements, 56%. In contrast, there were increased numbers of activated lymphocytes (CD3+HLA-DR+). Beyond the 1-year observation, we observed a trend to normalize parameters among the majority of subjects. CONCLUSION: A clear tendency to a decrease number of peripheral blood lymphocytes of various subtypes was observed among thoracic organ recipients in the first year posttransplantation with the exception of activated HLA-DR+ cells. After the first year, there was slow restoration of lymphocytes.

In the era of the universal use of statins dyslipidemia's are still common in heart transplant recipients: a cross-sectional study.

BACKGROUND: Statins are used in orthotopic heart transplant (OHT) recipients to avoid acute rejection episodes (ARE) during the first year after surgery and coronary vasculopathy (CAV) thereafter as established in prospective randomized trials, yielding the grounds for the universal use of this group of drugs. The aim of the study was to describe the occurrence of dyslipidemias among OHT recipients after introduction of guidelines suggesting the use of statins in all individuals able to tolerate this therapy. METHODS: Medical records of all OHT recipients undergoing routine clinical checkups between January and June 2010 were screened for the presence of dyslipidemia: total cholesterol>5 mmol/L; low-density lipoprotein (LDL)-cholesterol>3 mmol/L; triglycerides>1.65 mmol/L; high-density lipoprotein (HDL)<1 mmol/L in the serum. The study group consisted of 322 subjects including 265 males and 57 females of overall mean age of 53.6±12 and 7±4 years after OHT. There was coronary artery disease (CAD) before OHT in 113 (35%). The average number of ARE was 1.9±1.9 and CAV was diagnosed in 77 (24%) patients. There were 247 (77%) patients on statins. We analyzed clinical, ultrasound, and biochemical evaluations to characterize subjects with dyslipidemias. RESULTS: At least one dyslipidemia was observed among 212 (66%) including hypercholesterolemia in 121 (38%), high LDL in 135 (42%), hypertriglyceridemia in 110 (34%), and low HDL in 48 (15%) patients. The subjects with dyslipidemia were prone to be older, to have CAD before OHT, and to be hypertensive, overweight, and obese, as well as display an higher HbA1C when diabetic. They were treated less frequently with tacrolimus but showed higher drug levels, and more often were prescribed everolimus. CONCLUSIONS: Despite almost universal use of statins, dyslipidemias were present in 2/3 of OHT recipients. It was related to typical atherosclerotic risk factors; however, the influence of immunosuppressants seemed to also be significant.

Procalcitonin serum concentration in lung transplant recipients during mold colonization or infection.

BACKGROUND: This publication attempted to evaluate the frequency of mold colonization and infection and the procalcitonin serum concentrations (PCT) among lung transplant recipients. METHODS AND MATERIALS: We included 49 patients (36 males and 13 females) of mean age at transplantation of 47.1±13.6 years. Molds were isolated using routine microbiologic methods. PCT (ng/mL) was measured using an immunoluminescence assay with values below 0.5 showing no probability of infection, 0.5 to 2.0, a moderate infection risk; 2.0 to 10, a high infection risk; and above 10 high sepsis risk. RESULTS: Twenty-four (49%) patients revealed the presence of molds in material from the lower respiratory tract (sputum, tracheal, or tracheobronchial aspirate), mini-bronchoalveolar lavage. Aspergillus species was isolated in 14 (28.6%) patients, Penicillium in 7 (14.3%) patients, and Zygomycetes fungi in 9 (18.4%) patients. The average PCT value from 61 examinations of PCT during fungal isolation was 0.5±0.7 ng/mL. However, when the studied group was categorized according to the PCT range, the rates for the groups were no infection (n=30; 49.2%), moderate (n=20; 32.8%), high (n=9; 14.8%) and high sepsis risk (n=2; 3.3%). CONCLUSIONS: The mold colonization of transplanted lung is a frequent complication and should be considered even in the case of proper prophylaxis. Procalcitonin might be the marker helpful in mold infection diagnosis.