💥 The coexistence of IEVs with monogenic variants leads to a more aggressive HCM phenotype: earlier onset, greater hypertrophy, and reduced survival (MACE-free: 69% vs 93% at 70 yrs).

💥 Clinical takeaway: IEV assessment could be considered as part of HCM genetic testing.

⚡ Clinically, IEV carriers had:
👉 Earlier diagnosis (59 vs 61 yrs)
👉 Thicker LV walls
👉 Higher risk of adverse events
➡️ IEVs aren’t “benign” passengers—they modulate disease severity. #SoMeEditor

🧬 In >10k HCM cases vs >590k controls, 14 IEVs were identified across 8 genes.
🧬 Strikingly, 65% were in non-sarcomeric genes.
🧬 Contribution to HCM burden? 4.9%. #Genetics #HCM #SoMeEditor

🚨 New @CircAHA #ESC2025 SimPub alert!
🚨 HCM isn’t just driven by rare Mendelian mutations. This study highlights the role of intermediate-effect variants (IEVs)—variants with moderate effect & low penetrance—in shaping disease expression. #HCM #SoMeEditor

tinyurl.com/HCM-IEVs