Abstract 16374: Effect of Dapagliflozin According to Duration of Heart Failure: An Analysis of the DAPA-HF Trial

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Su E Yeoh ◽  
Kieran Docherty ◽  
Silvio E Inzucchi ◽  
Lars Kober ◽  
Mikhail Kosiborod ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cox Regression ◽  
Sglt2 Inhibitor ◽  
Patient Characteristics ◽  
Cardiovascular Death ◽  
Reduced Ejection Fraction ◽  
Duration Threshold ◽  
Effect Of Treatment ◽  
The Relationship

Introduction: The relationship between duration of heart failure (HF), patient characteristics, outcomes, and the effect of treatment is largely unknown. We investigated these questions in DAPA-HF. Hypothesis: We hypothesized that longer HF duration is associated with worse outcomes and that, compared with placebo, the benefit of the SGLT2 inhibitor, dapagliflozin, is consistent, irrespective of HF duration, in patients with HF and reduced ejection fraction (HFrEF). Methods: HF duration was categorised as 0-1, >1-2, >2-5 and >5 years. Outcomes were adjusted for prognostic variables and analysed using Cox regression. The primary endpoint was the composite of worsening HF or cardiovascular death. Treatment effect (dapagliflozin versus placebo) was examined within each duration category and by duration threshold. Results: The number patients in each category was: 1098 (0-1 year), 686 (>1-2 years), 1105 (>2-5 years) and 1855 (>5 years). Patients with longer-duration HF were older and more comorbid with worse quality of life. The primary outcome rate (per 100 person-years) increased with HF duration: 10.2 (95% CI 8.7-12.0) for the 0-1-year group, 10.6 (8.7-12.9) for >1-2 years, 15.5 (13.6-17.7) for >2-5 years and 15.9 (14.5-17.6) for >5 years. The adjusted hazard ratio was 0.98 (95% CI 0.75-1.27), 1.52 (1.22-1.89) and 1.60 (1.31-1.96) respectively, for >1-2, >2-5 and >5 years compared with 0-1 years. Similar trends were seen for all other outcomes. The benefit of dapagliflozin was consistent across HF duration for all outcomes and on threshold analysis (Figure). Conclusion: Patients with longer-duration HF had higher rates of worsening HF and death. The benefit of dapagliflozin was consistent irrespective of HF duration. Starting dapagliflozin has substantial benefits, even in patients with longstanding HFrEF.

Abstract 16587: More Than Five Years After FDA Approval, There Remains Very Limited Adoption of New Evidence-Based, Highly Effective Medications for the Treatment of Patients With Heart Failure, Especially Among Those on Medicare

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Joseph B Muhlestein ◽  
Heidi T May ◽  
Tami L Bair ◽  
Stacey Knight ◽  
Kirk U Knowlton ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cox Regression ◽  
Sglt2 Inhibitor ◽  
Clinical Effectiveness ◽  
Major Adverse Cardiovascular Events ◽  
Evidence Based ◽  
Cox Regression Analysis ◽  
Reduced Ejection Fraction ◽  
Highly Effective ◽  
Baseline Characteristics

Background: Over the past decade, the FDA has approved several new medications that are highly effective when added to existing standard therapy in the treatment of heart failure with reduced ejection fraction (HFrEF). It is possible that, despite the presence of substantial evidence regarding the clinical effectiveness of these new medications, their high cost and the complex medical reimbursement system in America may prevent their routine adoption. Methods: We analyzed 5,824 Intermountain Healthcare patients, age ≥18 years with a new clinical diagnosis of HFrEF (LVEF ≤35%), from 1/1/2015 onward, for the use of newly-approved sacubitril/valsartan or any sodium-glucose cotransporter-2 inhibitor (SGLT2-I). We collected baseline characteristics and medication utilization data. We followed the patients for 1.7±1.4 years for future major adverse cardiovascular events (MACE), including death, myocardial infarction (MI), stroke, and heart failure hospitalization (HFH). We identified differences between groups by multivariable Cox regression analysis. Results: Baseline characteristics and incidence of MACE, according to insurance status and the use of common HFrEF medications, are shown in the Table. Overall, only 344 (5.9%) and 169 (2.9%) of patients ever received a prescription for sacubitril/valsartan or an SGLT2 inhibitor, respectively. The figures show survival curves for MACE of patients receiving or not receiving the newly-approved medications. Conclusion: In this large, modern, real-world HFrEF population, the adoption of newly-approved evidence-based HFrEF medications is minimal in all patients and especially in Medicare patients. This lack of adoption is associated with a significant worsening in patient outcomes. These findings demonstrate a critical need to resolve our present healthcare financial crisis, which is almost certainly the reason for these findings.

scholarly journals EMPEROR-Preserved: SGLT2 inhibitors breakthrough in the management of heart failure with preserved ejection fraction

2021 ◽  
Vol 2021 (3) ◽  
Author(s):  
Kerolos Wagdy ◽  
Sherif Nagy
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Complex Disease ◽  
Hospital Admissions ◽  
Sglt2 Inhibitor ◽  
Cardiovascular Death ◽  
Sglt2 Inhibitors ◽  
Preserved Ejection Fraction ◽  
Reduced Ejection Fraction ◽  
Sglt2 Inhibition

Background: Heart failure with preserved ejection fraction (HFpEF) is a complex disease which accounts for more than half of all HF hospital admissions with high prevalence and lack of effective evidence-based management. Sodium-glucose cotransporter 2 (SGLT2) inhibitor is a new antidiabetic drug that recently gained a new role in the management of heart failure with reduced ejection fraction but its role in HFpEF had yet to be studied.Study and results: EMPEROR-Preserved trial set out to evaluate the effects of SGLT2 inhibition with empagliflozin on major heart failure outcomes in patients with HFpEF. The patients were randomized in a 1:1 fashion into two groups; to receive either empagliflozin 10 mg per day (n = 2,997) or placebo (n = 2,991) in addition to usual therapy. Empagliflozin led to a 21% risk reduction of the composite of cardiovascular death or hospitalization for heart failure, which was mainly related to a 29% lower risk of hospitalization for heart failure rather than effect on cardiovascular death empagliflozin. The effects SGLT2 inhibitors were consistent in all patients.

Plasma Proteomic Profile Predicts Survival in Heart Failure with Reduced Ejection Fraction

2021 ◽  
Author(s):  
Hongsheng Gui ◽  
Ruicong She ◽  
Jasmine Luzum ◽  
Jia Li ◽  
Timothy D. Bryson ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Risk Stratification ◽  
Risk Score ◽  
Cox Regression ◽  
Clinical Score ◽  
Cardiovascular Death ◽  
Reduced Ejection Fraction ◽  
C Statistic ◽  
Kaplan Meier

Background - It remains unclear whether the plasma proteome adds value to established predictors in heart failure (HF) with reduced ejection fraction (HFrEF). We sought to derive and validate a plasma proteomic risk score for survival in HFrEF patients (HFrEF-PRS). Methods - Patients meeting Framingham criteria for HF with EF<50% were enrolled (n=1017) and plasma underwent SOMAscan® profiling (4453 targets). Patients were randomly divided 2:1 into derivation and validation cohorts. The HFrEF-PRS was derived using Cox regression of all-cause mortality adjusted for clinical score and N-Terminal pro-B-Type Natriuretic Peptide (NTproBNP), then was tested in the validation cohort. Risk stratification improvement was evaluated by C-statistic, integrated discrimination index (IDI), continuous net reclassification index (NRI), and median improvement in risk score (MIRS) for 1-year and 3-year mortality. Results - Participants' mean age was 68 years, 48% identified as African American, 35% were female and 296 deaths occurred. In derivation (n=681), 128 proteins associated with mortality, 8 comprising the optimized HFrEF-PRS. In validation (n=336) the HFrEF-PRS associated with mortality (hazard ratio (HR) =2.27 [95% Confidence interval (95%CI) 1.84-2.82], p =6.3x10 -14 ), Kaplan-Meier curves differed significantly between HFrEF-PRS quartiles ( p =2.2x10 -6 ), and it remained significant after adjustment for clinical score and NTproBNP (HR=1.37, 95%CI 1.05-1.79, p =0.021). The HFrEF-PRS improved metrics of risk stratification (C-statistic change=0.009, p =0.612; IDI=0.041, p =0.010; NRI=0.391, p =0.078; MIRS=0.039, p =0.016) and associated with cardiovascular death and HF phenotypes (e.g. 6-minute walk distance, EF change). Most HFrEF-PRS proteins had little known connection to HFrEF. Conclusions - A plasma multi-protein score improved risk stratification in HFrEF patients and identified novel candidates.

scholarly journals Effects of canagliflozin on cardiovascular death and hospitalization for heart failure by baseline estimated glomerular filtration rate: integrated analyses from the CANVAS Program and CREDENCE

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K.W Mahaffey ◽  
G Bakris ◽  
J Blais ◽  
C.P Cannon ◽  
D Cherney ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cox Regression ◽  
Sglt2 Inhibitor ◽  
Cardiovascular Death ◽  
Funding Source ◽  
Private Company ◽  
Interaction Terms ◽  
Hazard Ratios ◽  
Death Event ◽  
Cv Disease

Abstract Background People with type 2 diabetes mellitus (T2DM) have a greater risk of cardiovascular (CV) disease, including hospitalization for heart failure (HHF), a complication that is more common as renal function declines. The sodium glucose co-transporter 2 (SGLT2) inhibitor canagliflozin (CANA) reduced the risk of HHF in patients with T2DM and high CV risk or nephropathy in the CANVAS Program and CREDENCE trials, respectively. Methods This post hoc analysis included integrated, pooled data from the CANVAS Program and the CREDENCE trial. The effects of CANA compared with placebo on CV death or HHF, HHF, and CV death were assessed in subgroups defined by baseline eGFR (&lt;45, 45–60, and &gt;60 mL/min/1.73 m2). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models, with subgroup by treatment interaction terms added to test for heterogeneity. Interaction P values were calculated by including treatment group and baseline eGFR in the model. Results A total of 14,543 participants from the CANVAS Program (N=10,142) and CREDENCE (N=4,401) were included, with mean age, 65 y; 65% male; 75% white; mean eGFR 70.3 mL/min/1.73 m2. 1919 (13.2%) participants had baseline eGFR &lt;45 mL/min/1.73 m2 (mean, 36.7 mL/min/1.73 m2), 2972 (20.4%) participants had eGFR 45–60 mL/min/1.73 m2 (mean, 53.1 mL/min/1.73 m2), and 9649 (66.3%) participants had eGFR &gt;60 mL/min/1.73 m2 (mean, 82.3 mL/min/1.73 m2). Rates of CV death or HHF, HHF, and CV death increased as eGFR declined (Figure). CANA significantly reduced the risk of CV death or HHF and HHF compared with PBO, with consistent effects observed across subgroups. Conclusions CV death or HHF, HHF, and CV death event rates increased with lower baseline eGFR. CANA significantly reduced the risk of CV death or HHF, jointly and individually, in participants with T2DM and high CV risk or CKD in the CANVAS Program and the CREDENCE trial, with consistent benefits observed regardless of baseline eGFR. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Janssen Scientific Affairs, LLC

scholarly journals Effects of SGLT2 inhibitor dapagliflozin in patients with heart failure with reduced ejection fraction

2020 ◽  
Vol 25 (8) ◽  
pp. 4049
Author(s):  
N. R. Khasanov
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Drug Class ◽  
Sglt2 Inhibitor ◽  
Cardiovascular Death ◽  
Sglt2 Inhibitors ◽  
Reduced Ejection Fraction ◽  
Patients With Heart Failure ◽  
Recommended Therapy

SGLT2 inhibitors have been shown to reduce the risk of cardiovascular events and the development and decompensation of heart failure (HF) in patients with type 2 diabetes (T2D). The improved prognosis in HF may be related not only to the hypoglycemic effect of this drug class. The DAPA-HF study, which included patients with HF with reduced ejection fraction, demonstrated the benefit of dapagliflozin in reducing the risk of cardiovascular death and worsening HF, as well as improving HF symptoms compared to placebo, regardless of the presence of T2D and the recommended therapy for HF.

scholarly journals Pressure–volume loop validation of TAPSE/PASP for right ventricular arterial coupling in heart failure with pulmonary hypertension

2020 ◽  
Author(s):  
Alexander Schmeisser ◽  
Thomas Rauwolf ◽  
Thomas Groscheck ◽  
Siegfried Kropf ◽  
Blerim Luani ◽  
...  
Keyword(s):  
Heart Failure ◽  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Cox Regression ◽  
Area Under The Curve ◽  
Characteristic Analysis ◽  
Reduced Ejection Fraction ◽  
Prognostic Assessment ◽  
Relationship Of ◽  
The Relationship

Abstract Aims The aim of this study was to validate the tricuspid annular plane systolic excursion/systolic pulmonary artery (PA) pressure (TAPSE/PASP) ratio with the invasive pressure–volume (PV) loop-derived end-systolic right ventricular (RV) elastance/PA elastance (Ees/Ea) ratio in patients with heart failure with reduced ejection fraction (HFREF) and secondary pulmonary hypertension (PH). Methods and results The relationship of TAPSE and TAPSE/PASP with RV-PV loop (single-beat)-derived contractility Ees, afterload Ea, and Ees/Ea was assessed in 110 patients with HFREF with and without secondary PH. The results were compared with other surrogate parameters such as the fractional area change/PASP ratio. The association of the surrogates with all-cause mortality was evaluated. In patients with PH (n = 74, 67%), TAPSE significantly correlated with Ees (r = 0.356), inverse with Ea (r = −0.514) but was most closely associated with Ees/Ea (r = 0.77). Placing TAPSE in a ratio with PASP slightly reduced the relationship to Ees/Ea (r = 0.71) but was more closely related to the parameters of PA vascular load, diastolic RV function, and RV energetics. The area under the curve of TAPSE/PASP and TAPSE for discriminating overall survival in receiver operating characteristic analysis was not different (P = 0.78. Prognostic relevant cut-offs were 17 mm for TAPSE and 0.38 mm/mmHg for TAPSE/PASP. Both parameters in multivariate cox regression remained independently prognostically relevant. Conclusion TAPSE is an easily and reliably obtainable and valid surrogate parameter for RV–PA coupling in PH due to HFREF. Putting TAPSE into a ratio with PASP did not further improve the coupling information or prognostic assessment. Trial Identifier DRKS—German Clinical Trials Register (DRKS00011133; https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00011133).

The relationship between clinical parameters and natriuretic peptides and quality of life in patients with heart failure with reduced ejection fraction

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
F Sawczak ◽  
A Kukfisz ◽  
K Przytarska ◽  
M Szczechla ◽  
H Krysztofiak ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Heart Failure ◽  
Ejection Fraction ◽  
Natriuretic Peptides ◽  
Nyha Class ◽  
Clinical Parameters ◽  
Reduced Ejection Fraction ◽  
Patients With Heart Failure ◽  
The Relationship

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Heart failure (HF) patients are exposed to severe symptoms of the disease, fatal prognosis, rehospitalizations and low quality of life status. Furthermore, it was observed that more patients with HF would rather live better than longer. Purpose The aim of the study was to determine the relationship between clinical parameters, natriuretic peptides level and quality of life (QoL) in patients with heart failure with reduced ejection fraction. Methods 111 patients hospitalized due to heart failure with reduced ejection fraction (HFrEF) were examined using WHOQOL-BREF questionnaire and divided into three groups of similar quantity due to their transformed score of somatic domain of QoL: first group with score &lt;45 - worst QoL (n = 33), second group with score between 45 and 55 (n = 42), and third with score &gt;55 - best QoL (n = 36). Then the group with highest scores, with best somatic QoL, was compared with those with lowest scores in respect of chosen clinical and biochemical parameters. Results Patients with the highest somatic domain score, comparing with the lowest, had significantly higher BMI (mean 29.8 ± 5.5 vs. 26.8 ± 5.7 kg/m2, p = 0.016), lower BNP level (465 vs. 967 pg/ml, median 275 vs. 690, p =0.005), higher LVEF (30.7 ± 12.0 vs. 23.9 ± 10.8%, p = 0.006), higher triglycerides level (2.02 ± 1.22 vs. 1.43 ± 0.76 mmol/l, p = 0.027) and iron level (17.8 ± 6.6 vs. 13.6 ± 5.5 µmol/l, p = 0.019) as well as transferrin saturation (28.0 ± 11.0 vs. 21.3 ± 8.9 %, p = 0.015). The percentage of patients with NYHA class I and II was higher in the group with the highest somatic domain score in comparison with the lowest (66.6% vs. 33.3% respectively, p = 0.034). Conclusions The somatic domain of WHOQOL-BREF in patients with HFrEF correlates with patients’ clinical state assessed with the NYHA class and BNP level. QoL status was not associated with age and gender which are depicted in the literature as the important aspects influencing QoL of the community.

Evaluation of the Efficacy of ST2 and NT-proBNP in the Diagnosis and Prediction of Short- Term Prognosis in Heart Failure with Reduced Ejection Fraction

2017 ◽  
Vol 9 (04) ◽  
Author(s):  
Shivananda B Nayak ◽  
Dharindra Sawh ◽  
Brandon Scott ◽  
Vestra Sears ◽  
Kareshma Seebalack ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Cardiac Biomarkers ◽  
Double Blind Study ◽  
Short Term ◽  
Double Blind ◽  
Reduced Ejection Fraction ◽  
The Mean ◽  
Design And Methods ◽  
The Relationship

Purpose: i) To determine the relationship between the cardiac biomarkers ST2 and NT-proBNP with ejection fraction (EF) in heart failure (HF) patients. ii) Assess whether a superiority existed between the aforementioned cardiac markers in diagnosing the HF with reduced EF. iii) Determine the efficacy of both biomarkers in predicting a 30-day cardiovascular event and rehospitalization in patients with HF with reduced EF iv) To assess the influence of age, gender, BMI, anaemia and renal failure on the ST2 and NT-proBNP levels. Design and Methods: A prospective double-blind study was conducted to obtain data from a sample of 64 cardiology patients. A blood sample was collected to test for ST2 and NT-proBNP. An echocardiogram (to obtain EF value), electrocardiogram and questionnaire were also obtained. Results: Of the 64 patients enrolled, 59.4% of the population had an EF less than 40%. At the end of the 30- day period, 7 patients were warded, 37 were not warded, one died and 17 were non respondent. Both biomarkers were efficacious at diagnosing HF with a reduced EF. However, neither of them were efficacious in predicting 30-day rehospitalization. The mean NT-proBNP values being: not rehospitalized (2114.7486) and 30 day rehospitalization (1008.42860) and the mean ST2 values being: not rehospitalized (336.1975), and 30-day rehospitalization. (281.9657). Conclusion: Neither ST2 or NT-proBNP was efficacious in predicting the short- term prognosis in HF with reduced EF. Both however were successful at confirming the diagnosis of HF in HF patients with reduced EF.

scholarly journals Clinical significance of Q waves in ischemic cardiomyopathy

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
E Rodenas Alesina ◽  
P Jordan ◽  
L Herrador ◽  
C Espinet-Coll ◽  
N Pizzi ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Primary Endpoint ◽  
Ischemic Cardiomyopathy ◽  
Cox Regression ◽  
Cox Model ◽  
Cardiovascular Death ◽  
P Value ◽  
Heart Failure Hospitalization ◽  
Total Cohort

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): CIBER-CV AIMS The scintigraphic translation of Q waves in patients with ischemic cardiomyopathy and LVEF &lt; 40% has not yet been assessed. The aim of this study was to explore the relationship between Q waves and necrotic tissue and to analyze their impact in prognosis. METHODS AND RESULTS A retrospective study enrolling 487 consecutive patients (67,0 [57,4 – 75,4] years), with ischemic cardiomyopathy, LVEF &lt;40% and narrow QRS who underwent stress-rest SPECT was conducted. Patients with Q waves (320 patients [65,7%]) had less comorbidity and ischemia, but more necrosis. Q waves correlated poorly with lack of viability (AUC = 0,63) and were independently associated with the subendocardial extent of the necrosis. After a follow-up of 5,07 years, the primary outcome (cardiovascular death, heart failure hospitalization or myocardial infarction) occurred in 192 (39,4%) patients, without differences between groups in multivariate analysis. After accounting for non-cardiovascular death as a competitive risk, the interaction between &gt;10% of ischemia and revascularization remained in Cox model both in the total cohort (aHR= 0,46 [0,24 – 0,86]), and in patients with Q waves (aHR = 0,27 [0,11–0,69]). CONCLUSION Patients with ischemic cardiomyopathy with Q waves have larger subendocardial scarring and more transmural necrosis, although correlation between Q waves and transmural scarring is poor. Revascularization if &gt;10% ischemia is present is associated with a better prognosis. Ischemia burden should be assessed and accordingly treated in these patients, and no differences in management should be made in the presence of Q waves. Table 1. Cox proportional hazards model Total cohort (N = 471) Patients with Q waves (N = 315) aHR p-value 95% CI aHR p-value 95% CI Age (per year) 1,02 0,007 1,01 - 1,04 n.s. Diabetes mellitus 1,35 0,047 1,00 - 1,81 1,54 0,016 1,09 - 2,20 eGFR &lt; 60 ml/min 1,59 0,005 1,15 - 2,21 1,96 &lt;0,001 1,36 - 2,82 Previous HF hospitalization 1,71 0,002 1,23 - 2,38 1,76 0,007 1,17 - 2,64 Previous PCI 1,32 0,069 0,98 - 1,78 n.s. Previous CABG n.s. 1,77 0,009 1,15 - 2,72 Angina or dyspnea 1,68 0,001 1,24 - 2,28 1,71 0,004 1,19 - 2,46 Indexed TDV (per quartile) 1,16 0,047 1,02 - 1,33 n.s. Revascularization*ischemia &gt; 10% 0,46 0,015 0,24 - 0,86 0,27 0,006 0,11 - 0,69 Cox regression for the primary endpoint (cardiovascular death, heart failure hospitalization or myocardial infarction), accounting for non-cardiovascular death as a competitive risk. Abstract Figure. Survival for the primary endpoint

O107 Depressive symptoms mediate the relationship between sleep quality and health-related quality of life in heart failure

Global Heart ◽  
2014 ◽  
Vol 9 (1) ◽  
pp. e29
Author(s):  
An-Yun Yeh ◽  
Susan J. Pressler ◽  
Seongkum Heo ◽  
Debra K. Moser ◽  
Sandra B. Dunbar ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Heart Failure ◽  
Depressive Symptoms ◽  
Sleep Quality ◽  
Health Related Quality ◽  
Related Quality ◽  
Health Related ◽  
The Relationship
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