Abstract 12221: Impact of Serum Uric Acid on Mortality in Heart Failure With Preserved Ejection Fraction

Background: 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. Methods and Results: Consecutive 424 patients, who admitted to our hospital for decompensated heart failure and diagnosed as HFpEF, were divided into two groups based on presence of hyperuricemia (serum uric acid ≥ 7 mg/dl). We compared patient characteristics, cardio-ankle vascular index and cardio-pulmonary exercise test findings between the two groups. Furthermore, we prospectively followed cardiac and all-cause mortality. The hyperuricemia group (n=254), as compared with non-hyperuricemia group (n=170), had higher prevalence of male gender (55.5 vs. 41.7%, P=0.005), hypertension (79.9 vs. 69.4%, P=0.013), diabetes mellitus (38.5 vs. 26.4%, P=0.010) and use of diuretics (72.4 vs. 41.7%, P<0.001). Furthermore, the hyperuricemia group had higher levels of B-type natriuretic peptide (112.3 vs. 71.4 pg/ml, P<0.001), lower levels of estimated GFR (53.2 vs. 69.7 ml/min/1.73m 2 , P<0.001), higher cardio-ankle vascular index (8.7 vs. 7.5, P<0.001), lower peak VO 2 (14.9 vs. 17.9 ml/kg/min, P<0.001) and higher VE/VCO 2 slope (34.9 vs. 31.9, P=0.02) compared with non-hyperuricemia group. In the follow up period (mean of 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 adjusting for confounding factors including chronic kidney disease and use of diuretics, hyperuricemia was an independent predictor of all-cause mortality (hazard ratio 1.98, P=0.039). Conclusion: Hyperuricemia is associated with arterial stiffness, impaired exercise capacity, and high mortality in HFpEF.

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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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Serum uric acid, influence of sacubitril/valsartan, and cardiovascular outcomes in heart failure with preserved ejection fraction: PARAGON-HF

European Heart Journal ◽

10.1093/ehjci/ehaa946.1066 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

S Selvaraj ◽

B.L Claggett ◽

D.V Veldhuisen ◽

I.S Anand ◽

B Pieske ◽

...

Keyword(s):

Heart Failure ◽

Uric Acid ◽

Ejection Fraction ◽

Serum Uric Acid ◽

Primary Outcome ◽

Adverse Outcomes ◽

Funding Source ◽

Preserved Ejection Fraction ◽

Private Company ◽

Increased Risk

Abstract Background Serum uric acid (SUA) is a biomarker of several pathobiologies relevant to the pathogenesis of heart failure with preserved ejection fraction (HFpEF), though by itself may also worsen outcomes. In HF with reduced EF, SUA is independently associated with adverse outcomes and sacubitril/valsartan reduces SUA compared to enalapril. These effects in HFpEF have not been delineated. Purpose To determine the prognostic value of SUA, relationship of change in SUA to quality of life and outcomes, and influence of sacubitril/valsartan on SUA in HFpEF. Methods We analyzed 4,795 participants from the Prospective Comparison of ARNI with ARB Global Outcomes in HF with Preserved Ejection Fraction (PARAGON-HF) trial. We related baseline hyperuricemia to the primary outcome (CV death and total HF hospitalization), its components, myocardial infarction or stroke, and a renal composite outcome. At the 4-month visit, the relationship between SUA change and Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OSS) and several biomarkers including N-terminal pro-B-type natriuretic peptide (NT-proBNP) were also assessed. We simultaneously adjusted for baseline and time-updated SUA to determine whether lowering SUA was associated with clinical benefit. Results Average age was 73±8 years and 52% were women. After multivariable adjustment, hyperuricemia was associated with increased risk for most outcomes (primary outcome HR 1.61, 95% CI 1.37, 1.90, Fig 1A). The treatment effect of sacubitril/valsartan for the primary outcome was not modified by baseline SUA (interaction p=0.11). Sacubitril/valsartan reduced SUA −0.38 mg/dL (95% CI: −0.45, −0.31) compared with valsartan (Fig 1B), with greater effect in those with baseline hyperuricemia (−0.50 mg/dL) (interaction p=0.013). Change in SUA was independently and inversely associated with change in KCCQ-OSS (p=0.019) and eGFR (p<0.001), but not NT-proBNP (p=0.52). Time-updated SUA was a stronger predictor of adverse outcomes over baseline SUA. Conclusions SUA independently predicts adverse outcomes in HFpEF. Sacubitril/valsartan significantly reduces SUA compared to valsartan, an effect that was stronger in those with higher baseline SUA, and reducing SUA was associated with improved outcomes. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Novartis

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Abstract 12849: Changes in N-terminal Pro Brain Natriuretic Peptide Levels Predicts Mortality and Heart Failure Hospitalization in Patients With Heart Failure and Preserved Ejection Fraction

Circulation ◽

10.1161/circ.132.suppl_3.12849 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Gianluigi Savarese ◽

Camilla Hage ◽

Ulf Dahlström ◽

Pasquale Perrone-Filardi ◽

Lars H Lund

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Brain Natriuretic Peptide ◽

Natriuretic Peptide ◽

Total Mortality ◽

Preserved Ejection Fraction ◽

Reduced Ejection Fraction ◽

Patients With Heart Failure ◽

The Impact

Introduction: Changes in N-terminal pro brain natriuretic peptide (NT-proBNP) have been demonstrated to correlate with outcomes in patients with heart failure (HF) and reduced ejection fraction (EF). However the prognostic value of a change in NT-proBNP in patients with heart failure and preserved ejection fraction (HFPEF) is unknown. Hypothesis: To assess the impact of changes in NT-proBNP on all-cause mortality, HF hospitalization and their composite in an unselected population of patients with HFPEF. Methods: 643 outpatients (age 72+12 years; 41% females) with HFPEF (ejection fraction ≥40%) enrolled in the Swedish Heart Failure Registry between 2005 and 2012 and reporting NT-proBNP levels assessment at initial registration and at follow-up were prospectively studied. Patients were divided into 2 groups according the median value of NT-proBNP absolute change that was 0 pg/ml. Median follow-up from first measurement was 2.25 years (IQR: 1.43 to 3.81). Adjusted Cox’s regression models were performed using total mortality, HF hospitalization (with censoring at death) and their composite as outcomes. Results: After adjustments for 19 baseline variables including baseline NT-proBNP, as compared with an increase in NT-proBNP levels at 6 months (NT-proBNP change>0 pg/ml), a reduction in NT-proBNP levels (NT-proBNP change<0 pg/ml) was associated with a 45.2% reduction in risk of all-cause death (HR: 0.548; 95% CI: 0.378 to 0.796; p:0.002), a 50.1% reduction in risk of HF hospitalization (HR: 0.49; 95% CI: 0.362 to 0.689; p<0.001) and a 42.6% reduction in risk of the composite outcome (HR: 0.574; 95% CI: 0.435 to 0.758; p<0.001)(Figure). Conclusions: Reductions in NT-proBNP levels over time are independently associated with an improved prognosis in HFPEF patients. Changes in NT-proBNP could represent a surrogate outcome in phase 2 HFPEF trials.

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GW27-e0786 Correlation between levels of serum uric acid with heart failure with preserved ejection fraction

Journal of the American College of Cardiology ◽

10.1016/j.jacc.2016.07.557 ◽

2016 ◽

Vol 68 (16) ◽

pp. C148

Author(s):

Zhao Xin ◽

Quanming Zhao

Keyword(s):

Heart Failure ◽

Uric Acid ◽

Ejection Fraction ◽

Serum Uric Acid ◽

Preserved Ejection Fraction

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P1634Comparison of inflammation based prognostic scores in patients with stable heart failure with reduced ejection fraction

European Heart Journal ◽

10.1093/eurheartj/ehz748.0393 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

H Arfsten ◽

A Cho ◽

S Prausmueller ◽

G Spinka ◽

J Novak ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Nyha Class ◽

Prognostic Score ◽

Univariate Analysis ◽

Reduced Ejection Fraction ◽

Lymphocyte Ratio ◽

Nutritional Risk Index ◽

All Cause Mortality ◽

The Impact

Abstract Background Elevated inflammatory markers and malnutrition are characteristic for heart failure with reduced ejection fraction (HFrEF) correlating with disease severity and prognosis. Nutritional decline is closely linked to inflammation. Evidence emerges that heart failure can be triggered by inflammation directly, meaning that progression of HF is a function of individual inflammatory host response. We aimed to investigate and compare the impact of well-established inflammation based scores and inflammation-related nutritional scores on survival in HFrEF. Methods Stable HFrEF-patients undergoing routine ambulatory care between 2011 and 2017 have been identified from a prospective registry. Comorbidities and laboratory data at baseline were assessed. All-cause mortality was defined the primary endpoint. The modified Glasgow Prognostic Score (mGPS: 0/1/2 based on CRP and albumin), the neutrophil-to-lymphocyte ratio (NLR), the monocyte-to-lymphocyte ratio (MLR), the platelet-to-lymphocyte ratio (PLR) as well as the Nutritional Risk Index (NRI = (1.519 × serum albumin, g/dL) + (41.7 × present weight (kg)/ideal body weight (kg)) and the Prognostic Nutritional Index (PNI = albumin (g l–1) × total lymphocyte count × 109 l–1) were calculated. The association of the scores with HF severity and impact on overall survival were determined. Results Data of 443 patients receiving well titrated guideline directed HF therapy have been analyzed. Median age was 64 years (IQR 53–72), 73% were male. Median body mass index (BMI) was 26.6kg/m2 (IQR 23.8–30.2), median NT-proBNP was 2053pg/ml (IQR 842–4345) with most patients presenting in NYHA class II (178, 40%) and III (173, 39%). The mGPS was 0 for 352 (80%), 1 for 76 (17%) and 2 for 14 (3%) patients, respectively. All scores correlated with HF severity reflected by NT-proBNP [p<0.001 for mGPS, r=−0.48; p<0.001 for PNI] and NYHA class [p<0.001 for mGPS and PNI]. All scores were associated with all-cause mortality in univariate analysis. After adjustment for age, gender and kidney function only mGPS, PLR, NRI and PNI remained significantly associated with outcome. Out of these the ROC were highest for PNI and mGPS [0.674 and 0.652 respectively] and solely these scores remained significantly associated with mortality after including NT-proBNP in the multivariate model [adj.HR 1.87 (95% CI: 1.20–2.91), p=0.006 for mGPS; 0.62 (95% CI: 0.40–0.96), p=0.032 for PNI]. Kaplan Meier analysis confirmed the discriminatory power of mGPS and PNI (Figure 1). Conclusions Enhanced inflammation and malnutrition are more common in advanced heart failure. Among established inflammation and nutritional scores merely mGPS and PNI are associated with survival in HFrEF patients independently of NT-proBNP. This relationship emphasizes the significance of the individual proinflammatory response on prognosis.This easily available score may help clinicians to identify HFrEF patients with worse prognosis with urgent need for intensified therapy and/or alternate treatment options.

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Outcomes of de novo and acute decompensated heart failure patients according to ejection fraction

Heart ◽

10.1136/heartjnl-2017-311813 ◽

2017 ◽

Vol 104 (6) ◽

pp. 525-532 ◽

Cited By ~ 23

Author(s):

Ki Hong Choi ◽

Ga Yeon Lee ◽

Jin-Oh Choi ◽

Eun-Seok Jeon ◽

Hae-Young Lee ◽

...

Keyword(s):

Heart Failure ◽

Mortality Rate ◽

Ejection Fraction ◽

De Novo ◽

Acute Decompensated Heart Failure ◽

Decompensated Heart Failure ◽

First Year ◽

Preserved Ejection Fraction ◽

University Hospitals ◽

Reduced Ejection Fraction

ObjectiveThere are conflicting results among previous studies regarding the prognosis of heart failure with preserved ejection fraction (HFpEF) compared with heart failure with reduced ejection fraction (HFrEF). This study aimed to compare the outcomes of patients with de novo acute heart failure (AHF) or acute decompensated HF (ADHF) according to HFpEF (EF≥50%), or HFrEF (EF<40%) and to define the prognosis of patients with HF with mid-range EF (HFmrEF, 40≤EF<50%).MethodsBetween March 2011 and February 2014, 5625 consecutive patients with AHF were recruited from 10 university hospitals. A total of 5414 (96.2%) patients with EF data were enrolled, which consisted of 2867 (53.0%) patients with de novo and 2547 (47.0%) with ADHF. Each of the enrolled group was stratified by EF.ResultsIn de novo, all-cause death rates were not significantly different between HFpEF and HFrEF (HFpEF vs HFrEF, 206/744 (27.7%) vs 438/1631 (26.9%), HRadj 1.15, 95% CI 0.96 to 1.38, p=0.14). However, among patients with ADHF, HFrEF had a significantly higher mortality rate compared with HFpEF (HFpEF vs HFrEF, 245/613 (40.0%) vs 694/1551 (44.7%), HRadj 1.25, 95% CI 1.06 to 1.47, p=0.007). Also, in ADHF, HFmrEF was associated with a significantly lower mortality rate within 1 year compared with HFrEF (HFmrEF vs HFrEF, 88/383 (23.0%) vs 430/1551 (27.7%), HRadj 1.31, 95% CI 1.03 to 1.65, p=0.03), but a significantly higher mortality rate after 1 year compared with HFpEF (HFmrEF vs HFpEF, 83/295 (28.1%) vs 101/469 (21.5%), HRadj 0.70, 95% CI 0.52 to 0.96, p=0.02).ConclusionsHFpEF may indicate a better prognosis compared with HFrEF in ADHF, but not in de novo AHF. For patients with ADHF, the prognosis associated with HFmrEF was similar to that of HFpEF within the first year following hospitalisation and similar to HFrEF 1 year after hospitalisation.

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Heart Failure

10.2310/fm.1409 ◽

2020 ◽

Author(s):

Sachin P Shah ◽

Mandeep R. Mehra

Keyword(s):

Heart Failure ◽

Chronic Heart Failure ◽

Ejection Fraction ◽

Acute Decompensated Heart Failure ◽

Heart Association ◽

Decompensated Heart Failure ◽

Advanced Heart Failure ◽

Circulatory Support ◽

Preserved Ejection Fraction ◽

Reduced Ejection Fraction

Heart failure is a syndrome related to abnormal cardiac performance with a consequence of impaired cardiac output at rest or with exertion and/or congestion, which usually leads to symptoms of fatigue, dyspnea, and edema. The syndrome is characterized by various phenotypes related to a vast array of etiologies with diverse management targets. The current broad categorization of heart failure separates patients based on ejection fraction. Further description of the phenotype beyond ejection fraction is imperative to correctly identify the etiology of heart failure and, ultimately, to choose medical, device, and surgical therapies appropriately. This review covers the epidemiology of heart failure, defining the phenotype and etiology of heart failure, recognition and management of acute decompensated heart failure, management of chronic heart failure with a reduced ejection fraction, implantable cardioverter-defibrillators in heart failure with a reduced ejection fraction, management of heart failure with a preserved ejection fraction, and advanced heart failure. Figures show the evolution of therapy in chronic heart failure from the symptom-directed model, the complex pathophysiology and principal aberrations underlying heart failure with preserved ejection fraction, and concepts underlying surgical therapy in advanced heart failure using Laplace’s law. Tables list various etiologies of heart failure; sensitivity and specificity of clinical, biomarker, and radiographic data in the diagnosis of acute decompensated heart failure; drugs and devices with a demonstrated survival benefit in heart failure with a reduced ejection fraction; neurohormonal antagonist dosing in heart failure with a reduced ejection fraction; randomized, placebo-controlled trials in heart failure with a preserved ejection fraction; categorization of heart failure according to American Heart Association/American College of Cardiology heart failure stage, New York Heart Association functional class, and Interagency Registry for Mechanically Assisted Circulatory Support level; and poor prognostic indicators in heart failure. This review contains 4 highly rendered figures, 8 tables, and 114 references.

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Heart Failure

10.2310/tywc.1409 ◽

2018 ◽

Author(s):

Sachin P Shah ◽

Mandeep R. Mehra

Keyword(s):

Heart Failure ◽

Chronic Heart Failure ◽

Ejection Fraction ◽

Acute Decompensated Heart Failure ◽

Heart Association ◽

Decompensated Heart Failure ◽

Advanced Heart Failure ◽

Circulatory Support ◽

Preserved Ejection Fraction ◽

Reduced Ejection Fraction

Heart failure is a syndrome related to abnormal cardiac performance with a consequence of impaired cardiac output at rest or with exertion and/or congestion, which usually leads to symptoms of fatigue, dyspnea, and edema. The syndrome is characterized by various phenotypes related to a vast array of etiologies with diverse management targets. The current broad categorization of heart failure separates patients based on ejection fraction. Further description of the phenotype beyond ejection fraction is imperative to correctly identify the etiology of heart failure and, ultimately, to choose medical, device, and surgical therapies appropriately. This review covers the epidemiology of heart failure, defining the phenotype and etiology of heart failure, recognition and management of acute decompensated heart failure, management of chronic heart failure with a reduced ejection fraction, implantable cardioverter-defibrillators in heart failure with a reduced ejection fraction, management of heart failure with a preserved ejection fraction, and advanced heart failure. Figures show the evolution of therapy in chronic heart failure from the symptom-directed model, the complex pathophysiology and principal aberrations underlying heart failure with preserved ejection fraction, and concepts underlying surgical therapy in advanced heart failure using Laplace’s law. Tables list various etiologies of heart failure; sensitivity and specificity of clinical, biomarker, and radiographic data in the diagnosis of acute decompensated heart failure; drugs and devices with a demonstrated survival benefit in heart failure with a reduced ejection fraction; neurohormonal antagonist dosing in heart failure with a reduced ejection fraction; randomized, placebo-controlled trials in heart failure with a preserved ejection fraction; categorization of heart failure according to American Heart Association/American College of Cardiology heart failure stage, New York Heart Association functional class, and Interagency Registry for Mechanically Assisted Circulatory Support level; and poor prognostic indicators in heart failure. This review contains 3 highly rendered figures, 7 tables, and 113 references.

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Association of admission and discharge anemia status with outcomes in patients hospitalized for acute decompensated heart failure: Differences between patients with preserved and reduced ejection fraction

European Heart Journal Acute Cardiovascular Care ◽

10.1177/2048872617730039 ◽

2017 ◽

Vol 8 (7) ◽

pp. 606-614 ◽

Cited By ~ 1

Author(s):

Katsuya Kajimoto ◽

Yuichiro Minami ◽

Shigeru Otsubo ◽

Naoki Sato

Keyword(s):

Heart Failure ◽

Confidence Interval ◽

Ejection Fraction ◽

Primary Endpoint ◽

Acute Decompensated Heart Failure ◽

Decompensated Heart Failure ◽

Hazard Ratio ◽

Preserved Ejection Fraction ◽

Reduced Ejection Fraction ◽

Heart Failure Patients

Background: In acute decompensated heart failure patients with a preserved or reduced ejection fraction, the association of admission and discharge anemia status with outcomes remains unclear. Methods and results: Of the 4842 patients enrolled in the Acute Decompensated Heart Failure Syndromes (ATTEND) registry, 4433 patients (2017 with a preserved and 2416 with a reduced ejection fraction) were examined to investigate associations among the anemia status at admission and discharge (no anemia, developed anemia, resolved anemia, or persistent anemia), a preserved or reduced ejection fraction and the primary endpoint (all-cause death and readmission for heart failure). In the preserved ejection fraction group, adjusted analysis showed that either developed or persistent anemia was associated with a significantly higher risk of the primary endpoint relative to no anemia (hazard ratio: 1.53; 95% confidence interval (CI): 1.11–2.11; p=0.009 and hazard ratio: 1.60; 95% CI: 1.26–2.04; p<0.001, respectively), but there was no association between resolved anemia and the primary endpoint (hazard ratio: 0.98; 95% CI: 0.67–1.45; p=0.937). In the reduced ejection fraction group, either developed or resolved anemia was associated with a tendency toward higher risk of the primary endpoint relative to no anemia (hazard ratio: 1.29; 95% CI: 0.95–1.62; p=0.089, and hazard ratio: 1.31; 95% CI: 0.96–1.77; p=0.085, respectively), while persistent anemia was associated with a significantly higher risk of the primary endpoint relative to no anemia (hazard ratio: 1.36; 95% CI: 1.12–1.65; p=0.002). Conclusions: In acute decompensated heart failure patients, the association of admission and discharge anemia status with outcomes differs markedly between patients with a preserved or reduced ejection fraction.

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