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

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S L Kristensen ◽  
R Roerth ◽  
P S Jhund ◽  
S Beggs ◽  
L Kober ◽  
...  

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

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Johnsen ◽  
M Sengeloev ◽  
P Joergensen ◽  
N Bruun ◽  
D Modin ◽  
...  

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 &lt;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&lt;0.001), epicardial (HR 1.20; 95% CI (1.13–1.27), per 1% decrease, p&lt;0.001), and whole wall (HR 1.20; 95% CI (1.14–1.27), per 1% decrease, p&lt;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


Open Heart ◽  
2021 ◽  
Vol 8 (1) ◽  
pp. e001425
Author(s):  
Marc Meller Søndergaard ◽  
Johannes Riis ◽  
Karoline Willum Bodker ◽  
Steen Møller Hansen ◽  
Jesper Nielsen ◽  
...  

AimLeft bundle branch block (LBBB) is associated with an increased risk of heart failure (HF). We assessed the impact of common ECG parameters on this association using large-scale data.Methods and resultsUsing ECGs recorded in a large primary care population from 2001 to 2011, we identified HF-naive patients with a first-time LBBB ECG. We obtained information on sex, age, emigration, medication, diseases and death from Danish registries. We investigated the association between the PR interval, QRS duration, and heart rate and the risk of HF over a 2-year follow-up period using Cox regression analysis.Of 2471 included patients with LBBB, 464 (18.8%) developed HF during follow-up. A significant interaction was found between QRS duration and heart rate (p<0.01), and the analyses were stratified on these parameters. Using a QRS duration <150 ms and a heart rate <70 beats per minute (bpm) as the reference, all groups were statistically significantly associated with the development of HF. Patients with a QRS duration ≥150 ms and heart rate ≥70 bpm had the highest risk of developing HF (HR 3.17 (95% CI 2.41 to 4.18, p<0.001). There was no association between the PR interval and HF after adjustment.ConclusionProlonged QRS duration and higher heart rate were associated with increased risk of HF among primary care patients with LBBB, while no association was observed with PR interval. Patients with LBBB with both a prolonged QRS duration (≥150 ms) and higher heart rate (≥70 bpm) have the highest risk of developing HF.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
D.J Vazquez Andres ◽  
A Hernandez Vicente ◽  
M Diez Diez ◽  
M Gomez Molina ◽  
A Quintas ◽  
...  

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&lt;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


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Gianluigi Savarese ◽  
Camilla Hage ◽  
Ulf Dahlström ◽  
Pasquale Perrone-Filardi ◽  
Lars H Lund

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.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Kieran Docherty ◽  
Silvio E Inzucchi ◽  
Lars Kober ◽  
Mikhail Kosiborod ◽  
Anna Maria Langkilde ◽  
...  

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.


2013 ◽  
Vol 34 (19) ◽  
pp. 1424-1431 ◽  
Author(s):  
F. P. Brouwers ◽  
R. A. de Boer ◽  
P. van der Harst ◽  
A. A. Voors ◽  
R. T. Gansevoort ◽  
...  

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Edouard L Fu ◽  
Alicia Uijl ◽  
Friedo W Dekker ◽  
Lars H Lund ◽  
Gianluigi Savarese ◽  
...  

Abstract Background and Aims Beta-blockers reduce mortality and morbidity in patients with heart failure (HF) with reduced ejection fraction (HFrEF). However, patients with advanced chronic kidney disease (CKD) were underrepresented in landmark trials. We evaluated if beta-blockers are associated with improved survival in patients with HFrEF and advanced CKD. Method We identified 3906 persons with an ejection fraction &lt;40% and advanced CKD (eGFR &lt;30 mL/min/1.73m2) enrolled in the Swedish Heart Failure Registry during 2001-2016. The associations between beta-blocker use, 5-year all-cause mortality, and the composite of time to cardiovascular (CV) mortality/first HF hospitalization were assessed by multivariable Cox regression. Analyses were adjusted for 36 variables, including demographics, laboratory measures, comorbidities, medication use, medical procedures, and socioeconomic status. To assess consistency, the same analyses were performed in a positive control cohort of 12,673 patients with moderate CKD (eGFR &lt;60-30 mL/min/1.73m2). Results The majority (89%) of individuals with HFrEF and advanced CKD received treatment with beta-blockers. Median (IQR) age was 81 (74-86) years, 36% were women and median eGFR was 26 (20-28) mL/min/173m2. During 5 years of follow-up, 2086 (53.4%) individuals had a subsequent HF hospitalization, and 2954 (75.6%) individuals died, of which 2089 (70.1%) due to cardiovascular causes. Beta-blocker use was associated with a significant reduction in 5-year all-cause mortality [adjusted hazard ratio (HR) 0.86; 95% confidence interval (CI) 0.76-0.96)] and CV mortality/HF hospitalization (HR 0.87; 95% CI 0.77-0.98). The magnitude of the associations between beta-blocker use and outcomes was similar to that observed for HFrEF patients with mild/moderate CKD, with adjusted HRs for all-cause mortality and CV mortality/HF hospitalization of 0.85 (95% CI 0.78-0.91) and 0.88 (95% CI 0.82-0.96), respectively. Conclusion Despite lack of trial evidence, the use of beta-blockers in patients with HFrEF and advanced CKD was high in routine Swedish care, and was independently associated with reduced mortality to the same degree as HFrEF with moderate CKD.


Heart ◽  
2020 ◽  
Vol 106 (15) ◽  
pp. 1160-1168 ◽  
Author(s):  
Mi Kyoung Son ◽  
Jin Joo Park ◽  
Nam-Kyoo Lim ◽  
Won-Ho Kim ◽  
Dong-Ju Choi

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


Author(s):  
Milton Packer ◽  
Stefan D. Anker ◽  
Javed Butler ◽  
Gerasimos S. Filippatos ◽  
João Pedro Ferreira ◽  
...  

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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