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Abstract: 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. [Copyright &y& Elsevier]

Speckle-tracking echocardiography analysis may identify minor, subtle myocardial dysfunction not detectable by standard echocardiography. This study aimed to explore longitudinal left ventricular (LV) and right ventricular (RV) function in relation to acute cellular rejections (ACRs) degree ≥ 2R and their response to intensify therapy with intravenous steroids. 45 adult heart transplant recipients were prospectively assessed from January 2016 until May 2017. Among the biopsy specimens with ACR grade ≥ 2R, we identified those that underwent echocardiography before the episode of ACR, at the time of pathologic diagnosis, and during therapeutic intervention with 3 days of receiving intravenous steroids. 23 patients (51%) had at least 1 episode of moderate ACR during follow-up, and all these episodes were asymptomatic, with LVEF remaining in the normal range. Complete strain data in the ACR group were collected for 15 patients for all three time points. The cases of biopsy-proven ACR grade 2R were associated with marked reductions in GLS, 4-chamber longitudinal strain (4CH LS), systolic strain rate (SR), RV free wall longitudinal strain (RV FW) and increase of LV mechanical dyssynchrony (SD-TPS) (Tab. 1). There was an acute improvement of all LV and RV longitudinal strain parameters in reaction to appropriate immunosuppressive therapy for ACR in addition to no significant regression of LV mechanical dispersion (Tab. 2). Measurements of LV and RV longitudinal strain are promising tools for the noninvasive assessment of ACR and to guide the pharmacological treatment of rejection. [ABSTRACT FROM AUTHOR]

The aim of study was to echocardiographicly evaluate right ventricular function as a predictor of outcome in COVID 19 patients (pts) who underwent heart transplantation using RV strain and speckle tracking. 15 pts (mean age 47, 12 male 3 female) underwent heart transplantation from October 2020 to May 2021. All pts underwent transthoracic echocardiography for the evaluation of RV free wall longitudinal peak systolic strain RVFWSL, TAPSE, RVd1, RVd2, RVd3, FAC, TRVmax, IVC diam and S'. All pts were PCR positive for SARSCoV2 and had cough, fever and malaise indicative of COVD19, therefore were also radiological signs of COVID19 pneumonia. Also HS troponin, procalcitonin and CRP were elevated. They were treated with antiviral drugs and immune - based therapy including corticosteroids and convalescent plasma, and received standard triple regimen of calcineurin inhibitors (tacrolimus), antimetabolite (Mycophenolan Mofetil).All echocardiographic measurements were obtained from apical 4-chamber RV with focusing on the lateral wall. RvV free wall longitudinal peak systolic strain (RVFWSL) were significantly reduced during infection compared to post infection time (-15% vs -20) and RV four-chamber strain (RV4CSL) (-11,3% vs 21%). The RV function correlated with recovery time among heart transplant patients which was longer and also correlates significantly with acute cellular rejection in myocardial biopsy (10 patients -66,6% had 2R by ISHLT). In comparison to 2D measurement (RV diameter 28+/- 35, TAPSE 17+/-22, FAC 34+/-45) we did not observe significant difference during infection and post infection time. The study confirms that RV4CSL and RVFWSL are independent predictors of outcome in COVID 19 patients who undergo Heart transplantation. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) remains one of the most dangerous viruses emerging in patients (pts) after heart transplant (HTx). A number of prevention strategies are available. However, there is no single recommended strategy to prevent the infection. Pre-emptive strategies implicate regular follow-ups and costs connected with the diagnostic protocols. In turn, generalized prophylaxis is connected with drug-related adverse effects and the cost of antiviral drugs. The purpose is to compare the pre-emptive therapy model with generalized prophylaxis and to find the strategy best matching our pts. Consecutive pts transplanted between May 2015 and May 2020 were enrolled in the study. To guide the pre-emptive strategy, the pp65 antigen was assessed in the 4th and 12th week after transplantation and additionally in the case of a suspected infection. As generalized prophylaxis, we used valganciclovir 900mg daily (dose adjusted to the renal function) for 110 days after transplant.130 pts were enrolled in the pre-emptive strategy (mean age at the time of transplant 54.6 ±12 years) 8 D+R-, 9 D-R-, 113 D±R+, according to CMV baseline serostatus. Generalized prophylaxis was implemented in 128 pts (mean age 55.2±11.6 years), 18 D+R-, 3 D-R-, 107 D±R+, respectively. In the pre-emptive strategy group, none of the pts with D-R- developed CMV infection. In the group of D±R+, 24 infections occurred, i.e. 5 symptomatic infections, 3 co-infections (> 3 months after HTx). None of the pts died due to CMV. In the D+R- group, 7 of 8 pts developed overt infection, and 4 of them died in the course of CMV infection. In the pre-emptive strategy group, prophylaxis was ceased in 7 patients due to drug-related adverse effects. CMV infection occurred in 2 pts (D+R-, after drug cessation). None of the pts developed CMV infection during the prophylaxis period. In 4 pts, CMV infection occurred after the prophylaxis period (D±R+: 3, D+R-: 1, respectively). None of the pts died due to CMV. Pre-emptive therapy with the use of pp65 antigen may be safely applied in the D-R- group. In the D+R- group, this model of pre-emptive therapy is completely insufficient. In the D±R+ group, testing should be done more frequently or generalized prophylaxis should be applied. Infections other than CMV should prompt the workup for CMV, also in the late period after HTx. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: 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 ≥ 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. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: 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 (VO2max) used at present. Materials and Methods: We analyzed 302 CHF patients stratified into 3 groups according to VO2max (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 VO2max between 10 and 14 or <10 mL/kg/min are at similar risk of death. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

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

Abstract: The aim of this study was to assess the effects of early thymoglobulin administration on cardiocyte nuclear status in orthotopic heart transplant (OHT) recipients. Material and Methods: We investigated endomyocardial biopsies (EMBs) from 31 OHT recipients and 10 control cases. OHT patients were divided into the standard group who were treated without thymoglobuline; an ATG group who received thymoglobulin electively, and a standard+ATG group who were administered thymoglobulin upon a drop in renal function. We evaluated only EMBs obtained at 1 and 4 weeks after OHT showing no significant rejection (ISHLT grades 0 to 1B). The morphometric studies were performed using a computerized, automated Quantimet image analysis system. Overall, 1750 cardiocyte nuclei were quantitated for area, length, breadth, perimeter, chromatin median grey level, and fullness factor. Statistical analysis was performed using the Mann- Whitney U test, the Wilcoxon test, and discriminant analysis. Results: All OHT groups showed significantly higher values (indicating nucleus enlargement) than the control group. All factors suggesting myocardial hypertrophy were significantly higher in the standard group; however, they decreased significantly with time. In contrast, the nuclear geometric parameters were significantly lower and stable throughout the study in the ATG group. The results of the standard+ATG group were intermediate, and their normalization as incomplete at the week 4 examination. Discriminant analysis revealed the closest Mahalanobis distance between control and ATG groups both at and weeks 1 and 4 after OHT. Conclusion: Thymoglobulin administered early after surgery protected cardiocyte hypertrophy in heart transplant recipients, mitigating graft ischemic damage. [Copyright &y& Elsevier]

Abstract: 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 &y& Elsevier]

Abstract: 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 &y& Elsevier]

Abstract: 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 μg I per 1 liter of urine. Severe deficiency (SID) is diagnosed when UI is <50 μg/L and a moderate deficiency (MID) when UI is <100 μg/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; μIU/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 μg/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. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]