Different role of advanced glycation end products in pathology of transplanted heart in patients with or without diabetes mellitus type 2.

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.

Microvasculopathy observed in early or late endomyocardial biopsies is not related to angiographically confirmed transplanted heart coronary vasculopathy.

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.

Fluctuations of exercise capacity in patients after kidney transplantation.

INTRODUCTION: The aim of this study was to assess changes in the exercise capacity in subjects with end-stage renal failure undergoing kidney transplantation. MATERIALS AND METHODS: The study group consisted of 16 subjects (9 males and 7 females) of mean age 43.3 +/- 11 years. The control group was composed of 7 healthy subjects (4 males and 3 females) of mean age 43.9 +/- 10 years. The first visit took place at 4-8 weeks after transplantation. Consecutive visits were scheduled for months 4, 10, 16, 24, 36, and 48 thereafter. Heart function was assessed using echocardiography and, an exercise test with analysis of peak oxygen consumption (VO(2)max). Results were correlated with VO(2)max (Pearson). The Mann-Whitney U test was used to compare study and control groups. RESULTS: The results of eligible VO(2)max tests were as follows (medians and ranges): 1 month (n = 15), 19.5 (8.8-27.5) mL/kg/min; 4 months (n = 9), 21.7 (16.0-29.3) mL/kg/min; 10 months (n = 8), 23.3 (13.1-30.0) mL/kg/min; 16 months (n = 9), 26.6 (18.3- 36.0) mL/kg/min; 24 months (n = 9), 22.3 (14.1-35.0) mL/kg/min; 36 months (n = 9) 20.9 (16.4-32.1) mL/kg/min; 48 months (n = 5), 19.7 (17.0-30.9) mL/kg/min; versus 26.8 (26.5-42.5) mL/kg/min in the control group. VO(2)max results achieved by the study group were significantly lower than that in the control group, except for months 16, 24, and 48. VO(2)max was significantly negatively correlated with the following ultrasound parameters: interventricular septum diastolic and systolic diameter, and left ventricle systolic volume. CONCLUSION: The exercise capacity of recipients seemed to be negatively affected by poor blood pressure control, resulting in heart muscle hypertrophy.

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

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

The effect of Epstein-Barr virus infection on medium-term survival after orthotopic heart transplantation.

UNLABELLED: Our aim was to assess the medium-time results after orthotopic heart transplantation (OHT) depending on the serostatus of heart transplant recipients at the time of transplantation. MATERIALS AND METHODS: We enrolled 120 patients in this retrospective study including 107 males and an overall mean age of 49.1 +/- 8.6 years ischemic heart disease (IHD) was the diagnosis before OHT in 46%. The mean follow-up was 48 months. The first diagnostic coronary angiography was routinely preformed at 1 year after OHT, and then every second year. We evaluated every incidence of a change in the coronary arteries, the presence of significant stenosis (requiring percutaneous coronary intervention), acute myocardial infarction, death, or retransplantation. Using indirect immunofluorescence assays we detected Epstein-Barr virus (EBV) antigenemia by identification of antibodies against early antigens of EBV (EA) of IgM and IgG classes as well as IgG antibodies against nuclear antigen of EBV (EBNA). Since April 2001 all three types of antibodies were routinely investigated on admission to the hospital for OHT. RESULTS: At the time of transplantation, IgM-EA antibodies were detected in 17 (14%) patients, IgG-EA in 35 (29%), and IgG-EBNA in 113 (94%). Survival rate, incidence of cardiac allograft vasculopathy and death, as a function of the serostatus of the heart recipient at the time of transplantation were estimated by Kaplan-Meier curves; the results were compared by log-rank tests. The findings among IgM EA, IgG EA, and IgG EBNA-positive and -negative groups were statistically comparable. CONCLUSION: Infection with EBV before OHT did not worsen the prognosis over the first 4 years after transplantation.

The influence of cytomegalovirus infection, confirmed by pp65 antigen presence, on the development of cardiac allograft vasculopathy.

AIM: We sought to determine the impact of cytomegalovirus (CMV) infection on cardiac allograft vasculopathy (CAV) development in the long term after orthotopic heart transplantation (OHT). MATERIALS AND METHODS: We enrolled 144 patients in this retrospective study including 128 men with an overall age at transplantation of 48.4 +/- 9.3 years. Before OHT, 45% exhibited ischemic heart disease (IHD). The mean follow-up was 62 months. Detection of CMV antigenemia was performed by identification of pp65-antigen on peripheral blood leukocytes. The first diagnostic coronary angiography was routinely performed at 1 year after heart transplantation and thence every second year. We evaluated every incidence of change in the coronary arteries, of significant stenosis (requiring percutaneous coronary intervention), acute myocardial infarction, of death or of transplantation. All patients were followed to the incidence of a cardiovascular event, death, or the end of observation. RESULTS: Of 144 patients, 33 were pp65 positive, namely 29 men with overall mean age at transplantation of 48 +/- 10.3 years. Before OHT, 52% had IHD. The incidence of CAV during follow-up was 24% (n = 8) in the pp65(+) and 22% (n = 24) in the pp65(-) group. It was significant in 3 (9%) versus 8 (24%) patients. There were 4 (12%) deaths in pp65(+) and 9 (8%) deaths in the pp65(-) groups. Kaplan-Meier survival curves to estimate the time for CAV development and death showed no significant differences by log-rank tests. CONCLUSION: No impact of CMV infection on CAV development was observed in first 5 years after OHT.