Abstract 14213: Different Prognostic Value of Proteinuria According to the Severity of Heart Failure in Patients With Heart Failure With Preserved Ejection Fraction

Introduction: Proteinuria reflects systemic inflammation and endothelial dysfunction, and is a prognosticator in heart failure with preserved ejection fraction (HFpEF). However, it remains elusive whether the prognostic impact of proteinuria is different according to the severity of HFpEF. Recently, we and other groups reported that echocardiographic diastolic dysfunction (DD) is a worse prognostic factor in HFpEF. Objectives: We aimed to clarify the prognostic value of proteinuria in HFpEF according to the severity of HFpEF. We used the evidence of DD as criteria of the severity of HFpEF. Methods: We assessed 575 discharged-alive patients (pts) in the PURSUIT-HFpEF registry. Pts were divided into 2 groups according to the absence (DD-) or presence of DD (DD+). DD was defined using the 2016 ASE recommendations. Each group was further classified into 2 subgroups according to the absence or presence of dipstick proteinuria (proteinuria trace or more). The study endpoint was a composite of all-cause mortality and HF hospitalization. Results: Median age 83 years and 58% female. The number of pts with DD-: 336 pts (221 pts: proteinuria-[G1], 115 pts: proteinuria+[G2]); and DD+: 239 pts (125 pts: proteinuria-[G3], 114 pts: proteinuria+[G4]). G4 had higher NT-proBNP level than G3, but not observed between G1 and G2. Proteinuria+ were more hypertensive, diabetic with worse renal function than proteinuria- in both DD-/DD+. The composite endpoint occurred more often in G4 than G3 (HR: 1.75, 95%CI: 1.18-2.62, log-rank P=0.005), but was similar between G1 and G2 (HR: 1.21, 95%CI: 0.76-1.92, log-rank P=0.431). Multivariable Cox regression adjusting for NT-proBNP, eGFR and other major confounding factors revealed that proteinuria was associated with the composite endpoint in DD+ (HR:1.85, 95% CI:1.16-2.93, P=0.009), but not in DD- (HR:0.96, 95% CI:0.55-1.69, P=0.900). Conclusions: Proteinuria may be an additive risk factor in pts with DD but not in those without DD in HFpEF.

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Prevalence and prognostic impact of somatic mutations in patients with heart failure and reduced ejection fraction

European Heart Journal ◽

10.1093/ehjci/ehaa946.0966 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

D.J Vazquez Andres ◽

A Hernandez Vicente ◽

M Diez Diez ◽

M Gomez Molina ◽

A Quintas ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Somatic Mutations ◽

Myocardial Dysfunction ◽

Study Endpoint ◽

Prognostic Impact ◽

Reduced Ejection Fraction ◽

Increased Risk ◽

Patients With Heart Failure

Abstract Introduction Somatic mutations in hematopoietic cells are associated with age and have been associated with higher mortality in apparently healthy adults, especially due to atherosclerotic disease. In animal models, somatic mutations are associated with atherosclerosis progression and myocardial dysfunction, especially when gene TET2 is affected. Preliminary clinical data, referred to ischemic heart failure (HF), have associate the presence of these acquired mutations with impaired prognosis. Purpose To study the prevalence of somatic mutations in patients with heart failure with reduced ejection fraction (HFrEF) and their impact on long-term prognosis. Methods We studied a cohort of elderly patients (more than 60 years old) hospitalized with HFrEF (LVEF<45%). The presence of somatic mutations was assessed using next generation sequencing (Illumina HiSeq 2500), with a mutated allelic fraction of at least 2% and a panel of 55 genes related with clonal hematopoiesis. Patients were followed-up for a median of three years. The study endpoint was a composite of death or readmission for worsening HF. Kaplan-Meier analysis (log-rank test) and Cox proportional hazards regression models were performed adjusting for age, sex and LVEF. Results A total of 62 patients (46 males (74.2%), age 74±7.5 years) with HFrEF (LVEF 29.7±7.8%) were enrolled in the study. The ischemic etiology was present in 54% of patients. Somatic mutations in Dnmt3a or Tet2 were present in 11 patients (17.7%). No differences existed in baseline characteristics except for a higher prevalence of atrial fibrillation in patients with somatic mutations (70% vs. 40%, p=0.007). During the follow-up period, 40 patients (64.5%) died and 38 (61.3%) had HF re-admission. The KM survival analysis for the combined event is shown in Figure 1. Compared with patients without somatic mutations and after adjusting for covariates, there was an increased risk of adverse outcomes when the somatic mutations were present (HR 3.6, 95% CI [1.6, 7.8], p=0.0014). This results remains considering death as a competing risk (Gray's test p=0.0097) and adjusting for covariates (HR = 2.21 95% CI [0.98, 5], p=0.0556). Conclusions Somatic mutation are present in patients with HFrEF and determine a higher risk of adverse events in the follow-up. Further studies are needed to assess the clinical implications of these findings. Figure 1 Funding Acknowledgement Type of funding source: None

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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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Abstract 13497: Prognostic Value of the Combination of the Echocardiographic Derived Pulmonary Artery Wedge Pressure and Body Mass Index in Patients With Heart Failure With Preserved Ejection Fraction: Insights From PURSUIT-HFpEF Registry

Circulation ◽

10.1161/circ.142.suppl_3.13497 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Kumpei Ueda ◽

Shungo Hikoso ◽

Daisaku D Nakatani ◽

Shunsuke Tamaki ◽

Masamichi Yano ◽

...

Keyword(s):

Heart Failure ◽

Body Mass Index ◽

Ejection Fraction ◽

Prognostic Value ◽

Left Ventricular ◽

Preserved Ejection Fraction ◽

Pulmonary Artery Wedge Pressure ◽

Patients With Heart Failure ◽

Wedge Pressure

Background: An elevated pulmonary artery wedge pressure (PAWP), a surrogate of left ventricular filling pressure, is associated with poor outcomes in patients with heart failure (HF). In addition, obesity paradox is well recognized in HF patients and body mass index (BMI) also provides a prognostic information. However, there is little information available on the prognostic value of the combination of the echocardiographic derived PAWP and BMI in patients with HF with preserved ejection fraction (HFpEF). Methods and Results: Patients data were extracted from The Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with Preserved Ejection Fraction (PURSUIT HFpEF) study, which is a prospective multicenter observational registry for acute decompensated heart failure (ADHF) patients with HFpEF. We analyzed 548 patients after exclusion of patients undergoing hemodialysis, patients with in-hospital death, missing follow-up data, or missing data to calculate PAWP or BMI. Body weight measurement and echocardiography were performed just before discharge. PAWP was calculated using the Nagueh formula [PAWP = 1.24* (E/e’) + 1.9] with e’ = [(e’ septal + e’ lateral ) /2]. During a mean follow up period of 1.5±0.8 years, 86 patients had all-cause death (ACD). Multivariate Cox analysis showed that both PAWP (p=0.020) and BMI (p=0.0001) were significantly associated with ACD, independently of age and previous history of HF hospitalization, after the adjustment with gender, left ventricular ejection fraction, NT-proBNP and estimated glomerular filtration rate. Kaplan-Meier curve analysis revealed that there was a significant difference in the risk of ACD when patients were stratified into 3 groups based on the median values of PAWP (17.3) and BMI (21.4). Conclusions: The combination of the echocardiographic derived PAWP and BMI might be useful for stratifying ADHF patients with HFpEF at risk for the total mortality.

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

Postgraduate Medical Journal ◽

10.1136/postgradmedj-2019-137434 ◽

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.

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Prognostic Impact of Statin Use in Patients With Heart Failure and Preserved Ejection Fraction

Circulation Journal ◽

10.1253/circj.cj-14-0865 ◽

2015 ◽

Vol 79 (3) ◽

pp. 574-582 ◽

Cited By ~ 39

Author(s):

Kotaro Nochioka ◽

Yasuhiko Sakata ◽

Satoshi Miyata ◽

Masanobu Miura ◽

Tsuyoshi Takada ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Prognostic Impact ◽

Preserved Ejection Fraction ◽

Patients With Heart Failure ◽

Statin Use

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Patients with Heart Failure and Preserved Ejection Fraction Are at Risk of Gastrointestinal Bleeding

Journal of Clinical Medicine ◽

10.3390/jcm8081240 ◽

2019 ◽

Vol 8 (8) ◽

pp. 1240 ◽

Cited By ~ 3

Author(s):

Lore Schrutka ◽

Benjamin Seirer ◽

Franz Duca ◽

Christina Binder ◽

Daniel Dalos ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Vitamin K ◽

Prognostic Value ◽

Vitamin K Antagonists ◽

Right Atrial ◽

Preserved Ejection Fraction ◽

Gi Bleeding ◽

Bleeding Events ◽

Patients With Heart Failure

Aims. Two thirds of patients with heart failure and preserved ejection fraction (HFpEF) have an indication for oral anticoagulation (OAC) to prevent thromboembolic events. However, evidence regarding the safety of OAC in HFpEF is limited. Therefore, our aim was to describe bleeding events and to find predictors of bleeding in a large HFpEF cohort. Methods and Results. We recorded bleeding events in a prospective HFpEF cohort. Out of 328 patients (median age 71 years (interquartile range (IQR) 67–77)), 64.6% (n = 212) were treated with OAC. Of those, 65.1% (n = 138) received vitamin-K-antagonists (VKA) and 34.9% (n = 72) non-vitamin K oral anticoagulants (NOACs). During a median follow-up time of 42 (IQR 17–63) months, a total of 54 bleeding events occurred. Patients on OAC experienced more bleeding events (n = 49 (23.1%) versus n = 5 (4.3%), p < 0.001). Major drivers of events were gastrointestinal (GI) bleeding (n = 18 (36.7%)]. HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) score (hazard ratios (HR) of 2.15 (95% confidence interval (CI) 1.65–2.79, p < 0.001)) was the strongest independent predictor for overall bleeding. In the subgroup of GI bleeding, mean right atrial pressure (mRAP: HR of 1.13 (95% CI 1.03–1.25, p = 0.013)) and HAS-BLED score (HR of 1.74 (95% CI 1.15–2.64, p = 0.009)] remained significantly associatiated with bleeding events after adjustment. mRAP provided additional prognostic value beyond the HAS-BLED score with an improvement from 0.63 to 0.71 (95% CI 0.58–0.84, p for comparison 0.032), by C-statistic. This additional prognostic value was confirmed by significant improvements in net reclassification index (61.3%, p = 0.019) and integrated discrimination improvement (3.4%, p = 0.015). Conclusion. OAC-treated HFpEF patients are at high risk of GI bleeding. High mRAP as an indicator of advanced stage of disease was predictive for GI bleeding events and provided additional risk stratification information beyond that obtained by HAS-BLED score.

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