Abstract Body (Do not enter title and authors here): Background
Septal myectomy is the traditional standard for obstructive hypertrophic cardiomyopathy (HCM), yet mavacamten, a selective cardiac myosin inhibitor, has emerged as a noninvasive alternative supported by recent randomized trials. Despite this, comparative real-world outcome data between mavacamten and septal myectomy remain limited.

Methods
We utilized the TriNetX Global Collaborative Network. Adults with HCM (ICD-10: I42.1, I42.2) who received either mavacamten (RxNorm: 2600867) or surgical myectomy (CPT: 33416) were included. Patients exposed to both therapies were excluded. We identified 1,422 mavacamten-treated patients and 2,125 patients who underwent myectomy. After 1:1 propensity score matching on demographics, comorbidities (hypertension, coronary disease, chronic kidney disease, diabetes), and medications (beta-blockers, antihypertensives), 1,119 patients remained in each cohort. The index event was defined as the date of initial mavacamten prescription or septal myectomy, respectively. Outcomes assessed over 365 days included atrial fibrillation, ventricular tachycardia, ventricular fibrillation, all-cause mortality, and hospitalization.

Results
Mavacamten was associated with significantly lower 1-year risks of atrial fibrillation (5.8% vs. 11.6%; risk difference: –5.8%; risk ratio [RR]: 2.01, 95% CI: 1.40–2.89; p<0.001), all-cause mortality (1.6% vs. 4.9%; risk difference: –3.3%; RR: 3.06, 95% CI: 1.81–5.17; p<0.001), and hospitalization (16.0% vs. 37.9%; risk difference: –21.9%; RR: 2.37, 95% CI: 2.03–2.76; p<0.001). There were no significant differences in rates of ventricular tachycardia (4.7% vs. 3.6%; p=0.236), ventricular fibrillation (0.9% in both groups), or heart failure (4.0% vs. 4.7%; p=0.479). NT-proBNP values were also not significantly different between groups (p=0.939).

Conclusion
In a real-world cohort of propensity-matched patients with hypertrophic cardiomyopathy, mavacamten was associated with significantly lower risks of atrial fibrillation, hospitalization, and all-cause mortality at one year compared to septal myectomy. These findings support mavacamten as a potential alternative or bridge to surgery in select patients, reinforcing the findings of VALOR-HCM in a real-world cohort. However, the results should be interpreted in the context of unmeasured confounding, absence of echocardiographic data (e.g., LVOT gradient or septal thickness), and reliance on administrative coding.