Abstract 9767: Direct-renin-inhibitor Aliskiren Therapy Consistently Suppresses Enhanced Cardiac Sympathetic Activity and Improves Left Ventricular Remodeling in Patients with Systolic Heart Failure
Introduction: Adding aliskiren to heart failure (HF) therapy was reported to reduce plasma brain natriuretic peptide (BNP) concentration. However, the effects of aliskiren on cardiac sympathetic nerve activity and on cardiac function have not yet been clarified. Hypothesis: We assessed the hypothesis that adding aliskiren to standard therapy would be effective to suppress cardiac sympathetic nerve function and improve cardiac function.
Methods: We enrolled 38 patients with mild HF (NYHA class II). The inclusion criteria were: 1) in stable condition for at least six months; 2) receiving standard therapy including an angiotensin-converting-enzyme inhibitor or angiotensin-receptor blocker and a beta-blocker; 3) have systolic dysfunction (left ventricular ejection fraction: LVEF of < 45%); 4) without diabetes; and 5) without renal dysfunction (serum creatinine of > 1.2 mg/dL). We randomly assigned 18 patients to receive additional aliskiren treatment of 150 mg/d (aliskiren group), while 20 patients continued standard therapy (control). All patients underwent neurohormonal measurements, echocardiography and 123I-metaiodobenzylguanidine (MIBG) imaging. In the MIBG images, the heart/mediastinum (H/M) ratio and cardiac washout rate (WR) were determined for evaluating cardiac sympathetic activity. The follow-up data were obtained three and 12 months later.
Results: In the aliskiren group, plasma renin activity and BNP fell significantly. MIBG analysis showed a consistent decrease in WR and a consistent increase in H/M ratio over 12 months only in the aliskiren group (WR %: 39.6 ± 3.1 vs 32.0 ± 2.1, 32.8 ± 3.7, p = 0.013, H/M: 2.80 ± 0.16 vs 3.12 ± 0.22, 3.05 ± 0.20 p = 0.015 at each follow-up period). The LVEF improved although not significantly (p = 0.074). The LV end-diastolic volume (EDV) and end-systolic volume (ESV) improved significantly (EDV index mL/m2: 92.8±6.4 vs 79.7±5.8, 82.3±5.3, p = 0.042 and ESV index: 56.6±4.8 vs 46.4±4.5, 48.6±4.4, p = 0.021). In the control group, these data remained unchanged.
Conclusions: In HF patients receiving standard therapy but still continuing to have cardiac dysfunction, the addition of aliskiren consistently suppresses cardiac sympathetic activity over 12 months and improves left ventricular remodeling.
- © 2012 by American Heart Association, Inc.