Leah A. John, MD MBA

🧬 LMNA cardiomyopathy: not all patients progress the same. Now we can quantify who will. We’ve become good at predicting: 👉 sudden death 👉 arrhythmic risk But heart failure? 👉 Still a blind spot in laminopathies 💥 This paper changes that. For the first time: 👉 a dedicated risk model for HF progression in LMNA patients 📊 The reality (and it’s not reassuring): • HF-MACE in ~10% at 5 years • ~45% lifetime risk by age 70 And if LVEF <30%: 👉 50% events within 1 year ehag104 ⚡ Four variables. That’s it. Independent predictors of HF progression: • Male sex • LVEF <50% • Missense variants (head/rod domains) • Complete LBBB 🔥 Translation: 👉 Genetics + conduction + early LV dysfunction = the HF trajectory is already written 📉 What’s really striking (Figure 4): • 0 risk factors → ~1.5% at 5 years • 1 factor → ~5% • ≥2 factors → ~22% ➡️ Not a spectrum ➡️ A stepwise risk escalation 🧠 And here’s the key insight: 👉 Even with preserved EF, risk is not low Patients with LVEF ≥50% + risk factors: → still meaningful HF risk (~11% at 5 years) ehag104 ⚠️ This challenges our mindset: We wait for EF to drop 👉 But the disease is already progressing 💡 Clinical implication (this is the real shift): Risk stratification in LMNA should not be: ❌ reactive ❌ EF-driven But: 👉 proactive + genotype-informed 🚀 What this enables: • Earlier follow-up intensification • Earlier HF therapy • Earlier referral for advanced HF pathways • Better selection for trials 🎯 Take-home message LMNA cardiomyopathy is predictable. 👉 Not just arrhythmias 👉 Heart failure too And if we wait for severe dysfunction… 👉 we are already late 💬 Should we start treating LMNA patients before EF declines? #Cardiology #LMNA #Cardiomyopathy #HeartFailure #Genetics #PrecisionMedicine #EPeeps #CardioTwitter 🧬🫀 doi.org/10.1093/eurheartj/eh…