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March 21, 2026Heart Failure ReviewsOpen Access

Cardiac myosin inhibitor monotherapy outperforms beta-blockers in improving exercise tolerance and reducing outflow obstruction in HCM.

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Why the study?

Beta-blockers have long been the cornerstone of medical therapy for obstructive hypertrophic cardiomyopathy without disease-modifying effects, prompting evaluation of cardiac myosin inhibitors as potential monotherapy or first-line alternatives.

Do cardiac myosin inhibitors improve exercise tolerance and LVOT obstruction compared to beta-blockers in patients with obstructive hypertrophic cardiomyopathy?

Population

Patients with obstructive hypertrophic cardiomyopathy

Comparison

Cardiac myosin inhibitors vs beta-blockers

Key result

Cardiac myosin inhibitors as monotherapy demonstrated superior efficacy compared to beta-blockers in improving exercise tolerance and reducing outflow tract obstruction in obstructive HCM.

Authors

AGAvishay GrupperASAaron L. SverdlovBCBaljash Cheema

Discussion

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Overview

Supports first-line CMI monotherapy in oHCM; challenges beta-blockers as standard initial therapy.

Key Points

  • This research aims to compare the effectiveness of cardiac myosin inhibitors with beta-adrenergic blockers in treating obstructive hypertrophic cardiomyopathy.
  • Reviews randomized trials on cardiac myosin inhibitors and beta-blockers.
  • Assesses exercise capacity, LVOT gradients, and functional class improvements.
  • Analyzes subgroup data from EXPLORER-HCM and FOREST-HCM trials.
  • Cardiac myosin inhibitors provided significant reductions in LVOT gradients.
  • Improved exercise capacity and quality of life were observed with myosin inhibitors.
  • Aficamten monotherapy outperformed metoprolol in peak oxygen uptake and functional status.

Structured PICO

Do cardiac myosin inhibitors improve exercise tolerance and LVOT obstruction compared to beta-blockers in patients with obstructive hypertrophic cardiomyopathy?

P
Population
Patients with obstructive hypertrophic cardiomyopathy (oHCM)
I
Intervention
Cardiac myosin inhibitors (mavacamten, aficamten)
C
Comparator
Beta-blockers (e.g., metoprolol)

Cardiac myosin inhibitors represent a paradigm shift in oHCM management, offering superior improvements in exercise capacity and hemodynamics compared to traditional beta-blockers, potentially positioning them as first-line therapy.

Limitations

  • Current data on head-to-head comparisons between CMIs and BB are limited, with most evidence derived from subgroup analyses or a single randomized trial
  • Long-term safety, durability of response, and optimal patient selection for CMI monotherapy versus combination therapy are not fully defined
  • Questions regarding treatment sequencing, cost-effectiveness, and real-world applicability require further clarification

Cite This Study

Grupper et al. (2026) studied this question. Cardiac myosin inhibitors as monotherapy demonstrated superior efficacy compared to beta-blockers in improving exercise tolerance and reducing outflow tract obstruction in obstructive HCM.

synapsesocial.com/papers/69be35836e48c4981c673dd4https://doi.org/10.1007/s10741-026-10603-9
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