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

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 >5.5 mmol/L) and moderate/severe hyperkalaemia (>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

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Towards quadruple therapy for heart failure with reduced ejection fraction: DAPA-HF secondary analysis data

Russian Journal of Cardiology ◽

10.15829/1560-4071-2020-3870 ◽

2020 ◽

Vol 25 (5) ◽

pp. 3870

Author(s):

Zh. D. Kobalava ◽

V. V. Medovchshikov ◽

N. B. Yeshniyazov

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Sglt2 Inhibitor ◽

Secondary Analysis ◽

Analysis Data ◽

Adverse Outcomes ◽

Reduced Ejection Fraction ◽

Sodium Glucose Cotransporter ◽

Patients With Heart Failure ◽

First Time

Patients with heart failure with reduced ejection fraction (HFrEF), despite optimal evidence-based treatment, have a high residual risk of adverse outcomes. The favorable results of studies on cardiovascular safety and the effectiveness of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes (T2D), including outcomes associated with heart failure, were the reason for studying the effectiveness in patients with HFrEF regardless of the T2D status. For the first time in the DAPA-HF study, the SGLT2 inhibitor dapagliflozin in patients with HFrEF showed a positive effect on hard endpoints. Data of the secondary analysis confirmed the effectiveness of dapagliflozin regardless of the T2D status, therapy, age, and quality of life. The results of DAPA-HF have become a serious statement for changing the standards of the guideline-recommended therapy of HFrEF.

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Prognostic value of global longitudinal layer specific strain for patients with heart failure with reduced ejection fraction

European Heart Journal ◽

10.1093/ehjci/ehaa946.0117 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

C Johnsen ◽

M Sengeloev ◽

P Joergensen ◽

N Bruun ◽

D Modin ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Prognostic Value ◽

Left Ventricular ◽

Volume Index ◽

Funding Source ◽

Reduced Ejection Fraction ◽

Patients With Heart Failure ◽

All Cause Mortality ◽

Echocardiographic Parameters

Abstract Background Novel echocardiographic software allows for layer-specific evaluation of myocardial deformation by 2-dimensional speckle tracking echocardiography. Endocardial, epicardial- and whole wall global longitudinal strain (GLS) may be superior to conventional echocardiographic parameters in predicting all-cause mortality in patients with heart failure with reduced ejection fraction (HFrEF). Purpose The purpose of this study was to investigate the prognostic value of endocardial-, epicardial- and whole wall GLS in patients with HFrEF in relation to all-cause mortality. Methods We included and analyzed transthoracic echocardiographic examinations from 1,015 patients with HFrEF. The echocardiographic images were analyzed, and conventional and novel echocardiographic parameters were obtained. A p value in a 2-sided test <0.05 was considered statistically significant. Cox proportional hazards regression models were constructed, and both univariable and multivariable hazard ratios (HRs) were calculated. Results During a median follow-up time of 40 months, 171 patients (16.8%) died. A lower endocardial (HR 1.17; 95% CI (1.11–1.23), per 1% decrease, p<0.001), epicardial (HR 1.20; 95% CI (1.13–1.27), per 1% decrease, p<0.001), and whole wall (HR 1.20; 95% CI (1.14–1.27), per 1% decrease, p<0.001) GLS were all associated with higher risk of death (Figure 1). Both endocardial (HR 1.12; 95% CI (1.01–1.23), p=0.027), epicardial (HR 1.13; 95% CI (1.01–1.26), p=0.040) and whole wall (HR 1.13; 95% CI (1.01–1.27), p=0.030) GLS remained independent predictors of mortality in the multivariable models after adjusting for significant clinical parameters (age, sex, total cholesterol, mean arterial pressure, heart rate, ischemic cardiomyopathy, percutaneous transluminal coronary angioplasty and diabetes) and conventional echocardiographic parameters (left ventricular (LV) ejection fraction, LV mass index, left atrial volume index, deceleration time, E/e', E-velocity, E/A ratio and tricuspid annular plane systolic excursion). No other echocardiographic parameters remained an independent predictors after adjusting. Furthermore, endocardial, epicardial and whole wall GLS had the highest C-statistics of all the echocardiographic parameters. Conclusion Endocardial, epicardial and whole wall GLS are independent predictors of all-cause mortality in patients with HFrEF. Furthermore, endocardial, epicardial and whole wall GLS were superior prognosticators of all-cause mortality compared with all other echocardiographic parameters. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Herlev and Gentofte Hospital

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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 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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Efficacy of Dapagliflozin on Renal Function and Outcomes in Patients with Heart Failure with Reduced Ejection Fraction: Results of DAPA-HF

Circulation ◽

10.1161/circulationaha.120.050391 ◽

2020 ◽

Cited By ~ 4

Author(s):

Pardeep S. Jhund ◽

Scott D. Solomon ◽

Kieran F. Docherty ◽

Hiddo J.L. Heerspink ◽

Inder S. Anand ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Kidney Function ◽

Adverse Outcomes ◽

Renal Outcome ◽

Pharmacological Management ◽

Reduced Ejection Fraction ◽

Patients With Heart Failure ◽

Rate Of Decline

Background: Many patients with heart failure and reduced ejection fraction (HFrEF) have chronic kidney disease (CKD) which complicates pharmacological management and is associated with worse outcomes. We assessed the safety and efficacy of dapagliflozin in patients with HFrEF, according to baseline kidney function, in the Dapagliflozin and Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF). We also examined the effect of dapagliflozin on kidney function after randomization. Many patients with heart failure and reduced ejection fraction (HFrEF) have chronic kidney disease (CKD) which complicates pharmacological management and is associated with worse outcomes. We assessed the safety and efficacy of dapagliflozin in patients with HFrEF, according to baseline kidney function, in the Dapagliflozin and Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF). We also examined the effect of dapagliflozin on kidney function after randomization. Methods: HFrEF patients with or without type 2 diabetes and an estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73m 2 were enrolled in DAPA-HF. We calculated the incidence of the primary outcome (CV death or worsening HF) according to eGFR category at baseline (<60 and ≥60 ml/min/1.73m 2 ) as well as using eGFR at baseline as a continuous measure. Secondary cardiovascular outcomes and a pre-specified composite renal outcome (≥ 50% sustained decline eGFR, end stage renal disease (ESRD) or renal death) were also examined, along with decline in eGFR over time. Results: Of 4742 with a baseline eGFR, 1926 (41%) had eGFR <60 ml/min/1.73m 2 . The effect of dapagliflozin on the primary and secondary outcomes did not differ by eGFR category or examining eGFR as a continuous measurement. The hazard ratio (95% confidence interval (CI)) for the primary endpoint in patients with CKD was 0.71 (0.59, 0.86) vs. 0.77 (0.64, 0.93) in those with an eGFR ≥60 ml/min/1.73m 2 (interaction p=0.54). The composite renal outcome was not reduced by dapagliflozin (HR=0.71, 95% CI 0.44, 1.16; p=0.17) but the rate of decline in eGFR between day 14 and 720 was less with dapagliflozin, -1.09 (-1.41, -0.78) vs. placebo -2.87 (-3.19, -2.55) ml/min/1.73m 2 per year (p<0.001). This was observed in those with and without type 2 diabetes (p for interaction=0.92) Conclusions: Baseline kidney function did not modify the benefits of dapagliflozin on morbidity and mortality in HFrEF and dapagliflozin slowed the rate of decline in eGFR, including in patients without diabetes. Clinical Trial Registration: https://clinicaltrials.gov Unique Identifier: NCT03036124

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CHA2DS2-VASc score and adverse outcomes in patients with heart failure with reduced ejection fraction and sinus rhythm

European Journal of Heart Failure ◽

10.1002/ejhf.613 ◽

2016 ◽

Vol 18 (10) ◽

pp. 1261-1266 ◽

Cited By ~ 14

Author(s):

Siqin Ye ◽

Min Qian ◽

Bo Zhao ◽

Richard Buchsbaum ◽

Ralph L. Sacco ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Sinus Rhythm ◽

Adverse Outcomes ◽

Reduced Ejection Fraction ◽

Patients With Heart Failure

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Dapagliflozin and the Incidence of Type 2 Diabetes in Patients With Heart Failure and Reduced Ejection Fraction: An Exploratory Analysis From DAPA-HF

10.2337/figshare.13235543 ◽

2020 ◽

Author(s):

Silvio E Inzucchi ◽

Kieran F Docherty ◽

Lars Køber ◽

Mikhail N Kosiborod ◽

Felipe A Martinez ◽

...

Keyword(s):

Heart Failure ◽

Type 2 Diabetes ◽

Ejection Fraction ◽

Sglt2 Inhibitor ◽

Adverse Outcomes ◽

Exploratory Analysis ◽

Diabetes Incidence ◽

Reduced Ejection Fraction ◽

Patients With Heart Failure

Objective The SGLT2 inhibitor dapagliflozin reduced the risk of cardiovascular mortality and worsening heart failure in the <a>Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure </a>trial (DAPA-HF). This report explores the effect of dapagliflozin on incident type 2 diabetes in the non-diabetic cohort enrolled in the trial. Research Design/Methods The subgroup of 2605 patients with heart failure and reduced ejection fraction (HFrEF), no prior history of diabetes, and a HbA1c of <6.5% at baseline was randomized to dapagliflozin 10 mg daily or placebo. In this exploratory analysis, surveillance for new onset diabetes was accomplished through periodic HbA1c testing as part of the study protocol and comparison between the treatment groups assessed through a Cox proportional hazards model. Results At baseline, the mean HbA1c was 5.8%. At 8 months, there were minimal changes, with a placebo-adjusted change in the dapagliflozin group of -0.04%. Over a median follow-up of 18 months, diabetes developed in 93/1307 patients (7.1%) in the placebo group and 64/1298 (4.9%) in the dapagliflozin group. Dapagliflozin led to a 32% reduction in diabetes incidence (HR 0.68, 95% CI, 0.50-0.94; p=0.019.) More than 95% of the participants who developed type 2 diabetes had prediabetes at baseline (HbA1c 5.7-6.4%.) Participants who developed diabetes in DAPA-HF had a higher subsequent mortality than those who did not. Conclusions In this exploratory analysis among patients with HFrEF, treatment with dapagliflozin reduced the incidence of new diabetes. This potential benefit needs confirmation in trials of longer duration and in people without heart failure.

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Dapagliflozin and the Incidence of Type 2 Diabetes in Patients With Heart Failure and Reduced Ejection Fraction: An Exploratory Analysis From DAPA-HF

10.2337/figshare.13235543.v1 ◽

2020 ◽

Author(s):

Silvio E Inzucchi ◽

Kieran F Docherty ◽

Lars Køber ◽

Mikhail N Kosiborod ◽

Felipe A Martinez ◽

...

Keyword(s):

Heart Failure ◽

Type 2 Diabetes ◽

Ejection Fraction ◽

Sglt2 Inhibitor ◽

Adverse Outcomes ◽

Exploratory Analysis ◽

Diabetes Incidence ◽

Reduced Ejection Fraction ◽

Patients With Heart Failure

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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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Validation of the HFA-PEFF- and H2FPEF score in Japanese patients with heart failure with preserved ejection fraction

European Heart Journal ◽

10.1093/ehjci/ehaa946.0998 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

K Iwakura ◽

T Onishi ◽

M Okada ◽

K Inoue ◽

Y Koyama ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Global Longitudinal Strain ◽

Japanese Patients ◽

Mean Value ◽

Diagnostic Tools ◽

Funding Source ◽

Preserved Ejection Fraction ◽

Private Company ◽

Patients With Heart Failure

Abstract Background Diagnosing heart failure with preserved ejection fraction (HFpEF) still remains challenging, and simple and reliable diagnostic tools have been required. Recently, novel and evidence-based diagnostic algorithms for HFpEF were proposed, such as H2FPEF score (Circulation. 2018) and HFA-PEFF score (Eur Heart J 2019), and their accuracy was validated in the outside patient group. However, there are regional and ethnic variations in patient characteristics of HFpEF, particularly between Western and Asian countries, and it is not elucidated whether these diagnostic scores are useful in Asian population. Purpose To investigate the validity of the HFA-PEFF- and H2FPEF score in Japanese patients with HFpEF. Methods We calculated H2FPEF score and the second step of HFA-PEFF score among the registered patients in the PURSUIT-HFpEF (Prospective, Multicenter, Observational Study of Patients with Heart Failure with Preserved Ejection Fraction) study, which is a multicenter registration of patients hospitalized for HFpEF. The obtained scores were compared with the scores of the HFpEF cohort in the previous validation studies. We followed the study patients for median of 360 days (IQR 237–630 days) to observe the major adverse cardiovascular events (MACE; composite of death, heart failure hospitalization and stroke). Results We enrolled 757 patients hospitalized for HFpEF between June 2016 and August 2019 for the present study. H2FPEF score was obtained in 588 (77.7%) patients among them. Compared with the HFpEF cohorts in the previously reported sub-analysis of TOPCAT trial, the PURSUIT-HFpEF cohort had lower mean value of HFpEF score (4.0±1.8 points vs. 6.0±2.0 points in Americans or 5.3±1.9 points in Russians). It had significantly higher proportion (40.3%, p<0.001) of patients in the low likelihood of HFpEF category (0–3 points) than the TOPCAT cohorts (8.0% in Americans and 19.6% in Russians). HFA-PEFF score was obtained in 615 (81.2%) patients, though global longitudinal strain was not available. The mean value of HFA-PEFF score was 5.0±0.8, and all patients had ≥2 points. The proportion of patients in the high likelihood of HFpEF category (5–6 points) was 88.3%, which was significantly higher (p<0.001) than those of the HFpEF cohort from Europe and USA in the previous validation study (Eur J Heart Fail 2019). There was no correlation between H2FPEF score and HFA-PEFF score (R=0.06, p=0.14). Cox proportional hazard model selected HFA-PEFF score as a significant predictor for MACE during follow-up period, whereas H2PEF score was not selected. Kaplan-Meier survival analysis demonstrated that patients with 6 points of HFA-PEFF score had higher incidence rate of MACE than those with ≤5 points (p=0.002). Conclusion The HFA-PEFF score could be more useful for the diagnosis and risk stratification for HFpEF than the H2PEF score in the Japanese cohort. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Roche Diagnostics K.K.; Fuji Film Toyama Chemical Co. Ltd.

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