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

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

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Catheter ablation of atrial fibrillation benefits the patients with heart failure and preserved ejection fraction as well as those with heart failure and reduced ejection fraction

European Heart Journal ◽

10.1093/ehjci/ehaa946.0430 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

R Yamauchi ◽

I Morishima ◽

Y Morita ◽

K Takagi ◽

H Nagai ◽

...

Keyword(s):

Heart Failure ◽

Catheter Ablation ◽

Ejection Fraction ◽

Cardiac Function ◽

Functional Class ◽

Reverse Remodeling ◽

Reduced Ejection Fraction ◽

Nyha Functional Class ◽

Patients With Heart Failure

Abstract Background Although catheter ablation of atrial fibrillation (AF) has recently been shown to improve the cardiac function and even mortality in patients with heart failure (HF) and reduced ejection fraction (HFrEF), few studies have examined the outcomes of AF catheter ablation in patients with HF with preserved ejection fraction (HFpEF). Purpose To verify the impact of AF catheter ablation on the cardiac function and HF status in patients with HFpEF. Methods We studied 306 patients with HF who had a history of an HF hospitalization and/or preprocedural serum BNP levels >100pg/ml (age, 68.9±8.2 years old; male, 66.3%; non-paroxysmal AF, 63.1%, left atrial diameter [LAD], 42.5±6.3 mm; left ventricular ejection fraction [LVEF], 60.6±12.0%) out of 596 consecutive patients who underwent pulmonary vein isolation-based catheter ablation of AF. The patients with an LVEF ≥50% were defined as having HFpEF (n=262; age, 69.0±8.2 years old; male, 64.5%; non-paroxysmal AF, 61.8%, LAD, 42.1±5.9 mm; left LVEF, 64.0±8.2%) and the remaining patients with an LVEF <50% were defined as having HFrEF (n=44, age, 67.9±8.7 years old; male, 77.0%; non-paroxysmal AF, 70.5%, LAD, 44.9±8.2 mm; LVEF, 40.1±10.2%). The patients received periodic follow-ups for 12 months after the catheter ablation. The cardiac function parameters including the echocardiographic findings and HF functional status of the patients were compared between baseline and 12 months, stratified by the HF subgroup. Results AF recurred in 60 patients with HFpEF (22.9%) and in 14 with HFrEF (31.8%) during the 12 month follow-up (p=0.27), however, sinus rhythm was maintained at 12 months in most of the patients (253 patients with HFpEF [96.6%] and 42 patients with HFrEF [95.5%]) (p=0.71). Figure 1 compares the changes in the cardiac function parameters and NYHA functional class from baseline to the 12-month follow-up stratified by the HF subgroup. Both the patients with HFpEF and HFrEF had significant improvements in the serum BNP levels, chest thorax ratio, and LVEF determined by echocardiography. LA reverse remodeling as shown by a significant reduction in the LAD was observed in both HF subgroups, however, the E/E', an index of the LV diastolic function, did not significantly change in either of the subgroups. Similar to the patients with HFrEF, an improvement in the NYHA functional class was seen in those with HFpEF. Conclusions Catheter ablation of AF may benefit patients with HFpEF as well as those with HFrEF. Sinus rhythm maintenance achieved by AF catheter ablation in patients with HFpEF may lead to LA reverse remodeling and a better LV systolic function, thereby improving the NYHA functional class. It is unclear whether changes in the LV diastolic function may contribute to this favorable process. Funding Acknowledgement Type of funding source: None

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P974 Sacubitril/valsartan is well tolerated in patients with heart failure and a history of cancer

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jez319.1197 ◽

2020 ◽

Vol 21 (Supplement_1) ◽

Author(s):

M K Frey ◽

E Han ◽

H Arfsten ◽

N Pavo ◽

M Huelsmann ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Cancer Patients ◽

Functional Class ◽

Reduced Ejection Fraction ◽

Non Hodgkin Lymphoma ◽

Patients With Heart Failure ◽

History Of ◽

History Of Cancer

Abstract Introduction Sacubitril/valsartan has been shown to significantly reduce cardiovascular mortality and hospitalisations due to heart failure in patients with reduced ejection fraction when compared to enalapril. Until now, sacubitril/valsartan has not been evaluated in patients with a history of cancer, as these patients were excluded from the pivotal trial, PARADIGM-HF. The aim of the current study was to assess tolerability of sacubitril/valsartan in patients with a history of cancer. Methods We retrospectively enrolled all patients at our heart failure out-patient unit who fulfilled the indication criteria to receive sacubitril/valsartan and had a history of cancer. Fifteen patients receiving sacubitril/valsartan had a diagnosis of histologically confirmed cancer: 26.7% breast cancer (n = 4), 13.3% osteosarcoma (n = 2), 13.3% colorectal cancer (n = 2), 13.3% renal cell carcinoma (n = 2), 6.7% non-Hodgkin lymphoma (n = 1), 6.7% lung cancer (n = 1), 6.7% prostate cancer (n = 1), 6.7% bladder carcinoma and 6.7% myeoloproliferative syndrome (n = 1). Surgery due to cancer was performed in 80% of patients (n = 12), 26.7% previously received chemotherapy (n = 6) and 40% radiation therapy (n = 4). Results Sacubitril/valsartan was withdrawn in 2 patients (13.3%) because of dizziness and pruritus respectively. After a mean follow-up of 13 ±8 months, NYHA functional class improved significantly (mean -0.5, p = 0.001), ejection fraction as assassed by echocardiography increased (mean +6.8%, p = 0.018) and NT-proBNP was significantly decreased (mean -1552pg/ml, p = 0.026). There was no significant change in creatinine levels (+0.046 mg/dl, p = 0.564 ). Conclusions In this pilot study we were able to show that sacubitril/valsartan is generally well tolerated in patients with a history of cancer. Patients with cardiotoxicity induced heart failure can be treated and uptitrated with sacubitril/valsartan to usual dosages similarly as in other causes of heart failure. Larger studies are needed to confirm these findings in cancer patients with cardiotoxicity.

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Impact of Sacubitril/Valsartan on Clinical and Echocardiographic Parameters in Heart Failure Patients With Reduced Ejection Fraction: Data From a Real Life 2-year Follow-Up Study

Frontiers in Pharmacology ◽

10.3389/fphar.2021.733475 ◽

2021 ◽

Vol 12 ◽

Author(s):

Giuseppe Armentaro ◽

Graziella D’Arrigo ◽

Marcello Magurno ◽

Alfredo F. Toscani ◽

Valentino Condoleo ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Real Life ◽

Functional Class ◽

Left Ventricular Ejection ◽

Reduced Ejection Fraction ◽

Repeated Observations ◽

Nyha Functional Class ◽

Echocardiographic Parameters

Heart failure (HF) represents a widespread health problem characterized by high morbidity and mortality. Sacubitril/Valsartan (sac/val) has improved clinical prognosis in patients affected by HF with reduced ejection fraction (HFrEF). The aim of this study was to evaluate the effectiveness and durability of sac/val treatment on the clinical, hemodynamic and echocardiographic parameters, in real-life consecutive HFrEF outpatients, evaluated up to 2-years of follow-up. We collected 300 repeated observations over time in 60 patients suffering of HFrEF and symptomatic despite optimal drug therapy. Patients with left ventricular ejection fraction (LVEF) <35 and II-III NYHA functional class were considered. All patients underwent to clinical-instrumental and laboratory determinations and Minnesota Living with HF Questionnaire (MLHFQ) every 6 months until 24 months to evaluate possible clinical benefits and adverse events. During a 2-year follow-up period and through a 6-monthly control of the study variables both clinical, hemodynamic, biochemical and echocardiographic parameters significantly improved, in particular cardiac index (CI), both atrial and ventricular volumes and global longitudinal strain (GLS). Furthermore, there was a reduction of NT-proBNP levels and betterment of renal function and NYHA functional class, demonstrating the efficacy and durability of sac/val treatment. In a multiple linear mixed model the longitudinal evolutions of CI were associated to concomitant changes of GLS and E/e’ ratio. Our study, contemplating the collection of 300 repeated observations in 60 patients, provides a complete and detailed demonstration of sac/val effects, showing effectiveness, safety and effect durability of the treatment every 6 months up to 2-years of follow-up with significant improvement of several clinical, hemodynamic and echocardiographic parameters in HFrEF outpatients.

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Effect of Empagliflozin on Worsening Heart Failure Events in Patients with Heart Failure and a Preserved Ejection Fraction: The EMPEROR-Preserved Trial

Circulation ◽

10.1161/circulationaha.121.056824 ◽

2021 ◽

Author(s):

Milton Packer ◽

Javed Butler ◽

Faiez Zannad ◽

Gerasimos Filippatos ◽

Joao Pedro Ferreira ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Statistical Significance ◽

Cardiovascular Death ◽

Functional Class ◽

Hazard Ratio ◽

Preserved Ejection Fraction ◽

Double Blind ◽

Clinical Trial Registration ◽

Patients With Heart Failure

Background: Empagliflozin reduces the risk of cardiovascular death or hospitalization for heart failure in patients with heart failure and a preserved ejection fraction, but additional data are needed about its effect on inpatient and outpatient heart failure events. Methods: We randomly assigned 5988 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 usual therapy, for a median of 26 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 cardiovascular death, hospitalization for heart failure or an emergent/urgent heart failure visit requiring intravenous treatment (432 vs 546 patients; empagliflozin vs placebo, respectively; hazard ratio 0.77, 95% CI: 0.67-0.87), P <0.0001. This benefit reached statistical significance at 18 days after randomization. Empagliflozin reduced the total number of heart failure hospitalizations that required intensive care (hazard ratio 0.71, 95% CI 0.52-0.96, P=0.028) and the total number of all hospitalizations that required a vasopressor or positive inotropic drug (hazard ratio 0.73, 95% CI: 0.55-0.97,P=0.033). As compared with placebo, fewer patients in the empagliflozin group reported outpatient intensification of diuretics (482 vs 610, hazard ratio 0.76, 95% CI: 0.67-0.86, P<0.0001), and patients assigned to empagliflozin were 20-50% more likely to have a better NYHA functional class, with significant effects at 12 weeks that were maintained for at least 2 years. The benefit on total heart failure hospitalizations was similar in patients with an ejection fraction of >40-<50% and 50-<60%, but was attenuated at higher ejection fractions. Conclusions: In patients with heart failure and a preserved ejection fraction, empagliflozin produced a meaningful, early and sustained reduction in the risk and severity of a broad range of inpatient and outpatient worsening heart failure events. Clinical Trial Registration: The registration identifier at ClinicalTrials.gov is NCT03057977

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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 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.

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Use of Free-Living Step Count Monitoring for Heart Failure Functional Classification: Validation Study (Preprint)

10.2196/preprints.12122 ◽

2018 ◽

Author(s):

Jonathan-F. Baril ◽

Simon Bromberg ◽

Yasbanoo Moayedi ◽

Babak Taati ◽

Cedric Manlhiot ◽

...

Keyword(s):

Heart Failure ◽

Pilot Study ◽

Ejection Fraction ◽

Functional Class ◽

Step Count ◽

Functional Classification ◽

Free Living ◽

Reduced Ejection Fraction ◽

Nyha Functional Class ◽

Daily Total

BACKGROUND The New York Heart Association (NYHA) functional classification system has poor inter-rater reproducibility. A previously published pilot study showed a statistically significant difference between the daily step counts of heart failure (with reduced ejection fraction) patients classified as NYHA functional class II and III as measured by wrist-worn activity monitors. However, the study’s small sample size severely limits scientific confidence in the generalizability of this finding to a larger heart failure (HF) population. OBJECTIVE This study aimed to validate the pilot study on a larger sample of patients with HF with reduced ejection fraction (HFrEF) and attempt to characterize the step count distribution to gain insight into a more objective method of assessing NYHA functional class. METHODS We repeated the analysis performed during the pilot study on an independently recorded dataset comprising a total of 50 patients with HFrEF (35 NYHA II and 15 NYHA III) patients. Participants were monitored for step count with a Fitbit Flex for a period of 2 weeks in a free-living environment. RESULTS Comparing group medians, patients exhibiting NYHA class III symptoms had significantly lower recorded 2-week mean daily total step count (3541 vs 5729 [steps], P=.04), lower 2-week maximum daily total step count (10,792 vs 5904 [steps], P=.03), lower 2-week recorded mean daily mean step count (4.0 vs 2.5 [steps/minute], P=.04,), and lower 2-week mean and 2-week maximum daily per minute step count maximums (88.1 vs 96.1 and 111.0 vs 123.0 [steps/minute]; P=.02 and .004, respectively). CONCLUSIONS Patients with NYHA II and III symptoms differed significantly by various aggregate measures of free-living step count including the (1) mean and (2) maximum daily total step count as well as by the (3) mean of daily mean step count and by the (4) mean and (5) maximum of the daily per minute step count maximum. These findings affirm that the degree of exercise intolerance of NYHA II and III patients as a group is quantifiable in a replicable manner. This is a novel and promising finding that suggests the existence of a possible, completely objective measure of assessing HF functional class, something which would be a great boon in the continuing quest to improve patient outcomes for this burdensome and costly disease.

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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.

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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

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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

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