Progression of Pulmonary Artery Systolic Pressures by Echocardiography among Ambulatory Patients without Pulmonary Hypertension at Baseline

S10 Journal of Cardiac Failure Vol. 19 No. 8S August 2013 human heart failure (HF). Methods: Thus, we measured serum NRG using ELISA in patients with HF, either due to ischemic (ISCH) or non-ischemic cardiomyopathy (NICM), and carefully characterized their clinical status to assess physiologic NRG response. Results: Serum NRG in 156 patients (mean age 60 6 13 years, 72% male, with mean LV ejection fraction (LVEF) of 30 6 14) who have symptomatic HF, either ISCH (n 5 68) or NICM (n 5 88), were measured. The entire cohort included 57% with hypertension, 32% diabetic and 38% with obesity while a high percentage were on optimal medical therapy including ACE inhibitor (82%), betablockers (91%) and diuretics (75%). There were no significant differences between groups regarding risk factors or percent on optimal medical therapy. Table 1 summarizes the NRG values and degree of HF between ISCH and NICM patients. Conclusion: Serum NRG values appear reduced in HF patients with ISCH compared to NICM etiology. This may reflect reduced production of this endothelial cell derived factor in the presence of advanced atherosclerosis.

a retrospective review of 31 pts with ICM and LVEF !40% who underwent PCI. All patients had 2 year follow up, were on optimal medical therapy (defined as use of beta blocker and ACE inhibitor), had transthoracic echocardiogram at baseline and after PCI and did not have cardiac resynchronization therapy devices. New York Heart Association (NYHA) Functional Classification was assessed on admission and during follow up. Results: Baseline demographics of patients are shown in table 1. Procedural success was 97%, with no peri-procedural death or myocardial infarctions. 33 stents were implanted in 31 pts (17 drug eluting, 14 bare metal). The distribution of vessels treated was as follows: LAD 61%, LCx 24%, RCA, 6%, bypass graft 9%. Overall LVEF improved from 3067% to 36613% post PCI, p 5 0.02; 69% of patients experienced an improvement in LVEF from 296 6% to 416 10% post PCI. During follow-up, 59% of pts had improvement in NYHA Functional Class of $ 1, 26% had no change and 15% had worsening of Functional Class by $ 1. Conclusion: In a small study of patients with ICM and LV dysfunction on optimal medical therapy, PCI appears to be feasible, safe, and is associated with improvements in LVEF and functional capacity.

024 Reduction in Exhaled Acetone Tracks with Weight Loss Following Diuretic Therapy in Acute Decompensated Heart Failure Lily Tranchito1, Zeynep Gul2, Frank Cikach1, Kevin Shrestha1, Raed Dweik1, W. H. Wilson Tang1; 1Cleveland Clinic, Cleveland, OH; 2Case Western Reserve University School of Medicine, Cleveland, OH Introduction: Exhaled breath volatile organic compounds (VOCs) are elevated in heart failure (HF). However, the relationship between exhaled VOC levels and HF disease severity is not well-established. Hypothesis: We hypothesize that in patients admitted with acute decompensated heart failure (ADHF), serial changes in exhaled acetone and pentane are associated with clinical indices of HF disease severity and diuretic response. Methods: In 44 patients admitted with ADHF between 7/12-3/ 13, we measured exhaled breath acetone and pentane levels at admission and at discharge after at least 48 hours of diuresis. Weight loss from admission to discharge was used as a marker of diuretic response. Results: In our study cohort (age 64614 years, LVEF 37618%, median admission NT-proBNP 2,947 pg/mL, PCWP 27610 mmHg), admission acetone and pentane levels correlated with lower LVEF (acetone: Spearman’s r5 -0.34, p!0.001; pentane: r5 -0.25, p50.013), higher PCWP (acetone: r50.41, p50.012; pentane: r50.44, p50.008), and higher NT-proBNP (acetone: r5 0.33, p50.005; pentane: r50.31, p50.008). Greater weight loss with diuretic therapy correlated with a greater reduction in acetone levels (r5 -0.51, p!0.001) but only trended with reduction in pentane (r5 -0.28, p50.07). In patients with above-median weight loss ($5 kg), patients demonstrated significantly greater percentage reduction in acetone (61% vs 16%, p50.01) but only trended in pentane (Figure). Conclusion: In patients admitted with ADHF, higher exhaled breath acetone and pentane levels are associated with lower LVEF, higher PCWP, and higher NT-proBNP. Greater reductions in exhaled breath acetone tracked with more weight loss in response to diuretics.

Table 1. Demographics

N 5 31 Age (yr) Men Caucasian BMI Hypertension Hyperlipidemia COPD Renal insufficency DM CAD NYHA NYHA follow up LVEF (%) LVEF (%) follow up

68614 20 (65%) 22 (71%) 27.866.5 31 (100%) 28 (90%) 5 (16%) 5 (16%) 14 (45%) 27 (87%) 2.3260.70 1.9260.78 3067 36613

Abbreviations: BMI 5 Body Mass Index; COPD 5 Chronic Obstructive Pulmonary Disease; DM 5 Diabetes Mellitus; CAD 5 Coronary Artery Disease

026 Progression of Pulmonary Artery Systolic Pressures by Echocardiography among Ambulatory Patients without Pulmonary Hypertension at Baseline Sarawut Siwamogsatham, Nektarios Souvaliotis, Lampros Papadimitriou, Song Li, Anjan Deka, Catherine Marti, Divya Gupta, Robert Cole, Sonjoy Laskar, Andrew L. Smith, Vasiliki Georgiopoulou, Javed Butler, Andreas Kalogeropoulos; Emory University, Atlanta, GA Introduction: Pulmonary hypertension (PH) is frequent among patients with heart failure (HF) and has substantial prognostic and therapeutic implications. However, data on the rate of progression to PH in HF are very limited and almost exclusively derived from patients with advanced (Stage D) HF. Patients prone to rapid progression to PH may be better candidates for novel PH therapies in Phase II-III clinical trials. Hypothesis: We hypothesized that, among patients with ambulatory (Stage C) HF and no evidence of PH at baseline, as evaluated by an echocardiographic pulmonary artery systolic pressure (PASP) estimate !45mmHg, (1) the progression of PH is highly variable; (2) higher PASP at baseline is associated with accelerated progression; and (3) standard HF prognostic factors explain only a small fraction of the variance in PH progression. Methods: We evaluated 106 ambulatory HF patients enrolled in a prospective cohort study (The Atlanta Cardiomyopathy Consortium) with (1) clinically available echocardiographic PASP at baseline; (2) baseline

Fig. 1. Percentage change in exhaled breath acetone and pentane levels across median weight loss (5 kg).

025 Percutaneous Coronary Intervention Improves Ejection Fraction in Ischemic Cardiomyopathy Meshe Chonde, Ryan Morrissey, Babak Azarbal, Jared Herr, Michele Hamilton; Cedars Sinai Medical Center, Los Angeles, CA Introduction: Coronary artery bypass grafting has been shown to improve left ventricular ejection fraction (LVEF) and heart failure symptoms in patients with ischemic cardiomyopathy (ICM). Data for percutaneous coronary intervention (PCI) as a means of coronary revascularization is limited. Methods: We conducted

The 17th Annual Scientific Meeting PASP !45 mmHg and (3) at least one follow-up PASP estimate $6 months later. We used mixed-effect models with random intercept and slope for PASP (i.e. effect of time) at the subject level to estimate mean slope of PASP and its individual variation. Results: Average number of serial echo studies was 3 (range, 2-6) over a median of 3.1 years (interquartile range, 2.0-4.1). Mean age was 56612; 52% were white; 44% were black; 58% were male; 41% had ischemic HF; left ventricular ejection fraction (LVEF) was 41616%; and baseline PASP was 3367 mmHg. Average slope of PASP progression was 1.0 mmHg/year (P50.01); however, there was significant individual variation, with 95% of values lying between -2.9 to 3.9 mmHg/year. Higher baseline PASP was associated with accelerated PH progression (Figure 1). Patients with morethan-moderate mitral regurgitation had a trend towards more rapid PH progression (1.4 vs. 0.4 mmHg/year; P50.055 for the interaction). However, age, left ventricular ejection fraction (LVEF) , NYHA class, and creatinine levels, among others, were not associated with progression of PH. Conclusion: In this cohort of ambulatory HF patients with no PH at baseline the progression of PH is highly variable with higher PASP at baseline being associated with accelerated progression. Standard HF prognostic factors explain only a small fraction of the variance in PH progression.



HFSA

S11

wall thickness (RWT) were calculated and ventricular remodeling was stratified based per American society of echocardiography recommendations. Patients with chronic kidney disease (CKD) were stratified on the basis of estimated glomerular filtration rate (GFR) calculated by the Cockroft-Gault formula corrected for body surface area. The patients were categorized into three groups: Mild CKD (CKD stages 12) and Moderate CKD (CKD stage 3-4) and Severe CKD (CKD stage 5). The groups were assessed for LVMI and prevalence and type of left ventricular remodeling. Multistep Regression analysis was performed to assess the association of LVMI and ventricular remodeling with renal function. Results: Kidney dysfunction as measures by glomerular filtration rate was significantly associated with LVMI (R2: 0.105; b: 0.352, p 0.002). The LVMI increased with higher stages of CKD (109635 g/m2, 125645 g/m2 and 128634 g/m2 in mild, moderate and severe CKD groups respectively). The RWT was 0.4360.11 in mild CKD and 0.466 0.10 in moderate and 0.4660.11 in the severe group. The prevalence of LV hypertrophy based on LVMI was 59% in the Mild CKD group and 66% in the moderate and severe CKD groups. Concentric hypertrophy was the most prevalent form of cardiac remodeling pattern seen in both the groups (Table 1). Conclusions: The left ventricular mass index is increased in patients with RAS with concomitant higher stages of CKD. Among LV remodeling patterns, concentric hypertrophy was the most prevalent pattern. Independent predictors of LVMI were renal function and diastolic blood pressure.

027 Regional Structural Uniformity of Left Ventricular Remodeling in Patients with Advanced Non Ischemic Cardiomyopathy Samuel F. Passi1,2, Nikos A. Diakos1,2, Abdallah G. Kfoury1, Craig H. Selzman1,2, Chi-Gang Yen1,2, Bruce B. Reid1,2, Omar Wever-Pinzon1, Edward M. Gilbert1,2, Deborah Budge1,2, Jose Nativi-Nicolau1,2, Elizabeth H. Hammond1,2, Craig A. High2, Dean Y. Li2, Josef Stehlik1,2, Stavros G. Drakos1,2; 1UTAH Cardiac Transplant Program (Division of Cardiology University of Utah, Intermountain Medical Center, VA Medical Center), Salt Lake City, UT; 2University of Utah Molecular Medicine, Salt Lake City, UT Background: Cardiomyocyte hypertrophy, myocardial fibrosis and decreased microvascular density are key structural characteristics of myocardial remodeling and heart failure (HF). We sought to examine whether these structural remodeling features have a uniform pattern across the left ventricle (LV). Methods: We studied 50 patients with end-stage HF and focused our analysis on the patients with non ischemic cardiomyopathy to minimize any regional differences related with coronary artery disease- induced ischemia and scar formation. Tissue from the apical and basal LV myocardium was obtained at the time of heart transplant. CD34 immunohistochemistry along with Masson’s Trichrome and Periodic Acid Schiff histochemical stains were performed for evaluation of microvascular density, myocardial fibrosis and cardiomyocyte hypertrophy, respectively. Analysis was performed on full thickness epicardium to endocardium sections with the use of state-of-the-art whole field digital microscopy. Results: We found no significant differences in myocardial fibrosis, microvascular density and cardiomyocyte cross section area between LV apex and base (Table). Conclusions: We did not observe significant differences in key structural remodeling features between the apical and the basal LV myocardium in patients with advanced non ischemic cardiomyopathy. This regional structural uniformity across the LV suggests that the tissue obtained from the apex at the time of left ventricular assist device implantation and explantation could be informative of the global LV myocardial structural state and as such can advance our understanding of mechanical unloading-induced changes on the failing human heart. Table 1. Regional structural remodeling characteristics in advanced non ischemic cardiomyopathy

Parameter Myocardial fibrosis (%) Microvascular density (# of vessels/um2) Cardiomyocyte Hypertrophy(um^2)

Left ventricular apex

Left ventricular base

p-value

18.561.9 2.1x10-360.1x10-3

19.761.8 2.3x10-360.1x10-3

0.65 0.13

849.9670.3

986.6688.2

0.29

Table 1. Left Ventricular Remodeling Pattern in Renal Artery Stenosis with Renal Dysfunction

LV Geometry Normal Concentric Remodeling Concentric Hypertrophy Eccentric Hypertrophy

Whole Cohort (n 5 77, 100%)

Mild CKD (n 5 23, 30 %)

Moderate CKD (n 5 39, 50 %)

Severe CKD (n 5 15, 20%)

13 14 31 19

4 (17.4) 5 (21.8) 10 (41.5) 4 (17.4)

7 (17.9) 6 (15.4) 14 (35.9) 12 (30.8)

2 3 7 3

(16.9) (18.2) (40.3) (24.7)

(13.3) (20.0) (46.7) (20.0)

029 Counter-Regulatory Interaction of Brain Natriuretic Peptide and Leptin in Recipients of Cardiac Resynchronization Therapy Ivan Cundrle, Bruce Johnson, Prachi Singh, Virend Somers, Lyle Olson; Mayo Clinic, Rochester, MN Introduction: In ob/ob knockout mice lack of leptin promotes hyperventilation. In vitro leptin expression by adipocytes is attenuated by natriuretic peptides. Cardiac resynchronization therapy (CRT) has been shown to decrease circulating brain natriuretic peptide (BNP) concentration. Hypothesis: Circulating leptin is inversely correlated to BNP concentration and leptin increases with CRT induced decrease of BNP. Methods: Consecutive, ambulatory heart failure (HF) patients were prospectively investigated pre- and post-CRT. NYHA class, BMI, left ventricular ejection fraction (LVEF), Minnesota Living with Heart Failure questionnaire (MLWHF), pCO2 by arterial blood gas, leptin and BNP plasma concentration were assessed pre- and 4-6 months post-CRT and compared by either paired t-test or Wilcoxon match pair test. Correlations between circulating leptin and BNP concentrations and change (D) of leptin to DBNP and DpCO2 were evaluated by Spearman rank correlation; p ! 0.05 considered significant. Results: Twenty-eight subjects were studied. Clinical endpoints significantly improved; leptin concentration significantly increased and BNP concentration decreased post-CRT (Table). Concentrations of BNP and leptin inversely correlated pre- (rho5 -0.65; p!0.01) and post-CRT (rho5 -0.64; p!0.01) and Dleptin was significantly inversely correlated to DBNP (rho5 -0.45; p50.03) and to DpCO2 (rho5 -0.48; p50.02). Conclusion: Circulating BNP and leptin concentrations are inversely correlated in HF patients with advanced HF. Decreased circulating BNP appears to contribute to increased leptin concentration post-CRT consistent with a counter-regulatory interaction. Increased leptin concentration post-CRT may promote improved ventilatory control by reduction of ventilatory drive.

028 The Effect of Renal Dysfunction on Left Ventricular Remodeling in Patients with Renal Artery Stenosis Abdur R. Khan, Mujeeb A. Sheikh, Christopher J. Cooper, Samer Khouri; University of Toledo Medical Center, Toledo, OH Objective: Renal dysfunction increase cardiac mortality. The objective of this study is to evaluate the effect and association of renal dysfunction on left ventricular remodeling in patients with renal artery stenosis (RAS). Methods: Seventy seven patients with angiographically proven renal artery stenosis were enrolled in the study. They underwent echocardiography prior to intervention along with the evaluation of demographic and clinical data. The left ventricular mass index (LVMI) and relative

pre CRT post CRT p

NYHA

BMI

LVEF (%)

MLWHF

BNP (pg/mL)

Leptin (ng/mL)

361 261 !0.01

3066 2965 0.17

2366 31615 !0.01

46624 26621 !0.01

115061113 7226707 !0.01

15.6614.5 18.7617.3 !0.04

BMI 5 body mass index; BNP 5 brain natriuretic peptide; LVEF 5 left ventricular ejection fraction; MLWHF 5 Minnesota Living with Heart Failure questionnaire; NYHA 5 New York Heart Association class