PMID- 36404399
OWN - NLM
STAT- MEDLINE
DCOM- 20230301
LR  - 20230323
IS  - 1879-0844 (Electronic)
IS  - 1388-9842 (Linking)
VI  - 25
IP  - 2
DP  - 2023 Feb
TI  - Effect of beta-blocker therapy on the response to mavacamten in patients with 
      symptomatic obstructive hypertrophic cardiomyopathy.
PG  - 260-270
LID - 10.1002/ejhf.2737 [doi]
AB  - AIMS: In the EXPLORER-HCM trial, mavacamten improved exercise capacity and 
      symptoms in patients with obstructive hypertrophic cardiomyopathy (oHCM). 
      Mavacamten effects on the primary endpoint, a composite of peak oxygen 
      consumption (VO(2) ) and New York Heart Association (NYHA) class, were greater in 
      patients not receiving background beta-blockers than in those receiving 
      beta-blockers. We sought to determine if the effect of background treatment was 
      consistent across other clinically meaningful parameters. METHODS AND RESULTS: 
      Subgroup analyses by beta-blocker use were performed in patients with oHCM from 
      the EXPLORER-HCM and mavacamten long-term extension (MAVA-LTE) studies. In 
      EXPLORER-HCM, 189 patients (75.3%) were receiving beta-blockers, and 62 (24.7%) 
      were receiving non-dihydropyridine calcium channel blockers or no background HCM 
      medication; 170 patients (90.4%) receiving beta-blockers had chronotropic 
      incompetence. Improvements in peak VO(2) at week 30 with mavacamten versus 
      placebo were lower with beta-blockers (mean difference [95% confidence interval 
      (CI)]: 1.04 [0.12, 1.95] ml/kg/min) than without beta-blockers (mean difference 
      [95% CI]: 2.69 [1.29, 4.09] ml/kg/min); improvements in non-heart rate-dependent 
      parameters (V(E) /VCO(2) slope) appeared unaffected by beta-blockers. 
      Improvements in functional capacity parameters at week 30 with mavacamten versus 
      placebo were independent of beta-blockade for post-exercise left ventricular 
      outflow tract gradient (mean difference [95% CI]: -37.9 [-48.0, -27.9] mmHg with 
      beta-blockers; -33.5 [-53.6, -13.3] mmHg without beta-blockers), proportion of 
      patients with reduction of >/=1 NYHA class, Kansas City Cardiomyopathy 
      Questionnaire clinical summary scores and N-terminal pro-B-type natriuretic 
      peptide. Mavacamten benefits were reproduced and maintained in MAVA-LTE 
      regardless of beta-blockade. CONCLUSION: Mavacamten improved measures of 
      functional capacity, left ventricular outflow tract obstruction, symptom burden 
      and biomarkers in patients with HCM regardless of beta-blocker use. Beta-blocker 
      use was often associated with chronotropic incompetence, affecting peak VO(2) and 
      other heart rate-dependent measures, but had minimal impact on heart 
      rate-independent measures.
CI  - (c) 2022 MyoKardia, Inc and The Authors. European Journal of Heart Failure 
      published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
FAU - Wheeler, Matthew T
AU  - Wheeler MT
AUID- ORCID: 0000-0001-8721-3022
AD  - Division of Cardiovascular Medicine, Center for Inherited Cardiovascular Disease, 
      Stanford University, Stanford, CA, USA.
FAU - Jacoby, Daniel
AU  - Jacoby D
AD  - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale 
      University, New Haven, CT, USA.
FAU - Elliott, Perry M
AU  - Elliott PM
AUID- ORCID: 0000-0003-3383-3984
AD  - University College London & St. Bartholomew's Hospital, London, UK.
FAU - Saberi, Sara
AU  - Saberi S
AD  - Division of Cardiovascular Medicine, Department of Internal Medicine, University 
      of Michigan Medical School, Ann Arbor, MI, USA.
FAU - Hegde, Sheila M
AU  - Hegde SM
AD  - Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard 
      Medical School, Boston, MA, USA.
FAU - Lakdawala, Neal K
AU  - Lakdawala NK
AD  - Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard 
      Medical School, Boston, MA, USA.
FAU - Myers, Jonathan
AU  - Myers J
AD  - Division of Cardiology, Veterans Affairs Palo Alto Healthcare System, Palo Alto, 
      CA, USA.
AD  - Stanford University, Palo Alto, CA, USA.
FAU - Sehnert, Amy J
AU  - Sehnert AJ
AD  - MyoKardia, Inc., a wholly owned subsidiary of Bristol Myers Squibb, Brisbane, CA, 
      USA.
FAU - Edelberg, Jay M
AU  - Edelberg JM
AD  - MyoKardia, Inc., a wholly owned subsidiary of Bristol Myers Squibb, Brisbane, CA, 
      USA.
FAU - Li, Wanying
AU  - Li W
AD  - MyoKardia, Inc., a wholly owned subsidiary of Bristol Myers Squibb, Brisbane, CA, 
      USA.
FAU - Olivotto, Iacopo
AU  - Olivotto I
AD  - Cardiomyopathy Unity, Azienda Ospedaliera Universitaria Careggi and University of 
      Florence, Florence, Italy.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20230201
PL  - England
TA  - Eur J Heart Fail
JT  - European journal of heart failure
JID - 100887595
RN  - 0 (Adrenergic beta-Antagonists)
RN  - 0 (Benzylamines)
RN  - 0 (MYK-461)
SB  - IM
CIN - Eur J Heart Fail. 2023 Feb;25(2):271-273. PMID: 36597820
MH  - Humans
MH  - Adrenergic beta-Antagonists/therapeutic use
MH  - Benzylamines/adverse effects
MH  - *Cardiomyopathy, Hypertrophic/diagnosis
MH  - Heart
MH  - *Heart Failure/drug therapy
OTO - NOTNLM
OT  - Beta-blockers
OT  - Exercise capacity
OT  - Mavacamten
OT  - Obstructive hypertrophic cardiomyopathy
OT  - Symptoms
EDAT- 2022/11/21 06:00
MHDA- 2023/03/03 06:00
CRDT- 2022/11/20 23:32
PHST- 2022/09/28 00:00 [revised]
PHST- 2022/03/29 00:00 [received]
PHST- 2022/11/16 00:00 [accepted]
PHST- 2022/11/21 06:00 [pubmed]
PHST- 2023/03/03 06:00 [medline]
PHST- 2022/11/20 23:32 [entrez]
AID - 10.1002/ejhf.2737 [doi]
PST - ppublish
SO  - Eur J Heart Fail. 2023 Feb;25(2):260-270. doi: 10.1002/ejhf.2737. Epub 2023 Feb 
      1.