Lukasz Pyka

Quilty effect correlates with biopsy-proven acute cellular rejection but does not predict transplanted heart coronary artery 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.

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.

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.

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.