Heart rate, beta-blocker use, and outcomes of heart failure with reduced ejection fraction

Aims High resting heart rate (HR ≥70 b.p.m.) is associated with worse clinical outcomes in heart failure with reduced ejection fraction (HFrEF). Heart rate, guideline-directed medical therapy (GDMT) with beta-blocker (BB), and cardiovascular outcomes were evaluated in a large integrated health network. Methods and results Using electronic health records we examined patients with chronic HFrEF (ejection fraction ≤35%) in sinus rhythm with at least 1 year of follow-up and available serial HR and medication data between 1 January 2000 and 31 December 2014. Among 6071 patients followed for median of 1330 days across 73 586 total visits, median HR remained stable over time with 61.2% of the follow-up period with HR  ≥70 b.p.m. At baseline, 27.9% of patients were on ≥ 50% GDMT target BB dose, 16.2% subjects at baseline, and 19.4% at the end of follow-up had HR ≥70 b.p.m. despite receiving ≥50% of target BB dose. In adjusted analyses, baseline HR was associated with all-cause mortality/heart failure (HF) hospitalization (hazard ratio 1.28 per 15 b.p.m. Heart rate increase; P < 0.001). In comparison, hazard ratio for BB dose was 0.97 (per 77.2 mg increase; P = 0.36). When evaluating patients based on HR and BB dose there was a significant difference in the cumulative hazard for all-cause mortality or HF hospitalization (P < 0.001). For HF hospitalization, hazard appeared to be more closely associated with HR rather than BB dose (P = 0.01). Conclusion In a real-world analysis, high resting HR was common in HFrEF patients and associated with adverse outcomes. Opportunities exist to improve GDMT and achieve HR control.

[1]  G. Parati,et al.  Prognostic role of β‐blocker selectivity and dosage regimens in heart failure patients. Insights from the MECKI score database , 2017, European journal of heart failure.

[2]  A. Rigby,et al.  Heart Rate and Rhythm and the Benefit of Beta-Blockers in Patients With Heart Failure. , 2017, Journal of the American College of Cardiology.

[3]  P. Ponikowski,et al.  Physicians' guideline adherence is associated with better prognosis in outpatients with heart failure with reduced ejection fraction: the QUALIFY international registry , 2017, European journal of heart failure.

[4]  Gerasimos S Filippatos,et al.  2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. , 2017, Journal of cardiac failure.

[5]  K. Alexander,et al.  Knowledge Gaps in Cardiovascular Care of Older Adults: A Scientific Statement from the American Heart Association, American College of Cardiology, and American Geriatrics Society: Executive Summary , 2016, Journal of the American Geriatrics Society.

[6]  Volkmar Falk,et al.  2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure , 2016, Revista espanola de cardiologia.

[7]  I. Piña,et al.  Heart Rate or Beta-Blocker Dose? Association With Outcomes in Ambulatory Heart Failure Patients With Systolic Dysfunction: Results From the HF-ACTION Trial. , 2016, JACC. Heart failure.

[8]  Volkmar Falk,et al.  2016 ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure. , 2016, Revista espanola de cardiologia.

[9]  J. Cleland,et al.  Prescribing patterns to optimize heart rate: analysis of 1,000 consecutive outpatient appointments to a single heart failure clinic over a 6-month period. , 2015, JACC. Heart failure.

[10]  C. Yancy,et al.  The prognostic significance of heart rate in patients hospitalized for heart failure with reduced ejection fraction in sinus rhythm: insights from the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study With Tolvaptan) trial. , 2013, JACC. Heart failure.

[11]  Anju Bhardwaj,et al.  Soluble Concentrations of the Interleukin Receptor Family Member ST2 and &bgr;-Blocker Therapy in Chronic Heart Failure , 2013, Circulation. Heart failure.

[12]  P. Ponikowski,et al.  Are hospitalized or ambulatory patients with heart failure treated in accordance with European Society of Cardiology guidelines? Evidence from 12 440 patients of the ESC Heart Failure Long‐Term Registry , 2013, European journal of heart failure.

[13]  K. Swedberg,et al.  Effects on outcomes of heart rate reduction by ivabradine in patients with congestive heart failure: is there an influence of beta-blocker dose?: findings from the SHIFT (Systolic Heart failure treatment with the I(f) inhibitor ivabradine Trial) study. , 2012, Journal of the American College of Cardiology.

[14]  G. Fonarow,et al.  Medication dosing in outpatients with heart failure after implementation of a practice-based performance improvement intervention: findings from IMPROVE HF. , 2012, Congestive heart failure.

[15]  M. Gold,et al.  Heart rate as a risk factor in chronic heart failure (SHIFT): the association between heart rate and outcomes in a randomised placebo-controlled trial , 2011 .

[16]  M. Cheitlin Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study , 2011 .

[17]  Natasha Wiebe,et al.  Meta-analysis: -Blocker Dose, Heart Rate Reduction, and Death in Patients With Heart Failure , 2009, Annals of Internal Medicine.

[18]  P. Armstrong,et al.  Meta-analysis: beta-blocker dose, heart rate reduction, and death in patients with heart failure. , 2009, Annals of internal medicine.

[19]  R. Ferrari,et al.  Heart rate as a prognostic risk factor in patients with coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a subgroup analysis of a randomised controlled trial , 2008, The Lancet.

[20]  B. Massie,et al.  β-Blocker dosing in community-based treatment of heart failure , 2007 .

[21]  B. Massie,et al.  Beta-blocker dosing in community-based treatment of heart failure. , 2007, American heart journal.

[22]  K. Swedberg,et al.  Under-utilization of evidence-based drug treatment in patients with heart failure is only partially explained by dissimilarity to patients enrolled in landmark trials: a report from the Euro Heart Survey on Heart Failure. , 2005, European heart journal.

[23]  D. DeMets,et al.  Effect of Carvedilol on the Morbidity of Patients With Severe Chronic Heart Failure: Results of the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) Study , 2002, Circulation.

[24]  Fach,et al.  Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in-Congestive Heart Failure (MERIT-HF) , 1999, The Lancet.

[25]  S Greenland,et al.  A critical look at methods for handling missing covariates in epidemiologic regression analyses. , 1995, American journal of epidemiology.