Abstract Body (Do not enter title and authors here): Background
For over 60 years, beta-blockers have been first-line therapy for symptomatic, obstructive hypertrophic cardiomyopathy (oHCM), although limited data support this recommendation. MAPLE-HCM (Phase 3 Multi-center, Randomized, Double-blind Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Metoprolol in Adults with Symptomatic Obstructive Hypertrophic Cardiomyopathy; NCT05767346) showed greater improvement in exercise capacity by peak VO₂ and secondary endpoints for aficamten vs metoprolol.

Research Question
To evaluate the incremental effect of aficamten vs metoprolol across multiple clinically relevant and patient centric measures in oHCM patients.

Methods
Patients with oHCM and left ventricular outflow tract gradients (LVOTG) ≥30 mmHg at rest and/or ≥50 mmHg with Valsalva were randomized to aficamten (n=88) or metoprolol (n=87) titrated based on vital signs and TTE results. Clinical response by treatment arm was assessed based on improvement in 5 endpoints reflecting oHCM disease burden: 1) LVOTG <30 mmHg at rest and <50 mmHg with Valsalva; 2) NYHA improvement of 1 or more class and/or increase in Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS) ≥10; 3) ≥50% reduction in NT-proBNP; 4) peak VO2 improvement of ≥1.0 mL/kg/min; and 5) decrease in left atrial volume index ≥10%. The clinical response of each participant was classified by number of efficacy outcomes achieved: non-responder (none), limited (1 or 2), positive (3 or 4) or complete (all 5).

Results
Baseline characteristics were similar for both treatment groups. For the overall cohort, mean age was 58 yrs (13.2); 73 (42%) female and 103 (70%) were NYHA II and 52 (30%) class III, with mean pVO2 =19.9 (5.1) mL/kg/min and KCCQ-CSS score =66 (16). At 24 weeks, compared with patients on metoprolol, treatment with aficamten was associated with more positive responses in each efficacy outcome (Table 1). For aficamten, NNT for each outcome ranged from 1.5 to 5. Patients treated with aficamten were more frequently complete or partial responders (78% vs 3%; p<0.001), whereas those treated with metoprolol were more frequently non- or limited responders (97% vs 20%; p<0.001) (Figure 1).

Conclusions
In symptomatic oHCM patients, treatment with aficamten was associated with superior treatment effect across several clinically relevant outcome measures compared with metoprolol. These observations support the emerging role for aficamten as monotherapy for oHCM.