Abstract 14880: Cardiorenal Response to Acute Volume Loading in Human Preclinical Diastolic Dysfunction (Stage B Heart Failure) After 12 weeks of Chronic SQ BNP Administration
Background: Preclinical diastolic dysfunction (PDD) is defined as normal systolic function, moderate or severe diastolic dysfunction by Doppler criteria but no heart failure (HF) symptoms. We previously demonstrated impaired cardiorenal endocrine response to stress by acute volume loading (AVL) exists in PDD, that is corrected by acute administration of SQ BNP. The objective is to determine if 12 weeks of SQ BNP administration twice daily will result in sustained enhancement of cardiorenal response to AVL.
Methods: We performed a randomized placebo-controlled double blinded proof of concept clinical trial comparing 12 weeks of SQ BNP, 10 μg/Kg bid (n=24) with Placebo (n=12) in patients with PDD. Each subject had study visits at baseline and after 12 wks. At each visit, echocardiogram, neurohumoral assessment and renal clearance studies with iothalmate and PAH to measure glomerular filtration rate (GFR) and renal plasma flow (RPF) were done before and after AVL (0.25 ml/kg/min normal saline for 60 min). (ClinicalTrials.gov Identifier: NCT00405548)
Results: 12 wks of SQ BNP resulted in improvement in LV filling pressure as measured by significant decrease in Doppler E/e’ ratio from baseline (14.9±4.1 to 12.6±3.5 p=0.004) that was unchanged in the placebo group (14.9±4.5 to 14.0±5.1 p=0.43). LA size was significantly reduced in the SQ BNP group (35.9±7.4 to 33.5±7.1 ml/m2 p=0.02) only. In response to AVL, SQ BNP resulted in a greater increase in urinary sodium excretion (404±507 vs -2.1±84 mEq/min, p< 0.001), urinary flow (3.3±5.3 vs -0.7±2.4 ml/min, p= 0.01), a strong trend for a greater increase in GFR (9.0±36 vs -6.3±37 ml/min/1.73m2, p=0.06) as compared to the placebo group. Echocardiography showed lower RV pressure (-3.7±4.9 vs 4.7±8.9 mmHg, p<0.05) in the SQ BNP group in response to AVL with normal saline as compared to placebo.
Conclusion: In PDD, 12 wks of SQ BNP administered bid resulted in improved LV filling pressure and sustained enhancement of cardiorenal response to AVL. Importantly, these studies demonstrate continued beneficial cardiorenal response to AVL 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.