Guideline implementation, drug sequencing, and quality of care in heart failure: design and rationale of TITRATE-HF

Pascal R.D. Clephas*, Jishnu Malgie, Jeroen Schaap, Stefan Koudstaal, Mireille Emans, Gerard C.M. Linssen, Grytsje A. de Boer, Loek van Heerebeek, C. Jan Willem Borleffs, Olivier C. Manintveld, Vanessa van Empel, Sandra van Wijk, Mieke van den Heuvel, Carlos da Fonseca, Kevin Damman, Jan van Ramshorst, Roland van Kimmenade, Arjen R.T. van de Ven, René A. Tio, Dennis van VeghelFolkert W. Asselbergs, Rudolf A. de Boer, Peter van der Meer, Stephen J. Greene, Hans Peter Brunner-La Rocca, Jasper J. Brugts*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Current heart failure (HF) guidelines recommend to prescribe four drug classes in patients with HF with reduced ejection fraction (HFrEF). A clear challenge exists to adequately implement guideline-directed medical therapy (GDMT) regarding the sequencing of drugs and timely reaching target dose. It is largely unknown how the paradigm shift from a serial and sequential approach for drug therapy to early parallel application of the four drug classes will be executed in daily clinical practice, as well as the reason clinicians may not adhere to new guidelines. We present the design and rationale for the real-world TITRATE-HF study, which aims to assess sequencing strategies for GDMT initiation, dose titration patterns (order and speed), intolerance for GDMT, barriers for implementation, and long-term outcomes in patients with de novo, chronic, and worsening HF. 

Methods and results: 

A total of 4000 patients with HFrEF, HF with mildly reduced ejection fraction, and HF with improved ejection fraction will be enrolled in >40 Dutch centres with a follow-up of at least 3 years. Data collection will include demographics, physical examination and vital parameters, electrocardiogram, laboratory measurements, echocardiogram, medication, and quality of life. Detailed information on titration steps will be collected for the four GDMT drug classes. Information will include date, primary reason for change, and potential intolerances. The primary clinical endpoints are HF-related hospitalizations, HF-related urgent visits with a need for intravenous diuretics, all-cause mortality, and cardiovascular mortality. 


TITRATE-HF is a real-world multicentre longitudinal registry that will provide unique information on contemporary GDMT implementation, sequencing strategies (order and speed), and prognosis in de novo, worsening, and chronic HF patients.

Original languageEnglish
Pages (from-to)550-559
Number of pages10
JournalESC heart failure
Issue number1
Early online date8 Dec 2023
Publication statusPublished - Feb 2024

Bibliographical note

Publisher Copyright:
© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.


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