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Association Between Coronary Heart Disease and Inflammatory Biomarker YKL-40 in Type 2 Diabetes Subjects
S16 Journal of Cardiac Failure Vol. 18 No. 8S August 2012 association between abnormal myocardial perfusion and impairment of LVIR in this disease is controversial. Objectives: We aimed at evaluating the effect of aerobic physical training (APT) on the myocardial perfusion abnormalities and on the LVIR elicited by physical exercise in patients with CMD. Methods: 12 patients (5469 y.o, 7 female) with diagnosis of CMD (characterized by anginal chest pain with multiple reversible perfusion defects (RPD) in myocardial perfusion Sestamibi-Tc99m-SPECT imaging, and normal coronary arteries at angiography) were submitted at baseline and after 4 months of APT to: Stress-rest Sestamibi-Tc99mSPECT imaging, and nuclear ventriculography at rest and during graded bicycle exercise. Results: At baseline the area of RPD was 45627%, and the visual semiquantitative score of RPD severity was 10.168.8. The LV ejection fraction (LVEF) at rest was 66610%, and presented no significant increase during effort (69611% p50,41, paired t-test). All patients presented abnormal LVEF during effort: 5 patients with no increase (plateau response), 5 with biphasic pattern (initial increase followed by decrease at the end of stress) and 2 presented progressive decrease of LVEF. After the APT period, 10 patients (83%) presented significant reduction of the RPD area, with total resolution of RPD in 8 patients (67%). The area of RPD reduced to 13.7624% (p50.002), and the visual semi-quantitative score of RPD severity reduced to 2.864.9, as compared to the baseline (p50.008). Despite the RPD reduction, the LVIR response to effort presented no improvement (rest LVEF56368%, and stress LVEF567615% p50.29) and 9 patients (75%) presented abnormal LVEF response during effort: 7 biphasic, 1 plateau,1 progressive decrease. Conclusion: The results showed that 4 months of APT is associated to reduction of stress induced reversible myocardial perfusion defects in patients with CMD. However, this beneficial effect is not associated with improvement of LV systolic function during effort, suggesting that both abnormalities are independent components of the clinical phenotype of CMD.
Hemodynamics at 1 year on PHTx, by TAPSE Parameter HR RAP mPAP CI SV index PVR PVR-TAPSE
TAPSE $ 2.0 cm
TAPSE ! 2.0 cm
75612 6.862.2 41611 3.561.1 48.2612.9 5.162.4 2.962.5
69616 10.365.8* 48610 2.560.7y 37.2 68.6* 8.965.2y 7.465.2y
048 Hemodynamic Significance of a Follow-Up TAPSE Value of 2.0 cm or Greater at One Year on PH Specific Therapy in Patients With PAH Anjali V. Fields1, Justin D. Roberts2, Paul R. Forfia1; 1Medicine/Cardiovascular Division, University of Pennsylvania, Philadelphia, PA; 2Medicine/Cardiovascular Division, Lehigh Valley Medical Center, Allentown, PA Recent work has shown that serial hemodynamic assessment on PH specific therapy (PHTx) is of far greater prognostic significance than baseline assessment in PAH. Patients with a serial cardiac index $2.5 lpm/m2 on PHTx have a much better outcome vs. subjects below that CI threshold. Preliminary work has also shown that a serial tricuspid annular plane systolic excursion (TAPSE) value $2.0 cm on PHTx is associated with much better patient survival than a serial TAPSE ! 2.0 cm. Herein, we hypothesized there would be significant hemodynamic differences between subjects with a TAPSE $2.0 cm vs. ! 2.0 cm at 1 year following PHTx. Methods: 34 patients with PAH (47% idiopathic, 29% scleroderma, 12% congenital associated, 12% portopulmonary) underwent invasive hemodynamic assessment and echo-Doppler exam at baseline, and 1 year following initiation of PHTx. Patients were dichotomized by their TAPSE value at 1 year on PHTx (TAPSE $ 2.0 cm vs. TAPSE ! 2.0 cm). Hemodynamic parameters were compared between the TAPSE groups. * P!0.05; y P!0.01. Results: At 1 year on PHTx, 25 subjects had a TAPSE$2.0 cm; 9 had a TAPSE ! 2.0 cm. There were no deaths in the TAPSE $2.0 cm group vs. 3 deaths and 1 lung transplant in TAPSE ! 2.0 cm group. See Table 1. Mean PA pressure did not differ based on serial TAPSE. However, subjects with a TAPSE $2.0 cm had a lower RA pressure, markedly better cardiac index, and 43% lower PVR at 1 year on PHTx. A serial TAPSE$2.0 cm was also associated with a much wider separation between TAPSE and PVR, indicating a more favorable interaction between RV function and RV afterload. 23 of 25 subjects with a serial TAPSE$2.0 cm had a CI $2.5 lpm/m2. Moreover, a TAPSE$2.0 cm predicted a CI $ 2.5 lpm/m2 with an odds ratio of 11:1. Conclusions: A TAPSE$2.0 cm at 1 year on PHTx is associated with a much more favorable hemodynamic profile vs. TAPSE ! 2.0 cm. TAPSE$2.0 cm is strongly predictive of a normal cardiac index in PAH patients on PHTx. These hemodynamic differences likely play a key role in PAH outcome differences based on TAPSE, and suggest that a TAPSE$2.0 cm represents a simple, non-invasive, yet robust treatment target in PAH.
049 Echocardiographic Characteristics of Left Ventricular Diastolic Dysfunction are Different Among Different Etiologies Sharma Kattel, Keiko Saito, Yuji Saito; Department of Medicine, University at Buffalo, NY Background: Left ventricular diastolic dysfunction (LVDD) is associated with a variety of conditions, such as advanced age, female gender, diabetes, hypertension, and left ventricular hypertrophy (LVH). However, it is unclear whether echocardiographic characteristics of LVDD are the same among pathologic conditions (such as LVH-related) and biological conditions (such as age-related). Methods: Out of the patients who were diagnosed LVDD by echocardiogram, 250 patients with LVH and 250 patients without LVH were randomly selected. LVDD was defined by abnormal patterns of Doppler mitral inflow and tissue Doppler. Left atrial pressure (LAP) was estimated by the formula: 1.9 +1.24 [early mitral inflow velocity (E)/ early mitral annular velocity (E’)]. Tei-Index (myocardial performance index) was implemented to assess global left ventricular (LV) function. Results: LAP was significantly higher in the LVH group (12.4 mmHg) when compared to the non-LVH group (10.3 mmHg) [P50.0001]. Tei-index was also higher in the LVH group (0.56) compared to the non-LVH group (0.50) [P50.001]. Conclusions: In the presence of LVH, both LAP and Tei-index were significantly higher in LVH patients, indicating worsened cardiac function. Our study suggests the risk of diastolic heart failure may be higher in pathological LVDD than biological LVDD.
050 Progressive Bi-Ventricular Dysfunction in a Large Animal Model of Heart Failure With Rapid Ventricular Pacing: Echocardiographic Parameters and Invasive Characterization Sarah Mangiafico1, Diego Bellavia1, Lisa C. Costello-Boerrigter1, Guido Boerrigter1, Gail Harty1, Elise Oehler1, Alessandro Cataliotti1, Corrado Tamburino2, John C. Burnett1; 1Cardiorenal Research Laboratory, Mayo Clinic, Rochester, MN; 2 University of Catania, Italy Introduction: Rapid ventricular pacing (RVP) is commonly used to induce heart failure (HF) in experimental studies but minimal information exists regarding cardiac structural and functional changes that occur with HF evolution. The aim of this study was to document with echocardiographic parameters (Ep) the induction of HF by RVP and to compare Ep with invasive assessment (IA) of cardiac function. Hypothesis: We hypothesized that Ep in conscious dogs correlate with IA by intracardiac catheterization in anesthetized dogs. We also hypothesized that the RVP model is also a model of bi-ventricular (BV) failure. Methods: Pacemakers were implanted in 4 dogs and maintained (240 bpm) for 11 days. Standard Ep and strain analysis were performed at baseline (Bs) and at day 11 with pacing temporarily off. At day 11 IA of cardiac function was compared with Ep. Results: At day 11, IA was performed in all dogs and was consistent with congestive HF. Compared to Bs, Ep showed increased left ventricular end-diastolic (LVED) diameter (38.7 to 44.2 mm, p50.01), LVED volume (64.761 to 8861 mL, p50.01), basal right ventricular (RV) dimension (1661 to 2061 mm, p50.01), whereas LV ejection fraction (EF) (7062 to 3269%, p50.002) and LV fractional shortening (3961 to1564%, p50.001) were reduced. Interventricular septal thickness (11.2 61 to 10.1 mm, p50.1) was unchanged suggesting non ischemic impairment. Compared to Bs, tricuspid anular plane systolic excursion, an indirect measure of RVEF, was decreased (1761 to 10.962 mm, p!0.05). Systolic pulmonary artery pressure increased (18 64 to 33.863 mmHg, p50.008) similar to what was observed with IA (2862 mmHg, p5NS). On day 11, RV free wall, longitudinal strain (sS), longitudinal myocardial displacement (sDi) were reduced, but strain rate (sSR) was unchanged. Compared to Bs both the longitudinal sS and longitudinal sSR of the LV basal segments were reduced (p!0.05 for both), while longitudinal sDi was unchanged. Cardiac output was decreased compared to Bs (4.02 to 2.06 L/min, p50.02) and was similar with IA (1.81 L/min, p5NS) while PCWP and RAP were increased. Conclusions: This study reports, for the first time, the Ep of progressive HF induced by RVP which was confirmed by IA. The RVP model of HF serves as an excellent model of BVsystolic failure in humans.
051 Association Between Coronary Heart Disease and Inflammatory Biomarker YKL-40 in Type 2 Diabetes Subjects Hyun Min Kim1, Chang Hee Jung2, Bong Soo Cha1, Hyun Chul Lee1, Byung-Wan Lee1; 1Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; 2Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea Aims: With advent of technical progress, novel cytokines including adipokines or hepatokines have been discovered and studies for their clinical implication, especially in cardiovascular disease (CVD). In this study, we investigated the clinical relevance of novel cytokines in Korean subjects with type 2 diabetes (T2D). Methods: We recruited 69 diabetic subjects without documented history of CVD, and performed coronary CT (c-CT) and determined novel cytokines (chemerin, omentin-1, YKL-40 and sCD26). Results: Subjects were classified into two group (abnormal finding on c-CT, group I, n521) vs. insignificant finding on c-CT, group II, n548). Chemerin, omentin, and sCD26 were not different between both groups. Group I had a significantly increased YLK-40 and decreased HDL-C than group II (p50.038, 0.036, respectively). After adjusting age, smoking, hypertension,
The 16th Annual Scientific Meeting and LDL-C, only YLK-40 showed borderline significance. And levels of YKL-40 were significantly associated with systolic/diastolic BP, fasting glucose, postprandial TG, 10year Framingham score and % stenosis of coronary artery. Conclusion: YKL-40 mainly secreted from inflammatory cells is associated CVD risk factors, and increased in diabetic subjects with abnormal finding on c-CT. We suggest that YKL-40 might be useful predictive biomarker for coronary heart disease in type 2 diabetic subjects.
052 Modifiable Predictors of a Peak Oxygen Consumption !14 ml/kg/min in Patients With Chronic Heart Failure Omar Saeed1, Kevin M. Gentile1, Jigar Patel1, Argelis Rivera1, William Lee2, Snehal R. Patel1, Simon Maybaum1, Jooyoung J. Shin1; 1Department of Internal Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; 2 Department of Epidemiology, Albert Einstein College of Medicine, Bronx, NY Background: Improving exercise capacity is a major goal in treatment of chronic heart failure (HF) patients. Though prior reports link several clinical markers with peak oxygen consumption (pVO2), there is a paucity of studies associating modifiable clinical predictors of a severely limited pVO2 (!14 ml/kg/min) in HF patients. Methods: We retrospectively reviewed chronic HF patients with an EF !45% who underwent a cardiopulmonary exercise test (CPET) at our center from Jan. 2008 to Oct. 2011. Submaximal CPETs were excluded. Patients were categorized into two groups: pVO2 !14 ml/kg/min and pVO2 $14 ml/kg/min. Logistic regression was applied to isolate clinical variables predictive of a pVO2 !14 ml/kg/min. Results: 234 patients were reviewed. Mean age was 5469 years and mean EF 2969%. 84 (36%) patients had a pVO2 of !14 ml/kg/min. In univariate analysis, clinical predictors of a pVO2!14 ml/kg/min with a significant crude OR (p ! 0.05) were: older age; higher body mass index (BMI) and NYHA class; lower EF and hemoglobin (hb); and longer QRS duration. In multivariate modeling (after adjusting for age) BMI, NYHA class, EF and hb remained significant predictors of a pVO2 !14 ml/kg/min. (Figure 1)Conclusion: In this population of HF patients, several clinical predictors of a pVO2 !14 ml/kg/min were identified. BMI and hemoglobin were two modifiable predictors isolated. This suggests that weight loss and higher hemoglobin may improve exercise performance in HF patients with severely limited pVO2.
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ApoA1 protein levels from myocardial tissues of non-matched donor hearts from 10 non-HF donors (Control) versus explanted hearts from 20 patients with end-stage HF with western blot (normalized by GADPH). Results: We first used a monoclonal antibody that quantifies native and oxidized ApoA1 (oxApoA1) alike and observed significantly higher level of total ApoA1 between HF and Control hearts (3.4 6 1.2 vs. 1.8 6 0.8, p50.0005). We then used a monoclonal antibody that is specifically designed to recognize MPO-modified oxApoA1 that has lost cholesterol efflux activity, and observed significantly higher levels of oxApoA1 in HF compared to Control hearts (2.9 6 0.9 vs. 1.5 6 0.4, p50.0002). Conclusion: Results collectively suggest ApoA1 is retained, oxidized, and functionally impaired in the failing human heart. These findings also imply that enhanced myocardial oxidative stress is present in human heart failure, and further investigations into the role of oxidation of counter-regulatory ApoA1 production in HF are warranted.
054 Circulating Levels of 4-1BB and 4-1BB Ligand Are Not Elevated in Human Heart Failure Haiyan Tan1, Andres Schuster2, W.H. Wilson Tang2; 1Structural Biology, St. Jude Children’s Research Hospital, Memphis, TN; 2Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH
Fig. 1. Adjusted Odds Ratios (aOR) for Peak Oxygen Consumption (pVO2) #14 ml/ kg/min.
053 Increased Oxidized Apolipoprotein A1 Levels in the Failing Human Heart Zhili Shao, Ying Huang, Christine S. Moravec, Stanley L. Hazen, W.H. Wilson Tang; Cleveland Clinic, Cleveland, OH
Background: 4-1BB (CD137) is a member of the activation-induced tumor necrosis factor receptor family that is a powerful T-cell co-stimulatory molecule, and has been linked to the development of autoimmune myocarditis. Increased gene expression of 4-1BB has been identified in peripheral blood mononuclear cells in patients with heart failure (HF). Circulating levels of 4-1BB and its ligand (4-1BBL) have been reported to be elevated in the setting of multiple sclerosis and in animal models of myocarditis. We hypothesize that elevated 4-1BB/4-1BBL can be detectable in the heart failure (HF) population. Methods: We measured 4-1BB/4-1BBL in serum samples of 126 patients with HF (73 with acute heart failure, 53 with chronic systolic HF) and 21 healthy controls. 4-1BB was tested using the R&D DuoSet Elisa Development system and the capture and detection antibodies for 4-1BBL ELISA were from R&D. BNP was measured by Abbott Architect assay. Wilcoxon Rank-Sum test was used to analyze the data. Results: In our study cohort, the median (interquartile ranges) of serum 4-1BB and 4-1BBL were 11pg/mL (4-30pg/mL) and 0 pg/mL [0-171pg/mL], respectively. Interestingly 57.8% of subjects did not have a detectable 4-1BBL level. Compared to healthy controls, we did not observe an increase in either 4-1BB or 4-1BBL levels in patients with HF [median levels for 4-1BB 12pg/mL vs 7pg/mL (p50.16) and 4-1BBL 0pg/mL vs 31pg/mL (p50.13)], nor did we observe any significant differences between those experiencing acute vs chronic heart failure [median levels for 4-1BB 11pg/mL vs 15pg/mL(p50.47) and 41BBL 0pg/mL vs 0pg/mL (p50.30)]. In patients with HF, there was no correlation between 4-1BB or 4-1BBL and BNP levels. Conclusion: In contrast to animal models, we did not observe a difference between circulating levels of 4-1BB and 4-1BBL in patients with systolic heart failure compared to healthy controls or among patients with acute versus chronic heart failure.
055 Background: Apolipoprotein A1 (ApoA1) is a high-density lipoprotein-associated protein that confers atheroprotection, but such beneficial effects can be modified by oxidative processes such as those generated from myeloperoxidase (MPO), rendering them “dysfunctional.” The precise of ApoA1 in heart failure (HF) is unknown, although epidemiology studies have suggested low ApoA1 rendering higher risk of development HF after adjusting for interim coronary disease. In animal studies, human ApoA1 gene transfer reduced the development of cardiomyopathy, and elevated circulating MPO levels have been associated with disease progression in human HF. We sought to examine whether oxidative modification of ApoA1 at the level of the myocardium is present in the failing human heart. Methods: We compared oxidized
Pulmonary Hypertension is a Manifestation of Congestive Heart Failure in Octogenarians with Severe Aortic Stenosis Amresh Raina1, Zachary M. Gertz2, William T. O’Donnell2, Kerri A. Smith2, Howard C. Herrmann2, Paul R. Forfia2; 1Cardiovascular Institute, Allegheny General Hospital, Pittsburgh, PA; 2Cardiovascular Division, Hospital of the University of Pennsylvania, Philadelphia, PA
Background: Some studies have suggested pulmonary hypertension (PH) in severe AS is a risk factor for adverse outcomes with aortic valve replacement
Hemodynamics at 1 year on PHTx, by TAPSE Parameter HR RAP mPAP CI SV index PVR PVR-TAPSE
TAPSE $ 2.0 cm
TAPSE ! 2.0 cm
75612 6.862.2 41611 3.561.1 48.2612.9 5.162.4 2.962.5
69616 10.365.8* 48610 2.560.7y 37.2 68.6* 8.965.2y 7.465.2y
048 Hemodynamic Significance of a Follow-Up TAPSE Value of 2.0 cm or Greater at One Year on PH Specific Therapy in Patients With PAH Anjali V. Fields1, Justin D. Roberts2, Paul R. Forfia1; 1Medicine/Cardiovascular Division, University of Pennsylvania, Philadelphia, PA; 2Medicine/Cardiovascular Division, Lehigh Valley Medical Center, Allentown, PA Recent work has shown that serial hemodynamic assessment on PH specific therapy (PHTx) is of far greater prognostic significance than baseline assessment in PAH. Patients with a serial cardiac index $2.5 lpm/m2 on PHTx have a much better outcome vs. subjects below that CI threshold. Preliminary work has also shown that a serial tricuspid annular plane systolic excursion (TAPSE) value $2.0 cm on PHTx is associated with much better patient survival than a serial TAPSE ! 2.0 cm. Herein, we hypothesized there would be significant hemodynamic differences between subjects with a TAPSE $2.0 cm vs. ! 2.0 cm at 1 year following PHTx. Methods: 34 patients with PAH (47% idiopathic, 29% scleroderma, 12% congenital associated, 12% portopulmonary) underwent invasive hemodynamic assessment and echo-Doppler exam at baseline, and 1 year following initiation of PHTx. Patients were dichotomized by their TAPSE value at 1 year on PHTx (TAPSE $ 2.0 cm vs. TAPSE ! 2.0 cm). Hemodynamic parameters were compared between the TAPSE groups. * P!0.05; y P!0.01. Results: At 1 year on PHTx, 25 subjects had a TAPSE$2.0 cm; 9 had a TAPSE ! 2.0 cm. There were no deaths in the TAPSE $2.0 cm group vs. 3 deaths and 1 lung transplant in TAPSE ! 2.0 cm group. See Table 1. Mean PA pressure did not differ based on serial TAPSE. However, subjects with a TAPSE $2.0 cm had a lower RA pressure, markedly better cardiac index, and 43% lower PVR at 1 year on PHTx. A serial TAPSE$2.0 cm was also associated with a much wider separation between TAPSE and PVR, indicating a more favorable interaction between RV function and RV afterload. 23 of 25 subjects with a serial TAPSE$2.0 cm had a CI $2.5 lpm/m2. Moreover, a TAPSE$2.0 cm predicted a CI $ 2.5 lpm/m2 with an odds ratio of 11:1. Conclusions: A TAPSE$2.0 cm at 1 year on PHTx is associated with a much more favorable hemodynamic profile vs. TAPSE ! 2.0 cm. TAPSE$2.0 cm is strongly predictive of a normal cardiac index in PAH patients on PHTx. These hemodynamic differences likely play a key role in PAH outcome differences based on TAPSE, and suggest that a TAPSE$2.0 cm represents a simple, non-invasive, yet robust treatment target in PAH.
049 Echocardiographic Characteristics of Left Ventricular Diastolic Dysfunction are Different Among Different Etiologies Sharma Kattel, Keiko Saito, Yuji Saito; Department of Medicine, University at Buffalo, NY Background: Left ventricular diastolic dysfunction (LVDD) is associated with a variety of conditions, such as advanced age, female gender, diabetes, hypertension, and left ventricular hypertrophy (LVH). However, it is unclear whether echocardiographic characteristics of LVDD are the same among pathologic conditions (such as LVH-related) and biological conditions (such as age-related). Methods: Out of the patients who were diagnosed LVDD by echocardiogram, 250 patients with LVH and 250 patients without LVH were randomly selected. LVDD was defined by abnormal patterns of Doppler mitral inflow and tissue Doppler. Left atrial pressure (LAP) was estimated by the formula: 1.9 +1.24 [early mitral inflow velocity (E)/ early mitral annular velocity (E’)]. Tei-Index (myocardial performance index) was implemented to assess global left ventricular (LV) function. Results: LAP was significantly higher in the LVH group (12.4 mmHg) when compared to the non-LVH group (10.3 mmHg) [P50.0001]. Tei-index was also higher in the LVH group (0.56) compared to the non-LVH group (0.50) [P50.001]. Conclusions: In the presence of LVH, both LAP and Tei-index were significantly higher in LVH patients, indicating worsened cardiac function. Our study suggests the risk of diastolic heart failure may be higher in pathological LVDD than biological LVDD.
050 Progressive Bi-Ventricular Dysfunction in a Large Animal Model of Heart Failure With Rapid Ventricular Pacing: Echocardiographic Parameters and Invasive Characterization Sarah Mangiafico1, Diego Bellavia1, Lisa C. Costello-Boerrigter1, Guido Boerrigter1, Gail Harty1, Elise Oehler1, Alessandro Cataliotti1, Corrado Tamburino2, John C. Burnett1; 1Cardiorenal Research Laboratory, Mayo Clinic, Rochester, MN; 2 University of Catania, Italy Introduction: Rapid ventricular pacing (RVP) is commonly used to induce heart failure (HF) in experimental studies but minimal information exists regarding cardiac structural and functional changes that occur with HF evolution. The aim of this study was to document with echocardiographic parameters (Ep) the induction of HF by RVP and to compare Ep with invasive assessment (IA) of cardiac function. Hypothesis: We hypothesized that Ep in conscious dogs correlate with IA by intracardiac catheterization in anesthetized dogs. We also hypothesized that the RVP model is also a model of bi-ventricular (BV) failure. Methods: Pacemakers were implanted in 4 dogs and maintained (240 bpm) for 11 days. Standard Ep and strain analysis were performed at baseline (Bs) and at day 11 with pacing temporarily off. At day 11 IA of cardiac function was compared with Ep. Results: At day 11, IA was performed in all dogs and was consistent with congestive HF. Compared to Bs, Ep showed increased left ventricular end-diastolic (LVED) diameter (38.7 to 44.2 mm, p50.01), LVED volume (64.761 to 8861 mL, p50.01), basal right ventricular (RV) dimension (1661 to 2061 mm, p50.01), whereas LV ejection fraction (EF) (7062 to 3269%, p50.002) and LV fractional shortening (3961 to1564%, p50.001) were reduced. Interventricular septal thickness (11.2 61 to 10.1 mm, p50.1) was unchanged suggesting non ischemic impairment. Compared to Bs, tricuspid anular plane systolic excursion, an indirect measure of RVEF, was decreased (1761 to 10.962 mm, p!0.05). Systolic pulmonary artery pressure increased (18 64 to 33.863 mmHg, p50.008) similar to what was observed with IA (2862 mmHg, p5NS). On day 11, RV free wall, longitudinal strain (sS), longitudinal myocardial displacement (sDi) were reduced, but strain rate (sSR) was unchanged. Compared to Bs both the longitudinal sS and longitudinal sSR of the LV basal segments were reduced (p!0.05 for both), while longitudinal sDi was unchanged. Cardiac output was decreased compared to Bs (4.02 to 2.06 L/min, p50.02) and was similar with IA (1.81 L/min, p5NS) while PCWP and RAP were increased. Conclusions: This study reports, for the first time, the Ep of progressive HF induced by RVP which was confirmed by IA. The RVP model of HF serves as an excellent model of BVsystolic failure in humans.
051 Association Between Coronary Heart Disease and Inflammatory Biomarker YKL-40 in Type 2 Diabetes Subjects Hyun Min Kim1, Chang Hee Jung2, Bong Soo Cha1, Hyun Chul Lee1, Byung-Wan Lee1; 1Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; 2Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea Aims: With advent of technical progress, novel cytokines including adipokines or hepatokines have been discovered and studies for their clinical implication, especially in cardiovascular disease (CVD). In this study, we investigated the clinical relevance of novel cytokines in Korean subjects with type 2 diabetes (T2D). Methods: We recruited 69 diabetic subjects without documented history of CVD, and performed coronary CT (c-CT) and determined novel cytokines (chemerin, omentin-1, YKL-40 and sCD26). Results: Subjects were classified into two group (abnormal finding on c-CT, group I, n521) vs. insignificant finding on c-CT, group II, n548). Chemerin, omentin, and sCD26 were not different between both groups. Group I had a significantly increased YLK-40 and decreased HDL-C than group II (p50.038, 0.036, respectively). After adjusting age, smoking, hypertension,
The 16th Annual Scientific Meeting and LDL-C, only YLK-40 showed borderline significance. And levels of YKL-40 were significantly associated with systolic/diastolic BP, fasting glucose, postprandial TG, 10year Framingham score and % stenosis of coronary artery. Conclusion: YKL-40 mainly secreted from inflammatory cells is associated CVD risk factors, and increased in diabetic subjects with abnormal finding on c-CT. We suggest that YKL-40 might be useful predictive biomarker for coronary heart disease in type 2 diabetic subjects.
052 Modifiable Predictors of a Peak Oxygen Consumption !14 ml/kg/min in Patients With Chronic Heart Failure Omar Saeed1, Kevin M. Gentile1, Jigar Patel1, Argelis Rivera1, William Lee2, Snehal R. Patel1, Simon Maybaum1, Jooyoung J. Shin1; 1Department of Internal Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; 2 Department of Epidemiology, Albert Einstein College of Medicine, Bronx, NY Background: Improving exercise capacity is a major goal in treatment of chronic heart failure (HF) patients. Though prior reports link several clinical markers with peak oxygen consumption (pVO2), there is a paucity of studies associating modifiable clinical predictors of a severely limited pVO2 (!14 ml/kg/min) in HF patients. Methods: We retrospectively reviewed chronic HF patients with an EF !45% who underwent a cardiopulmonary exercise test (CPET) at our center from Jan. 2008 to Oct. 2011. Submaximal CPETs were excluded. Patients were categorized into two groups: pVO2 !14 ml/kg/min and pVO2 $14 ml/kg/min. Logistic regression was applied to isolate clinical variables predictive of a pVO2 !14 ml/kg/min. Results: 234 patients were reviewed. Mean age was 5469 years and mean EF 2969%. 84 (36%) patients had a pVO2 of !14 ml/kg/min. In univariate analysis, clinical predictors of a pVO2!14 ml/kg/min with a significant crude OR (p ! 0.05) were: older age; higher body mass index (BMI) and NYHA class; lower EF and hemoglobin (hb); and longer QRS duration. In multivariate modeling (after adjusting for age) BMI, NYHA class, EF and hb remained significant predictors of a pVO2 !14 ml/kg/min. (Figure 1)Conclusion: In this population of HF patients, several clinical predictors of a pVO2 !14 ml/kg/min were identified. BMI and hemoglobin were two modifiable predictors isolated. This suggests that weight loss and higher hemoglobin may improve exercise performance in HF patients with severely limited pVO2.
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ApoA1 protein levels from myocardial tissues of non-matched donor hearts from 10 non-HF donors (Control) versus explanted hearts from 20 patients with end-stage HF with western blot (normalized by GADPH). Results: We first used a monoclonal antibody that quantifies native and oxidized ApoA1 (oxApoA1) alike and observed significantly higher level of total ApoA1 between HF and Control hearts (3.4 6 1.2 vs. 1.8 6 0.8, p50.0005). We then used a monoclonal antibody that is specifically designed to recognize MPO-modified oxApoA1 that has lost cholesterol efflux activity, and observed significantly higher levels of oxApoA1 in HF compared to Control hearts (2.9 6 0.9 vs. 1.5 6 0.4, p50.0002). Conclusion: Results collectively suggest ApoA1 is retained, oxidized, and functionally impaired in the failing human heart. These findings also imply that enhanced myocardial oxidative stress is present in human heart failure, and further investigations into the role of oxidation of counter-regulatory ApoA1 production in HF are warranted.
054 Circulating Levels of 4-1BB and 4-1BB Ligand Are Not Elevated in Human Heart Failure Haiyan Tan1, Andres Schuster2, W.H. Wilson Tang2; 1Structural Biology, St. Jude Children’s Research Hospital, Memphis, TN; 2Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH
Fig. 1. Adjusted Odds Ratios (aOR) for Peak Oxygen Consumption (pVO2) #14 ml/ kg/min.
053 Increased Oxidized Apolipoprotein A1 Levels in the Failing Human Heart Zhili Shao, Ying Huang, Christine S. Moravec, Stanley L. Hazen, W.H. Wilson Tang; Cleveland Clinic, Cleveland, OH
Background: 4-1BB (CD137) is a member of the activation-induced tumor necrosis factor receptor family that is a powerful T-cell co-stimulatory molecule, and has been linked to the development of autoimmune myocarditis. Increased gene expression of 4-1BB has been identified in peripheral blood mononuclear cells in patients with heart failure (HF). Circulating levels of 4-1BB and its ligand (4-1BBL) have been reported to be elevated in the setting of multiple sclerosis and in animal models of myocarditis. We hypothesize that elevated 4-1BB/4-1BBL can be detectable in the heart failure (HF) population. Methods: We measured 4-1BB/4-1BBL in serum samples of 126 patients with HF (73 with acute heart failure, 53 with chronic systolic HF) and 21 healthy controls. 4-1BB was tested using the R&D DuoSet Elisa Development system and the capture and detection antibodies for 4-1BBL ELISA were from R&D. BNP was measured by Abbott Architect assay. Wilcoxon Rank-Sum test was used to analyze the data. Results: In our study cohort, the median (interquartile ranges) of serum 4-1BB and 4-1BBL were 11pg/mL (4-30pg/mL) and 0 pg/mL [0-171pg/mL], respectively. Interestingly 57.8% of subjects did not have a detectable 4-1BBL level. Compared to healthy controls, we did not observe an increase in either 4-1BB or 4-1BBL levels in patients with HF [median levels for 4-1BB 12pg/mL vs 7pg/mL (p50.16) and 4-1BBL 0pg/mL vs 31pg/mL (p50.13)], nor did we observe any significant differences between those experiencing acute vs chronic heart failure [median levels for 4-1BB 11pg/mL vs 15pg/mL(p50.47) and 41BBL 0pg/mL vs 0pg/mL (p50.30)]. In patients with HF, there was no correlation between 4-1BB or 4-1BBL and BNP levels. Conclusion: In contrast to animal models, we did not observe a difference between circulating levels of 4-1BB and 4-1BBL in patients with systolic heart failure compared to healthy controls or among patients with acute versus chronic heart failure.
055 Background: Apolipoprotein A1 (ApoA1) is a high-density lipoprotein-associated protein that confers atheroprotection, but such beneficial effects can be modified by oxidative processes such as those generated from myeloperoxidase (MPO), rendering them “dysfunctional.” The precise of ApoA1 in heart failure (HF) is unknown, although epidemiology studies have suggested low ApoA1 rendering higher risk of development HF after adjusting for interim coronary disease. In animal studies, human ApoA1 gene transfer reduced the development of cardiomyopathy, and elevated circulating MPO levels have been associated with disease progression in human HF. We sought to examine whether oxidative modification of ApoA1 at the level of the myocardium is present in the failing human heart. Methods: We compared oxidized
Pulmonary Hypertension is a Manifestation of Congestive Heart Failure in Octogenarians with Severe Aortic Stenosis Amresh Raina1, Zachary M. Gertz2, William T. O’Donnell2, Kerri A. Smith2, Howard C. Herrmann2, Paul R. Forfia2; 1Cardiovascular Institute, Allegheny General Hospital, Pittsburgh, PA; 2Cardiovascular Division, Hospital of the University of Pennsylvania, Philadelphia, PA
Background: Some studies have suggested pulmonary hypertension (PH) in severe AS is a risk factor for adverse outcomes with aortic valve replacement