Showkat A. Haji

Donor hepatitis-C seropositivity is an independent risk factor for the development of accelerated coronary vasculopathy and predicts outcome after cardiac transplantation

BACKGROUND It is possible, but unproven, that hepatitis C (HCV) infection accelerates atherosclerosis. We evaluated the hypothesis that donor HCV seropositivity predicts mortality and the development of coronary vasculopathy in cardiac transplant recipients. METHODS Thirty-four cardiac transplant recipients who were seronegative for HCV at the time of transplantation received hearts from HCV-seropositive donors. We compared the mortality and the incidence of vasculopathy in this group of patients (study group) with a group of 183 successive heart transplant recipients (control group) with no evidence of HCV in the donor or in the recipient. RESULTS After transplantation, 75% of the HCV-seronegative patients who received hearts from HCV-seropositive donors had detectable and persistent viremia (presence of HCV-RNA by reverse-transcription polymerase chain reaction). After a mean follow-up of 4.2 +/- 1.9 years, mortality was 2.8-fold greater in the study group than in controls (95% confidence interval [CI], 1.3-5.7; p = 0.006). The risk of having any vasculopathy after a mean follow-up of 3.4 +/- 1.6 years and after adjustment for other significant risk factors was 3-fold greater (hazards ratio, 3.08; 95% CI 1.52-6.20; p = 0.001) in the HCV group compared with controls. The risk of developing advanced vasculopathy was much greater in the study group compared with controls (hazard ratio, 9.4; 97% CI, 3.3-26.6; p = < 0.0001). The risk of mortality (p = 0.005) and vasculopathy (p = < 0.0001) was greatest in patients with combined donor HCV seropositivity and the presence of antibodies against donor B cells by flow cytometry. CONCLUSION We conclude that donor hepatitis-C virus seropositivity is an independent risk factor for increased mortality and for the development of accelerated allograft vasculopathy after cardiac transplantation. These observations may have implications for the use of HCV-positive donors in heart transplant recipients.

Myocardial ischemic-fibrotic injury after human heart transplantation is associated with increased progression of vasculopathy, decreased cellular rejection and poor long-term outcome.

OBJECTIVES We sought to assess the influence of peritransplant ischemia and fibrosis on the development of allograft vasculopathy, acute cellular rejection and long-term outcome. BACKGROUND Allograft vasculopathy is a common long-term complication of cardiac transplantation. One of the potential risk factors is peritransplant allograft ischemia. METHODS One hundred forty heart transplant recipients had baseline and one-year intravascular ultrasound analysis done to assess the progression of allograft vasculopathy. Serial endomyocardial biopsies were evaluated for cellular rejection, vascular rejection, ischemia and fibrosis. Based on histology, patients were classified into one of the following groups: nonischemic (n = 32), ischemia (n = 24), fibrosis (n = 62) or vascular rejection (n = 22). Three-color flow cytometry crossmatching (FCXM) was used to assess donor-specific human lymphocyte antigens (HLA) sensitization. Long-term outcome of patients in each group was assessed by estimating incidence of graft failure or deaths over a seven-year follow up. RESULTS Patients in the fibrosis group had the lowest incidence of donor-specific HLA sensitization (40%, p = 0.008) and lowest average episodes of cellular rejection (1.7 +/- 1.4, p = 0.04), but they had increased coronary vasculopathy progression (change in coronary intimal thickness = 0.59 +/- 0.28 mm, p < 0.0001) and poor seven-year event-free survival (49%, p = 0.01). CONCLUSIONS The development of fibrosis after cardiac transplantation is associated with advanced coronary vasculopathy, although a low incidence of acute cellular rejection is noted, suggesting the presence of nonimmune mechanisms in mediating the pathogenesis of allograft vasculopathy.

Computerized scoring of histopathology for predicting coronary vasculopathy, validated by intravascular ultrasound

BACKGROUND Allograft coronary vasculopathy results from a complex interplay between immunologic and non-immunologic factors. We devised a computerized biopsy scoring method based on histopathology to predict the development of coronary vasculopathy. METHODS One hundred forty heart transplant recipients underwent serial intravascular ultrasound analysis at baseline (within 1 month) and at 1 year after transplantation and were evaluated for development of coronary vasculopathy (change in coronary maximal intimal thickness, CMIT). We evaluated serial endomyocardial biopsy specimens for cellular rejection, vascular rejection, ischemia, and fibrosis. In a mathematical model, we computed a biopsy score in each patient based on the duration and severity of histopathology. RESULTS We found a significant correlation between biopsy score (RY) and progression of coronary vasculopathy (r = 0.54, p = 0.001). Using a sensitivity analysis method, an RY value of > or =560 predicted development of coronary vasculopathy with a sensitivity of 86%, specificity of 62%, and diagnostic accuracy of 80%. Compared with patients with low-risk biopsy scores (RY < 560, n = 37), patients with high-risk biopsy scores (RY > or = 560, n = 103) had increased progression of coronary vasculopathy (CMIT, 0.59 +/- 0.29 vs 0.19 +/- 0.10 mm, p < 0.001) and worse 7-year event-free survival (60% vs 91%, p = 0.01). CONCLUSION The biopsy score is an effective method for predicting the development of coronary vasculopathy and for predicting outcome in cardiac transplant recipients.

51 PREDICTORS OF LEFT VENTRICULAR DILATATION IN YOUNG ADULTS: THE BOGALUSA HEART STUDY

Background Left ventricular (LV) dilatation may be an early sign of cardiac compensation to LV dysfunction. Determinants of LV dilatation in young asymptomatic adults are unknown. Methods and Results A sample of 506 asymptomatic subjects (mean age 32 ± 3 years) enrolled in the Bogalusa Heart Study underwent echocardiographic examination. LV dilatation (LV end-diastolic diameter > 5.5 cm) as measured by M-mode echocardiography was found in 31 (6%) subjects. Subjects with LV dilatation had higher systolic (119 ± 15 vs 112 ± 12 mm Hg, p = .007) and diastolic (79 ± 12 vs 75 ± 9 mm Hg, p = .04) blood pressures. Similarly subjects with LV dilatation had a higher body mass index (BMI 32 ± 9 vs 27 ± 6, p < .0001). Age, sex, race and metabolic parameters (glucose, insulin and lipoprotein levels) did not differ significantly between the subjects with and without LV dilatation. After correction for age, sex and race differences, obesity (BMI > 30) was associated with a threefold (odds ratio 2.9, CI 1.4-6.1) and hypertension (defined as per JNC 7 criteria) was also associated with a threefold (odds ratio 3.0, CI 1.2-7.1) increased incidence of LV dilatation. There was an incremental increase in LV end-diastolic dimension depending on the presence of hypertension or obesity and subjects with both obesity and hypertension had the highest degree of LV end-diastolic dimensions. Conclusion Obesity and hypertension may play an important role in early LV dilatation in an otherwise healthy young population.