Improvement in left ventricular ejection fraction after pharmacological up-titration in new-onset heart failure with reduced ejection fraction

J. F. Nauta, B. T. Santema, M. H. L. van der Wal, A. Koops, J. Warink-Riemersma, K. van Dijk, F. Inkelaar, S. Pruckl, J. Suwijn, V. M. van Deursen, W. C. Meijers, J. Coster, B. D. Westenbrink, R. A. de Boer, Y. Hummel, J. van Melle, D. J. van Veldhuisen, P. van der Meer, A. A. Voors*

*Corresponding author for this work

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Objective Recent studies have reported suboptimal up-titration of heart failure (HF) therapies in patients with heart failure and a reduced ejection fraction (HFrEF). Here, we report on the achieved doses after nurse-led up-titration, reasons for not achieving the target dose, subsequent changes in left ventricular ejection fraction (LVEF), and mortality. Methods From 2012 to 2018, 378 HFrEF patients with a recent (< 3 months) diagnosis of HF were referred to a specialised HF-nurse led clinic for protocolised up-titration of guideline-directed medical therapy (GDMT). The achieved doses of GDMT at 9 months were recorded, as well as reasons for not achieving the optimal dose in all patients. Echocardiography was performed at baseline and after up-titration in 278 patients. Results Of 345 HFrEF patients with a follow-up visit after 9 months, 69% reached >= 50% of the recommended dose of renin-angiotensin-system (RAS) inhibitors, 73% reached >= 50% of the recommended dose of beta-blockers and 77% reached >= 50% of the recommended dose of mineralocorticoid receptor antagonists. The main reasons for not reaching the target dose were hypotension (RAS inhibitors and beta-blockers), bradycardia (beta-blockers) and renal dysfunction (RAS inhibitors). During a median follow-up of 9 months, mean LVEF increased from 27.6% at baseline to 38.8% at follow-up. Each 5% increase in LVEF was associated with an adjusted hazard ratio of 0.84 (0.75-0.94, p = 0.002) for mortality and 0.85 (0.78-0.94, p = 0.001) for the combined endpoint of mortality and/or HF hospitalisation after a mean follow-up of 3.3 years. Conclusions This study shows that protocolised up-titration in a nurse-led HF clinic leads to high doses of GDMT and improvement of LVEF in patients with new-onset HFrEF.

Original languageEnglish
Pages (from-to)383-393
Number of pages11
JournalNetherlands Heart Journal
Early online date14-Jun-2021
Publication statusPublished - Jul-2021


  • Heart failure
  • Guideline adherence
  • Target doses
  • Multidisciplinary care
  • Heart failure with reduced ejection fraction

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