renal function and thyroid status in heart failure

versus 22% in normal VMs. Changes in AP profile were associated with a more pro-nounced decrement in cell shortening in hypertrophied VMs than normal VMs. Thesestudies support the idea that CaMKII is activated in hypertrophied hearts. In cell cul-ture experiments we found that VMs infected with CA-CaMKII had greater phos-phorylation at PLB-Thr17 compared to VMs with DN-CaMKII and GFP. VMsinfected with CA-CaMKII showed a significant decrease in cell shortening (2.206 0.20%) versus cells with DN-CaMKII (4.54 6 0.55%) and GFP (3.81 6

0.27%). At five days post-infection, VMs with CA-CaMKII showed pronouncedcell death (98%) in comparison to cells with DN-CaMKII (32%) and GFP (35%).Conclusions: Our results show that activation of CaMKII leads to phosphorylationof PLB-Thr17 resulting in positive inotropic effects that were reversed by acute CaM-KII inhibition. However, the predominant effect of chronic CaMKII activation bothin-vivo and in-vitro was reduced VM contractility and viability. These studies suggestthat persistent activation of CaMKII is an important mediator of depressed cardiacfunction in the hypertrophied heart.

1.0 and 34.0 6 1.0 grams, week 1 and 8, respectively; p 5 NS). The mean infarct size atweek 1 and 8 weeks was unchanged in Yorkshire swines, and increased from 18.2 6 2.0to 21.1 6 2.9% of LV volume at week 1 to 8 in the minipigs. Conclusion: Together ourresults demonstrate that we successfully created a reproducible novel porcine heart fail-ure model that mimics the pathophysiology in post-MI patients. This animal model willfacilitate the conduct and evaluation of pre- clinical studies for new heart failure ther-apies showing reliable safety and efficiency results for investigative new drugs (IND).

074Lack of Correlation between Endothelial Function and Six-Minute Walk TestPerformance in Patients with Heart FailureFausan S. Tsai1, Parta Hatamizadeh2, Fahed Bitar2, Uri Elkayam2; 1Department ofMedicine, Los Angeles County/University of Southern California Medical Center,Los Angeles, CA; 2Division of Cardiovascular Medicine, Los Angeles County/University of Southern California Medical Center, Los Angeles, CA

Introduction and Hypothesis: The significance of endothelial function in heart fail-ure has not been established. The six-minute walk test (6MWT) assesses exercise ca-pacity and quality of life, and is a predictor of death and hospitalization in patientswith heart failure. We sought to determine whether the degree of endothelial functioncorrelates with 6MWT performance. Methods: September 2005 to February 2006,patients with chronic heart failure in stable condition were enrolled. Exclusion crite-ria included lung disease, primary valvular disease, and conditions affecting the6MWT or peripheral artery tonometry (PAT). Endothelial function was evaluatednoninvasively using PAT (Endo-Pat 2000, Itamar). The PAT index, lower in endothe-lial dysfunction, was calculated by dividing the post-occlusion pulse wave amplitudeby the baseline. Patients then completed the 6MWT, with vitals measured pre- andpost-walk. Results: A total of 78 patients enrolled. Five were excluded because com-plete arterial occlusion was not achieved during PAT. Data on the remaining 73 (23females; 41 [56.2%] Hispanic, 21 [28.8%] African-American; mean age 54; meanejection fraction 24.9%) were analyzed. Patients were on either an angiotensin-con-verting enzyme inhibitor or angiotensin receptor blocker (70 [95.9%]), beta-blockers(58 [79.5%]), and statins (37 [50.7%]). PAT index ranged from 1.0 to 3.2 (mean 1.8þ/- 0.5), and distance walked 124 to 584 m. Longer distances correlated significantlywith male gender, younger age, taller height, and shorter duration of heart failure.The PAT index did not correlate with distance walked. Pre- and post-walk heartrate (r 5 �0.19, P 5 0.02 and r 5 �0.24, P 5 0.04 respectively) and post-walk re-spiratory rate (r 5 �0.29, P 5 0.01) negatively correlated with PAT index. Conclu-sion: There was no relationship between magnitude of endothelial function, asmeasured by PAT, and distance walked. This study suggests that exercise capacityas measured by 6MWT is multifactorial.

075Improving the Stethoscope: Optimizing Computerized Analysis of Heart Tonesin Emergency Department Patients with Possible Heart FailureAlan B. Storrow1, Karen F. Miller1, Chuan Zhou2, Joe Mayor3, Jeff Harrow3, Jin H.Han1, Paul A. Harris4, Vladimir Polyshchuk4, Vladimir Kudriavtsev; 1EmergencyMedicine, Vanderbilt University, Nashville, TN; 2Biostatistics, VanderbiltUniversity, Nashville, TN; 3School of Medicine, Meharry Medical College,Nashville, TN; 4Biosignetics Corporation, Exeter, NH

The 11th Annual Scientific Meeting � HFSA S95

072Renal Function and Thyroid Status in Heart FailureJuan D. Martinez1, Susan T. Bionat1, Ramanna Merla1, Rastogi Saurabh1, Joanne S.Bionat1, Fenwei Wang1, Smita Maity1, Yochai Birnbaum1, Alejandro Barbagelata1;1Internal Medicine, Division of Cardiology, University of Texas Medical Branch,Galveston, TX

Introduction: Thyroid hormone has multiple known effects on renal and cardiovas-cular function. Renal dysfunction has been associated with poor prognosis in patientswith heart failure (HF). Limited information is available describing correlation be-tween renal function and thyroid function in HF patients. We investigate renal func-tion in HF patients with and without hypothyroidism. Methods: We determined theassociation between renal function and thyroid function in systolic HF by cross-sec-tional analysis of 75 patients followed at a university HF clinic. Data were gatheredvia chart review. Patients were excluded based on presence of diabetes mellitus andelevated hemoglobin A1C (O 7) and/or elevated microalbumin to creatinine ratio (O3500). Patients diagnosed with systolic heart failure (LVEF ! 40%) were grouped bythose known to have hypothyroidism (n 5 30) and those with normal thyroid function(TSH ! 5.50 and O 0.35 uIU/mL; n 5 45). Hypothyroid patients were further sub-divided into controlled (TSH ! 5.5 and O 0.35 uIU/mL; n 5 17) and uncontrolled(n 5 13) hypothyroidism. Glomerular filtration rate (GFR) was determined using thesimplified modified diet renal disease (MDRD) formula, integrating sex, age, raceand creatinine. TSH and GFR for each patient at one given time were analyzed.Groups were compared using one tail, unequal variance student t-test. Results: Base-line characteristics were similar between the groups. Renal function was considerablyworse in HF patients with hypothyroidism (n 5 30, 63.95 þ/- 21.43 ml/min/1.73m2)compared to those with normal thyroid function (n 5 45, 75.45 þ/-31.48 ml/min/1.73m2; p 5 0.032). There was no significant difference in renal function in thosewith normal thyroid function compared to controlled hypothyroidism (66.89 þ/-24.18 ml/min/1.73m2; p 5 0.131). There was a significantly decreased GFR in un-controlled hypothyroid patients (60.2 þ/- 17.4 ml/min/1.73m2) compared to normalthyroid patients (p 5 0.015). Conclusion and Discussion: HF patients with uncon-trolled hypothyroidism have worse renal function as compared to HF patients withnormal thyroid. This implies that strict control of hypothyroidism must be maintainedin patients with heart failure as it may impact prognosis.

073Novel Adult Porcine Model of Heart Failure after Myocardial Infarction forLong-Term Follow-Up StudiesKarl H. Schuleri1, Andrew J. Boyle2, Marco Centola1, Jeffrey M. Zimmet1, RobertEvers1, Kris S. Evers1, Joshua M. Hare3, Albert C. Lardo1; 1Medicine/Division ofCardiology, Johns Hopkins University, Baltimore, MD; 2Medicine/Division ofCardiology, UCSF, San Francisco, CA; 3Medicine/Division of Cardiology,University of Miami, Miami, FL

Introduction: Advances in medical therapies for heart failure all rely heavily on testingin animal models. Porcine models of myocardial infarction have been used because ofthe similarities between porcine and human hearts. However, the standard farm pigs ismainly used at a young age, grows rapidly and continues to put on significant amountsof body and heart weight over time, which makes long term follow-up studies difficultto conduct and to interpret. Therefore, we sought to develop an adult pig model which issuitable for long term follow-up, and does not physiologically increase in heart massduring the study period. Results & Methods: Myocardial infarction (MI) was inducedin Gottingen mini-pigs by 120 to 150min left ascending coronary artery (LAD) occlu-sion followed by reperfusion, which resulted in a reproducible model of transmural MIand subsequent heart failure. We evaluated the functional baseline characteristics in 21minipigs prior to the MIeprocedure. The left ventricular ejection fraction (LVEF) is51.4 6 0.8%, left ventricular endiastolic volume (LVEDV) is 38.3 6 2.2 cc, and leftventricular systolic volume (LVSV) is 19.5 6 1.0 cc. We compared our new adult mini-pig model to the commonly used one-hour LAD-occlusion Yorkshire swine model. Themortality from anterior MI in Gottingen mini-swine is 24%, and in Yorkshire swine is20% (p 5 NS). Serial cardiac MR imaging was performed at week 1 and 8 post-MI ina subgroup of 8 Yorkshire swines and 8 minipigs. The endiastolic left ventricular massincreased 42.6 6 4.3 to 52.8 6 6.6 grams from one week to 8 weeks post MI (p 5 0.02)in the Yorkshire swine while it remained unchanged in the Gottingen minipigs (34.2 6

While computerized analysis of digitally captured heart tones has shown promise,practical translation of this technology to emergency department (ED) patientswith acute dyspnea is challenging. We used a computrized noise score to estimatethe suitability of recorded heart tones to identify the presence of added sounds (S3or S4). A ThinkLabs Electronic Stethoscope was used to digitally record heart tonesat 30-90 degrees in the 4th or 5th left intercostal space in 159 ED patients over 50years old with signs and symptoms of possible heart failure. Phonocardiograph Mon-itor software was used to blindly test 212 recordings for suitability to detect an added(S3 or S4) heart tone by establishing a noise score (% of noise relative to the max-imum signal amplitude). Noise scores were defined a priori as: ! 6 good, 6-12 fair,12-20 poor, and O 20 unacceptable. Mean noise score 6 SD was 16.38 6 10.7. Un-acceptable scores were present in over a fourth of patients (Table). There was no sig-nificant difference between the subgroup measured from 30 to 45 degrees and thoseO 45 degrees (t test, p 5 0.59). Trained operator experience also suggested thatwhile ED ambient noise could be largely eliminated, physiological sounds (e.g.breathing, patient movement) and technical issues (stethoscope position, investigatormovement) were responsible for noise. Computer analysis for added heart tones canbe achieved in acutely ill ED patients but has a high percentage of noise. Optimaltechnique for capture of heart tones consistently acceptable for digital S3 and S4analysis requires further refinement before widespread clinical adoption.

Percent (N) of Noise Score Categories

Good Fair Poor Unacceptable

All (n 5 212) 10.9 (23) 30.2 (64) 31.1 (66) 27.8 (59)30e45 degrees (n 5 159) 11.9 (19) 30.8 (49) 28.3 (45) 28.9 (46)O 45 degrees (n 5 53) 7.5 (4) 28.3 (15) 39.6 (21) 24.5 (13)