Prognostic Significance of Changes in Heart Rate Following Uptitration of Beta-Blockers in Patients with Sub-Optimally Treated Heart Failure with Reduced Ejection Fraction in Sinus Rhythm versus Atrial Fibrillation

Ify Mordi (Lead / Corresponding author), Bernadet T. Santema, Marielle Kloosterman, Anna-Maria Choy, Michiel Rienstra, Isabelle C Van Gelder, Stefan D. Anker, John G. F. Cleland, Kenneth Dickstein, Gerasimos S. Filippatos, Pim van der Harst, Hans L. Hillege, Marco Metra, Leong Loke Ng, Wouter Ouwerkerk, Piotr Ponikowski, Nilesh J. Samani, Dirk Jan van Veldhuisen, Aeilko H. Zwinderman, Faiez Zannad & 2 others Adriaan A. Voors, Chim Lang

Research output: Contribution to journalArticle

Abstract

Background In patients with heart failure with reduced ejection fraction (HFrEF) on sub-optimal doses of beta-blockers, it is conceivable that changes in heart rate following treatment intensification might be important regardless of underlying heart rhythm. We aimed to compare the prognostic significance of both achieved heart rate and change in heart rate following beta-blocker uptitration in patients with HFrEF either in sinus rhythm (SR) or atrial fibrillation (AF). Methods We performed a post-hoc analysis of the BIOSTAT-CHF study. We evaluated 1,548 patients with HFrEF (mean age 67 years, 35% AF). Median follow-up was 21 months. Patients were evaluated at baseline and at 9 months. The combined primary outcome was all-cause mortality and heart failure (HF) hospitalisation stratified by heart rhythm and heart rate at baseline. Results Despite similar changes in heart rate and beta-blocker dose, a decrease in heart rate at nine months was associated with reduced incidence of the primary outcome in both SR and AF patients (HR per 10bpm decrease – SR: 0.83 (0.75-0.91), p<0.001; AF: 0.89 (0.81-0.98), p=0.018), whereas the relationship was less strong for achieved heart rate in AF (HR per 10bpm higher - SR: 1.26 (1.10-1.46), p=0.001; AF: 1.08 (0.94-1.23), p=0.18). Achieved heart rate at 9 months was only prognostically significant in AF patients with high baseline heart rates (p for interaction 0.017 vs. low). Conclusions Following beta-blocker uptitration, both achieved and change in heart rate were prognostically significant regardless of starting heart rate in SR, however, they were only significant in AF patients with high baseline heart rate.
LanguageEnglish
Number of pages9
JournalClinical Research in Cardiology
Early online date4 Jan 2019
DOIs
Publication statusE-pub ahead of print - 4 Jan 2019

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Atrial Fibrillation
Heart Failure
Heart Rate
Hospitalization
Mortality

Keywords

  • Heart failure
  • heart rate
  • atrial fibrillation
  • beta-blockers

Cite this

Mordi, Ify ; Santema, Bernadet T. ; Kloosterman, Marielle ; Choy, Anna-Maria ; Rienstra, Michiel ; Van Gelder, Isabelle C ; Anker, Stefan D. ; Cleland, John G. F. ; Dickstein, Kenneth ; Filippatos, Gerasimos S. ; van der Harst, Pim ; Hillege, Hans L. ; Metra, Marco ; Ng, Leong Loke ; Ouwerkerk, Wouter ; Ponikowski, Piotr ; Samani, Nilesh J. ; van Veldhuisen, Dirk Jan ; Zwinderman, Aeilko H. ; Zannad, Faiez ; Voors, Adriaan A. ; Lang, Chim. / Prognostic Significance of Changes in Heart Rate Following Uptitration of Beta-Blockers in Patients with Sub-Optimally Treated Heart Failure with Reduced Ejection Fraction in Sinus Rhythm versus Atrial Fibrillation. In: Clinical Research in Cardiology . 2019.
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title = "Prognostic Significance of Changes in Heart Rate Following Uptitration of Beta-Blockers in Patients with Sub-Optimally Treated Heart Failure with Reduced Ejection Fraction in Sinus Rhythm versus Atrial Fibrillation",
abstract = "Background In patients with heart failure with reduced ejection fraction (HFrEF) on sub-optimal doses of beta-blockers, it is conceivable that changes in heart rate following treatment intensification might be important regardless of underlying heart rhythm. We aimed to compare the prognostic significance of both achieved heart rate and change in heart rate following beta-blocker uptitration in patients with HFrEF either in sinus rhythm (SR) or atrial fibrillation (AF). Methods We performed a post-hoc analysis of the BIOSTAT-CHF study. We evaluated 1,548 patients with HFrEF (mean age 67 years, 35{\%} AF). Median follow-up was 21 months. Patients were evaluated at baseline and at 9 months. The combined primary outcome was all-cause mortality and heart failure (HF) hospitalisation stratified by heart rhythm and heart rate at baseline. Results Despite similar changes in heart rate and beta-blocker dose, a decrease in heart rate at nine months was associated with reduced incidence of the primary outcome in both SR and AF patients (HR per 10bpm decrease – SR: 0.83 (0.75-0.91), p<0.001; AF: 0.89 (0.81-0.98), p=0.018), whereas the relationship was less strong for achieved heart rate in AF (HR per 10bpm higher - SR: 1.26 (1.10-1.46), p=0.001; AF: 1.08 (0.94-1.23), p=0.18). Achieved heart rate at 9 months was only prognostically significant in AF patients with high baseline heart rates (p for interaction 0.017 vs. low). Conclusions Following beta-blocker uptitration, both achieved and change in heart rate were prognostically significant regardless of starting heart rate in SR, however, they were only significant in AF patients with high baseline heart rate.",
keywords = "Heart failure, heart rate, atrial fibrillation, beta-blockers",
author = "Ify Mordi and Santema, {Bernadet T.} and Marielle Kloosterman and Anna-Maria Choy and Michiel Rienstra and {Van Gelder}, {Isabelle C} and Anker, {Stefan D.} and Cleland, {John G. F.} and Kenneth Dickstein and Filippatos, {Gerasimos S.} and {van der Harst}, Pim and Hillege, {Hans L.} and Marco Metra and Ng, {Leong Loke} and Wouter Ouwerkerk and Piotr Ponikowski and Samani, {Nilesh J.} and {van Veldhuisen}, {Dirk Jan} and Zwinderman, {Aeilko H.} and Faiez Zannad and Voors, {Adriaan A.} and Chim Lang",
note = "This project was funded by a grant from the European Commission: FP7-242209-BIOSTAT-CHF. This study was supported by the Dutch Heart Foundation, CVON 2014-11 RECONNECT. IRM is supported by a NHS Education for Scotland/Chief Scientist Office Postdoctoral Clinical Lectureship (PCL/17/07).",
year = "2019",
month = "1",
day = "4",
doi = "10.1007/s00392-018-1409-x",
language = "English",
journal = "Clinical Research in Cardiology",
issn = "1861-0684",
publisher = "Springer Verlag",

}

Mordi, I, Santema, BT, Kloosterman, M, Choy, A-M, Rienstra, M, Van Gelder, IC, Anker, SD, Cleland, JGF, Dickstein, K, Filippatos, GS, van der Harst, P, Hillege, HL, Metra, M, Ng, LL, Ouwerkerk, W, Ponikowski, P, Samani, NJ, van Veldhuisen, DJ, Zwinderman, AH, Zannad, F, Voors, AA & Lang, C 2019, 'Prognostic Significance of Changes in Heart Rate Following Uptitration of Beta-Blockers in Patients with Sub-Optimally Treated Heart Failure with Reduced Ejection Fraction in Sinus Rhythm versus Atrial Fibrillation', Clinical Research in Cardiology . https://doi.org/10.1007/s00392-018-1409-x

Prognostic Significance of Changes in Heart Rate Following Uptitration of Beta-Blockers in Patients with Sub-Optimally Treated Heart Failure with Reduced Ejection Fraction in Sinus Rhythm versus Atrial Fibrillation. / Mordi, Ify (Lead / Corresponding author); Santema, Bernadet T.; Kloosterman, Marielle; Choy, Anna-Maria; Rienstra, Michiel; Van Gelder, Isabelle C; Anker, Stefan D.; Cleland, John G. F.; Dickstein, Kenneth; Filippatos, Gerasimos S.; van der Harst, Pim; Hillege, Hans L.; Metra, Marco; Ng, Leong Loke; Ouwerkerk, Wouter; Ponikowski, Piotr; Samani, Nilesh J.; van Veldhuisen, Dirk Jan; Zwinderman, Aeilko H.; Zannad, Faiez; Voors, Adriaan A.; Lang, Chim.

In: Clinical Research in Cardiology , 04.01.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Prognostic Significance of Changes in Heart Rate Following Uptitration of Beta-Blockers in Patients with Sub-Optimally Treated Heart Failure with Reduced Ejection Fraction in Sinus Rhythm versus Atrial Fibrillation

AU - Mordi, Ify

AU - Santema, Bernadet T.

AU - Kloosterman, Marielle

AU - Choy, Anna-Maria

AU - Rienstra, Michiel

AU - Van Gelder, Isabelle C

AU - Anker, Stefan D.

AU - Cleland, John G. F.

AU - Dickstein, Kenneth

AU - Filippatos, Gerasimos S.

AU - van der Harst, Pim

AU - Hillege, Hans L.

AU - Metra, Marco

AU - Ng, Leong Loke

AU - Ouwerkerk, Wouter

AU - Ponikowski, Piotr

AU - Samani, Nilesh J.

AU - van Veldhuisen, Dirk Jan

AU - Zwinderman, Aeilko H.

AU - Zannad, Faiez

AU - Voors, Adriaan A.

AU - Lang, Chim

N1 - This project was funded by a grant from the European Commission: FP7-242209-BIOSTAT-CHF. This study was supported by the Dutch Heart Foundation, CVON 2014-11 RECONNECT. IRM is supported by a NHS Education for Scotland/Chief Scientist Office Postdoctoral Clinical Lectureship (PCL/17/07).

PY - 2019/1/4

Y1 - 2019/1/4

N2 - Background In patients with heart failure with reduced ejection fraction (HFrEF) on sub-optimal doses of beta-blockers, it is conceivable that changes in heart rate following treatment intensification might be important regardless of underlying heart rhythm. We aimed to compare the prognostic significance of both achieved heart rate and change in heart rate following beta-blocker uptitration in patients with HFrEF either in sinus rhythm (SR) or atrial fibrillation (AF). Methods We performed a post-hoc analysis of the BIOSTAT-CHF study. We evaluated 1,548 patients with HFrEF (mean age 67 years, 35% AF). Median follow-up was 21 months. Patients were evaluated at baseline and at 9 months. The combined primary outcome was all-cause mortality and heart failure (HF) hospitalisation stratified by heart rhythm and heart rate at baseline. Results Despite similar changes in heart rate and beta-blocker dose, a decrease in heart rate at nine months was associated with reduced incidence of the primary outcome in both SR and AF patients (HR per 10bpm decrease – SR: 0.83 (0.75-0.91), p<0.001; AF: 0.89 (0.81-0.98), p=0.018), whereas the relationship was less strong for achieved heart rate in AF (HR per 10bpm higher - SR: 1.26 (1.10-1.46), p=0.001; AF: 1.08 (0.94-1.23), p=0.18). Achieved heart rate at 9 months was only prognostically significant in AF patients with high baseline heart rates (p for interaction 0.017 vs. low). Conclusions Following beta-blocker uptitration, both achieved and change in heart rate were prognostically significant regardless of starting heart rate in SR, however, they were only significant in AF patients with high baseline heart rate.

AB - Background In patients with heart failure with reduced ejection fraction (HFrEF) on sub-optimal doses of beta-blockers, it is conceivable that changes in heart rate following treatment intensification might be important regardless of underlying heart rhythm. We aimed to compare the prognostic significance of both achieved heart rate and change in heart rate following beta-blocker uptitration in patients with HFrEF either in sinus rhythm (SR) or atrial fibrillation (AF). Methods We performed a post-hoc analysis of the BIOSTAT-CHF study. We evaluated 1,548 patients with HFrEF (mean age 67 years, 35% AF). Median follow-up was 21 months. Patients were evaluated at baseline and at 9 months. The combined primary outcome was all-cause mortality and heart failure (HF) hospitalisation stratified by heart rhythm and heart rate at baseline. Results Despite similar changes in heart rate and beta-blocker dose, a decrease in heart rate at nine months was associated with reduced incidence of the primary outcome in both SR and AF patients (HR per 10bpm decrease – SR: 0.83 (0.75-0.91), p<0.001; AF: 0.89 (0.81-0.98), p=0.018), whereas the relationship was less strong for achieved heart rate in AF (HR per 10bpm higher - SR: 1.26 (1.10-1.46), p=0.001; AF: 1.08 (0.94-1.23), p=0.18). Achieved heart rate at 9 months was only prognostically significant in AF patients with high baseline heart rates (p for interaction 0.017 vs. low). Conclusions Following beta-blocker uptitration, both achieved and change in heart rate were prognostically significant regardless of starting heart rate in SR, however, they were only significant in AF patients with high baseline heart rate.

KW - Heart failure

KW - heart rate

KW - atrial fibrillation

KW - beta-blockers

U2 - 10.1007/s00392-018-1409-x

DO - 10.1007/s00392-018-1409-x

M3 - Article

JO - Clinical Research in Cardiology

T2 - Clinical Research in Cardiology

JF - Clinical Research in Cardiology

SN - 1861-0684

ER -