Novel Protein Therapeutics for Systolic Heart Failure

Objectives The objective of the present study was to translate our laboratory investigations to establish safety and efficacy of 8 weeks of chronic SQ BNP administration in human Stage C HF. Background B-Type natriuretic peptide (BNP) is a cardiac hormone with vasodilating, natriuretic, renin-angiotensin (RAS) inhibiting and lusitropic properties. We have previously demonstrated that chronic cardiac hormone replacement with subcutaneous (SQ) administration of BNP in experimental heart failure (HF) resulted in improved cardiovascular function. Methods We performed a randomized double-blind placebo-controlled proof of concept study comparing eight weeks of SQ BNP (10 μg/Kg bid) (n=20) with Placebo (n=20) in patients with EF<35% and NYHA class II–III HF. Primary outcomes were LV volumes and LV mass determined by cardiac MRI. Secondary outcomes include LV filling pressure by Doppler echo, humoral function and renal function. Results Eight weeks of chronic SQ BNP resulted in a greater reduction of LV systolic and diastolic volume index and LV mass index as compared to placebo. There was a significantly greater improvement of Minnesota Living with Heart Failure (MLHF) score, LV filling pressure as demonstrated by the reductions of E/e′ ratio and decrease in LA volume index as compared to placebo. GFR was preserved with SQ BNP, as was the ability to activate plasma cGMP. (p<0.05 vs placebo) Conclusion In this pilot proof of concept study, chronic protein therapy with SQ BNP improved LV remodeling, LV filling pressure and MLHF score in patients with stable systolic HF on optimal therapy. RAS was suppressed and GFR preserved. SQ BNP represents a novel, safe and efficacious protein therapeutic strategy in human HF. Further studies are warranted to determine if these physiologic observations can be translated into improved clinical outcomes and ultimately delay the progression of HF.