Abstract 2093: Myocardial Upregulation of mRNA Angiotensin II Receptor Subtype 1 (AGTR1) at One Year of Heart Transplantation is Associated with Worse Long-term Clinical Outcome Including Skin Cancer.

Abstract

Background: We have previously shown that myocardial upregulation of mRNA gene expression of angiotensin II receptor subtype 1 (AGTR1) is associated with transplant vasculopathy evidenced by coronary intravascular ultrasound at one year following heart transplantation. Objectives: This study was undertaken to evaluate the long-term clinical outcome of heart transplant patients in relation to upregulation of mRNA AGTR1. Methods: A total of 45 heart transplant patients, mean age 55±12 years (78% male) had heart biopsy analysis for mRNA AGTR1 (Taqman PCR) at one year of transplantation. Dual Immunofluorescence staining for AGTR1 and vWF was also performed. Patients were divided into 2 groups according to the mRNA AGTR1 expression: Group I (n= 24), AGTR1 ≤2.0 and Group II (n=21), AGTR1 > 2.0. Patients underwent annual coronary angiography and were followed up for a mean period of 7.6±2.1 years. Transplant coronary vasculopathy was defined as angiographic evidence of coronary obstruction greater than 30% in the absence of donor coronary artery disease. Results: The 2 groups had similar baseline characteristics. During follow up, Group II patients tended to have increased risk of diabetes mellitus (57.1% versus 29.2%, P= 0.058) and renal insufficiency (61.9% versus 33.3%, P= 0.055) defined by serum creatinine greater than 1.5 mg/dl. Group II patients had a worse survival (10 year K-M survival: 61% versus 86%, log-rank P= 0.061) and increased vasculopathy (10 year K-M freedom from vasculopathy: 19% versus 66%, log-rank P= 0.036). Since the renin-angiotensin system has been implicated in the development of various cancers, we also evaluated the clinical outcome of malignancy in relation to mRNA AGTR1. Interestingly, the 10 year K-M freedom from any malignancy tended to be worse in Group II patients (46% versus 77%, log-rank P= 0.063) and statistically significantly different in skin cancer (57% versus 86%, log-rank P= 0.034). Conclusions: Myocardial upregulation of mRNA AGTR1 at one year of heart transplantation is associated with worse clinical outcome including skin cancer. These findings may call for the need of prospective randomized trials to evaluate if the natural course of these patients could be altered with the use of angiotensin receptor blockers.