PMID- 32073676
OWN - NLM
STAT- MEDLINE
DCOM- 20210423
LR  - 20210423
IS  - 1932-8737 (Electronic)
IS  - 0160-9289 (Print)
IS  - 0160-9289 (Linking)
VI  - 43
IP  - 5
DP  - 2020 May
TI  - Beta-blockers withdrawal in patients with heart failure with preserved ejection 
      fraction and chronotropic incompetence: Effect on functional capacity rationale 
      and study design of a prospective, randomized, controlled trial (The Preserve-HR 
      trial).
PG  - 423-429
LID - 10.1002/clc.23345 [doi]
AB  - BACKGROUND: The pathophysiology of heart failure with preserved ejection fraction 
      (HFpEF) is complex and multifactorial. Chronotropic incompetence (ChI) has 
      emerged as a crucial pathophysiological mechanism. Beta-blockers, drugs with 
      negative chronotropic effects, are commonly used in HFpEF, although current 
      evidence does not support its routine use in these patients. HYPOTHESIS: We 
      postulate beta-blockers may have deleterious effects in HFpEF and ChI. This work 
      aims to evaluate the short-term effect of beta-blockers withdrawal on functional 
      capacity assessed by the maximal oxygen uptake (peakVO2) in patients with HFpEF 
      and ChI. METHODS: This is a prospective, crossover, randomized (1:1) and 
      multicenter study. After randomization, the clinical and cardiac rhythm will be 
      continuously registered for 30 days. PeakVO2 is assessed by cardiopulmonary 
      exercise testing (CPET) at 15 and 30 days in both groups. Secondary endpoints 
      include quality of life, cognitive, and safety assessment. Patients with stable 
      HFpEF, functional class New York Heart Association (NYHA) II-III, chronic 
      treatment with beta-blockers, and ChI will be enrolled. A sample size estimation 
      [alfa: 0.05, power: 90%, a 20% loss rate, and delta change of mean peakVO2: +1.2 
      mL/kg/min (SD +/- 2.0)] of 52 patients is necessary to test our hypothesis. 
      RESULTS: Patients started enrolling in October 2018. As January 14th, 2020, 28 
      patients have been enrolled. It is projected to enroll the last patient at the 
      end of July 2020. CONCLUSIONS: Optimizing therapy that improves functional 
      capacity remains an unmeet priority in HFpEF. Deprescribing beta-blockers in 
      patients with HFpEF and ChI seems a plausible intervention to improve functional 
      capacity. This trial is an attempt towards precision medicine in this complex 
      syndrome. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03871803.
CI  - (c) 2020 The Authors. Clinical Cardiology published by Wiley Periodicals, Inc.
FAU - Palau, Patricia
AU  - Palau P
AD  - FISABIO. Universitat Jaume I, Castellon, Spain.
FAU - Seller, Julia
AU  - Seller J
AD  - Cardiology Department, Hospital de Denia, Alicante, Spain.
FAU - Dominguez, Eloy
AU  - Dominguez E
AUID- ORCID: 0000-0001-7583-8818
AD  - FISABIO. Universitat Jaume I, Castellon, Spain.
FAU - Gomez, Ines
AU  - Gomez I
AD  - Cardiology Department, Hospital Clinico Universitario de Santiago de Compostela, 
      Santiago de Compostela, A Coruna, Spain.
AD  - CIBERCV, Madrid, Spain.
FAU - Ramon, Jose Maria
AU  - Ramon JM
AD  - CIBERCV, Madrid, Spain.
AD  - Cardiology Department, Hospital Clinico Universitario, INCLIVA. Universitat de 
      Valencia, Valencia, Spain.
FAU - Sastre, Clara
AU  - Sastre C
AD  - CIBERCV, Madrid, Spain.
AD  - Cardiology Department, Hospital Clinico Universitario, INCLIVA. Universitat de 
      Valencia, Valencia, Spain.
FAU - de la Espriella, Rafael
AU  - de la Espriella R
AD  - CIBERCV, Madrid, Spain.
FAU - Santas, Enrique
AU  - Santas E
AD  - CIBERCV, Madrid, Spain.
AD  - Cardiology Department, Hospital Clinico Universitario, INCLIVA. Universitat de 
      Valencia, Valencia, Spain.
FAU - Minana, Gema
AU  - Minana G
AUID- ORCID: 0000-0001-8777-2588
AD  - CIBERCV, Madrid, Spain.
AD  - Cardiology Department, Hospital Clinico Universitario, INCLIVA. Universitat de 
      Valencia, Valencia, Spain.
FAU - Chorro, Francisco J
AU  - Chorro FJ
AD  - CIBERCV, Madrid, Spain.
AD  - Cardiology Department, Hospital Clinico Universitario, INCLIVA. Universitat de 
      Valencia, Valencia, Spain.
FAU - Gonzalez-Juanatey, Jose Ramon
AU  - Gonzalez-Juanatey JR
AD  - Cardiology Department, Hospital Clinico Universitario de Santiago de Compostela, 
      Santiago de Compostela, A Coruna, Spain.
AD  - CIBERCV, Madrid, Spain.
FAU - Nunez, Julio
AU  - Nunez J
AUID- ORCID: 0000-0003-1672-7119
AD  - CIBERCV, Madrid, Spain.
AD  - Cardiology Department, Hospital Clinico Universitario, INCLIVA. Universitat de 
      Valencia, Valencia, Spain.
LA  - eng
SI  - ClinicalTrials.gov/NCT03871803
PT  - Clinical Trial Protocol
PT  - Journal Article
DEP - 20200219
PL  - United States
TA  - Clin Cardiol
JT  - Clinical cardiology
JID - 7903272
RN  - 0 (Adrenergic beta-Antagonists)
RN  - 12794-10-4 (Benzodiazepines)
SB  - IM
MH  - Adrenergic beta-Antagonists/*therapeutic use
MH  - Benzodiazepines/*therapeutic use
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Heart Failure/*drug therapy/physiopathology
MH  - Humans
MH  - Male
MH  - Multicenter Studies as Topic
MH  - Prospective Studies
MH  - Randomized Controlled Trials as Topic
MH  - Research Design
MH  - Stroke Volume/drug effects
MH  - Ventricular Function, Left/*drug effects
PMC - PMC7244302
OTO - NOTNLM
OT  - chronotropic incompetence
OT  - exercise capacity
OT  - heart failure with preserved ejection fraction
OT  - quality of life
COIS- The authors declare no potential conflict of interests.
EDAT- 2020/02/20 06:00
MHDA- 2021/04/24 06:00
PMCR- 2020/02/19
CRDT- 2020/02/20 06:00
PHST- 2019/12/14 00:00 [received]
PHST- 2020/02/03 00:00 [revised]
PHST- 2020/02/05 00:00 [accepted]
PHST- 2020/02/20 06:00 [pubmed]
PHST- 2021/04/24 06:00 [medline]
PHST- 2020/02/20 06:00 [entrez]
PHST- 2020/02/19 00:00 [pmc-release]
AID - CLC23345 [pii]
AID - 10.1002/clc.23345 [doi]
PST - ppublish
SO  - Clin Cardiol. 2020 May;43(5):423-429. doi: 10.1002/clc.23345. Epub 2020 Feb 19.