Relationship between Symptomatic Dyspnea and Renal Function in Patients With Acute Heart Failure Syndromes: Results from the URGENT-Dyspnoea Study (Ularitide Global Evaluation in Acute Decompensated Heart Failure)

S14 Journal of Cardiac Failure Vol. 16 No. 8S August 2010 subxiphoid access and positioned on the left posterior lateral region of the heart. An ICD lead and coronary sinus (CS) lead was implanted transvenously in the RV apex and great cardiac vein respectively to fluoroscopically compare the relative pericardial lead location. Post implant follow-ups of the canines included standard electrical measurements and fluoroscopic examination from multiple angles to identify pericardial lead position and assess the acute and chronic stability of the lead. Results: All pericardial leads were successfully implanted in 15 minutes or less without complications. The customized delivery tool proved advantageous in navigating the pericardial lead to the target site and no post-implant complications were observed. The pericardial leads remained mechanically stable over the 90-day period with no observable changes in position. Electrical performance was shown to be comparable throughout the study relative to tranvenous CS leads (Table 1). Conclusions: The new pericardial lead can be accurately placed through a minimally-invasive method via subxiphoid access to the pericardial space using the customized delivery tool without needing direct visualization. This new lead showed chronic mechanical and electrical stability throughout the study.

036 Human Preclinical Systolic and Diastolic Dysfunction Is Characterized by Impaired Cardiorenal Endocrine Response to Acute Volume Overload Paul M. McKie, Sherry L. Benike, Lynn K. Harstad, Elise A. Oehler, Lisa C. Costello-Boerrigter, John A. Schirger, Robert A. Simari, Margaret M. Redfield, John C. Burnett, Horng H. Chen; Mayo Clinic, Rochester Background: Preclinical systolic dysfunction (PSD) is defined by LVEF ! 45% without symptoms of heart failure (HF). Preclinical diastolic dysfunction (PDD) is defined as normal systolic function, moderate or severe diastolic dysfunction determined by Doppler criteria, and no symptoms of HF. In PSD and PDD we hypothesized there is impaired cardiorenal endocrine activation, characterized by altered atrial natriuretic peptide (ANP) release and natriuresis, in response to acute volume loading (AVL). We further hypothesized that this impaired cardiorenal endocrine activation could be rescued by exogenous B-type natriuretic peptide (BNP) which is the most natriuretic of the natriuretic peptides. Methods: In PDD (n 5 18), PSD (n 5 20), and healthy controls (n 5 20) we employed a double blinded, placebo-controlled cross-over design to determine the renal response to AVL (0.25 ml/kg/min of normal saline for 60 minutes) in the presence or absence of exogenous BNP (subcutaneous 25 mg/kg bolus). *p ! 0.05. Results: AVL in healthy controls resulted in maintenance of plasma ANP, increased urinary cGMP excretion* (the second messenger molecule of ANP), and increased natriuresis*. In contrast, in subjects with PSD and PDD there was a paradoxical decrease in plasma ANP (PSD -8 6 20*; PDD 35 6 104* pg/ml), decreased urinary cGMP excretion (PSD 86 6 160*; PDD 107 6 157* pmol/min), and attenuated natriuresis. In response to exogenous BNP, PSD and PDD subjects responded similarly to healthy controls to AVL with similar increases in urinary cGMP excretion and natriuresis. Conclusion: In PSD and PDD there is reduced ANP release and renal cGMP activation in response to AVL which results in impaired sodium excretion. This significantly impaired cardiorenal endocrine response may contribute to progression of HF. Importantly, the impaired renal excretory response to volume overload is rescued by exogenous BNP in PSD and PDD.

037 Relationship between Symptomatic Dyspnea and Renal Function in Patients With Acute Heart Failure Syndromes: Results from the URGENT-Dyspnoea Study (Ularitide Global Evaluation in Acute Decompensated Heart Failure) Kori Sauser1, Peter Pang1, D. Mark Courtney1, Judd Hollander2, Sean P. Collins3, Alan Storrow4, Richard M. Nowak5, Miguel Tavares6, Alexandre Mebazaa7, Mihai Gheorghiade1; 1Northwestern University, Chicago, IL; 2University of Pennsylvania, Philadelphia, PA; 3University of Cincinnati, Cincinnati, OH; 4Vanderbilt University, Nashville, TN; 5Henry Ford Hospital, Detroit, MI; 6Hospital Geral de Santo Antonio, Porto, Portugal; 7University Paris Diderot; Hopital Lariboisiere, Paris, France Study Objectives: Dyspnea is the most common complaint in ED patients with acute heart failure syndromes (AHFS). AHFS patients with baseline renal impairment may be more difficult to treat and have worse outcomes. The association between renal function and dyspnea improvement has not been well characterized. We hypothesized that ED patients with AHFS and baseline renal dysfunction would have more refractory dyspnea after standard ED therapy. Methods: Sub-analysis of the URGENT Dyspnoea study; this international, multi-center prospective cohort study quantified dyspnea with 11-point VAS at time 0 & 6h. Glomerular filtration rate (GFR) estimated using Modification of Diet in Renal Disease equation; patients categorized as normal (GFR O 60) and impaired function (GFR ! 60). Main outcome of VAS change O 3 defined clinically significant reduction in dyspnea. Differences in proportions analyzed using 95% CIs. Difference between mean GFR among those with and without significant dyspnea reduction analyzed with Student’s t-test. Results: 524 patients had AHFS; 21 excluded for no creatinine. Mean age was 67.8 years and 56.7% were male. Mean GFR was 58.0 mL/min (range 3.7 to 188.6). Mean change in dyspnea score was improvement by 2.3 points (range 10 to 4). When comparing the proportion with dyspnea improvement in the normal

GFR group (37.8%) with the reduced GFR group (41%) there was no significant difference (95% CI for difference e11.8 to 5.3%). There was no significant difference in mean GFR when comparing patients with dyspnea improvement vs. no significant improvement, (56.8 vs. 58.7; 95% CI for difference -2.9 to 6.5). Conclusion: In this sample of ED patients with AHFS and objective measurement of dyspnea, there was no significant difference in dyspnea improvement between patients with reduced versus normal baseline renal function. Approximately 40% of patients regardless of renal function reported quantifiably significant reduction in dyspnea.

038 Differences in Accuracy of Doppler-Estimated Pulmonary Vascular Resistance Relate to the Degree of Left Atrial Pressure Contribution to Pulmonary Hypertension Anthony F. Yu, Yan Wang, Lucas Marzec, James N. Kirkpatrick, Paul R. Forfia; Medicine/Cardiovascular Division, University of Pennsylvania, Philadelphia, PA Background: Prior studies have shown reasonable correlations between invasivelyderived pulmonary vascular resistance (PVR) and Doppler-estimated PVR, using the ratio of tricuspid regurgitation velocity to a surrogate of pulmonary flow (TRV/ VTIRVOT). Using this approach, the pulmonary artery wedge pressure (PAWP) term is ignored, potentially making this approach inaccurate in patients with left sided heart failure (HF). We sought to determine how TRV/VTIRVOT relates to PVR in patients with pulmonary hypertension related to an elevated PAWP vs. a normal PAWP. Methods: Invasive hemodynamics were obtained by right heart catheterization, along with simultaneous Doppler examination in 16 patients with decompensated systolic HF and 50 patients with pulmonary arterial hypertension (PAH). The TRV/VTIRVOT was correlated with invasive PVR, as well as total pulmonary resistance (TPR). Hemodynamics and Doppler Data for HF and PAH Cohorts HF mPAP PAWP TPG CI PVR TPR TPR-PVR TRV/VTI rvot

33 23 10 2.3 2.2 8.0 5.8 368

6 6 6 6 6 6 6 6

8 7 5 0.9 1.2 3.8 3.2 191

PAH

P value

6 6 6 6 6 6 6 6

0.02 !0.001 !0.001 0.83 !0.001 0.04 !0.001 0.33

42 11 31 2.4 8.7 11.4 2.8 320

14 5 15 0.7 5.1 6.1 1.8 155

Results: Table 1 summarizes the hemodynamics in the HF and PAH cohorts. Both groups had pulmonary hypertension, however the PAH patients expectedly had much lower PAWP, and higher transpulmonary gradient and PVR. The PAWP comprised 26%, and 70% of mean PAP in the PAH and HF groups, respectively. As such, the difference between TPR and PVR was nearly two fold higher in the HF patients vs. PAH. In keeping, there was no correlation between TRV/VTIRVOT and PVR in the HF cohort (r 5 -0.03), however there was a modest, significant correlation to TPR (r 5 0.54). In contrast, the correlations were similar between TRV/VTIRVOT and PVR (r 5 0.77) and TPR (r 5 0.79) in the PAH group. Despite these results, the average TRV/VTIRVOT values did not differ between HF and PAH patients. Conclusions:The ratio of TRV/VTIRVOT is a poor measure of PVR in HF patients, relative to PAH patients. This likely relates to failure to correct for the PAWP using this method. The TRV/VTIRVOT should thus be used cautiously in patients with known or suspected left atrial hypertension.

039 Novel Large Animal Model of Acute Experimental Hypertensive Heart Failure Paul M. McKie, S. Jeson Sangaralingham, Tomoko Ichiki, Alessandro Cataliotti, Guido Boerrigter, Horng H. Chen, John C. Burnett; Mayo Clinic, Rochester Background: Systolic hypertension especially in women and blacks is increasingly recognized and present in approximately 50% of subjects with acute decompensated heart failure (ADHF). Importantly, an abrupt increase in blood pressure may indeed be the mechanism for ADHF in such subjects. To date there is a lack of a large animal model of ADHF with hypertension to allow detailed characterization of the hemodynamic and neurohumoral phenotype and to test potential therapeutic agents. Objectives: Develop a novel large animal model of pacing induced ADHF and angiotensin II (ANG II) induced hypertension and characterize its cardiorenal and neurohumoral phenotype. Methods: Heart failure (HF) was induced by ventricular pacing at 180 beats per minute for 10 days in normal canines (n 5 7). On day 11, in the presence of pacing induced HF, hypertension was induced by continuous infusion of ANG II (40ng/kg/min). We compare this model to normal canines (without HF) with hypertension induced by ANG II. *p ! 0.05 vs BL (1-way ANOVA). yp ! 0.05 vs. Normal (2-way ANOVA). Results: Baseline (BL) mean arterial pressure (MAP) (Figure 1A) was lower in HF vs. normals. There were signficant increases in MAP in both groups with