P6313RAAS inhibition improves event-free survival in cardiac transplant recipients: results of the prospective cohort study

Abstract

Abstract Background Despite known achievements, long-term survival of heart transplant (HT) recipients still needs to be improved. The Renin-Angiotensin-Aldosterone System (RAAS) hyper-activation could be the result of heart denervation and immune suppressive therapy in these patients. Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) have been shown to be beneficial in patients with hypertension, heart failure (HF) and diabetic nephropathy. Purpose The study was aimed to assess the effects of ACEI and ARB on the prognosis and cardiac transplant remodelling in HT recipients. Methods Four hundred ninety-six critical HF patients had cardiac transplant surgery between January 2012 and December 2016 in Shumakov National Research Centre of Transplantology, and Artificial Organs (Moscow, Russian Federation) which accounted to 57.9% of all heart transplantations (HTx) performed in the country during that period. All patients >18 years old who survived 30 days after the operation without known contraindications for ACEI or ARB were sequentially included in the study. A non-randomised controlled trial study design was used. Study endpoints included death from any cause and re-transplantation due to the irreversible cardiac transplant failure. Results 385 HT recipients (mean age 46.3±2.3 years, 51 females and 334 males) enrolled in the study. Thirty days after the HTx, a RAAS inhibitor was assigned to 141 recipients. Patients receiving ACEI or ARB had significantly better event-free survival than the control group (log-rank p=0.045) during the follow-up for 1856.5±68.3 days. Unadjusted analysis revealed other factors related to the risk of death or irreversible HT failure: recipient age <37 years old, donor age>44 years old, aortic cross-clamping time >117 min, peri-operational ECMO>3 days of duration, acute renal failure requiring dialysis during first 30 days after the operation, right atrium size, mitral regurgitation 2+, tricuspid regurgitation 1+, donor's heart posterior wall thickness (PWT) >12mm, and left ventricle (LV) end-diastolic dimension (EDD). When adjusted to the RAAS inhibitors use, only the donor's age and early renal failure remained significant. LV EDD did not change over time in both groups, whereas LV PWT in the control group significantly increased from 12.3±0.3 to 13.5±0.5 mm (p<0.05). Conclusions Heart transplant recipients who received RAAS inhibitors had better survival and less LV hypertrophy progression that could reflect the beneficial effects of ACEI and ARB after heart transplantation.