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Interleukin-6 Plays a Detrimental Role in LV Remodeling after an Acute Myocardial Infarction
S32 Journal of Cardiac Failure Vol. 23 No. 8S August 2017 (P < .0001) and ≥2R rejection (P = .043) were both associated with LGD status. Conclusions: These data showed elevated BNP levels surrounding the time of documented LGD after cardiac transplantation. Thus, our results add to the current literature supporting serial BNP testing as a prognostic tool for the occurrence of LGD in this patient population. Prospective studies are needed to validate these findings. References 1. Bader FM, Rogers RK, Kfoury AG, Gilbert EM, Horne BD, Stehlik J, et al. Time-dependent changes in B-type natriuretic peptide after heart transplantation: correlation with allograft rejection and function. Congest Heart Fail 2009;15:63–7. 2. Martínez-Dolz L, Almenar L, Hervás I, Moro J, Agüero J, Sánchez-Lázaro I, et al. Prognostic relationship between two serial determinations of B-type natriuretic peptide and medium-long-term events in heart transplantation. JHLT 2008;27:735–40. 3. Damodaran A, Dardas T, Wu AH, Dyke DB, Hummel SL, Cowger JA, et al. Changes in serial B-type natriuretic peptide level independently predict cardiac allograft rejection. JHLT 2012;31:708–14.
074 Interleukin-6 Plays a Detrimental Role in LV Remodeling after an Acute Myocardial Infarction Anweshan Samanta1, Amy Cantilena2, Guangming Cheng3, Arash Davani3, Magdy Girgis3, Lei Chen3, Lin Zhao3, Robert J. Vincent3, Jeryl Hauptman3, Buddhadeb Dawn3; 1 University of Missouri—Kansas City, Kansas City, Missouri; 2University of Kansas School of Medicine, Kansas City, Kansas; 3University of Kansas Medical Center, Kansas City, Kansas Introduction: Interleukin-6 (IL-6), a proinflammatory cytokine, has been implicated in various cardiovascular diseases, including myocardial ischemic injury. Although its expression has been shown to rise in the aftermath of an acute myocardial infarction (MI), its exact role in left ventricular (LV) remodeling and pathogenesis of ischemic cardiomyopathy remains unclear. Hypothesis: We hypothesized that the absence of IL-6 will have a favorable impact on LV remodeling after a reperfused MI. Methods: To simulate a human myocardial infarction, we used a model of reperfused MI because most MIs in humans are followed by spontaneous or interventional reperfusion. Agematched male C57BL/6 control mice and IL-6 knockout (KO) mice were subjected to a 30-min occlusion of the LAD coronary artery followed by reperfusion. Cardiac structure and function were serially assessed by echocardiography at baseline (4 d before MI), at 48 h and 35 d after MI. Mice were sacrificed after 35 days for histological and biochemical assessments. Results: At 48 h post-MI, ejection fraction (EF) was similarly and significantly reduced in both groups compared with baseline, indicating that the ischemic injury was similar in both groups. However, 35 d after MI, IL-6 KO mice exhibited significantly greater EF compared with control mice (49.5 ± 2.2% in IL-6 KO mice vs 42.6 ± 1.3% in control mice). IL-6 KO mice had significantly smaller LV mass and cardiomyocyte size. Moreover, LV end-diastolic volume was significantly smaller in IL-6 KO mice, indicating superior remodeling. Conclusions: Genetic deletion of IL-6 ameliorates LV remodeling and systolic dysfunction after a reperfused myocardial infarction, indicating a deleterious role of IL-6 in LV remodeling after acute myocardial ischemia/reperfusion injury. Modulation of IL-6 signaling may therefore have therapeutic potential for patients after MI at risk for adverse remodeling and development of heart failure.
elevations in galectin-3 independently identified high risk HF patients and was able to phenotype renal dysfunction into high and low risk subtypes.
076 Risk Stratification in HFPEF Patients According to eGFR Level Derived From CKD-EPI Equations with or Without Serum Cystatin C Inclusion Tatiana Nikiforova1, Dmitry Shchekochikhin1, Anastasia Lomonosova1, Houssem El Manaa1, Alexandra Shilova2, Philippe Kopylov1; 1First Moscow State Medical University, Moscow, Russian Federation; 2Pirogov Russian National Research Medical University (RNRMU), Moscow, Russian Federation HFPEF is a common HF phenotype with increase in incidence and prevalence. There is no direct prognostic estimator for these patients to the date. Decreased GFR is an independent negative prognostic factor in different heart failure patients populations. Several formulas are accepted for estimating GFR. However, the best equation for eGFR estimating in HFPEF patients for prognosis estimation remains unknown. The aim of the study is to compare prognostic significance of decreased eGFR derived by CKDEPI equation based on serum creatinine and serum cystatin C versus CKD-EPI equation based on serum creatinine only in patients with first decompensation of HFPEF. Materials and Methods: 117 HFPEF patients (average age 71,6 ± 9,1 years; 65,8% - women) were included.85,5% of the patients had atrial fibrillation with persistent form in 38,5%.25,6% had diabetes mellitus. 32,5% had ischemic origin of HF. HFPEF was diagnosed according to ECS guidelines. All patients signed informed consent. The study was approved by local and institutional ethical committee. After discharge, the patients were mentored by phone monthly during first six months and every three months until 24 month period. Mortality, HF hospitalization and combined end point were used. Kaplan-Mayer curves with Log-rank test were used for survival analysis. P value of 0,05 or less was considered to be significant. Results: Average eGFR at inclusion was 50,2 ± 16,9 ml/min/1.73 sq.m by CKD-EPI equation based on serum creatinine and 46,4 ± 16,1 ml/min/1.73 sq.m by CKD-EPI equation based on serum creatinine in cystatin C (p < 0,05). Addition of cystatin C to equation reclassified the patients by CKD stage with increase in prevalence of 3B/4 stage (41,0% vs 35,9%; p < 0,05). During followup 45,3% of the patients reached combine end-point, mortality was 11,9%, HF rehospitalization was 33,3%. Study population was divided for two groups, with eGFR > 45 ml/min/1.73 sq.m or eGFR < 45 ml/min/1.73 sq.m by both formulas. The groups divided by CKD-EPI formula based on serum creatinine only did not differ in mortality, morbidity and combined end-point during survival analysis (p = 0,07; p = 0,7 and p = 0,2). However, if the patients were divided by CKD-EPI equation with both serum creatinine and serum cystatine C, the patients with eGFR < 45 ml/min/1.73 sq.m demonstrated significantly increased achievement of combined end-point (p = 0,03) and increased mortality (p = 0,03). Conclusions: Decreased baseline eGFR by CKD-EPI equation based on serum creatinine and cystatine C levels is a negative prognostic factor in patients with first decompensation of HFPEF. Significance of serum cystatine C level in HFPEF can be attributed to more accurate renal function measurement or nonrenal factors, such as alerted collagen turnover.
077 075 Urine Galectin-3 Levels Identify High Risk Renal Dysfunction in Patients with Heart Failure Tariq Ahmad, Veena Rao, Zobia Chunara, Devin Mahoney, Keyanna Jackson, Daniel Hodson, Catherine Tarleton, Daniel Thomas Jr., Michael Chen, Daniel Jacoby, Ralph Riello, Jeffrey Testani; Yale University, New Haven, Connecticut Background: Galectin-3 (Gal-3) is a well-established mediator of tissue fibrosis across multiple tissues, including heart and kidney. Despite early optimism for the marker in patients with heart failure (HF), plasmagal-3 levels appear to largely reflect nonspecific systemic processes and correlate poorly with cardiac tissue fibrosis. However, urine levels of Gal-3 may report more precisely on local pathology in the kidney since urine is a fluid that bathes only renal tissue. Objective: To understand whether urinegal-3 can provide unique information about the prognosis and phenotype of renal dysfunction in HF. Methods: We enrolled 132 consecutive HF patients presenting to an outpatient treatment and evaluation center. Plasma and pre-diuretic urine levels of Gal-3 were measured. Renal dysfunction was defined as an estimated glomerular filtration rate (eGFR <60 ml/min/1.73 m2). Results: Urinegal-3 was associated with an increased risk of death [HR 1.49 per log increase, 95% CI (1.11–1.98), P = .008]. This relationship was nonlinear, with the majority of the risk concentrated in the top quartile of urinegal-3 [HR 2.7 top quartile vs. reminder of cohort, 95% CI (1.4–5.2), P = .003]. This association persisted after controlling for a comprehensive set of prognostic variables including eGFR, natriuretic peptides, and the renal injury marker urine NGAL [HR 4.09, 95% CI (1.45–11.48); P < .01]. On the contrary, elevated plasmagal-3 levels were not associated with mortality after multivariable adjustment: [HR 1.26 95% CI (0.80–1.99); P = .3]. Importantly, renal dysfunction was free from adverse prognostic importance in patients with low urine Gal-3 levels (HR = 0.96, 95% CI 0.4–2.2, P = .92) but associated with a severely elevated risk in patients with elevated urine Gal-3 (HR = 7.5, 95% CI 1.5–68, P = .038, P interaction = 0.033). Conclusions: Urine, but not serum,
In Dialysis Dependent Renal Failure Patients Plasma BNP is Associated with Mean Pulmonary Artery Pressure but Not Left Ventricular Filling Pressure Luai Alhazmi, Shafiq Qaiser, Zaid Ammari, Mohammed Ruzieh, Osama Dasa, George Moukarbel; University of Toledo, Toledo, Ohio Introduction: Association between plasma BNP levels, left ventricular LV filling pressure, intravascular volume status and pulmonary arterial hypertension has been described in normal and chronic kidney disease patients. Relationship between BNP, LV filling and pulmonary artery pressures in dialysis dependent renal failure patients is not well known. We hypothesized that in dialysis dependent renal failure patients, plasma levels of BNP will correlate with LV filling and pulmonary artery pressures. Methods and Results Renal transplant database was searched for adult dialysis dependent renal failure patients who had plasma BNP level measurement and invasive hemodynamic assessment by right heart catheterization within the 1-month period. LV filling pressures were assessed by pulmonary capillary wedge pressure measurement PCWP. Cardiac output CO was calculated using Fick equation. Eighty six (age, mean 57 ± 12y, hemodialysis 81%, peritoneal dialysis 19%), predominantly Caucasian (61%), male (69%) patients were included. Co-morbid conditions included hypertension (98%), diabetes mellitus (59%), coronary artery disease (40%), congestive heart failure (24%) and overweight/ obesity (BMI, mean 29 ± 5). Mean BNP level was 811 ± 1224 pg/ml and serum creatinine 7.4 ± 4 mg/dl. Invasive hemodynamics; mean right atrial pressure was 8 ± 4, pulmonary artery (PA) 25 ± 9, PCWP 14 ± 7 mmHg, CO 8.5 ± 2.3 L/min and cardiac index 4.4 ± 1.5 L/min/m2. Multivariable logistic regression and correlation analyses were performed using IBM SPSS v23.0. A statistically significant association was found between plasma BNP level and mean PA pressure (P = .023, 95%CI 9, 116) but not between BNP and PCWP (P = .642). A positive correlation between BNP and mean PA pressure (r = 0.6, P < .001) was observed (Fig. 1). Conclusion In dialysis dependent renal failure patients, plasma BNP level is associated with pulmonary artery pressure but not with LV filling pressure suggesting that BNP is not reliable indicator of intravascular volume status in this specific population.
074 Interleukin-6 Plays a Detrimental Role in LV Remodeling after an Acute Myocardial Infarction Anweshan Samanta1, Amy Cantilena2, Guangming Cheng3, Arash Davani3, Magdy Girgis3, Lei Chen3, Lin Zhao3, Robert J. Vincent3, Jeryl Hauptman3, Buddhadeb Dawn3; 1 University of Missouri—Kansas City, Kansas City, Missouri; 2University of Kansas School of Medicine, Kansas City, Kansas; 3University of Kansas Medical Center, Kansas City, Kansas Introduction: Interleukin-6 (IL-6), a proinflammatory cytokine, has been implicated in various cardiovascular diseases, including myocardial ischemic injury. Although its expression has been shown to rise in the aftermath of an acute myocardial infarction (MI), its exact role in left ventricular (LV) remodeling and pathogenesis of ischemic cardiomyopathy remains unclear. Hypothesis: We hypothesized that the absence of IL-6 will have a favorable impact on LV remodeling after a reperfused MI. Methods: To simulate a human myocardial infarction, we used a model of reperfused MI because most MIs in humans are followed by spontaneous or interventional reperfusion. Agematched male C57BL/6 control mice and IL-6 knockout (KO) mice were subjected to a 30-min occlusion of the LAD coronary artery followed by reperfusion. Cardiac structure and function were serially assessed by echocardiography at baseline (4 d before MI), at 48 h and 35 d after MI. Mice were sacrificed after 35 days for histological and biochemical assessments. Results: At 48 h post-MI, ejection fraction (EF) was similarly and significantly reduced in both groups compared with baseline, indicating that the ischemic injury was similar in both groups. However, 35 d after MI, IL-6 KO mice exhibited significantly greater EF compared with control mice (49.5 ± 2.2% in IL-6 KO mice vs 42.6 ± 1.3% in control mice). IL-6 KO mice had significantly smaller LV mass and cardiomyocyte size. Moreover, LV end-diastolic volume was significantly smaller in IL-6 KO mice, indicating superior remodeling. Conclusions: Genetic deletion of IL-6 ameliorates LV remodeling and systolic dysfunction after a reperfused myocardial infarction, indicating a deleterious role of IL-6 in LV remodeling after acute myocardial ischemia/reperfusion injury. Modulation of IL-6 signaling may therefore have therapeutic potential for patients after MI at risk for adverse remodeling and development of heart failure.
elevations in galectin-3 independently identified high risk HF patients and was able to phenotype renal dysfunction into high and low risk subtypes.
076 Risk Stratification in HFPEF Patients According to eGFR Level Derived From CKD-EPI Equations with or Without Serum Cystatin C Inclusion Tatiana Nikiforova1, Dmitry Shchekochikhin1, Anastasia Lomonosova1, Houssem El Manaa1, Alexandra Shilova2, Philippe Kopylov1; 1First Moscow State Medical University, Moscow, Russian Federation; 2Pirogov Russian National Research Medical University (RNRMU), Moscow, Russian Federation HFPEF is a common HF phenotype with increase in incidence and prevalence. There is no direct prognostic estimator for these patients to the date. Decreased GFR is an independent negative prognostic factor in different heart failure patients populations. Several formulas are accepted for estimating GFR. However, the best equation for eGFR estimating in HFPEF patients for prognosis estimation remains unknown. The aim of the study is to compare prognostic significance of decreased eGFR derived by CKDEPI equation based on serum creatinine and serum cystatin C versus CKD-EPI equation based on serum creatinine only in patients with first decompensation of HFPEF. Materials and Methods: 117 HFPEF patients (average age 71,6 ± 9,1 years; 65,8% - women) were included.85,5% of the patients had atrial fibrillation with persistent form in 38,5%.25,6% had diabetes mellitus. 32,5% had ischemic origin of HF. HFPEF was diagnosed according to ECS guidelines. All patients signed informed consent. The study was approved by local and institutional ethical committee. After discharge, the patients were mentored by phone monthly during first six months and every three months until 24 month period. Mortality, HF hospitalization and combined end point were used. Kaplan-Mayer curves with Log-rank test were used for survival analysis. P value of 0,05 or less was considered to be significant. Results: Average eGFR at inclusion was 50,2 ± 16,9 ml/min/1.73 sq.m by CKD-EPI equation based on serum creatinine and 46,4 ± 16,1 ml/min/1.73 sq.m by CKD-EPI equation based on serum creatinine in cystatin C (p < 0,05). Addition of cystatin C to equation reclassified the patients by CKD stage with increase in prevalence of 3B/4 stage (41,0% vs 35,9%; p < 0,05). During followup 45,3% of the patients reached combine end-point, mortality was 11,9%, HF rehospitalization was 33,3%. Study population was divided for two groups, with eGFR > 45 ml/min/1.73 sq.m or eGFR < 45 ml/min/1.73 sq.m by both formulas. The groups divided by CKD-EPI formula based on serum creatinine only did not differ in mortality, morbidity and combined end-point during survival analysis (p = 0,07; p = 0,7 and p = 0,2). However, if the patients were divided by CKD-EPI equation with both serum creatinine and serum cystatine C, the patients with eGFR < 45 ml/min/1.73 sq.m demonstrated significantly increased achievement of combined end-point (p = 0,03) and increased mortality (p = 0,03). Conclusions: Decreased baseline eGFR by CKD-EPI equation based on serum creatinine and cystatine C levels is a negative prognostic factor in patients with first decompensation of HFPEF. Significance of serum cystatine C level in HFPEF can be attributed to more accurate renal function measurement or nonrenal factors, such as alerted collagen turnover.
077 075 Urine Galectin-3 Levels Identify High Risk Renal Dysfunction in Patients with Heart Failure Tariq Ahmad, Veena Rao, Zobia Chunara, Devin Mahoney, Keyanna Jackson, Daniel Hodson, Catherine Tarleton, Daniel Thomas Jr., Michael Chen, Daniel Jacoby, Ralph Riello, Jeffrey Testani; Yale University, New Haven, Connecticut Background: Galectin-3 (Gal-3) is a well-established mediator of tissue fibrosis across multiple tissues, including heart and kidney. Despite early optimism for the marker in patients with heart failure (HF), plasmagal-3 levels appear to largely reflect nonspecific systemic processes and correlate poorly with cardiac tissue fibrosis. However, urine levels of Gal-3 may report more precisely on local pathology in the kidney since urine is a fluid that bathes only renal tissue. Objective: To understand whether urinegal-3 can provide unique information about the prognosis and phenotype of renal dysfunction in HF. Methods: We enrolled 132 consecutive HF patients presenting to an outpatient treatment and evaluation center. Plasma and pre-diuretic urine levels of Gal-3 were measured. Renal dysfunction was defined as an estimated glomerular filtration rate (eGFR <60 ml/min/1.73 m2). Results: Urinegal-3 was associated with an increased risk of death [HR 1.49 per log increase, 95% CI (1.11–1.98), P = .008]. This relationship was nonlinear, with the majority of the risk concentrated in the top quartile of urinegal-3 [HR 2.7 top quartile vs. reminder of cohort, 95% CI (1.4–5.2), P = .003]. This association persisted after controlling for a comprehensive set of prognostic variables including eGFR, natriuretic peptides, and the renal injury marker urine NGAL [HR 4.09, 95% CI (1.45–11.48); P < .01]. On the contrary, elevated plasmagal-3 levels were not associated with mortality after multivariable adjustment: [HR 1.26 95% CI (0.80–1.99); P = .3]. Importantly, renal dysfunction was free from adverse prognostic importance in patients with low urine Gal-3 levels (HR = 0.96, 95% CI 0.4–2.2, P = .92) but associated with a severely elevated risk in patients with elevated urine Gal-3 (HR = 7.5, 95% CI 1.5–68, P = .038, P interaction = 0.033). Conclusions: Urine, but not serum,
In Dialysis Dependent Renal Failure Patients Plasma BNP is Associated with Mean Pulmonary Artery Pressure but Not Left Ventricular Filling Pressure Luai Alhazmi, Shafiq Qaiser, Zaid Ammari, Mohammed Ruzieh, Osama Dasa, George Moukarbel; University of Toledo, Toledo, Ohio Introduction: Association between plasma BNP levels, left ventricular LV filling pressure, intravascular volume status and pulmonary arterial hypertension has been described in normal and chronic kidney disease patients. Relationship between BNP, LV filling and pulmonary artery pressures in dialysis dependent renal failure patients is not well known. We hypothesized that in dialysis dependent renal failure patients, plasma levels of BNP will correlate with LV filling and pulmonary artery pressures. Methods and Results Renal transplant database was searched for adult dialysis dependent renal failure patients who had plasma BNP level measurement and invasive hemodynamic assessment by right heart catheterization within the 1-month period. LV filling pressures were assessed by pulmonary capillary wedge pressure measurement PCWP. Cardiac output CO was calculated using Fick equation. Eighty six (age, mean 57 ± 12y, hemodialysis 81%, peritoneal dialysis 19%), predominantly Caucasian (61%), male (69%) patients were included. Co-morbid conditions included hypertension (98%), diabetes mellitus (59%), coronary artery disease (40%), congestive heart failure (24%) and overweight/ obesity (BMI, mean 29 ± 5). Mean BNP level was 811 ± 1224 pg/ml and serum creatinine 7.4 ± 4 mg/dl. Invasive hemodynamics; mean right atrial pressure was 8 ± 4, pulmonary artery (PA) 25 ± 9, PCWP 14 ± 7 mmHg, CO 8.5 ± 2.3 L/min and cardiac index 4.4 ± 1.5 L/min/m2. Multivariable logistic regression and correlation analyses were performed using IBM SPSS v23.0. A statistically significant association was found between plasma BNP level and mean PA pressure (P = .023, 95%CI 9, 116) but not between BNP and PCWP (P = .642). A positive correlation between BNP and mean PA pressure (r = 0.6, P < .001) was observed (Fig. 1). Conclusion In dialysis dependent renal failure patients, plasma BNP level is associated with pulmonary artery pressure but not with LV filling pressure suggesting that BNP is not reliable indicator of intravascular volume status in this specific population.