Serial sodium values and adverse outcomes in heart failure with preserved ejection fraction

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 14922: Prognostic Value of Baseline BNP and NT-ProBNP and its Interaction With Spironolactone in Patients With Heart Failure and Preserved Ejection Fraction in the TOPCAT Trial

Circulation ◽

10.1161/circ.132.suppl_3.14922 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Inder S Anand ◽

Scott D Solomon ◽

Brian Claggett ◽

Sanjiv J Shah ◽

Eileen O’Meara ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Primary Outcome ◽

Cox Regression ◽

Selection Criterion ◽

Adverse Outcomes ◽

Preserved Ejection Fraction ◽

Patient Selection Criterion ◽

Increased Risk ◽

Patients With Heart Failure

Background: Plasma natriuretic peptides (NP) are helpful in the diagnosis of heart failure (HF) with preserved ejection fraction (HFpEF) and predict adverse outcomes. Levels of NP beyond a certain cut-off level are often used as inclusion criteria in clinical trials to ensure that the patients have HF, and to select patients at higher risk. Whether treatments have a differential effect on outcomes across the spectrum of NP levels is unclear. In the I-Preserve trial a benefit of irbesartan on all outcomes was only seen in HFpEF patients with low but not high NP levels. We hypothesized that in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial, spironolactone might have a greater benefit in patients with lower NP levels. Methods and Results: BNP (n=468) or NT-proBNP (n=400) levels were available at baseline in 868 patients with HFpEF enrolled in the natriuretic peptide stratum (BNP ≥100 pg/mL or an NT- proBNP ≥360 pg/mL) of the TOPCAT trial. In a multi-variable Cox regression model, that included age, gender, region (Americas vs. Russia/Georgia), atrial fibrillation, diabetes, eGFR, BMI and heart rate, higher BNP or NT-proBNP as a continuous, standardized log-transformed variable or grouped by terciles (see Figure for BNP & NT-proBNP tercile values) was independently associated with an increased risk of the primary endpoint of cardiovascular mortality, aborted cardiac arrest, or hospitalization for heart failure (Figure-1). There was a significant interaction between the effect of spironolactone and baseline BNP or NT-proBNP terciles for the primary outcome (P=0.02, Figure-2), with greater benefit of the drug in the lower compared to higher NP terciles. Conclusions: The benefit of spironolactone in lower risk HFpEF patients may indicate effects of the drug on early, but not late higher-risk stage of the disease. These findings question the strategy of using elevated NP as a patient selection criterion in HFpEF trials.

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Clinical Significance of Mean and Pulse Pressure in Patients With Heart Failure With Preserved Ejection Fraction

Hypertension ◽

10.1161/hypertensionaha.121.17782 ◽

2021 ◽

Author(s):

Fang-Fei Wei ◽

Yuzhong Wu ◽

Ruicong Xue ◽

Xiao Liu ◽

Xin He ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Pulse Pressure ◽

Total Mortality ◽

Posterior Wall ◽

Left Ventricular ◽

Adverse Outcomes ◽

Sensitivity Analyses ◽

Preserved Ejection Fraction ◽

Patients With Heart Failure

It remains debated whether pulse pressure is associated with left ventricular traits and adverse outcomes over and beyond mean arterial pressure (MAP) in patients with heart failure (HF) with preserved ejection fraction. We investigated these associations in 3428 patients with HF with preserved ejection fraction (51.5% women; mean age, 68.6 years) enrolled in the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist). We computed association sizes and hazards ratios with 1-SD increase in MAP and pulse pressure. In multivariable-adjusted analyses, association sizes ( P ≤0.039) for MAP were 0.016 cm and 0.014 cm for septal and posterior wall thickness, −0.15 for E/A ratio, −0.66 for E/e′, and −0.64% for ejection fraction, independent of pulse pressure. With adjustment additionally applied for MAP, E/A ratio and longitudinal strain increased with higher pulse pressure with association sizes amounting to 0.067 ( P =0.026) and 0.40% ( P =0.023). In multivariable-adjusted analyses of both placebo and spironolactone groups, lower MAP and higher pulse pressure predicted the primary composite end point ( P ≤0.028) and hospitalized HF ( P ≤0.002), whereas MAP was also significantly associated with total mortality ( P ≤0.007). Sensitivity analyses stratified by sex, median age, and region generated confirmatory results with exception for the association of adverse outcomes with pulse pressure in patients with age ≥69 years. In conclusion, the clinical application of MAP and pulse pressure may refine risk estimates in patients with HF with preserved ejection fraction. This finding may help further investigation for the development of HF with preserved ejection fraction preventive strategies targeting pulsatility and blood pressure control.

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A3420 Nocturnal pulse pressure was associated with adverse outcomes in heart failure with preserved ejection fraction of clinical scenario 1

Journal of Hypertension ◽

10.1097/01.hjh.0000548595.42163.ae ◽

2018 ◽

Vol 36 ◽

pp. e147

Author(s):

Takahiro Komori ◽

Satoshi Hoshide ◽

Toshinobu Saito ◽

Kazuomi Kario

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Pulse Pressure ◽

Adverse Outcomes ◽

Clinical Scenario ◽

Preserved Ejection Fraction

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Influence of polypharmacy on patients with heart failure with preserved ejection fraction: a retrospective analysis on adverse outcomes in the TOPCAT trial

British Journal of General Practice ◽

10.3399/bjgp21x714245 ◽

2020 ◽

Vol 71 (702) ◽

pp. e62-e70

Author(s):

Yuzhong Wu ◽

Wengen Zhu ◽

Xin He ◽

Ruicong Xue ◽

Weihao Liang ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Retrospective Analysis ◽

Heart Function ◽

Left Ventricular ◽

Adverse Outcomes ◽

Left Ventricular Ejection ◽

Controlled Study ◽

Preserved Ejection Fraction ◽

Ventricular Ejection Fraction

BackgroundPolypharmacy is common in heart failure (HF), whereas its effect on adverse outcomes in patients with HF with preserved ejection fraction (HFpEF) is unclear.AimTo evaluate the prevalence, prognostic impacts, and predictors of polypharmacy in HFpEF patients.Design and settingA retrospective analysis performed on patients in the Americas region (including the US, Canada, Argentina, and Brazil) with symptomatic HF and a left ventricular ejection fraction ≥45% in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial, an international, randomised, double-blind, placebo-controlled study conducted during 2006–2013 in six countries.MethodPatients were categorised into four groups: controls (<5 medications), polypharmacy (5–9 medications), hyperpolypharmacy, (10–14 medications), and super hyperpolypharmacy (≥15 medications). The outcomes and predictors in all groups were assessed.ResultsOf 1761 participants, the median age was 72 years; 37.5% were polypharmacy, 35.9% were hyperpolypharmacy, and 19.6% were super hyperpolypharmacy, leaving 7.0% having a low medication burden. In multivariable regression models, three experimental groups with a high medication burden were all associated with a reduction in all-cause death, but increased risks of HF hospitalisation and all-cause hospitalisation. Furthermore, several comorbidities (dyslipidemia, thyroid diseases, diabetes mellitus, and chronic obstructive pulmonary disease), a history of angina pectoris, diastolic blood pressure <80 mmHg, and worse heart function (the New York Heart Association functional classification level III and IV) at baseline were independently associated with a high medication burden among patients with HFpEF.ConclusionA high prevalence of high medication burden at baseline was reported in patients with HFpEF. The high medication burden might increase the risk of hospital readmission, but not the mortality.

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Prognostic Relevance of Elevated Plasma Osmolality on Admission in Acute Decompensated Heart Failure With Preserved Ejection Fraction: Insights From PURSUIT-HFpEF Registry

10.21203/rs.3.rs-131158/v1 ◽

2020 ◽

Author(s):

Akito Nakagawa ◽

Yoshio Yasumura ◽

Chikako Yoshida ◽

Takahiro Okumura ◽

Jun Tateishi ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Plasma Osmolality ◽

Adverse Outcomes ◽

Cox Proportional Hazard Model ◽

Proportional Hazard ◽

Preserved Ejection Fraction ◽

Proportional Hazard Model ◽

Cox Proportional Hazard ◽

Kaplan Meier

Abstract BackgroundComplicated pathophysiology makes it difficult to identify the prognosis of heart failure with preserved ejection fraction (HFpEF). While plasma osmolality has been reported to have prognostic importance, mainly in heart failure with reduced ejection fraction (HFrEF), its prognostic meaning for HFpEF has not been elucidated. MethodsWe prospectively studied 960 patients in PURSUIT-HFpEF, a multicenter observational study of acute decompensated HFpEF inpatients. We divided patients into three groups according to the quantile values of plasma osmolality on admission. During a follow-up averaging 366 days, we examined the primary composite endpoint of cardiac mortality or heart failure re-admission using Kaplan-Meier curve analysis and Cox proportional hazard testing. Results216 (22.5%) patients reached the primary endpoint. Kaplan-Meier curve analysis revealed that the highest quantile of plasma osmolality on admission (higher than 300.3 mOsm/kg) was significantly associated with adverse outcomes (Log-rank P = 0.0095). Univariable analysis in the Cox proportional hazard model also revealed significantly higher rates of adverse outcomes in the higher plasma osmolality on admission (hazard ratio [HR] 7.29; 95% confidence interval [CI] 2.25–23.92, P = 0.0009). Multivariable analysis in the Cox proportional hazard model also showed that higher plasma osmolality on admission was significantly associated with adverse outcomes (HR 4.70; 95% CI 1.33–17.35, P = 0.0160) independently from other confounding factors such as age, gender, comorbid of atrial fibrillation, hypertension history, diabetes, malnutrition, and N-terminal pro-B-type natriuretic peptide elevation. ConclusionsHigher plasma osmolality on admission was prognostically important for acute decompensated HFpEF inpatients.

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The impact of frailty and aging on prognosis in patients with heart failure with preserved ejection fraction – insights from PURSUIT-HFpEF registry

European Heart Journal ◽

10.1093/ehjci/ehaa946.0961 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

M Okada ◽

K Inoue ◽

T Onishi ◽

K Iwakura ◽

T Yamada ◽

...

Keyword(s):

Heart Failure ◽

Confidence Interval ◽

Ejection Fraction ◽

Hazard Ratio ◽

Adverse Outcomes ◽

Funding Source ◽

Preserved Ejection Fraction ◽

Clinical Endpoint ◽

Patients With Heart Failure

Abstract Introduction Frailty and aging are two common conditions both associated with increased vulnerability to stressful events with high risk of adverse outcomes. Purpose To evaluate the association between frailty and aging and their impacts on clinical outcome in patients with heart failure with preserved ejection fraction (HFpEF). Methods Analysis was performed from a prospective multicenter observational registry for HFpEF (PURSUIT-HFpEF Registry) conducted in the Osaka region of Japan. A total of 757 patients hospitalized for acute heart failure (diagnosed by using Framingham criteria) met the inclusion criteria: a left ventricular ejection fraction ≥50% and brain natriuretic peptide ≥100pg/ml. We included 483 patients (age, 80±9 years; men, 45%; atrial fibrillation, 35%) whose follow-up data after survival discharge were available. Patients' frailty and aging were evaluated using the clinical frailty scale (CFS) and age quartiles (Q1: <76 years (n=122), Q2: 76–82 years (n=111), Q3: 82–87 years (n=127), Q4: >87 years (n=123)), respectively. The primary clinical endpoint was defined as the composite of death, re-hospitalization for heart failure, and cerebrovascular accident. Results The median (interquartile range) CFS rating was 3 (2–5), and there was a little correlation between CFS rating and age (r2=0.16, p<0.001). The prevalence of frailty, defined as a CFS rating >4 (n=132), was positively correlated with age quartiles (Q1: 9.0%, Q2: 21.4%, Q3: 29.9%, Q4: 48.0%, p<0.001). During the median follow-up period 396 days (interquartile range, 344–698) after discharge, the clinical endpoint was observed in 172 patients. The incidence was higher in patients with frailty than those without it (49.6% vs. 30.4%, log-rank p<0.001). It was also correlated with age quartiles (Q1: 23.0%, Q2: 34.2%, Q3: 36.2%, Q4: 48.8%, log-rank p=0.001). Multivariate Cox regression analysis revealed that frailty (hazard ratio, 1.52; 95% confidence interval, 1.09–2.10; p=0.013) and age (hazard ratio per quartile increase, 1.24; 95% confidence interval, 1.07–1.43; p=0.004) were both associated with the clinical endpoint. Subgroup analysis in 352 patients without frailty also revealed the significant impact of age on the endpoint (1.26; 1.06–1.51; p=0.008). However, in 131 patients with frailty, there was no significant impact of age on the endpoint (1.16; 0.90–1.51; p=0.25). Conclusions Frailty was common and was associated with aging in HFpEF patients. Although they were both associated with unfavorable events, aging was no longer a significant predictor of adverse outcomes under the frailty conditions. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Roche Diagnostics K.K. and Fuji Film Toyama Chemical Co. Ltd.

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