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 ◽  
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.

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

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

Association of Hyper-Polypharmacy With Clinical Outcomes in Heart Failure With Preserved Ejection Fraction

2021 ◽  
Author(s):  
Masatoshi Minamisawa ◽  
Brian Claggett ◽  
Kota Suzuki ◽  
Sheila M. Hegde ◽  
Amil M. Shah ◽  
...  
Keyword(s):  
Heart Failure ◽  
Adverse Events ◽  
Ejection Fraction ◽  
Primary Outcome ◽  
Hazard Ratio ◽  
Preserved Ejection Fraction ◽  
Serious Adverse Events ◽  
Increased Risk ◽  
Patients With Heart Failure ◽  
The Relationship

Background: Polypharmacy is associated with a poor prognosis in the elderly, however, information on the association of polypharmacy with cardiovascular outcomes in heart failure with preserved ejection fraction is sparse. This study sought to investigate the relationship between polypharmacy and adverse cardiovascular events in patients with heart failure with preserved ejection fraction. Methods: Baseline total number of medications was determined in 1758 patients with heart failure with preserved ejection fraction enrolled in the Americas regions of the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist), by 3 categories: nonpolypharmacy (<5 medications), polypharmacy (5–9), and hyper-polypharmacy (≥10). We examined the relationship of polypharmacy status with the primary outcome (cardiovascular death, HF hospitalization, or aborted cardiac arrest), hospitalizations for any reason, and serious adverse events. Results: The proportion of patients taking 5 or more medications was 92.5% (inclusive of polypharmacy [38.7%] and hyper-polypharmacy [53.8%]). Over a 2.9-year median follow-up, compared with patients with polypharmacy, hyper-polypharmacy was associated with an increased risk for the primary outcome, hospitalization for any reason and any serious adverse events in the univariable analysis, but not significantly associated with mortality. After multivariable adjustment for demographic and comorbidities, hyper-polypharmacy remained significantly associated with an increased risk for hospitalization for any reason (hazard ratio, 1.22 [95% CI, 1.05–1.41]; P =0.009) and any serious adverse events (hazard ratio, 1.23 [95% CI, 1.07–1.42]; P =0.005), whereas the primary outcome was no longer statistically significant. Conclusions: Hyper-polypharmacy was common and associated with an elevated risk of hospitalization for any reason and any serious adverse events in patients with heart failure with preserved ejection fraction. There were no significant associations between polypharmacy status and mortality.

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

Hypertension ◽  
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.

Abstract 11159: Prolonged QRS Duration Predicts Outcomes in Heart Failure With Preserved Ejection Fraction

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Jacob Joseph ◽  
Brian L Claggett ◽  
Inder S Anand ◽  
Jerome L Fleg ◽  
Thao Huynh ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Primary Outcome ◽  
Statistical Significance ◽  
Study Cohort ◽  
Preserved Ejection Fraction ◽  
Entire Study ◽  
Increased Risk ◽  
Qrs Duration ◽  
Entire Study Cohort

Introduction: QRS widening on the surface electrocardiogram (ECG) is a marker of disease progression in heart failure (HF) with reduced ejection fraction. We hypothesized that prolonged QRS duration would similarly identify patients with HF with preserved ejection fraction (HFPEF) at high risk for cardiovascular (CV) events. Methods: We examined the relationship of baseline QRS duration to primary outcome [composite of CV death, aborted cardiac arrest, or HF hospitalization (HFH)] and HFH alone in TOPCAT, a multicenter, randomized, placebo-controlled trial of spironolactone in HFPEF. QRS duration was analyzed as a dichotomous variable (≥ 120 ms or < 120 ms). Multivariable analyses were conducted including variables that were significantly associated with QRS duration ≥ 120 ms (Table 1). Analyses were conducted in the entire study cohort as well as in separate analyses for only subjects enrolled from the Americas or from Russia/Georgia independently. Results: QRS duration was known in 3426 of 3445 TOPCAT patients. Compared to those with QRS duration < 120ms, 613 (17.9%) subjects had a QRS duration ≥ 120 ms and were older (72.9 years vs. 67.8 years; p < 0.0001) and more likely to be men (62% vs. 45%; p<0.0001). A QRS duration ≥ 120 ms was independently associated with an increased risk of primary outcome and HFH in the entire study cohort and in the subset of patients enrolled in the Americas but was of borderline statistical significance in Russia/Georgia (Table 1). No statistical interaction was observed between treatment with spironolactone and QRS duration (p value for interaction= 0.33). Conclusions: QRS duration identifies HFPEF subjects at a higher risk of adverse clinical outcomes; spironolactone had a similar effect on outcomes independent of QRS duration. This easily obtainable marker may be an important component of risk stratification in this syndrome.

scholarly journals H2FPEF score predicts 1-year rehospitalisation of patients with heart failure with preserved ejection fraction

2020 ◽  
pp. postgradmedj-2019-137434
Author(s):  
Yifei Tao ◽  
Wenjing Wang ◽  
Jing Zhu ◽  
Tao You ◽  
Yi Li ◽  
...  
Keyword(s):  
Heart Failure ◽  
Regression Analysis ◽  
Ejection Fraction ◽  
Cox Regression ◽  
Area Under The Curve ◽  
Support Vector ◽  
Preserved Ejection Fraction ◽  
Cox Regression Analysis ◽  
Non Invasive ◽  
Patients With Heart Failure

BackgroundHeart failure with preserved ejection fraction (HFpEF) has received widespread attention in recent years. There is currently a lack of valuable predictors for the prognosis of this disease. Here, we aimed to identify a non-invasive scoring system that can effectively predict 1-year rehospitalisation for patients with HFpEF.MethodsWe included 151 consecutive patients with HFpEF in a prospective cohort study and investigated the association between H2FPEF score and 1-year readmission for heart failure using multivariate Cox regression analysis.ResultsOur findings indicated that obesity, age >70 years, treatment with ≥2 antihypertensives, echocardiographic E/e’ ratio >9 and pulmonary artery pressure >35 mm Hg were independent predictors of 1-year readmission. Three models (support vector machine, decision tree in R and Cox regression analysis) proved that H2FPEF score could effectively predict 1-year readmission for patients with HFpEF (area under the curve, 0.910, 0.899 and 0.771, respectively; p<0.001).ConclusionOur study demonstrates that the H2FPEF score has excellent predictive value for 1-year rehospitalisation of patients with HFpEF.

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

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: &lt;76 years (n=122), Q2: 76–82 years (n=111), Q3: 82–87 years (n=127), Q4: &gt;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&lt;0.001). The prevalence of frailty, defined as a CFS rating &gt;4 (n=132), was positively correlated with age quartiles (Q1: 9.0%, Q2: 21.4%, Q3: 29.9%, Q4: 48.0%, p&lt;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&lt;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.

scholarly journals High Plasma Docosahexaenoic Acid Associated to Better Prognoses of Patients with Acute Decompensated Heart Failure with Preserved Ejection Fraction

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 371
Author(s):  
Naoaki Matsuo ◽  
Toru Miyoshi ◽  
Atsushi Takaishi ◽  
Takao Kishinoue ◽  
Kentaro Yasuhara ◽  
...  
Keyword(s):  
Heart Failure ◽  
Docosahexaenoic Acid ◽  
Ejection Fraction ◽  
Primary Outcome ◽  
Cox Regression ◽  
Risk Index ◽  
Preserved Ejection Fraction ◽  
Cox Regression Analysis ◽  
Nutritional Risk Index ◽  
All Cause Mortality

The clinical relevance of polyunsaturated fatty acids (PUFAs) in heart failure remains unclear. The aim of this study was to investigate the association between PUFA levels and the prognosis of patients with heart failure with preserved ejection fraction (HFpEF). This retrospective study included 140 hospitalized patients with acute decompensated HFpEF (median age 84.0 years, 42.9% men). The patients’ nutritional status was assessed, using the geriatric nutritional risk index (GNRI), and their plasma levels of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), and dihomo-gamma-linolenic acid (DGLA) were measured before discharge. The primary outcome was all-cause mortality. During a median follow-up of 23.3 months, the primary outcome occurred in 37 patients (26.4%). A Kaplan–Meier analysis showed that lower DHA and DGLA levels, but not EPA or AA levels, were significantly associated with an increase in all-cause death (log-rank; p < 0.001 and p = 0.040, respectively). A multivariate Cox regression analysis also revealed that DHA levels were significantly associated with the incidence of all-cause death (HR: 0.16, 95% CI: 0.06–0.44, p = 0.001), independent of the GNRI. Our results suggest that low plasma DHA levels may be a useful predictor of all-cause mortality and potential therapeutic target in patients with acute decompensated HFpEF.

scholarly journals Dapagliflozin reduces the risk of hyperkalaemia in patients with heart failure and reduced ejection fraction: a secondary analysis DAPA-HF

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S.L Kristensen ◽  
K.F Docherty ◽  
P.S Jhund ◽  
O Bengtsson ◽  
D.L Demets ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Cox Regression ◽  
Secondary Analysis ◽  
Adverse Outcomes ◽  
Funding Source ◽  
Private Company ◽  
Reduced Ejection Fraction ◽  
Life Saving ◽  
Patients With Heart Failure

Abstract Background Hyperkalaemia often limits the use of mineralocorticoid receptor antagonists (MRAs) in patients with heart failure and reduced ejection fraction (HFrEF), denying these patients a life-saving therapy. Purpose To determine whether treatment with the sodium-glucose cotransporter 2 (SGLT-2) inhibitor dapagliflozin reduces the risk of hyperkalaemia associated with MRA use in patients with HFrEF. Methods The risk of developing mild hyperkalaemia (potassium &gt;5.5 mmol/L) and moderate/severe hyperkalaemia (&gt;6.0 mmol/L) was examined in the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF) according to background MRA use, and randomized treatment assignment, by use of Cox regression analyses. Results Overall, 3370 (70.1%) patients in DAPA-HF were treated with an MRA. Mild hyperkalaemia and moderate/severe hyperkalaemia occurred in 182 (11.1%) and 23 (1.4%) patients treated with dapagliflozin as compared to 204 (12.6%) and 40 (2.4%) of patients given placebo (Table and Figure). This yielded a hazard ratio (HR) of 0.86 (0.70–1.05) for mild hyperkalaemia and 0.50 (0.29, 0.85) for moderate/severe hyperkalaemia, comparing dapagliflozin to placebo. Conclusions Patients with HFrEF and taking a MRA who were randomized to dapagliflozin had half the incidence of moderate/severe hyperkalaemia, compared with those randomized to placebo. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): DAPA-HF study was funded by AstraZeneca

scholarly journals CARNITINE INSUFFICIENCY IS ASSOCIATED WITH ADVERSE OUTCOMES IN PATIENTS WITH HEART FAILURE WITH PRESERVED EJECTION FRACTION

2016 ◽  
pp. 1-7
Author(s):  
Y. Kinugasa ◽  
S. Sugihara ◽  
K. Yamada ◽  
M. Miyagi ◽  
K. Matsubara ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Risk Index ◽  
Left Ventricular ◽  
Adverse Outcomes ◽  
Free Carnitine ◽  
Preserved Ejection Fraction ◽  
Nutritional Risk Index ◽  
Patients With Heart Failure ◽  
Composite Endpoints

Background: L-carnitine is an essential nutrient that plays a vital role in fatty acid energy metabolism of the heart and skeletal muscles. Primary or secondary carnitine insufficiency contributes to progressive left ventricular systolic dysfunction and physical frailty. However, the clinical features of patients with heart failure with preserved ejection fraction (HFpEF) and carnitine insufficiency remain unclear. Objectives: The present study aimed to evaluate the clinical characteristics and outcomes of these patients. Design: A prospective cohort study. Setting: Tottori University hospital. Participants: 117 patients who were hospitalized with HFpEF (ejection fraction ≥45%). Measurement: All measurements were obtained at hospital discharge. Carnitine insufficiency was defined as the lowest quantile of free carnitine level (<56.3 μmol/L) or the highest quantile of acylcarnitine to free carnitine ratio (≥0.35). Nutritional status and physical activity were assessed by the Geriatric Nutritional Risk Index (GNRI) and Barthel index (BI). Left ventricular diastolic function was assessed by echocardiography. The composite endpoints were hospitalization for heart failure and death from cardiac causes. Results: Patients with carnitine insufficiency (44.4%) had lower values of GNRI and BI, higher B-type natriuretic peptide levels, and lower early diastolic mitral annular velocity in the subgroups with sinus rhythm compared with those with preserved carnitine (all p<0.05). During a mean follow-up of 472±249 days, composite endpoints occurred in 26.5% of patients. Multivariate Cox hazard analysis showed that carnitine insufficiency was an independent predictor of cardiac events (p<0.05). Conclusions: Carnitine insufficiency is associated with adverse outcomes in patients with HFpEF.

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