Abstract Body (Do not enter title and authors here): Background
Understanding the natural history and factors contributing to heterogeneous outcomes in patients with early-stage hypertrophic cardiomyopathy (HCM) is crucial to improving patient management.

Aim
Utilizing a real-world data cohort spanning multiple centers, we described the natural history of early-stage HCM patients and identified risk factors for disease progression.

Methods
SOLENOID is an observational study conducted in five academic centers (two in France, UK, Spain and the US). Inclusion criteria were patients with confirmed HCM seen between 2010 and 2022 in NYHA class I, or in “early stage” NYHA class II (defined by an NT-pro BNP<300 pg/ml, resting or provoked LVOT<50 mmHg, LAVi<35 ml/m2, E/e’<14, without a history of atrial fibrillation (AF), and not on HCM-specific therapy).
The endpoint was a composite of NYHA class worsening, new onset of AF and cardiovascular hospitalization. To identify risk factors, univariate analyses were conducted in each center, and then aggregated through a meta-analysis.

Results
A total of 1044 patients were included with a median follow-up of 3.9 years (IQR 1.5-7.0). The mean age was 53±16 years, with 30% females and 42% of NYHA I were treated with beta-blockers. Genetic tests in 57% of patients revealed mutations, primarily in MYBPC3 (29%) and MYH7 (12%).
During follow-up, the composite endpoint has an incidence of 27% and 41% at 3 and 5 years. The main contributor was NYHA class worsening with an incidence of 24% and 35% at 3 and 5 years. AF at inclusion (log-HR=1.56, p<0.001), baseline level of NT-proBNP (log-HR=0.75, p<0.001) and age at inclusion (log-HR=0.24, p=0.005) were the main predictors of the composite endpoint.

Conclusion
Nearly 30% of the early-stage HCM patients experienced disease progression within a 3 year follow-up period, highlighting a medical unmet need. Further studies are needed to assess whether the population characterized by elevated NT-proBNP, or pre-existing AF at inclusion, may benefit from more intensive surveillance and, in future HCM-specific therapy.