Download - Journal of Cardiac Failure

The 18th Annual Scientific Meeting
HFSA
S23
Neurohormones/Cytokines I
055
Neutrophil to Lymphocyte Ratio is Associated with Adverse Long Term
Outcomes in Heart Failure Patients
Muhammad Hammadah1, Stanley L. Hazen2, W.H. Wilson Tang2; 1Cleveland Clinic,
Cleveland, OH; 2Cleveland Clinic, Cleveland, OH
Introduction: Neutrophil-to-lymphocyte (N/L) ratio has been associated with
adverse outcomes in patients with acute coronary syndromes, increased arterial stiffness and increased risk short-term mortality in patients with acute heart failure. We
aimed to investigate the prognostic value of neutrophil-to-lymphocyte ratio on long
term outcomes in patients with chronic heart failure. Methods: 1579 heart failure undergoing coronary angiogram were enrolled. Absolute neutrophil and lymphocyte
count was assessed on enrolment and (N/L) ratio was calculated. Patient were grouped quintiles based on levels of (N/L) ratio. Kaplan Meir analysis was used to assess 5
year mortality. Results: In our population (age 66 611, Male 65%, DM 38%, HTN
79%, MI 55%), mean absolute neutrophil and lymphocyte counts were 4.7 6 2.2
x103cells/micro Liter and 1.5 6 0.7 x103cells/micro Liter respectively. Median
(IQR) (N/L) ratio was 3.1 (2.2-4.7)%. Positive correlation was found between (N/
L) ratio and high-sensitivity C-reactive protein (R50.25, p!0.001). Patients
with increased (N/L) ratio had significantly increased 5 year mortality (log rank
!0.001, Figure). Conclusion: Neutrophil to lymphocyte ratio is associated with
increased 5 year mortality in heart failure patients.
the presence of IgG-b1AR-AAb to worse outcomes in patients with heart
failure (HF), but those were performed when beta-blocker utilization were low
(!10%). Recent immunoabsorption studies have further demonstrated the association between removal of total IgG3 subclass and improvement in cardiac function.
Hypothesis: We hypothesize that b1AR-AAb are prevalent in patients with HF, the
presence of b1AR-AAb IgG3 subclass may have detrimental impact on long-term
prognosis. Methods: We measured b1AR-AAb total IgG and IgG3 subclass by
ELISA in 121 patients with stable HF at Cleveland Clinic, with longitudinal
follow-up of composite endpoint of all-cause mortality, urgent cardiac transplant,
or HF hospitalizations. Results: In our study cohort (mean age 55611 years,
67% male, 31% ischemic, mean left ventricular ejection fraction [LVEF]
32613%), total IgG and IgG3 b1AR-AAb titers were found to be positive in 41
(34%) and 26 (21%) patients, respectively. Both total IgG (42% vs. 21%,
p50.03) and IgG3 (27% vs. 8%, p50.03) b1AR-AAb were detected more
commonly in the patients with non-ischemic than ischemic etiology. There were
no significant differences in systolic blood pressure, heart rate, LVEF or plasma
BNP levels between total IgG or IgG3 b1AR-AAb positive and negative groups.
During 2.261.2 years follow up, the occurrence of the composite endpoint was
similar between total IgG-b1AR-AAb negative and positive patients, but was
significantly more common in patients without IgG3-b1AR-AAb than in those
with IgG3-b1AR-AAb (p50.048, Log-rank test). IgG3-b1AR-AAb was associated
with significant reduction of the composite endpoint even after adjusted for LVEF,
heart rate, and eGFR (HR 0.31, 95%CI 0.07-0.92, p50.03). Conclusions: b1ARAAbs are prevalent in a contemporary HF population. Contrary to our hypothesis,
we observed that IgG3-b1AR-AAb, but not total IgG, was associated with more
favorable rather than detrimental outcomes in HF patients. Since anti-adrenergic
therapy may block IgG3-b1AR-AAbs’ detrimental effects on cardiomyocytes. the
inconsistency of our findings with prior reports may be explained by broad use
of b-blockers (97%) in the present study.
057
Endothelin-1 Is Independently Associated with the Annual Risk of Heart Failure
Hospitalization
Eitan A. Friedman1, David C. Shisler1, John A. Todd2, Joel Estis2, Adnan Shah2,
Niamh Nolan2, Daniel J. Lenihan1; 1Vanderbilt University, Nashville, TN;
2
Singulex, Inc., Alameda, CA
Figure
056
Presence of IgG3 Autoantibody Against b1-Adrenergic Receptors is Associated
with More Favorable Outcome in Patients with Heart Failure in the BetaBlocker Era
Yuji Nagatomo1, W.H. Wilson Tang2; 1Cleveland Clinic, Cleveland, OH; 2Cleveland
Clinic, Cleveland, OH
Background: Auto-antibodies recognizing b1 adrenergic receptor (b1AR-AAbs)
have been shown to exert agonist-like effects. Previous studies have linked
Introduction: The diagnosis and management of heart failure (HF) in the U.S. is an
extraordinary medical expense and is recognized as a common reason for hospitalization. It is estimated that with resources directed toward the high risk patients, a
large percentage of repeat hospitalizations for HF could be prevented. The current
ACC/AHA guidelines recommend testing BNP in the ambulatory setting to guide
clinical decisions. Other biomarkers, such as high sensitivity troponin (cTnI) and
those that reflect inflammation or endothelial function, may also help diagnose
HF and assess prognosis. We sought to investigate whether multiple biomarkers,
NTproBNP, cTnI, Interleukin-6 (IL-6) and Endothelin-1 (ET-1), may enhance identification of HF patients at risk for hospitalization. Methods: 200 patients (age 54
6 15 yrs) with HF distributed among ACC/AHA stages A-D were selected from our
institution’s registry. Plasma samples were obtained at enrollment, and NTproBNP,
cTnI, IL-6, and ET-1 were measured using high sensitivity single-molecule counting technology (ErennaÒ Immunoassay System, Singulex). Univariate and multivariate analyses were performed to test the association of baseline biomarker
concentrations and hospitalization during the 12 months following enrollment. Results: 122 of the 200 patients (61%) had no HF hospitalizations over 12 months. Of
the patients who were hospitalized, NTProBNP and ET-1 concentrations were
significantly higher than in those who were not (Table 1). cTnI and IL-6 concentrations tended to be higher in patients who were hospitalized. Additionally, elevated
NTProBNP, cTnI, and ET-1 levels using a 50% cut-off were significantly associated
with increased odds ratios for admission of 2.9, 2.5, and 3.8, respectively. When
fully adjusted for age, sex, blood pressure, ACC/AHA stage, and the other biomarkers, ET-1 still remained predictive of hospitalization with an adjusted odds ratio of 4.6. Conclusion: NTproBNP, cTnI, and ET-1 are associated with the annual
risk of heart failure hospitalization, though only ET-1 is independently associated.
These biomarkers may assist in identifying a subset of patients who would benefit
from intensive clinical management to decrease hospitalization and subsequent
morbidity.
Table 1 (057). Biomarker Concentrations and Odd Ratios Predicting HF Hospitalization
Biomarker Concentrations (pg/mL): Median (IQR)
Biomarker
NTproBNP
cTnI
ET-1
IL-6
HF Hospitalization - NO
897
9.4
4.5
8.4
(217,2388)
(4.7,24.6)
(3.6,5.6)
(4.9,15.7)
HF Hospitalization - YES
2007
13.3
5.2
13.5
(706,4791)
(9.6,24.5)
(4.6,7.7)
(7.4,24.5)
Odds Ratios: (95% CI)
P-Value
0.0140
0.0900
0.0024
0.0944
Unadjusted
2.9
2.5
3.8
1.8
(1.2,7.3)
(1.1,6.2)
(1.5,9.7)
(0.8,4.2)
Adjusted
1.4
1.1
4.6
0.8
(0.4,4.9)
(0.3,3.7)
(1.4,15.6)
(0.3,2.6)