Right ventricular dysfunction by 3D echocardiography is the best predictor for death and re-hospitalization in patients with heart failure with reduced ejection fraction

Abstract Background In patients with heart failure with reduced ejection fraction (HFrEF), right ventricular (RV) size and dysfunction by 2-dimensional echocardiography (2DE) were identified as risk factors for mortality and morbidity, but 3-dimensional echocardiography (3DE) enabled itself as a more reproducible and accurate method. Aim To assess the comparative prognostic value of parameters of RV size and dysfunction, measured by 2DE and 3DE, in patients with ischemic and non-ischemic HFrEF, on optimal clinical care, at long-term follow-up. Methods 142 consecutive patients (62±12 yrs, 104 males) with HFrEF, in sinus rhythm, were assessed by 2DE and 3DE, including RV full-volume acquisitions. RV diameter (RVd), RV end-systolic (RV_EDA) and end-diastolic areas (RV_ESA), RV fractional area change (RVFAC), and 2D_TAPSE were measured by 2DE. RV end-diastolic (RV_EDV) and end-systolic volumes (RV_ESV), RV ejection fraction (RV_EF), and 3D_TAPSE were measured by a dedicated 3DE software. Patients were followed for 37±16 months after the index event. Primary outcome was cardiac death (CD). Secondary outcomes were: 1) HF hospitalizations (HFH); 2) a composite cardiac events (CE) end-point of CD or HFH, myocardial infarction, coronary revascularization, arrhythmias, or CRT. Results 38 CD, 47 HFH, and 62 CE occurred during follow-up. Mean RVd was 34±7 mm, RV_EDA 20±11 cm2, RV_ESA 12±5 cm2, RV_FAC 37±13%, RV_EDV 84±25 ml/m2, RV_ESV 52±22 ml/m2, and RV_EF 39±10%. Mean 2D_TAPSE was 18±4 mm, while mean 3D_TAPSE was 16±4 mm. By 2DE, only RV_ESA and RV_FAC, but not RV_EDA or RVd, correlated with CD, HFH, and CE. 2D_TAPSE correlated with HFH, but not with CD or CE, while 3D_TAPSE correlated with all primary and secondary outcomes. By 3DE, RV_ESV, but not RV_EDV, correlated with CD, HFH, and CE. Moreover, 3D RV_EF had better correlations with primary and secondary outcomes than 2D RV_FAC (z=3.8, z=2.5, and z=2.5, all p<0.01). By multivariate linear regression analysis including RV_ESA, RV_FAC, RV_ESV, RV_EF, and 3D_TAPSE, only RV_EF was an independent predictor for CD and HFH (r2=0.68 and r2=0.30, both p<0.001). Conclusion In patients with ischemic and non-ischemic HFrEF, 3DE parameters of RV size and dysfunction are better predictors for death and re-hospitalization than 2DE parameters. The RV_EF measured by 3DE was the best predictor for death in patients with HFrEF. Funding Acknowledgement Type of funding source: None

Download Full-text

1184 Left atrial volumes by 3-dimensional but not 2-dimensional echocardiography predict cardiac death and events in patients with heart failure with reduced ejection fraction

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jez319.683 ◽

2020 ◽

Vol 21 (Supplement_1) ◽

Author(s):

A E Velcea ◽

A A Andronic ◽

R C Rimbas ◽

L M Luchian ◽

A Chitroceanu ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Cardiac Death ◽

Left Atrial ◽

Multivariate Linear Regression Analysis ◽

Reduced Ejection Fraction ◽

3 Dimensional ◽

Patients With Heart Failure ◽

Lv Volume ◽

Dimensional Echocardiography

Abstract Background Patients with heart failure with reduced ejection fraction (HFrEF) are at high risk for mortality and morbidity. Left atrial volumes (LAVs), measured by 2-dimensional echocardiography (2DE), have been suggested as possible prognostic markers. However, LAVs measured by 2DE are prone to errors due to geometric assumptions and increased variability, whereas 3-dimensional echocardiography (3DE) has been proved to be a more accurate and reproducible method for volume assessment. Purpose To assess the comparative prognostic value of LAVs, measured by 2DE and 3DE, in patients with ischemic and non-ischemic HFrEF, on best clinical care. Methods 135 consecutive patients (59 ± 15 years, 91 males), diagnosed with HFrEF, in sinus rhythm, were assessed by 2DE and 3DE, including full-volume multi-beat acquisitions of the LA and left ventricle (LV). Maximal and minimal indexed LAVs were measured from the 2DE datasets using biplane area-length formula (2D_LAVmax and 2D_LAVmin); and from the 3DE datasets using a dedicated software package (3D_LAVmax and 3D_LAVmin). Patients were followed for 23 ± 14 months after the index event. Primary outcome was cardiac death (CD); secondary outcomes were: 1) HF hospitalization (HFH); 2) a composite cardiac events (CE) end-point, of cardiac death or hospitalization for heart failure, myocardial infarction, coronary revascularization, arrhythmias, or cardiac resynchronization therapy. Results 26 CD, 32 HFH, and 48 CE occurred during follow-up. 2DE and 3DE measurements are in the table. LAVs measured by 2DE did not correlate with outcome. However, 3D_LAVmax and 3D_LAVmin correlated with CD (r = 0.40 and r = 0.38) and CE (r = 0.30 and r = 0.29), all p < 0.05, but not with HFH. By multivariate linear regression analysis, only 3D_LAVmax and 3D_LAVmin were independent predictors for CD and CE, in patients with HFrEF (r²=0.30 and r²=0.32; p < 0.01). Conclusion In patients with HFrEF, LA volumes measured by 3DE, but not by 2DE, were independent predictors for cardiac death and events. However, even LA volumes by 3DE did not have predictive value for future HF rehospitalizations. Echo features for patients with HFrEF 3D end-diastolic LV volume (ml/m2) 101 ± 32 3D end-systolic LV volume (ml/m2) 71 ± 29 3D LV ejection fraction (%) 30 ± 8 2D_LAVmax (ml/m2) 52 ± 18 2D_LAVmin (ml/m²) 31 ± 15 3D_LAVmax (ml/m2) 43 ± 18 3D_LAVmin (ml/m2) 29 ± 16

Download Full-text

Effects of Sacubitril/Valsartan on the Right Ventricular Arterial Coupling in Patients with Heart Failure with Reduced Ejection Fraction

Journal of Clinical Medicine ◽

10.3390/jcm9103159 ◽

2020 ◽

Vol 9 (10) ◽

pp. 3159

Author(s):

Daniele Masarone ◽

Vittoria Errigo ◽

Enrico Melillo ◽

Fabio Valente ◽

Rita Gravino ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Pulmonary Artery ◽

Right Ventricle ◽

Right Ventricular ◽

Ventricular Dysfunction ◽

Left Ventricular ◽

Reduced Ejection Fraction ◽

Patients With Heart Failure

Background: right ventricle-pulmonary artery (RV-PA) coupling assessed by measuring the tricuspid anular plane systolic excursion (TAPSE)/pulmonary artery systolic pressure (PASP) ratio has been recently proposed as an early marker of right ventricular dysfunction in patients with heart failure with a reduced ejection fraction (HFrEF). Methods: As the effects of sacubitril/valsartan therapy on RV-PA coupling remain unknown, this study aimed to analyse the effect of this drug on TAPSE/PASP in patients with HFrEF. We retrospectively analysed all outpatients with HFrEF referred to our unit between October 2016 and July 2018. Results: At the 1-year follow-up, sacubitril/valsartan therapy was associated with a significant improvement in TAPSE (18.26 ± 3.7 vs. 19.6 ± 4.2 mm, p < 0.01), PASP (38.3 ± 15.7 vs. 33.7 ± 13.6, p < 0.05), and RV-PA coupling (0.57 ± 0.25 vs. 0.68 ± 0.30 p < 0.01). These improvements persisted at the 2-year follow-up. In the multivariable analysis, the improvement in the RV-PA coupling was independent of the left ventricular remodelling. Conclusions: in patients with HFrEF, sacubitril/valsartan improved the RV-PA coupling; however, further trials are necessary to evaluate the role of sacubitril/valsartan in the treatment of right ventricle (RV) dysfunction either associated or not associated with left ventricular dysfunction.

Download Full-text

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

Download Full-text

Abstract 12849: Changes in N-terminal Pro Brain Natriuretic Peptide Levels Predicts Mortality and Heart Failure Hospitalization in Patients With Heart Failure and Preserved Ejection Fraction

Circulation ◽

10.1161/circ.132.suppl_3.12849 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Gianluigi Savarese ◽

Camilla Hage ◽

Ulf Dahlström ◽

Pasquale Perrone-Filardi ◽

Lars H Lund

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Brain Natriuretic Peptide ◽

Natriuretic Peptide ◽

Total Mortality ◽

Preserved Ejection Fraction ◽

Reduced Ejection Fraction ◽

Patients With Heart Failure ◽

The Impact

Introduction: Changes in N-terminal pro brain natriuretic peptide (NT-proBNP) have been demonstrated to correlate with outcomes in patients with heart failure (HF) and reduced ejection fraction (EF). However the prognostic value of a change in NT-proBNP in patients with heart failure and preserved ejection fraction (HFPEF) is unknown. Hypothesis: To assess the impact of changes in NT-proBNP on all-cause mortality, HF hospitalization and their composite in an unselected population of patients with HFPEF. Methods: 643 outpatients (age 72+12 years; 41% females) with HFPEF (ejection fraction ≥40%) enrolled in the Swedish Heart Failure Registry between 2005 and 2012 and reporting NT-proBNP levels assessment at initial registration and at follow-up were prospectively studied. Patients were divided into 2 groups according the median value of NT-proBNP absolute change that was 0 pg/ml. Median follow-up from first measurement was 2.25 years (IQR: 1.43 to 3.81). Adjusted Cox’s regression models were performed using total mortality, HF hospitalization (with censoring at death) and their composite as outcomes. Results: After adjustments for 19 baseline variables including baseline NT-proBNP, as compared with an increase in NT-proBNP levels at 6 months (NT-proBNP change>0 pg/ml), a reduction in NT-proBNP levels (NT-proBNP change<0 pg/ml) was associated with a 45.2% reduction in risk of all-cause death (HR: 0.548; 95% CI: 0.378 to 0.796; p:0.002), a 50.1% reduction in risk of HF hospitalization (HR: 0.49; 95% CI: 0.362 to 0.689; p<0.001) and a 42.6% reduction in risk of the composite outcome (HR: 0.574; 95% CI: 0.435 to 0.758; p<0.001)(Figure). Conclusions: Reductions in NT-proBNP levels over time are independently associated with an improved prognosis in HFPEF patients. Changes in NT-proBNP could represent a surrogate outcome in phase 2 HFPEF trials.

Download Full-text

Abstract 16392: The Effect of Dapagliflozin on Anemia in Patients With Heart Failure and Reduced Ejection Fraction: An Analysis of DAPA-HF

Circulation ◽

10.1161/circ.142.suppl_3.16392 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Kieran Docherty ◽

Silvio E Inzucchi ◽

Lars Kober ◽

Mikhail Kosiborod ◽

Anna Maria Langkilde ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Primary Outcome ◽

Placebo Treatment ◽

Cardiovascular Death ◽

Treatment Allocation ◽

Reduced Ejection Fraction ◽

Improved Outcomes ◽

Patients With Heart Failure

Background: Anemia is common and associated with worse outcomes in patients with heart failure and reduced ejection fraction (HFrEF). We examined: 1) whether dapagliflozin corrected anemia in these patients, and 2) the effect of dapagliflozin on outcomes, in patients with or without anemia, in DAPA-HF. Methods: Anemia was defined as baseline hematocrit <39% in men and <36% in women (WHO). Correction of anemia was defined as two consecutive hematocrit measurements above these thresholds at any time during follow-up (follow-up visits: 2 weeks, 2 and 4 months and 4-monthly thereafter). The primary outcome was a composite of worsening HF (hospitalization or urgent visit requiring intravenous therapy) or cardiovascular death. Findings: Of the 4744 patients randomized in DAPA-HF, 4691 had a baseline hematocrit and 1032 were anemic (22.0%). Anemia was corrected in 62% of patients in the dapagliflozin group, compared with 41% of patients in the placebo group (odds ratio 2.37 [95% CI 1.84-3.04]; p<0.001). The effect of dapagliflozin on the primary outcome was consistent in anemic and non-anemic patients (HR 0.68 [95% CI 0.52-0.88] versus 0.76 [0.65-0.89]; P-interaction=0.44) [Figure]. A consistent benefit was also observed for the secondary outcomes, irrespective of anemia status t baseline. Patients with resolution of anemia had better outcomes than those with persisting anemia: rate of primary outcome 9.9 per 100 patient-years (95% CI 8.0-12.4) in those with resolution versus 24.1 per 100 patient-years (20.4-28.3) in those without anemia resolution. Interpretation: Anemia was common in patients in DAPA-HF and associated with worse outcomes. Resolution of anemia was associated with better outcomes than persistence of anemia, regardless of treatment allocation. Although dapagliflozin corrected anemia more often than placebo, treatment with dapagliflozin improved outcomes, irrespective of anemia status.

Download Full-text

P2630Incidence and prognostic impact of new-onset left bundle branch block in patients with heart failure and reduced ejection fraction

European Heart Journal ◽

10.1093/eurheartj/ehz748.0953 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

S L Kristensen ◽

R Roerth ◽

P S Jhund ◽

S Beggs ◽

L Kober ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Left Bundle Branch Block ◽

Bundle Branch Block ◽

Reduced Ejection Fraction ◽

Patients With Heart Failure ◽

All Cause Mortality ◽

Qrs Duration ◽

New Onset

Abstract Background Cardiac resynchronization therapy (CRT) improves survival in patients with heart failure, reduced ejection fraction (HFrEF) and left bundle branch block (LBBB). However, little is known about the incidence of LBBB in HFrEF and the risk factors for developing this. We addressed these questions in the PARADIGM-HF and ATMOSPHERE trials. Methods We identified 7703 patients with a non-paced rhythm on their baseline ECG, a QRS<130 ms, and at least one follow-up ECG (done at annual visits and end of study). Patients were stratified by baseline QRS duration (≤100 ms - reference; 101–115 ms and 116–129 ms) and followed until development of QRS duration ≥130 ms with a LBBB configuration or latest available ECG. The crude LBBB incidence rate per 100 person-years (py) was identified in the three QRS duration subgroups. Additionally, we examined risk of the primary composite outcome of cardiovascular death or HF hospitalization, and all-cause mortality, in patients with incident LBBB vs. no incident LBBB. Results Overall, 313 of 7703 patients (4%) developed LBBB during a mean follow-up of 2.7 years, yielding an incidence rate of 1.5 per 100 py. The rate ranged from 0.9 in those with QRS ≤100 ms to 4.0 per 100 py in patients with QRS 116–129 ms. Other predictors of incident LBBB included male sex, age, lower LVEF, HF duration and absence of AF. The risk of the primary composite endpoint was higher among those who developed incident LBBB vs no incident LBBB; event rates 13.5 vs 10.0 per 100 py, yielding an adjusted HR of 1.43 (1.05–1.96). For all-cause mortality the corresponding rates were 12.6 vs 7.3 per 100 py; HR 1.55 (1.16–2.07) (Table 1). Table 1. Risk of outcomes according to incident LBBB during follow-up No. events Crude rate per 100py Adjusted* HR (95% CI) HF hospitalization or CV death No incident LBBB 2145 10.0 (9.6–10.4) 1.00 (ref.) Incident LBBB 43 13.5 (10.0–18.2) 1.43 (1.05–1.96) All-cause mortality No incident LBBB 1662 7.3 (6.9–7.6) 1.00 (ref.) Incident LBBB 48 12.6 (9.5–16.7) 1.55 (1.16–2.07) Conclusion Among patients with HFrEF, the annual incidence of new-onset LBBB (and a potential indication for CRT), was around 1.5%, ranging from 1% in those with QRS duration below 100 ms to 4% in those with QRS 116–129 ms. Incident LBBB was associated with a much higher risk of adverse outcomes, highlighting the importance of repeat ECG monitoring in patients with HFrEF. Acknowledgement/Funding Novartis

Download Full-text

Right ventricular recovery during follow-up is associated with improved survival in patients with chronic heart failure with reduced ejection fraction

European Journal of Heart Failure ◽

10.1002/ejhf.639 ◽

2016 ◽

Vol 18 (12) ◽

pp. 1462-1471 ◽

Cited By ~ 15

Author(s):

Frank Lloyd Dini ◽

Erberto Carluccio ◽

Anca Simioniuc ◽

Paolo Biagioli ◽

Gianpaolo Reboldi ◽

...

Keyword(s):

Heart Failure ◽

Chronic Heart Failure ◽

Ejection Fraction ◽

Right Ventricular ◽

Reduced Ejection Fraction

Download Full-text

High Right Ventricular Stroke Work Index Is Associated with Worse Kidney Function in Patients with Heart Failure with Preserved Ejection Fraction

Cardiorenal Medicine ◽

10.1159/000486629 ◽

2018 ◽

Vol 8 (2) ◽

pp. 123-129 ◽

Cited By ~ 3

Author(s):

Napatt Kanjanahattakij ◽

Natee Sirinvaravong ◽

Francisco Aguilar ◽

Akanksha Agrawal ◽

Parasuram Krishnamoorthy ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Right Ventricular ◽

Linear Regression Analysis ◽

Stroke Work ◽

Work Index ◽

Patients With Heart Failure ◽

Stroke Work Index ◽

Ventricular Stroke Work Index ◽

Right Ventricular Stroke Work

Background: In patients with heart failure with preserved ejection fraction (HFpEF), worse kidney function is associated with worse overall cardiac mechanics. Right ventricular stroke work index (RVSWI) is a parameter of right ventricular function. The aim of our study was to determine the relationship between RVSWI and glomerular filtration rate (GFR) in patients with HFpEF. Method: This was a single-center cross-sectional study. HFpEF is defined as patients with documented heart failure with ejection fraction > 50% and pulmonary wedge pressure > 15 mm Hg from right heart catheterization. RVSWI (normal value 8–12 g/m/beat/m2) was calculated using the formula: RVSWI = 0.0136 × stroke volume index × (mean pulmonary artery pressure – mean right atrial pressure). Univariate and multivariate linear regression analysis was performed to study the correlation between RVSWI and GFR. Result: Ninety-one patients were included in the study. The patients were predominantly female (n = 64, 70%) and African American (n = 61, 67%). Mean age was 66 ± 12 years. Mean GFR was 59 ± 35 mL/min/1.73 m2. Mean RVSWI was 11 ± 6 g/m/beat/m2. Linear regression analysis showed that there was a significant independent inverse relationship between RVSWI and GFR (unstandardized coefficient = –1.3, p = 0.029). In the subgroup with combined post and precapillary pulmonary hypertension (Cpc-PH) the association remained significant (unstandardized coefficient = –1.74, 95% CI –3.37 to –0.11, p = 0.04). Conclusion: High right ventricular workload indicated by high RVSWI is associated with worse renal function in patients with Cpc-PH. Further prospective studies are needed to better understand this association.

Download Full-text

Impact of atrial fibrillation in patients with heart failure and reduced, mid-range or preserved ejection fraction

Heart ◽

10.1136/heartjnl-2019-316219 ◽

2020 ◽

Vol 106 (15) ◽

pp. 1160-1168 ◽

Cited By ~ 3

Author(s):

Mi Kyoung Son ◽

Jin Joo Park ◽

Nam-Kyoo Lim ◽

Won-Ho Kim ◽

Dong-Ju Choi

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Ejection Fraction ◽

Reduced Ejection Fraction ◽

Propensity Score Matching Analysis ◽

Increased Risk ◽

Multicentre Cohort Study ◽

Patients With Heart Failure ◽

Registration Number

ObjectiveTo determine the prognostic value of atrial fibrillation (AF) in patients with heart failure (HF) and preserved, mid-range or reduced ejection fraction (EF).MethodsPatients hospitalised for acute HF were enrolled in the Korean Acute Heart Failure registry, a prospective, observational, multicentre cohort study, between March 2011 and February 2014. HF types were defined as reduced EF (HFrEF, LVEF <40%), mid-range EF (HFmrEF, LVEF 40%–49%) or preserved EF (HFpEF, LVEF ≥50%).ResultsOf 5414 patients enrolled, HFrEF, HFmrEF and HFpEF were seen in 3182 (58.8%), 875 (16.2%) and 1357 (25.1%) patients, respectively. The prevalence of AF significantly increased with increasing EF (HFrEF 28.9%, HFmrEF 39.8%, HFpEF 45.2%; p for trend <0.001). During follow-up (median, 4.03 years; IQR, 1.39–5.58 years), 2806 (51.8%) patients died. The adjusted HR of AF for all-cause death was 1.06 (0.93–1.21) in the HFrEF, 1.10 (0.87–1.39) in the HFmrEF and 1.22 (1.02–1.46) in the HFpEF groups. The HR for the composite of all-cause death or readmission was 0.97 (0.87–1.07), 1.14 (0.93–1.38) and 1.03 (0.88–1.19) in the HFrEF, HFmrEF and HFpEF groups, respectively, and the HR for stroke was 1.53 (1.03–2.29), 1.04 (0.57–1.91) and 1.90 (1.13–3.20), respectively. Similar results were observed after propensity score matching analysis.ConclusionsAF was more common with increasing EF. AF was seen to be associated with increased mortality only in patients with HFpEF and was associated with an increased risk of stroke in patients with HFrEF or HFpEF.Trial registration numberNCT01389843

Download Full-text

Effect of Empagliflozin on the Clinical Stability of Patients with Heart Failure and a Reduced Ejection Fraction: The EMPEROR-Reduced Trial

Circulation ◽

10.1161/circulationaha.120.051783 ◽

2020 ◽

Cited By ~ 2

Author(s):

Milton Packer ◽

Stefan D. Anker ◽

Javed Butler ◽

Gerasimos S. Filippatos ◽

João Pedro Ferreira ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Functional Class ◽

Hazard Ratio ◽

Double Blind ◽

Reduced Ejection Fraction ◽

Risk Of Death ◽

Nyha Functional Class ◽

Patients With Heart Failure

Background: Empagliflozin reduces the risk of cardiovascular death or hospitalization for heart failure in patients with heart failure and a reduced ejection fraction, with or without diabetes, but additional data are needed about the effect of the drug on inpatient and outpatient events that reflect worsening heart failure. Methods: We randomly assigned 3730 patients with class II-IV heart failure with an ejection fraction of ≤40% to double-blind treatment with placebo or empagliflozin (10 mg once daily), in addition to recommended treatments for heart failure, for a median of 16 months. We prospectively collected information on inpatient and outpatient events reflecting worsening heart failure and prespecified their analysis in individual and composite endpoints. Results: Empagliflozin reduced the combined risk of death, hospitalization for heart failure or an emergent/urgent heart failure visit requiring intravenous treatment (415 vs 519 patients; empagliflozin vs placebo, respectively; hazard ratio 0.76, 95% CI: 0.67-0.87), P <0.0001. This benefit reached statistical significance at 12 days after randomization. Empagliflozin reduced the total number of heart failure hospitalizations that required intensive care (hazard ratio 0.67, 95% CI 0.50-0.90, P=0.008) and that required a vasopressor or positive inotropic drug or mechanical or surgical intervention (hazard ratio 0.64, 95% CI: 0.47-0.87, P=0.005). As compared with placebo, fewer patients in the empagliflozin group reported intensification of diuretics (297 vs 414), hazard ratio 0.67, 95% CI: 0.56-0.78, P<0.0001. Additionally, patients assigned to empagliflozin were 20-40% more likely to experience an improvement in NYHA functional class and were 20-40% less likely to experience worsening of NYHA functional class, with statistically significant effects that were apparent 28 days after randomization and maintained during long-term follow-up. The risk of any inpatient or outpatient worsening heart failure event in the placebo group was high (48.1 per 100 patient-years of follow-up), and it was reduced by empagliflozin (hazard ratio 0.70, 95% CI: 0.63-0.78), P<0.0001. Conclusions: In patients with heart failure and a reduced ejection fraction, empagliflozin reduced the risk and total number of inpatient and outpatient worsening heart failure events, with benefits seen early after initiation of treatment and sustained for the duration of double-blind therapy. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT03057977

Download Full-text