Search

Background: Continuous-flow left ventricular assist devices (LVADs) have been extensively used in a strategy of bridge to orthotopic heart transplant and destination therapy. The usage of LVAD, however, is not free from limitations such as device-related adverse events, including pump thrombosis (PT). We aimed to develop an algorithm of early PT detection based on the maintenance parameters monitored by the implanted device., Methods: We analyzed log files of 101 patients implanted with HeartWare pump (HVAD) with 18 PT events among them. For signal processing, we used the open-high-low-close format transformation and typical price (TP) technical analysis indicator. Model parameters were tuned with 5-fold cross-validation, and the final performance was measured on a separate group of patients., Results: Our algorithm achieved 100% sensitivity and 100% specificity of indications. In the final evaluation, alarms preceded the clinical acknowledgement of events by 2 days and 20 h on average. In the worst-case scenario, an alarm was raised 1 day and 8 h prior to the event., Conclusions: The proposed algorithm could be installed to work directly with the device controller and provide clinicians with automatic readings analysis, raising an alarm when there is a high probability of thromboembolism. Early event detection could enable better thrombosis management and improve prognosis in patients implanted with HVAD., (© 2022 International Center for Artificial Organs and Transplantation and Wiley Periodicals LLC.)

Heart transplantation is performed in patients with end-stage heart failure. The number of suitable donors for patients on the urgent heart transplantation waiting list is still low, and effort has been made to increase the number of suitable donors, including extended-criteria donors. We present a case report of heart retransplantation because of graft failure from an hepatitis B core antibody (anti-HBcore-positive, HBcAb [+]) and HBs antigen-negative (HBsAg [-]) donor to a seronegative recipient. We show that the procedure, with the use of antiviral prophylaxis, is a safe option for the recipient. Based on anatomopathologic and histopathologic examination of the explanted graft, we also suggest that acute cellular rejection in the transplanted heart may exist despite negative findings in right-sided endomyocardial biopsy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: An increasing number of patients with end‑stage heart failure implies a wider use of left ventricular assist devices (LVADs). Irreversible pulmonary hypertension (PH) is a predictor of unfavorable prognosis and a contraindication to orthotopic heart transplant (OHT)., Aims: The aim of this study was to evaluate the effect of continuous‑flow LVAD (CF‑LVAD) support on pulmonary pressure and pulmonary vascular resistance (PVR) as well as the impact of pre‑LVAD hemodynamic parameters on survival during LVAD support., Methods: Data collected from 106 patients who underwent CF‑LVAD implantation in the years 2009 to 2018 (men, 95.3%; mean [SD] age, 51.8 [12] years; mean [SD] INTERMACS profile, 2.9 [1.6]; mean [SD] LVAD support time, 661 [520] days; follow‑up until May 2019) were retrospectively analyzed., Results: Right heart catheterization was performed before LVAD implantation in 94 patients (88.7%), after implantation-in 31 (29.2%), and before and after implantation-in 28 (26.4%). We observed mean pulmonary artery pressure (mPAP) >25 mm Hg in 65 patients (61.3%) and PVR >2.5 Wood units in 33 patients (31.1%) before LVAD implantation. A significant improvement after CF‑LVAD implantation was noted in mPAP, pulmonary capillary wedge pressure, transpulmonary gradient, PVR, cardiac output (P <0.001 for all parameters), and cardiac index (P = 0.003). All patients with initially irreversible PH became eligible for OHT during LVAD support. Survival during LVAD support did not depend on initial mPAP and PVR., Conclusions: In patients with end‑stage heart failure, CF‑LVAD support leads to a significant reduction of pre‑ and postcapillary PH. Survival on CF‑LVAD support is independent of elevated mPAP and PVR before implantation, which suggests that LVADs decrease the risk associated with PH.

Oxidative stress is defined as an imbalance between the production of free radicals and their elimination by the antioxidant defense system. However, the role of oxidative stress in cardiac allograft vasculopathy (CAV) has not been fully understood. Therefore, this study is aimed at determining the role of oxidative-antioxidative balance disturbances in patients after HT. Furthermore, we sought to analyze factors associated with the presence of CAV, with particular emphasis placed on oxidative stress markers. The study analyzed data of 194 consecutive patients after HT who underwent routine visits in the Transplantation Clinic between 2015 and 2016. Total oxidant status (TOS) and total antioxidant capacity (TAC) were measured by the method described by Erel. The oxidative stress index (OSI) was defined as the ratio of the TOS to TAC levels. Patients' mean age was 55.4 ± 15.0 years, and 73.4% were men. The frequency of CAV was 50%. The area under the receiver operating characteristic curves indicated a good discriminatory power of TAC and TOS (0.8940 (0.8515-0.9365); 0.8620 (0.8126-0.9114), respectively) as well as excellent discriminatory power of OSI (0.9530 (0.9279-0.9781)) for CAV detection. Multivariate analysis of the Cox proportional hazard model confirmed that OSI (hazard ratio (HR) = 1.294 (1.204-1.391), p < 0.0001), age (HR = 1.023 (1.006-1.041), p = 0.0091), and high-sensitivity C-reactive protein (HR = 1.049 (1.016-1.083), p = 0.0151) were independently associated with CAV presence. In conclusion, TAC and TOS had a good discriminatory power and OSI had excellent strength for detecting CAV. The independent factors of CAV were higher OSI and CRP levels, as well as older recipient age., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2020 Wioletta Szczurek et al.)

Introduction: An increasing number of patients with end‑stage heart failure, along with a shortage of heart donors, necessitates the use of mechanical circulatory support., Objectives: This single‑center retrospective study evaluated short- and long term outcomes of continuous‑flow left ventricular assist device (CF LVAD) therapy in patients with end stage heart failure., Patients and Methods: We collected and assessed data of 79 patients (77 men, 2 women; mean age, 50.3 years; mean INTERMACS profile, 3.1) implanted with a CF‑LVAD between 2009 and 2017 (HeartMate 3 in 19 patients [24%]; HeartMate 2 in 9 [11.4%]; and HeartWare in 51 [64.6%])., Results: The mean time on CF-LVAD support was 604 days (range, 1–1758 days). There were 2 device exchanges due to pump thrombosis and 1 explantation due to heart regeneration; 9 patients (11.4%) underwent heart transplant. Stroke (nondisabling, 48%) occurred in 27.8% of patients (ischemic in 9 patients; hemorrhagic, in 14; both types, in 1) despite the standardized anticoagulation regimen. Major gastrointestinal bleeding and pump thrombosis were reported in 13 patients (16.5%), while 18 patients (22.8%) developed driveline infections (recurrent in 15 patients [19%]). Hemorrhagic stroke and bacteremia had a negative impact on survival. Hemorrhagic stroke was the main cause of death. Survival probability was 0.9 at 1 month and 0.81, 0.71, 0.61, and 0.53 at 1, 2, 3, and 4 years, respectively., Conclusions: Although CF‑LVAD support is associated with substantial adverse events, they do not significantly affect mortality (except hemorrhagic stroke and bacteremia). Novel devices seem to overcome these limitations, but larger studies are needed to support these findings.

BACKGROUND Cardiac allograft vasculopathy is a major cause of cardiac allograft rejection. Percutaneous coronary intervention has become the main form of treatment of significant focal lesions. Despite the significance of the problem, data remain scarce. With a large population of transplant recipients undergoing coronary angiography at our center, we decided to analyze the implications of the use of everolimus-eluting second-generation stents by performing 6-month clinical and angiographic follow-up. MATERIAL AND METHODS From December 2012 and August 2019, 319 patients after heart transplantation undergoing coronary angiography at our institution were analyzed. Subsequently, 22 patients underwent de novo angioplasty with second-generation everolimus-eluting stents. The primary study endpoint was angiographic restenosis as evaluated by quantitative coronary angiography. Secondary outcomes included binary restenosis, target lesion revascularization, and cardiac death during the follow-up period (6 months). RESULTS Patient comorbidities included hypertension (77.3%), type 2 diabetes mellitus (68.2%), dyslipidemia (68.2%), and obesity (31.8%). Primary success was obtained in all of the treated lesions. The analysis of quantitative coronary angiography after 6-month follow-up revealed low late lumen loss (0.22±0.40). Significant restenosis was observed in 1 of the cases. There were no deaths in the 6-month observation period. CONCLUSIONS In the analyzed population, invasive strategy with second-generation everolimus-eluting stents for de novo lesions in cardiac allograft vasculopathy resulted in a low rate of binary restenosis, low late lumen loss, and no deaths during the 6-month follow-up.

Introduction: The study is a prospective clinical observation of patients after orthotopic heart transplantation in a large academic medical center in relation to COVID-19 morbidity. The study population was comprised of 552 patients. All patients were consulted and advised by telephone as regards the prophylaxis of SARS-CoV-2 infection. Hospital and outpatient follow-ups were limited to the minimum. Preventive modification of immunosuppression was not recommended in relation to the pandemic. Three patients with multiple comorbidities (a woman aged 60, a man aged 59, and another man aged 83; 2.25 years, 5.5 years, and 7.5 years after heart transplantation, respectively) and one patient with concomitant arterial hypertension (a woman aged 48, 5.5 years after heart transplantation) presented with a symptomatic COVID-19 infection. Three of the patients were on tacrolimus immunosuppression, and both female patients were additionally on therapy with mycophenolate mofetil, which was discontinued following the diagnosis of infection. One male patient received combined therapy of cyclosporine A and mycophenolate mofetil. The 60-year-old woman presented with gastrointestinal manifestations of the COVID-19 infection which were of moderate severity. The recovery was achieved. The 59-year-old man presented with myocardial infarction, exacerbated renal insufficiency that required hemodialysis and cardiorespiratory failure complicated by bacterial sepsis. As a result, the patient died. The 83-year-old male patient reporting fever, myalgia, fatigue, cough and dyspnea was admitted to hospital and deceased due to septic shock two days after admission. The 48-year old woman who presented with mild symptoms of the upper respiratory tract infection recovered after two weeks. Symptomatic treatment was used in all the patients. Another male patient (aged 45 years, 8 years after orthotopic heart transplant with no significant comorbidities) was an asymptomatic carrier of SARS-CoV-2 and remained under hospital care., Conclusions: Of 552 patients after orthotopic heart transplantation, two SARS-CoV-2-related deaths were reported., (© National Institute of Public Health – National Institute of Hygiene.)

Patients with severe heart failure (HF), who are not eligible for cardiac transplantation and receive optimal medical management, based mainly on the use of pharmacological treatment and devices such as resynchronization therapy (implantable cardioverter-defibrillator), achieve poor clinical outcomes and constitute a group with extremely poor prognosis. Currently, the technology used in the latest generation left ventricular assist devices (LVADs), such as the HeartMate 3, makes it possible to achieve patient survival at the level obtained by patients after heart transplantation, and they can be used not only in patients eligible for heart transplantation as a bridge to transplant, but also in those with significantly worse prognosis, who are ineligible for heart transplantation as destination therapy. The objective of this publication is to present recommendations from experts in cardiology and cardiac surgery, supported by clinical trial results, on the use of LVADs as a destination therapy in HF patients who are not eligible for cardiac transplantation. The paper also presents the issue of cardiac transplantation and extracorporeal membrane oxygenation therapy in Poland, as well as current challenges faced by interventional cardiology and cardiac surgery in Poland.

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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

BACKGROUND Recent advances in ultrasound strain imaging facilitate more precise monitoring of subtle myocardial changes and thus may allow for more appropriate assessment of myocardium after orthotopic heart transplantation (OHT). This study aimed to explore longitudinal left ventricular (LV) and right ventricular (RV) function by speckle-tracking echocardiography (STE) during a 12-month follow-up period in relation to acute cellular rejection (ACR) degree ≥2R and the response to intense immunosuppressive therapy with intravenous steroids. MATERIAL AND METHODS Forty-five adult heart transplant recipients were prospectively assessed at a single center from January 2016 until June 2017. Echocardiography was performed serially at baseline and together with routine biopsies at 2 weeks and 1, 2, 3, 6, 9, and 12 months after OHT. Changes in graft function were evaluated using STE before and during ACR and in the resolving period of ACR. RESULTS A total of 220 pairs of biopsy specimens and strain recordings were analyzed. Moderate ACR was seen in 30 biopsies (13.6%). In the serial assessment, longitudinal strain parameters of the LV (global and 4-, 2-, 3-chamber longitudinal strain) and RV (global and free wall longitudinal strain) were decreased at baseline and improved significantly (P<0.001) within 12 months after OHT. The degree of improvement was not influenced by ACR. There were no significant differences in circumferential, radial, or longitudinal strain rate, or mechanical dyssynchrony. Reduced LV and RV longitudinal strain was related to ACR degree 2R and increased significantly (P<0.0005) during 3 days of intravenous methylprednisolone therapy. CONCLUSIONS Using the STE technique, we have documented an acute improvement in mechanical myocardial function following ACR steroid therapy and a progressive recovery of LV and RV longitudinal function during the first year after OHT.

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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: The aim of the study is to describe both professional and social activities of patients after heart transplant., Material and Methods: Ninety-five heart transplant patients treated at the Silesian Center for Heart Diseases in Zabrze were surveyed, comprising 29 women (30.5%) and 66 men (69.5%). The average age of respondents was 54.3 years old (standard deviation (SD) = 15 years); the average period that had elapsed since the heart transplant was 7.1 years (SD = 4 years). We designed a questionnaire as a tool for collecting information from patients., Results: Twenty-five percent of patients worked at the time of completion of the questionnaire. Eighty percent of those patients were working before and after the transplant, 20%--only after transplantation (p < 0.05). A different job position at a new workplace had 47.8% of patients, 34.8% of them had the same job position at the same work place as they had had before, 63.4% of the heart transplant respondents were pensioners. Eighty-two percent of patients had a certificate with a designated degree of disability--among them: 69% had a certificate for a significant degree of disability, 22%--for a moderate degree of disability. Among those surveyed, 52.5% said that their financial situation had not changed whereas 34.5% of those surveyed reported a change for the worse. Thirty-seven percent of respondents reported changes in family relationships. Seventy-seven percent reported that they received help from family members, as compared with 19% who did not., Conclusions: Only 25.3% of the patients treated at the Silesian Centre for Heart Diseases after heart transplant are employed and it is one of the lowest employment rates in this category of patients in Europe. One third of working patients have the same work place as they had before their operation. Heart transplant is a cause of changes in family relationships. Most often family bonds are strengthened but sometimes family members become nervous, impatient and unwilling to talk about the transplant., (This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.)

Background: Identification of risk is essential to prevent cardiac allograft vasculopathy (CAV) and graft failure due to CAV (GFDCAV) in heart transplant patients, which account for 30% of all deaths. Early CAV detection involves invasive, risky, and expensive monitoring approaches. We determined whether prediction of CAV and GFDCAV improves by adding inflammatory markers to a previously validated atherothrombotic (AT) model., Methods and Findings: AT and inflammatory markers interleukin-6 (IL-6) and C-reactive protein (CRP) were measured in heart biopsies and sera of 172 patients followed prospectively for 8.9±5.0 years. Models were estimated for 5- and 10-year risk using (1) the first post-transplant biopsy only, or (2) all biopsies obtained within 3 months. Multivariate models were adjusted for other covariates and cross-validated by bootstrapping. After adding IL-6 and CRP to the AT models, we evaluated the significance of odds ratios (ORs) associated with the additional inflammatory variables and the degree of improvement in the area under the receiver operating characteristic curve (AUROC). When inflammatory markers were tested alone in prediction models, CRP (not IL-6) was a significant predictor of CAV and GFDCAV at 5 (CAV: p<0.0001; GFDCAV: p = 0.005) and 10 years (CAV: p<0.0001; GFDCAV: p = 0.003). Adding CRP (not IL-6) to the best AT models improved discriminatory power to identify patients destined to develop CAV (using 1st biopsy: p<0.001 and p = 0.001; using all 3-month biopsies: p<0.04 and p = 0.008 at 5- and 10-years, respectively) and GFDCAV (using 1st biopsy: 0.92 vs. 0.95 and 0.86 vs. 0.89; using all 3-month biopsies: 0.94 vs. 0.96 and 0.88 vs. 0.89 at 5- and 10-years, respectively), as indicated by an increase in AUROC., Conclusions: Early inflammatory status, measured by a patient's CRP level (a non-invasive, safe and inexpensive test), independently predicts CAV and GFDCAV. Adding CRP to a previously established AT model improves its predictive power.

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.

Background: Even though coronary angiography (CAG) underestimates coronary allograft vasculopathy (CAV) development, especially in the distal parts of arteries, it remains a frame of reference for International Society for Heart and Lung Transplantation (ISHLT) CAV classification. A retrospective analysis was performed to assess the prognostic value of CAG findings., Methods: Among 310 orthotopic heart transplantation (OHT) recipients with at least 2 CAGs at 2-year intervals, we identified 197 (146 men and 41 women; 55 ± 13 years) without lesions (Group 0), 27 (15 men and 12 women; 58 ± 8 years) in whom mild changes remained in consecutive CAGs (Group 1), 28 (24 men and 4 women; 58 ± 10 years) in whom mild lesions decreased in consecutive CAGs (Group 1REG), and 58 (53 men and 5 women; 56 ± 10 years) in whom the stenosis criteria of ISHLT CAV 2 or 3 were covered (Group 2). We compared survival and other clinical variables among the groups., Results: The average follow-up was 10 ± 4 years. Forty-one (21%) deaths occurred in Group 0, 15 (56%) in Group 1 (p = 0.002), 9(31%) in Group 1REG (p = NS), and 26 (46%) in Group 2 (p = 0.004, chi-square test). Time free from all-cause death was significantly shorter in Group 1 (T1/2 = 8 years) than in Group 0 (T1/2 = 15.5 years; p = 0.00072, log-rank test). Time free from cardiovascular death was significantly shorter in Groups 1 and 2, as was time free from CAV-related death in Groups 1, 1REG, and 2. Multivariate analysis, using a Cox proportional hazards model, revealed that Group 1 inclusion criterion of CAG findings is an independent predictor of all-cause death, cardiovascular death, and CAV-related death., Conclusions: Persistent mild coronary lesions, observed in consecutive CAG, predicted shorter survival of OHT recipients., (© 2013 International Society for Heart and Lung Transplantation Published by International Society for the Heart and Lung Transplantation All rights reserved.)

Background: For over 40 years now orthotopic heart transplantation (OHT) has been the treatment of choice in patients with advanced heart failure. For many years patients undergoing OHT have been treated with the classical approach involving anastomosis of the donor atria with the recipient atria resulting in a heart in which the atria are enlarged. An alternative method for OHT is the bicaval anastomosis technique, which involves connecting both of the donor's venae cavae with the recipient's venae cavae., Aim: To assess left ventricular (LV) filling in patients undergoing OHT using the classical (biatrial) versus bicaval approach., Methods: We analysed 60 patients who had undergone OHT between 1 and 36 months before. Myocardial biopsy at echocardiography revealed grade 0 or 1A rejection in all the patients. All the patients were also in NYHA functional class I. The patients were divided in two groups: patients who had undergone biatrial anastomosis (Group 1, n = 40) and patients who had undergone bicaval OHT (Group 2, n = 20). In order to render the results independent of pre-OHT blood pressure values in the pulmonary circulation we assessed the values of right ventricular systolic pressure (RVSP), mean pulmonary artery pressure (PAP) and transpulmonary gradient (TPG) in all the patients before OHT. We assessed the following echocardiographic parameters: peak early filling velocity (E-wave), peak atrial filling velocity (A-wave), E-wave deceleration time, early diastolic mitral valve ring motion velocity (E'), E/E', isovolumetric relaxation time of the LV, duration of the A-wave, right atrial area and left atrial area, LV mass, LV mass index, LV end-diastolic and end-systolic dimension, and the severity of tricuspid regurgitation (TR)., Results: The values of RVSP, PAP and TPG in the study groups before OHT did not differ significantly. The values of E (86.5 ± 12.5 vs. 67.3 ± 8.5; p < 0.001), E' (11.9 ± 1.1 vs. 10.9 ± 0.9; p = 0.003) and E/E' (7.4 ± 1.5 vs. 6.1 ± 0.85; p = 0.006) differed between the groups and were significantly higher in the group undergoing surgery using the biatrial approach. The duration of the A-wave was significantly longer in the group undergoing surgery using the bicaval approach (129.0 ± 5.1 vs. 136.7 ± 10.0; p = 0.001). There were no significant differences in the other parameters of LV filling. Right atrial area was significantly lower in the group undergoing surgery using the bicaval approach (19.2 ± 3.0 vs. 14.0 ± 2.0; p < 0.001). LV size, LV mass and LV mass index did not differ significantly between the groups. The lack of TR was more commonly observed in the group undergoing surgery using the bicaval approach at the limit of p = 0.05. Pacemaker implantation was required in 12 (30%) patients from the group undergoing surgery using the classical method and 2 (10%) patients from the group undergoing OHT using the bicaval approach (p = 0.04)., Conclusions: Certain echocardiographic parameters suggest a better LV filling in patients undergoing OHT using the bicaval approach. Preservation of the right atrial geometry in patients undergoing OHT using the bicaval approach plays an important role in LV filling.

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., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: The aim of this study was to assess the effect of early steroid withdrawal on renal function, diabetes mellitus (DM) and coronary artery vasculopathy of the transplanted heart (CAV) development and late rejection in orthotopic heart transplant (OHT) recipients., Material/methods: 76 patients undergoing OHT in years 2000-2004 (6 women, 50% ischemic, 49±7 years, BMI 24±3.6, glomerular filtration ratio (GFR) - 68-20 ml/kg/min, LVEF 57±6%) receiving maintenance immunosuppression (cyclosporine, prednisone and azathioprine or mycophenolate mofetil) were observed for 5 years in groups, depending on steroid withdrawal time: Group 1 (N=48) - withdrawal later than 12 months post-OHT, Group 2 (N=28) - withdrawal up to 12 months post-OHT. Number of serious rejection episodes (SRE >ISHLT grade 2), time to first SRE after steroid withdrawal (TTSRE), need for steroid reinforcement, CAV presence, need for percutaneous coronary intervention (PCI), DM and abnormal GFR were compared between groups. P<0.05 was significant., Results: Steroids were administered for 615±188 days in group 1 (G1) and 309±96 days in group 2 (G2). There was a difference between group 1 and 2 in the number of SREs before 12 months (2.4±1.6 vs. 1.6±1.3) and before steroid withdrawal (2.4±1.6 vs. 1.5±1.3), but not in number (0.15±0.62 vs. 0.14±0.36) and percent of patients with an SRE (8.3 vs. 14.3%) after steroid withdrawal. There was no difference in TTSRE (314±312 vs. 199±122 days), need for steroid reinforcement (6.3 vs. 14.3%), time from steroid withdrawal to reinforcement (377±317 vs. 246±130 days), CAV (8.3 vs. 3.6%), PCI (4.2 vs. 3.6%), GFR 60-90 ml/kg/min (30.8 vs. 20.0%), and GFR <60 ml/kg/min (64.1 vs. 80.0%) at 5 years. DM was diagnosed in 58.3 and 71.4% of patients at discharge (p=NS) and in 51.3 and 80% at 5 years in group 1 and 2, respectively (p=0.018)., Conclusions: Patients with earlier steroid withdrawal presented DM and tended to present more severe stages of kidney failure more often. Despite lower frequency of CAV, they tended to require PCI equally often.

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., (Copyright © 2011 Elsevier Inc. All rights reserved.)

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., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Restrictive spirometry pattern is commonly associated with chronic heart failure (CHF), but its prognostic value is poorly documented. Utility of Lower Limit of Normal (LLN)-based spirometry interpretation has not yet been evaluated in CHF patients. Impact of restrictive pattern defined according to classic or LLN criteria on prognosis in CHF patients was therefore addressed., Material/methods: 171 CHF patients on long-term beta-antagonist treatment with PeakVO2 >12 ml/kg/min (147 men, 49±9 years, LVEF 26±8%, 51% ischemic) were divided into groups based on their spirometry: Group 1A (N=129) - classic criteria: no restriction, Group 2A (N=12) - classic criteria: restrictive pattern, Group 1B (N=90) - LLN criteria: no restriction, Group 2B (N=26) - LLN criteria: restrictive pattern. PeakVO2 in the study groups equaled 12.1-19.9 ml/kg/min. Control group (N=30) - PeakVO2 >20 ml/kg/min, absence of restriction or obstruction (FEV1%FVC ≥70) defined by classic criteria. Classic criteria: VCin% <70 and FEV1%FVC ≥70. LLN criteria: VCin%

Background: Thyroid hormones are essential for the correct functioning of the entire body. Diagnosis of thyroid disorders in patients after heart transplant in the early post-operative period and the implementation of correct treatment may prevent life-threatening complications., Material/methods: The aim of the study was to determine whether the complicated postoperative course (ie, hypothyroidism, hyperthyroidism or low fT3 syndrome) in patients in the first month after heart transplantation was connected with impaired thyroid hormone management. The analysis encompassed material from 98 patients treated with heart transplantation between February 9, 2004 and January 4, 2010. Hyperthyroidism was diagnosed in 21 patients (19M/2F, 52±7 years of age), hypothyroidism in was diagnosed in 13 patients (10M/3F, 46±12 years old), and low fT3 syndrome was diagnosed in 18 patients (14M/4F, 43±12 years old)., Results: Patients with fT3 syndrome had the highest mortality (16.7%, NS), highest incidence of acute rejection (38.9%, NS), highest number of reoperations (27.8%, NS), and highest incidence of bacterial (16.7%, NS) and fungal infections (11.1%, NS). Cytomegaloviral infections occurred most frequently in patients with hyperthyroidism (23.8%, NS). Patients with hypothyroidism (84.6%, NS) were hospitalized the longest (>30 days), had the highest tendency towards pleural effusion (23.1%, NS) and pericardial effusion with tamponade (15.5%, NS), bradycardia with pacemaker (15.4%, NS) and renal failure requiring hemodiafiltration (15.4%, NS) (Table 1)., Conclusions: 1. The thyroid test panel should be performed in all patients in the early post-heart transplant period. 2. The diagnosis of thyroid disorders should be immediately followed by correct treatment aimed at restoring the euthyroid state, with a view to facilitate recovery and rehabilitation as well as to shorten the hospitalization time, thereby lowering treatment costs.,

Background: Previous studies have shown conflicting results about the value of heart rate turbulence (HRT) for risk stratification of patients (pts) with chronic heart failure (CHF). We prospectively evaluated the relation between HRT and progression toward end-stage heart failure or all-cause mortality in patients with CHF., Methods: HRT was assessed from 24-hour Holter recordings in 110 pts with CHF (54 in NYHA class II, 56 in class III-IV; left ventricular ejection fraction (LVEF) 30%+/- 10%) on optimal pharmacotherapy and quantified as turbulence onset (TO,%), turbulence slope (TS, ms/RR interval), and turbulence timing (beginning of RR sequence for calculation of TS, TT). TO > or = 0%, TS < or = 2.5 ms/RR, and TT >10 were considered abnormal. End point was development of end-stage CHF requiring heart transplantation (OHT) or all-cause mortality., Results: During a follow-up of 5.8 +/- 1.3 years, 24 pts died and 10 required OHT. TO, TS, TT, and both (TO and TS) were abnormal in 35%, 50%, 30%, and 25% of all patients, respectively. Patients with at least one relatively preserved HRT parameter (TO, TS, or TT) (n = 98) had 5-year event-free rate of 83% compared to 33% of those in whom all three parameters were abnormal (n = 12). In multivariate Cox regression analysis, the most powerful predictor of end point events was heart rate variability (SDNN < 70 ms, hazard ratio (HR) 9.41, P < 0.001), followed by LVEF < or = 35% (HR 6.23), TT > or = 10 (HR 3.14), and TO > or = 0 (HR 2.54, P < 0.05)., Conclusion: In patients with CHF on optimal pharmacotherapy, HRT can help to predict those at risk for progression toward OHT or death of all causes.

Background: Transplanted heart coronary artery disease (TxCAD) may occur in a significant proportion of patients following cardiac transplantation. Drug-eluting stents (DES) have been successfully used in patients with CAD, but their efficacy in TxCAD patients has not been well established., Aim: To compare long-term results of intracoronary implantation of DES and BMS in patients suffering from TxCAD., Methods: We performed a retrospective analysis of all intracoronary stent implantations for TxCAD with at least one control coronary angiography performed during follow-up. We identified 28 DES (all sirolimus-eluting stents, SES) and 28 BMS implantations in 23 patients. The mean follow-up time was 410+/-58 days after DES, and 572+/-434 days after BMS implantation (p=0.004). We compared the occurrence of in-stent restenosis (ISR) in DES and BMS, and survival of patients in the context of risk factors that were identified for each stent implantation separately., Results: There were 2 (7%) ISR revealed in DES patients (mean time from PCI to restenosis 492+/-58 days) vs. 17 (61%) ISR in BMS patients (mean time from PCI to restenosis 475+/-345 days) (p<0.001). There were 3 (18%) deaths in patients with DES, 4 (31%) in patients with BMS, and 1 (14%) in a patient with DES and BMS (NS). The risk factor profile was comparable, except for higher age at the time of transplantation (46+/-7 vs. 41+/-6 years, p=0.011) and stent implantation (54+/-7 vs. 49+/-6 years, p<0.001) for DES., Conclusion: Favourable long-term results of DES compared with BMS implantation for TxCAD suggest the preferential use of DES in heart transplant recipients.

Objective: Kidney injury represents a major clinical problem in orthotopic heart transplant (OHT) patients which seriously increases the mortality rate. The aim of this work was to evaluate the utility of a new kidney damage marker-neutrophil gelatinase-associated lipocalin (NGAL)-and its correlations with cystatin C, creatinine, and glomerular filtration rate (GFR) among patients after heart or lung transplantation., Materials and Methods: We examined serum samples from 71 patients after heart transplantation, 7 patients after lung transplantation, and 20 healthy controls to measure serum NGAL using an enzyme-linked immunosorbent assay (ELISA) method; cystatin C using latex immunonephelometry; and creatinine using the alkaline-picrate method., Results: Serum NGAL levels were significantly elevated among transplant patients, but did not significantly correlate with cystatin C in the transplant group (R = .13; P = .11) or in the control group (R = .26; P = .26), or GFR in the transplant group (R = -.09; P = .25) or in the control cohort (R = .22; P = .36). In the transplant group, serum NGAL positively correlated with serum creatinine (R = .27; P = .001)., Conclusions: Plasma NGAL was not a specific biomarker for monitoring chronic renal disorders. We did not exclude other pathologies that might contribute to increased serum NGAL levels.

Background: Cardiopulmonary exercise testing is an important component of evaluation when orthotopic heart transplantation (OHT) is considered for chronic heart failure (CHF) patients. However there is a question about the accuracy of interpretations of peak oxygen consumption (VO(2)max) used at present., Materials and Methods: We analyzed 302 CHF patients stratified into 3 groups according to VO(2)max (mL/kg/min): group 1 = <10 (n = 37); group 2 = 10-14 (n = 121) and group 3 = >14 (n = 144). We compared the mortality rate, the OHT rate, time to OHT, time to death and pulmonary function tests (PFT) among the groups using ANOVA Kruskal-Wallis tests for analysis in Statistica 7.1., Results: No important differences were observed between groups 1 and 2 (P > .05), but first in comparison with group 3 (P < .05) in terms of mortality (48.6% vs 33.1% vs 21.5%), number of OHT (24.3% vs 32.2% vs 14.6%), time to death (15.4 vs 16.6 vs 34.4 months) or PFT results (forced expiratory volume in the first second forced vital capacity and peak expiratory flow, all as direct or as percent of normal values). In contrast, time to OHT (4.6 vs 6.9 vs 10.9 months) and percent of normal vital capacity (72% vs 81% vs 91%) differed significantly among all groups (P < .05)., Conclusion: Patients with VO(2)max between 10 and 14 or <10 mL/kg/min are at similar risk of death.

Background: Morphometric studies based on the measurement of cardiocyte nuclei have focused on progressive hypertrophy rather than shape, which is a deciding factor for the diagnosis of hypertrophy in myocardial diseases. The aim of this research was to demonstrate how the digital morphology of cardiocyte nuclei change correlated with the type of myocardial pathology., Materials and Methods: The study groups encompassed 7 hearts with dilated cardiomyopathy (DCM) and 8 hearts with ischemic heart disease (IHD) which were explanted. A comparative group consisting of myocardial hypertrophy was contrasted with a control group of donor heart fragments. Cardiocyte nuclei were evaluated morphometrically on histologic slides. We calculated the nuclear area, length, breadth, perimeter, roundness, elongation, fullness factors, and nuclear chromatin mean gray level. The results were subjected to discriminant analysis., Results: All karyometric measurements analyzed by backward discriminant analysis showed only 2 powerful factors: nuclear breadth and chromatin mean gray level. The Mahalanobis distance showed the proximity of control and hypertrophy groups, whereas differences between IHD and DCM were nonsignificant., Conclusion: The lack of karyometric differences between IHD and DCM suggested a common morphologic response for long-lasting progressive injury. The main morphologic differences were dependent on nuclear chromatin activity/stainability and nuclear breadth, suggesting darker and thinned nuclei in normal and adaptative stages and irregular brighter nuclei in cardiomyopathies.

Background: According to the World Health Organization, iodine excreted in urine is a measure of its supply. According to the International Council for Control of Iodine Deficiency Disorders (ICCIDD), the urinary iodine (UI) should be >100 microg I per 1 liter of urine. Severe deficiency (SID) is diagnosed when UI is <50 microg/L and a moderate deficiency (MID) when UI is <100 microg/L., Materials and Methods: UI analysis among 32 heart transplant recipients (26 men and 6 women); of overall mean age of 50.4 +/- 12.6 years was performed using the modified Program Against Micronutrient Malnutrition method, a spectrophotometric measurement based on the Sandell-Kolthoff reaction. Results were compared with those of thyroid stimulating hormone (TSH; microIU/mL), of free tri-iodothyronine (FT3; pg/mL), and thyroxine (FT4; ng/dL)., Results: The average UI among the whole group was 126.4 +/- 109.6 microg/L. SID occurred in 12 patients (37.5%) and MID in 4 (12.5%); namely, mean UI of 17.0 +/- 9.6 and 79.5 +/- 5.6, respectively. In the other 16 patients (50%), the average UI was high, namely, 220.1 +/- 72.1 IU/mL. TSH, FT3, and FT4 in the whole group were within normal ranges. However, FT4 values significantly differed when SID and MID patients were compared with those displaying the recommended UI: 0.8 +/- 0.2 and 0.9 +/- 0.1 versus 1.1 +/- 0.2 respectively (P < .05). We noted decreased values of TSH in 5 patients (15.6%) and of FT3 or FT4 in 6 subjects (18.8%)., Conclusion: There exists significant iodine deficiency among heart transplant recipients. Measurements of urinary iodine together with thyroid gland hormones may be essential to prevent thyroid gland disturbances in these patients.

Oxidized low-density lipoproteins (ox-LDL) have been shown to be strongly atherogenic and immunogenic in experimental animals and in humans. Autoantibodies against ox-LDL and its various epitopes have been detected in sera and in atherosclerotic lesions. LDL oxidation may also lead to generation of oxidized derivatives of cholesterol (eg, 7-ketocholesterol [7-ketoCh]), which are characterized by high levels of cytotoxicity, muta- and carcinogenicity, as well as immunosuppressive effects and probable immunogenic properties. The aim of this study was to quantify autoantibodies to 7-ketoCh in sera from patients after orthotopic heart transplantation (OHT). IgG antibodies were measured in sera from 81 patients after OHT and 73 healthy volunteers using and enzyme-linked immunosorbent assay (ELISA) method. For the antigen we used 7-ketoCh hemisuccinate conjugated to bovine serum albumin. Anti-7-ketoCh antibodies were detected in all examined sera. Their concentrations were significantly higher among OHT patients than the control group, namely, 109.0 +/- 109.7 vs 53.5 +/- 20.0 U/mL (P < .005). Also, we observed a direct relationship between antibody concentration and time after OHT. Our results showed that the low molecular product of LDL oxidation, 7-ketoCh, was immunogenic possibly playing a role in the progression of atherosclerosis among OHT patients.

Background: Chronic heart failure and airway obstruction produce overlapping syndromes. Existent criteria for the diagnosis and grading of airway obstruction based on spirometry results may be inadequate in the presence of coexistent cardiac failure. The cardiac component of pulmonary function tests (PFT) can be measured in patients undergoing orthotopic heart transplantation (OHT)., Materials and Methods: Before and 1 year after OHT between 2006 and 2008 PFT were performed in 29 patients according to existent guideline. Willcoxon matched pair tests were used for analysis in Statistica 7.1. The general group characteristic included age, gender, New York Heart Association class, CCS class, body mass index, present medications, blood and chemistry tests, as well as exercise tolerance tests, right heart catheterization, and echocardiography results., Results: One year after OHT we observed significant improvements in forced expiratory volume in the first second (FEV1) and its percent of normal value (FEV1%) as well as forced vital capacity (FVC), FVC%, vital capacity (VC) and VC%: namely, 2.56 L versus 2.96 L; 82% versus 93%; 3.30 L versus 3.81 L; 85% versus 97%; 3.38 L versus 4.04 L and 85% versus 100% (all P < .01). FEV1 and FVC increments of: 0.39 and 0.471 respectively, exceeded the cutoff point of 12% of predicted value established as the spirometry criterion for reversibility of obstruction. Elimination of heart failure by OHT did not significantly change the FEV1 to FVC ratio (FEV1%FVC)., Conclusion: Chronic heart failure contributed to significant FEV1 reduction, which limits the usefulness of PFT for diagnosis and grading of airway obstruction. FEV1%FVC, the main diagnostic criterion of chronic obstructive lung disease, seems to be an index independent of concomittant heart function impairment.

Unlabelled: Most methods used in the risk assessment of heart transplant candidates do not include new biomarkers., Aims: The aim of the study was to examine the value of NTproBNP and hsCRP and their combined use together with HFSS score in the risk assessment of patients with heart failure enlisted for heart transplantation., Methods: Data of 658 patients enlisted for heart transplantation in all active transplantation centers were stored in a prospective registry. The composite end point-death or urgent transplantation was recorded during the follow-up., Results: Death or urgent transplantation was recorded in 161 (24%) of pts. 102 (15%) patients died and 59 (9%) were transplanted urgently. Kaplan-Meier curves for risk of death or urgent transplantation where highly significant when pts were stratified by the quartiles of NT proBNP (P < .000001) or quartiles according to the hsCRP level on admission (P < .002). In the multivariate Cox proportional hazard model, the significance was observed for NTproBNP (P < .01) and HFSS (P < .02), and borderline significance for hsCRP (P = .057). When ROC analyses of the area under the curve (AUC) values were considered, AUC area was for HFSS - 0.645, for NTproBNP - 0.653 and for hsCRP - 0.566. When all those variables were included together in the model, the AUC value rose to 0.6943. Based on those results a weighted risk model with all three parameters was proposed., Conclusion: HFSS, NTproBNP and hsCRP levels are independent stratification variables of survival or need for urgent heart transplantation. Their predictive value is moderately increased when they are analyzed together.

Background: Despite morphologic differences of lymphocytes aggregation between nonrejection (0 on the International Society for Heart and Lung Transplantation [ISHLT] scale) and moderate focal cellular rejection (1a, ISHLT), genetic and clinical differences have not been shown in Cardiac Allograft Rejection Gene Observation (CARGO) studies. Therefore, we sought to compare the expression of selected antigens associated with apoptosis in heart transplant recipients in the context of grade 0 versus grade 1a cellular rejection episodes. We assessed the expression of annexin V, a nonspecific apoptosis marker, Bcl-2 as opposed to antiapoptotic activity of Bcl-xL and Bcl-xL/S., Materials and Methods: We retrospectively examined 17 heart transplant patients (2 women and 15 men) of overall mean age of 46.2 +/- 13.9 years and body mass index of 25.7 +/- 3.2. Ten biopsies showed rejection grade 0 and the other 10, grade 1a on the ISHLT scale, comprising groups A and B, respectively. Endomyocardial biopsy specimens were processed using routine immunohistochemical methods. The expression of apoptotic molecules was assessed according to the IHC method: 0, the lack of expression; 1, trace; 2, distinct; and 3, strong. A correlation was analyzed between particular molecular expressions., Results: We observed a significant increase in Bcl-2 expression associated with rejection. The expression of other antigens did not show a significant tendency. No correlation was noted among group A, whereas in group B those were significant strong and negative correlations with Bcl-2 and Bcl-xL/S., Conclusion: Bcl-2 expression corresponded to the morphologic progression of graft rejection as opposed to Bcl-xL/S activity.

Introduction: The aim of the study was to examine the potential relation between microvasculopathy observed in endomyocardial biopsies (EMBs) and clinical coronary vasculopathy (CAV) after orthotopic heart transplantation (OHT)., Materials and Methods: We preformed a retrospective analysis involving 68 OHT patients in whom the procedure was performed before 1999. The CAV(+) group consisted of 37 subjects (35 males/2 females) of overall mean age of 45 +/- 11 years. Ischemic cardiomyopathy was the diagnosis in 57% of the cohort that displayed CAV established by angioplasty, myocardial infarction, or CAV-related death. The control group contained 31 subjects (24 male/7 female) of overall mean age of 43 +/- 16 years. The pretransplant diagnosis was ischemic c-pathy in 39%. These subjects displayed negative coronary angiography at 10 years after OHT. Based upon studies early after OHT 55 subjects were divided based on the myocardial blush grade (MBG) upon coronary angiography performed between 4th and 6th week after surgery: one cohort of six individuals showed decreased MBG (6 males) of mean age 52 +/- 7 years. There was prior ischemic c-pathy in 50%. In contrast, 49 subjects showed a normal MBG (43 males/67 females) of overall mean age of 45 +/- 12 years. Ischemic c-pathy had been present in 39%. Microvasculopathy was defined as the presence of prominent endothelial cells, vacuolation of the endothelium, thickening of the basal membrane and/or muscle layer, the presence of lymphocytes in the arteriolar wall, periarteriolar fibrosis, or stenotic arteriolar lumenia in the 12- and 36 month EMB (CAV groups) or the 4-week EMB (MBG groups)., Results: Rejection grades were comparable in CAV(+) and CAV(-) groups, but decreased in normal MBG group. The only significant difference was observed in the occurrence of basal membrane thickening, which was present in 22% of subjects from the CAV(+) group and 3% of individuals from the CAV(-) group in the 12-month EMB., Conclusion: Microvasculopathy observed early or late after OHT was not related to angiographically confirmed CAV.

Background: Aim of the study was to localize advanced glycation end products (AGEs) in late endomyocardial biopsies (EMBs) of orthotopic heart transplant (OHT) recipients with and without diabetes mellitus (DM) to correlate their presence with acute rejection episodes (ARE) and cardiac allograft vasculopathy (CAV)., Materials and Methods: Elective EMBs were performed at 3 years post-OHT in 64 subjects, with DM (59 M/5 F), of overall mean age of 49 +/- 8 years and 24 patients, without DM (21 M/3 F), of overall mean age of 42 +/- 10y. Localization of myocardial AGEs in paraffin sections was assessed immunochemically using mouse monoclonal anti-AGE antibodies (clone 6d12) on cardiomyocytes, stromal cells, connective tissue elements and capillaries., Results: The occurrence of AGEs was similar in DM versus non-DM subjects: namely, cardiocytes 73% versus 63%, stroma 33% versus 33%, connective tissue 13% versus 9%, and capillaries 31% versus 33%, respectively. Only in the DM group. The acute rejection episodes and mean EMB score significantly correlated with AGE presence in cardiomyocytes (r = 0.29/0.3; P = .02/.02; Spearman). There was no relation between AGE occurrence and CAV diagnosis among DM subjects, while the time free from angiographically confirmed CAV or a CAV-related event was significantly shorter among non-DM recipients without AGEs in capillaries and/or cardiocytes (P = .014/.017/.014/.03, respectively; log-rank)., Conclusion: AGE occurrence in OHT recipients with DM was related to ARE, but not to CAV; in contrast, among non-DM patients it was not correlated with ARE, but their absence predicted CAV.

Introduction: The aim of the study was to analyze the influence of body weight of the adult heart recipient on the chance to obtain a transplant., Methods: We analyzed the data from all 658 patients listed for heart transplantation., Results: During the follow-up period, 325 (49%) of listed patients underwent transplantation with 102 (15%) succumbing before heart transplantation. The mean weight of transplanted patients was 73.7 +/- 13.7 kg and 81.2 +/- 15.4 kg for those not transplanted (P < .00001). Patients were divided according to body weight in two groups: light = below 80 kg (n = 360) or heavy > or = 80 kg or above (n = 297). On the transplant list, 111 heavy patients (37%) versus 213 light patients (59%) underwent the procedure, a significant difference. The waiting time among light patients was 255 versus heavy patients of 395 days (P < .005). There was a similar number of deaths before transplantation among the light (n = 56 360 patients; 15.5%) versus the heavy group (49/297; 16%). Upon multivariate Cox mode analysis independent factors related to not receiving a heart transplant were greater weight, systolic blood pressure, pulmonary vascular resistance, Heart Failure Survival Score (HFSS) score and lower N-terminal pro-brain natriuretic peptide (NTproBNP) levels., Conclusions: Among adult heart transplant candidates, the chance to receive a heart transplant significantly decreased when the recipient's weight exceeded 80 kg. Patients with a body weight more than 110 kg had a poor chance to receive a heart transplantation.

Background: Antiapoptotic as well as replacement and proliferative mechanisms take place in the myocardium in dilated cardiomyopathy (DCM) and ischemic heart disease (IHD). We sought to estimate antiapoptotic, proliferative and replacement activities in cardiomyopathies., Materials: The study groups included seven hearts with DCM and eight with IHD, which had been explanted at the time of transplantation. The comparator group consisted of cases of myocardial hypertrophy and the control group, donor fragments., Methods: Antiapoptotic and proliferative responses were determined immunohistochemically as Bcl-2 and Ki67 expression by semiquantitative assessment of the intensity of staining. We also measured and statistically analyzed the integrative morphometric measurements of the fraction of fibrosis area, the nucleosarcoplasmic ratio, and cardiocyte diameter., Results: No Bcl-2 expression was observed in the controls. The strongest reaction was seen in the DCM group, then in the IHD, and in the comparator group of myocardial hypertrophy. Proliferative activity was seen only in endocardial and interstitial fibroblasts in DCM and IHD cases. The cardiocyte diameter showed no statistical association between myocardial hypertrophy and IHD, or IHD and DCM, whereas the nucleosarcoplasmic ratios were significantly different from control groups for all comparisons. Myocardial fibrosis showed the highest values in DCM and IHD. Discriminant analysis showed the value of interstitial fibrosis and cardiocyte diameter to categorize the analyzed groups., Conclusions: Antiapoptotic Bcl-2 activity seemed to play an important role in cardiocyte preservation, while proliferative activity was resticted to interstitial connective tissue cells as a replacement process. Myocardial Bcl-2 expression, the extent of myocardial fibrosis, and cardiocyte diameter may serve as additional diagnostic tools to differentiate cardiomyopathies.

Fortynine heart transplant recipients were evaluated during the first weeks after orthotopic heart transplantation. Using the ICD-10 (International Classification of Diseases-10th revision) criteria, we studied the incidence of anxiety disorders as well as 17 demographic and medical factors potentially influencing the probability of their occurrence. A smaller 36-person group was evaluated using standard psychopathologic scales for anxiety and mood disorders. Cox regression analysis was used to specify which of 11 demographic and medical factors influenced the time to occurrence of the first episode of a mental disorder. Anxiety episodes occurred in 25 patients, depressive episodes in 27, (hypo)manic in 3, and 12 manifested a slightly elevated mood. The risk of occurrence of anxiety and mood disorders was highest during the first 3 weeks after OHT. "False alarms," namely, calls to the clinic not ending up in transplantation, and coexisting illnesses were related to higher incidences and earlier appearance of anxiety and mood disorders. The risk of occurrence of an anxiety syndrome was greater among older patients. Anxiety syndromes were manifested earlier in patients who underwent transplantation due to ischemic cardiomyopathy than in patients with heart failure caused by other factors. A greater number of false alarms, of long-lasting hospitalizations, and of low mean cyclosporine levels were risk factors for depressive episodes.

Background: Clinical studies with intravascular ultrasound have suggested that even subclinical cytomegalovirus (CMV) infections increase intimal hyperplasia in transplanted heart coronary arteries after 1 year. The potential influence of CMV on microvasculopathy development is not known. The Aim of our study was to compare the occurrence of microvasulopathy in endomyocardial biopsies (EMBs) of heart transplant recipients with versus without CMV infection., Materials and Methods: We performed a case-controlled, retrospective study of 58 subjects diagnosed with CMV infection by the presence of pp65 antigen. The 49 men and 91 women of overall age 49 +/- 8 years showed ischemic cardiomyopathy in 52%. We matched a control cohort of 58 subjects without CMV disease. Microvasculopathy was assessed using 4-degree grading system developed by Hiemann et al for elective EMBs performed at 1 and 12 months after transplantation., Results: Significant acute rejection episodes were observed among 22% versus 21% of 1-month EMBs, and 3% versus 5% of 12-month EMBs for CMV(+) versus control group subjects respectively. The commonest microvasculopathy was nonstenotic thickening (grade B) 60% versus 59% (35 versus 34 patients) among 1-month EMBs; and 50% versus 60% (29 vs 35 patients) among 12-month EMBs, respectively. Progression of microvasculopathy score between 1- and 12-month EMB was observed in 40% versus 41% of subjects, and regression occurred in 22% versus 21%, respectively. None of differences was significant., Conclusion: Our data do not support the thesis that CMV infection promotes microvasculopathy development among heart transplant recipients.

Objective: Acute cellular rejection in heart transplants is characterized by an active lymphocytic infiltration, whereas the humoral response shows complement deposits in myocardial tissue. Both reactions may produce hemodynamic compromise during the first months after orthotopic heart transplantation (OHT). The aim of this study was to estimate the coexistence of humoral rejection symptoms in the first posttransplant biopsy with mild/moderate cellular rejection as an additional prognostic factor., Materials and Methods: The study group included 13 biopsies obtained from 11 men and 2 women of overall mean age of 52.6 +/- 5.3 years who displayed International Society for Heart and Lung Transplantation (ISHLT) mild/moderate rejection grades. The control group consisted of 11 biopsies obtained from 8 men and 3 women of overall mean age of 54.8 +/- 3.6 years with no signs of rejection. Complement deposits were determined immunohistochemically using anti-C4d antibodies (Quidel Corporation)., Results: None of the control cases showed a positive reaction, whereas 3 men in the study group of mean age of 56.1 +/- 5.8 years revealed regional positive anti-C4d expression with cellular infiltrates. This expression occurred in all myocardial components adjacent to lymphocytic infiltrations. The survival rates were comparable in both the pure cellular versus the mixed rejection groups. The relative rate of grade 3 rejection in the posttransplantation period was increased among patients with mixed types of rejection., Conclusions: The term "mixed acute rejection" should be applied to cases with coincidence of 2 forms of acute rejection. It seemed to be associated with more frequent grade 3 rejection processes upon long-term follow-up.

Objective: The aim of this study was to assess the predictive value of microvascular abnormalities and lipofuscin observed in endomyocardial biopsy samples for the development of cardiac allograft vasculopathy., Methods: The study group consisted of 68 cardiac allograft recipients (63 men and 5 women, 43 +/- 12 years old). We performed a re-evaluation of 1071 endomyocardial biopsy specimens to search for microvascular diseases and lipofuscin in cardiocytes. Endomyocardial biopsy specimens with an International Society for Heart and Lung Transplantation rejection grade of 2 or more and those without arterioles were excluded. Abnormalities found in the remaining 517 specimens were correlated with the grade of rejection. Biopsy specimens obtained 2 weeks, 12 months, and 36 months after transplantation were compared with coronary angiography results, clinical events of cardiac allograft vasculopathies, and survivals. Kaplan-Meier curves were constructed to compare the time to the development of cardiac allograft vasculopathy or death., Results: Enlarged endothelial cells, lymphocytes inside the arteriolar wall, occluded arteriolar lumen, endothelial vacuolization, and hypertrophy of the vascular muscle were significantly correlated with rejection grade. Although none of the vascular abnormalities predicted cardiac allograft vasculopathy, patients with lipofuscin deposits at the 12-month biopsy specimens were characterized by the rapid development of angiography-confirmed cardiac allograft vasculopathy (P < .08) and events related to cardiac allograft vasculopathy (P < .03, log-rank test)., Conclusion: Microvascular abnormalities correlate with mild cellular rejection, but they do not seem to be predictive for development of cardiac allograft vasculopathy detected by angiography. The presence of lipofuscin in 12-month endomyocardial biopsy specimens may be predictive of development of angiographically confirmed cardiac allograft vasculopathy.

Background: The appropriate therapy after orthotopic heart transplantation (OHT) is determined by the results of endomyocardial biopsies (EMBs). The Quilty effect (QE) is a recognized cause of discrepancies in EMB grading, but its clinical implications remain unclear. In this study we assess the correlation of the QE with biopsy-proven acute cellular rejection (AR) and coronary artery vasculopathy (CAV)., Methods: We reassessed 5,361 EMB samples, obtained from 429 patients, based on QE occurrence and its impact on EMB score. Next, we divided all patients with at least 1 year of follow-up into two groups: a QE(+) group (n = 202, 58.7% of sample, 172 males/30 females, 44.8 +/- 12 years of age) and a QE(-) group (n = 142, 41.3% of sample, 124 males/18 females, 45.4 +/- 12 years of age), and compared AR and CAV occurrences., Results: The QE was observed in 669 EMBs (12.5%), and at least 1 EMB with QE was found among the 231 patients (53.8%). The initial QE occurrence took place during the first 3 months after OHT in 68% of QE(+) patients, and >1 year post-OHT in 13% of patients. The average EMB score was significantly higher in QE(+) biopsies. A comparison of the two groups revealed a significantly higher number of AR episodes and number of patients with at least one episode of AR in QE(+) patients. There was no significant difference in number of CAV occurrences between groups., Conclusions: The QE seems to be a marker of the same increased immune system activity that can lead to AR. A relationship between QE and CAV was not supported by the present results.