Abstract Body (Do not enter title and authors here): Background
Beta-blockers (BB) and non-dihydropyridine calcium channel blockers (CCB) are first-line therapies for hypertrophic cardiomyopathy (HCM) used both upon symptom onset and for pre-symptomatic patients. However, there is limited evidence supporting their efficacy, particularly from randomized controlled trials.

Aims
In this study we assessed the prevalence, discontinuation rates, and effectiveness of BB/CCB for NYHA class I HCM patients.

Methods
Utilizing data from a real world cohort spanning 4 centers, we evaluated BB/CCB effectiveness in NYHA class I patients with HCM. The effectiveness analysis for a composite endpoint (NYHA class worsening and cardiovascular-related hospitalization) was performed independently at each center and an aggregated analysis was performed. NT-proBNP level analysis was performed where longitudinal data was available. Patients initiating therapy during follow-up were compared to untreated controls, adjusting for confounders (duration since HCM diagnosis, left atrial volume index (LAVi), E/e' lateral ratio, medical history, NT-ProBNP levels) using inverse probability weighting and Stürmer trimming. The association between treatment and the risk of composite endpoint was assessed through Cox regression, while mixed models for repeated measures were used for NT-proBNP levels.

Results
Among the 735 patients, 64% initiated BB/CCB therapy with a 33% discontinuation rate at 4 years. A total of 222 patients with extreme propensity scores were excluded. As shown in Table 1., no benefit from BB/CCB in reducing the composite endpoint risk (HR=1.08, p=0.79) was observed. This was consistent across the different components of the endpoint. Additionally, no benefit in reducing NT-proBNP levels after 1 year was detected (Least Means Square difference=0.02, p=0.79).

Conclusion
Initiation of BB/CCB for NYHA I HCM patients did not appear to reduce the risk of progression measured by the functional capacity, CV hospitalization and NT-proBNP. Despite the inherent limitation of observational studies, these findings together with the high discontinuation rate of the therapy, underscore the need for further research to validate optimal treatment strategies for pre-symptomatic HCM patients.