Serum Uric Acid is an Independent Predictor for All-Cause Death and Rehospitalization in Patients with Acute Decompensated Heart Failure: Insights from KCHF Registry

Abstract Background Elevated serum uric acid (UA) level has been shown to be associated with reduced survival among patients (pts) with heart failure. Sodium glucose cotransporter 2 (SGLT2) inhibitors have been reported to lower serum uric acid level in pts with type 2 diabetes mellitus (T2D). Empagliflozin, one of the SGLT2 inhibitors, has been shown to reduce the risk of cardiovascular mortality in T2D pts with cardiovascular disease, and involvement of UA lowering effect by empagliflozin in the reduction of cardiovascular mortality has been suggested. However, little is known about the effect of empagliflozin as add-on therapy on serum UA level in T2D pts with acute decompensated heart failure (ADHF). Purpose We sought to elucidate the effect of empagliflozin as add-on therapy on serum UA level in T2D pts with ADHF. Methods We enrolled 38 consecutive T2D pts admitted for ADHF. On admission, enrolled pts were randomly assigned in a 1:1 ratio to either empagliflozin add-on therapy (EMPA(+)) or conventional glucose-lowering therapy (EMPA(−)). All pts in EMPA(+) group received empagliflozin (10 mg/day) throughout the study period. Left ventricular ejection fraction (LVEF) was measured at baseline using echocardiography. Body weight and vital signs, such as blood pressure and heart rate, were measured, and blood and urine samples were collected at baseline and 1, 2, 3 and 7 days after randomization. Renal handling of UA was evaluated by fractional excretion of UA (FEUA). Results Twenty pts were assigned to the EMPA(+) group, and 18 pts were assigned to the EMPA(−) group. There were no significant baseline differences in LVEF, plasma brain natriuretic peptide level, body mass index, or serum creatinine level between the EMPA(+) and EMPA(−) groups. In addition, prevalence rate of hyperuricemia, serum UA level, and FEUA did not significantly differ between the two groups at baseline. However, there was significant difference in the change in serum UA level from baseline at 2, 3 and 7 days after randomization between the two groups (Figure A). As a result, serum UA level was significantly lower in the EMPA(+) group than in the EMPA(−) group at 7 days after randomization (6.2±1.8 mg/dL vs 7.8±1.8 mg/dL, p=0.0127). Moreover, FEUN of the EMPA(+) group was significantly higher at 1, 2 and 7 days after randomization (Figure B), which suggested that serum UA level was lowered in the EMPA(+) group by increased urinary excretion of UA. Figure 1 Conclusions This study demonstrated that empagliflozin as add-on therapy can lower serum UA level in T2D pts with ADHF through the effect on the urinary excretion rate of UA.

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Serum Uric Acid Increase through the Treatment of Acute Decompensated Heart Failure Might Predict Adverse Outcome

Journal of Cardiac Failure ◽

10.1016/j.cardfail.2017.08.293 ◽

2017 ◽

Vol 23 (10) ◽

pp. S60

Author(s):

Yuji Nagatomo ◽

Hironori Yamamoto ◽

Mayuko Tsugu ◽

Keitaro Mahara ◽

Mitsuaki Isobe ◽

...

Keyword(s):

Heart Failure ◽

Uric Acid ◽

Serum Uric Acid ◽

Adverse Outcome ◽

Acute Decompensated Heart Failure ◽

Decompensated Heart Failure

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On admission serum sodium and uric acid levels predict 30 day rehospitalization or death in patients with acute decompensated heart failure

ESC Heart Failure ◽

10.1002/ehf2.12135 ◽

2017 ◽

Vol 4 (2) ◽

pp. 162-168 ◽

Cited By ~ 12

Author(s):

Ahmad Amin ◽

Mitra Chitsazan ◽

Fatemeh Shiukhi Ahmad Abad ◽

Sepideh Taghavi ◽

Nasim Naderi

Keyword(s):

Heart Failure ◽

Uric Acid ◽

Serum Sodium ◽

Acute Decompensated Heart Failure ◽

Decompensated Heart Failure

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Abstract 12859: Prognostic Value of Neutrophil to Lymphocyte Ratio in Acute Decompensated Heart Failure With Reduced or Preserved Left Ventricular Ejection Fraction

Circulation ◽

10.1161/circ.132.suppl_3.12859 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Takahisa Yamada ◽

Takashi Morita ◽

Yoshio Furukawa ◽

Shunsuke Tamaki ◽

Yusuke Iwasaki ◽

...

Keyword(s):

Heart Failure ◽

Left Ventricular Ejection Fraction ◽

Prognostic Value ◽

Independent Predictor ◽

Acute Decompensated Heart Failure ◽

Prognostic Significance ◽

Decompensated Heart Failure ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Ventricular Ejection Fraction

Backgrounds: Neutrophil-to-lymphocyte ratio (NLR) has recently emerged as a measure of inflammation and as a prognosticating biomarker in various medical conditions ranging from infectious disease to cardiovascular disease. The prognostic significance of NLR in patients admitted with acute decompensated heart failure (ADHF) is not established. The aim of this study was to investigate the prognostic impact of NLR in ADHF patients, relating to reduced or preserved left ventricular ejection fraction (HFrEF or HFpEF). Methods and Results: We studied 264 patients admitted with ADHF and discharged with survival (HFrEF(LVEF<50%); n=144, HFpEF(LVEF≥50%;n=120). There was no significant difference in NLR at the discharge between patients with HFrEF (2.1±1.1) and HFpEF (2.1±1.0). During a follow up period of 4.2±3.2 yrs, 87 pts died. NLR was significantly associated with mortality in patients with HFrEF (p<0.0001) and HFpEF (p=0.006) at univariate Cox analysis. All cause-death was significantly frequently observed in patients with the highest tertile of NLR (>2.2) than those with the middle or lowest tertile of NLR(<1.5) in patients with HFrEF (60% vs 36% vs 20%, p<0.0001, respectively) and HFpEF (43% vs 20% vs 14%, p=0.004, respectively). After adjustment for baseline characteristics, echocardiographical findings, and blood tests such as hemoglobin, sodium level and estimated glomerular filtration rate, NLR remained a significant independent predictor for mortality in patients with HFrEF (hazard ratio: 1.23 [95%CI 1.04-1.54], p=0.017), while NLR tended to be a independent predictor in those with HFpEF (hazard ratio:1.29 [95%CI 0.98-1.71], p=0.07). Conclusion: NLR at the discharge provides a prognostic value for the prediction of total mortality in ADHF patients with HFrEF and HFpEF, although the prognostic significance of NLR in patients with HFpEF was weakened by adjustment for relevant covariates.

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Abstract 12854: Uric Acid In-hospital Change Provides the Additional Long-Term Prognostic Information to Acute Kidney Injury in Patients Admitted for Acute Decompensated Heart Failure

Circulation ◽

10.1161/circ.132.suppl_3.12854 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Takahisa Yamada ◽

Takashi Morita ◽

Yoshio Furukawa ◽

Shunsuke Tamaki ◽

Yusuke Iwasaki ◽

...

Keyword(s):

Heart Failure ◽

Uric Acid ◽

Acute Decompensated Heart Failure ◽

Kidney Injury ◽

Fold Increase ◽

Decompensated Heart Failure ◽

Cvd Risk ◽

Prognostic Information ◽

Stage 1

Backgrounds: Acute kidney injury (AKI) during heart failure treatment is associated with poor outcome in patients admitted with acute decompensated heart failure (ADHF). In patients with ADHF,increased uric acid (UA) level is also a prognostic marker, but there is no information available on the long-term prognostic significance of UA in-hospital change, relating to AKI in patients admitted for ADHF. Methods and Results: We studied 237 patients admitted with ADHF and discharged with survival. The measurements of serum UA and creatinine (Cr) levels were repeated during hospitalization, and the change of UA was obtained by subtracting the value at admission or discharge from the maximum value. AKI was defined according to AKI Network criteria (stage 1, ≥0.3mg/dl absolute or 1.5-to 2.0-fold relative increase in Cr; stage 2, >2- to 3-fold increase in Cr; stage 3, >3-fold increase in Cr or Cr≥4.0mg/dl with an acute rise of ≥0.5mg/dl). During a follow-up period of 4.3±3.3 yrs, 59 patients had cardiovascular death (CVD). At multivariate Cox analysis, UA change (p=0.02) and stage 2 or 3 AKI (p=0.01) were significantly associated with CVD, independently of age, systolic blood pressure, serum sodium, hemoglobin, UA and Cr levels, although stage 1 AKI showed no significant association with CVD. Patients with both higher degree of UA change (top quartile:≥4.4 mg/dl) and stage 2 or 3 AKI had a significant increased CVD risk, compared to patients with either higher UA change or stage 2 or 3 AKI (75% vs 34%, p=0.006, hazard ratio 3.8[95%CI 1.4-8.6]). Furthermore, patients with either higher UA change or stage 2 or 3 AKI also had a significant increased CVD risk, compared to patients with none of these two variables (34% vs 19%, p=0.01, hazard ratio 2.0[95%CI 1.1-3.5]). Conclusion: Uric acid in-hospital change could provide the additional long-term prognostic information to moderate to severe AKI in patients admitted for ADHF.

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Relationship of hyperuricemia with mortality in heart failure patients with preserved ejection fraction

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00533.2015 ◽

2015 ◽

Vol 309 (7) ◽

pp. H1123-H1129 ◽

Cited By ~ 24

Author(s):

Takeshi Shimizu ◽

Akiomi Yoshihisa ◽

Yuki Kanno ◽

Mai Takiguchi ◽

Akihiko Sato ◽

...

Keyword(s):

Heart Failure ◽

Uric Acid ◽

Ejection Fraction ◽

Serum Uric Acid ◽

Decompensated Heart Failure ◽

Cardiopulmonary Exercise Test ◽

Preserved Ejection Fraction ◽

Reduced Ejection Fraction ◽

All Cause Mortality ◽

The Impact

Serum uric acid is a predictor of cardiovascular mortality in heart failure with reduced ejection fraction. However, the impact of uric acid on heart failure with preserved ejection fraction (HFpEF) remains unclear. Here, we investigated the association between hyperuricemia and mortality in HFpEF patients. Consecutive 424 patients, who were admitted to our hospital for decompensated heart failure and diagnosed as having HFpEF, were divided into two groups based on presence of hyperuricemia (serum uric acid ≥7 mg/dl or taking antihyperuricemic agents). We compared patient characteristics, echocardiographic data, cardio-ankle vascular index, and cardiopulmonary exercise test findings between the two groups and prospectively followed cardiac and all-cause mortality. Compared with the non-hyperuricemia group ( n = 170), the hyperuricemia group ( n = 254) had a higher prevalence of hypertension ( P = 0.013), diabetes mellitus ( P = 0.01), dyslipidemia ( P = 0.038), atrial fibrillation ( P = 0.001), and use of diuretics ( P < 0.001). Cardio-ankle vascular index (8.7 vs. 7.5, P < 0.001) and V̇e/V̇co2 slope (34.9 vs. 31.9, P = 0.02) were also higher. In addition, peak V̇o2 (14.9 vs. 17.9 ml·kg−1·min−1, P < 0.001) was lower. In the follow-up period (mean 897 days), cardiac and all-cause mortalities were significantly higher in those with hyperuricemia ( P = 0.006 and P = 0.004, respectively). In the multivariable Cox proportional hazard analyses after adjustment for several confounding factors including chronic kidney disease and use of diuretics, hyperuricemia was an independent predictor of all-cause mortality (hazard ratio 1.98, 95% confidence interval 1.036–3.793, P = 0.039). Hyperuricemia is associated with arterial stiffness, impaired exercise capacity, and high mortality in HFpEF.

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Is Serum Uric Acid Level an Independent Predictor of Heart Failure Among Patients With Coronary Artery Disease?

Clinical Cardiology ◽

10.1002/clc.22083 ◽

2013 ◽

Vol 36 (2) ◽

pp. 110-116 ◽

Cited By ~ 8

Author(s):

Alon Eisen ◽

Michal Benderly ◽

Uri Goldbourt ◽

Moti Haim

Keyword(s):

Heart Failure ◽

Coronary Artery Disease ◽

Uric Acid ◽

Coronary Artery ◽

Serum Uric Acid ◽

Uric Acid Level ◽

Acid Level ◽

Independent Predictor ◽

Serum Uric Acid Level ◽

Artery Disease

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Prednisone lowers serum uric acid levels in patients with decompensated heart failure by increasing renal uric acid clearance

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2015-0490 ◽

2016 ◽

Vol 94 (7) ◽

pp. 797-800 ◽

Cited By ~ 1

Author(s):

Chao Liu ◽

Yuzhi Zhen ◽

Qingzhen Zhao ◽

Jian-Long Zhai ◽

Kunshen Liu ◽

...

Keyword(s):

Heart Failure ◽

Uric Acid ◽

Serum Uric Acid ◽

Optimal Dose ◽

Decompensated Heart Failure ◽

High Dose ◽

Acid Clearance ◽

Uric Acid Clearance ◽

Dose Prednisone ◽

Medium Dose

Clinical studies have shown that large doses of prednisone could lower serum uric acid (SUA) in patients with decompensated heart failure (HF); however, the optimal dose of prednisone and underlying mechanisms are unknown. Thirty-eight patients with decompensated HF were randomized to receive standard HF care alone (n = 10) or with low-dose (15 mg/day, n = 8), medium-dose (30 mg/day, n = 10), or high-dose prednisone (60 mg/day, n = 10), for 10 days. At the end of the study, only high-dose prednisone significantly reduced SUA, whereas low- and medium-dose prednisone and standard HF care had no effect on SUA. The reduction in SUA in high-dose prednisone groups was associated with a significant increase in renal uric acid clearance. In conclusion, prednisone can reduce SUA levels by increasing renal uric acid clearance in patients with decompensated HF.

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Prognostic impact of uric acid in patients with acute decompensated heart failure

Terapevticheskii arkhiv ◽

10.26442/00403660.2021.09.201033 ◽

2021 ◽

Vol 93 (9) ◽

pp. 1066-1072

Author(s):

Svetlana N. Nasonova ◽

Anastasiya E. Lapteva ◽

Igor V. Zhirov ◽

Dzambolat R. Mindzaev ◽

Sergey N. Tereshchenko

Keyword(s):

Heart Failure ◽

Uric Acid ◽

Acute Decompensated Heart Failure ◽

Nyha Class ◽

Decompensated Heart Failure ◽

Prognostic Impact ◽

Diuretic Resistance ◽

End Point ◽

Significant Difference ◽

Moderate Negative Correlation

Aim. To evaluate the prognostic impact of serum uric acid (SUA) on clinical outcomes in patients with acute decompensated heart failure, as well as identify the correlation between hyperuricemia and renal function and diuretic resistance in these patients. Materials and methods. The study included 175 patients (125 men and 50 women) with NYHA class IIIV acute decompensated heart failure. Median age was 64 (5675) years. The Information regarding the survival was obtained 3 years after the admission by telephone calls. Results. 57 patients reached the end point (death from all causes); therefore, all patients were divided into groups: "alive", "dead". The SUA levels did not differ in the groups. The only significant difference in the studied parameters was the estimated glomerular filtration rate (eGFR), which was significantly higher in the "alive" group [70.5 (52.894) and 56 (4079), respectively; p=0.006]. A moderate negative correlation was found between SUA levels and eGFR in the correlation analysis (r=-0.313, p0.001). A comparative analysis showed, that SUA level on admission was significantly higher in patients who subsequently received increased doses of diuretics than in patients with a satisfactory response to standard doses of diuretics [567.8 (479.6791.9) and 512 (422.4619.4), respectively; p=0.011]. Also, higher eGFR level on admission was observed in patients from the normal SUA level group than in patients from the hyperuricemia group [94 (74.5101.5) and 63 (48.881.3), respectively; p=0.002]. Conclusion. We found no significant differences in the uric acid level in patients who reached the end point and those who did not reach it during the three-year follow-up. However, the found correlation between uric acid levels and diuretic resistance calls for further research.

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Abstract 18615: Subclinical Thyroid Dysfunction, Rather than Low-T3 Syndrome, is an Independent Predictor of Adverse Cardiac Events in Patients with Acute Decompensated Heart Failure

Circulation ◽

10.1161/circ.130.suppl_2.18615 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Tomohiro Hayashi ◽

Takuya Hasegawa ◽

Hideaki Kanzaki ◽

Akira Funada ◽

Makoto Amaki ◽

...

Keyword(s):

Heart Failure ◽

Thyroid Dysfunction ◽

Independent Predictor ◽

Acute Decompensated Heart Failure ◽

Decompensated Heart Failure ◽

Left Ventricular ◽

Cardiac Events ◽

Low T3 Syndrome ◽

Low T3 ◽

Adverse Cardiac Events

Background: Altered thyroid hormone metabolism characterized by low triiodothyronine (T3) levels is a common finding in patients with severe systemic diseases, called low T3 syndrome (LT3-S). Additionally, subclinical thyroid dysfunction, defined as abnormal thyroid-stimulation hormone (TSH) and normal thyroxine (T4) levels, causes left ventricular dysfunction. However, the prevalence and prognostic impact of LT3-S and subclinical thyroid dysfunction in patients with acute decompensated heart failure (ADHF) have not been investigated. Methods: We examined consecutive 287 patients with ADHF who received thyroid function tests and no thyroid medications at admission (age 69±15 years, 166 male). Thyroid dysfunction was defined as follows: LT3-S as free T3< 4.0 pmol/L; euthyroidism as TSH of 0.45 to 4.49 mIU/L; subclinical hypothyroidism (Sc-hypo) as TSH of 4.5 to 19.9 mIU/L; subclinical hyperthyroidism (Sc-hyper) as TSH< 0.45mIU/L with normal free T4 levels for the last two. We sought to investigate the impact of the indices of thyroid function and the thyroid disorders above to predict cardiac death and re-hospitalization for heart failure after discharge. Results: At admission for ADHF, 155 patients (54%) showed LT3-S, and 62 (22%) Sc-hypo, and 5 (2%) Sc-hyper, and 196 (68%) euthyroidism. Cox proportional hazards model analysis revealed that TSH and fT4, not fT3, were independent predictors of adverse cardiac events among variables including age, sex, estimated glomerular filtration rate, left ventricular ejection fraction and B-type natriuretic peptide. Indeed, Sc-hypo was an independent predictor (HR 2.21, 95% CI 1.41-3.43, p< 0.001), whereas LT3-S and SC-hyper was not (p = 0.49 and 0.24, respectively). Conclusion: Although LT3-S was observed in about half of ADHF patients, the presence of LT3-S did not indicate poor prognosis after discharge. Meanwhile, Sc-hypo at admission was an independent predictor of adverse cardiac events in ADHF patients.

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