Abstract 14335: Asymptomatic Left Ventricular Systolic Dysfunction (Stage B Heart Failure) and Response to Chronic Protein Therapy With SQ BNP
Background: In Stage B systolic HF (EF<45%, NYHA class I symptoms), we have previously demonstrated an impaired cardiorenal endocrine response to acute volume loading (AVL) which is corrected by acute administration of SQ BNP. Our objective was to determine if 12 weeks of SQ BNP administration twice daily results in sustained enhancement of the cardiorenal response to AVL.
Methods: A randomized placebo-controlled double blinded proof of concept trial comparing 12 weeks of SQ BNP, 10 μg/Kg bid (n=22) with Placebo (n=12), in patients with EF<45% and NYHA Class I. Each subject had 2 study visits, one at baseline and the other after 12 weeks. At each visit, echocardiogram, neurohumoral assessment and renal clearance studies with iothalmate to measure glomerular filtration rate (GFR)) were done before and after AVL (0.25 ml/kg/min of normal saline for 60 minutes).(ClinicalTrials.gov Identifier: NCT00405639)
Results: 12 weeks of SQ BNP resulted in a significant increase in LVEF (39±9 to 41±9%, p<0.05) and decrease in LV end-systolic diameter (48±7 to 46±8 mm, p< 0.05) from baseline; there was also a strong trend towards reduced LV mass (-5.8 g/m2, p=0.07). There were no significant changes in these parameters with placebo. After 12 weeks of SQ BNP, in response to AVL, SQ BNP resulted in a greater increase in GFR (4.4±15 vs -9.3±15.2 ml/min/1.73m2, p< 0.05) and urinary sodium excretion (184.9±301.4 vs -18.7±95.3 mEq/min, p< 0.05) as compared to placebo. Further, there was a greater increase in LVEF (4±5 vs -1±3%, p< 0.05), with smaller end-systolic diameter (-3±3 vs -1±1 mm, p< 0.05) and E/e’ ratio (12±6 vs 15±3, p< 0.05) and a trend for lower RV pressure (0.1±3.1 vs 3.6±3.8 mmHg, p= 0.06) in the SQ BNP group in response to AVL compared to placebo.
Conclusion: In Stage B systolic HF, 12 weeks of SQ BNP twice daily resulted in improved and sustained ability of the kidney to respond to intravascular volume overload with an increase in GFR and sodium excretion compared to standard of care. This enhanced renal response was associated with enhanced myocardial structure and function with no evidence of pharmacological tolerance. Further studies are warranted to determine if these physiologic observations can be translated into a delay in the progression to symptomatic HF.
- © 2013 by American Heart Association, Inc.