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Trial objective/population: SEQUOIA-HCM aimed to determine the efficacy and safety of aficamten in adult patients with symptomatic obstructive HCM. #CardsJC

Study design: It is an international, phase 3, double-blinded, randomized placebo-controlled trial involving 80 sites. 🌍 Any thoughts about the design? #CardsJC

Which patients with HCM were included? 📍LV wall thickness ≥ 15mm 📍EF ≥ 60% 📍LVOT gradient ≥ 30 mm Hg at rest and ≥ 50 mm Hg after Valsalva 📍NYHA II-III 📍⬇️ exercise capacity

Now let's look at key baseline characteristics:

Is this a representative HCM population? Specially looking at: 🌎 79% White patient representation 🧬17.5% with pathogenic sarcomeric variant 💊Prevalence of BB, CCB, disopyramide use 🫀NYHA Class ratio #CardsJC

Primary endpoint: Δ in peak oxygen uptake during cardiopulmonary exercise in 24 weeks Key secondary endpoints: Δ in peak LVOT gradients Δ in KCCQ-CSS Δ in NYHA functional class Are these endpoints sufficient to answer the objective? 📊🔍 #CardsJC

Now what we all have been waiting for, the key finding: ⭐️ Mean change from baseline to week 24 in peak VO2 uptake, for aficamten vs. placebo, was: 1.8 vs. 0.0 mL/kg/min (p < 0.0001)

Does this convince you of the utility of aficamten? #CardsJC

What about the secondary outcomes? ⭐️ Δ in KCCQ-CSS: 12 vs. 5* ⭐️ Δ in LVOT gradient ≤30 mm Hg after Valsalva: 49.3% vs. 3.6%* ⭐️ Δ in LVOT gradient: -47.6 vs. 1.8 mm Hg* ⭐️ Δ in NYHA functional class: 58.5% vs 24.3%* Do these results surprise you? #CardsJC

Any thoughts about the prevalence of adverse events in each group? 🚨Serious AE in 8 patients (5.6%) in the aficamten group and in 13 patients (9.3%) in the placebo group #CardsJC

Did aficamten cause any 📉in EF? 🚨EF in aficamten group was modestly lower by –4.8% (–6.3, –3.2) 🚨 After washout, no Δ in LVEF in both groups: –1% (–2, 0) 🚨 Transient ⬇️ of < 50% in EF in 5 pts (3.5%) in aficamten group and in 1 pt (0.7%) in placebo group Thoughts? #CardsJC

Is the exercise capacity benefit of aficamten 5-20mg in pts with symptomatic HCM believable? #CardsJC

Clinically, this is relevant since aficamten can improve the way that pts with obstructive HCM feel and function. This trial highlights the benefits of CMI drug therapy in pts with obstructive HCM, which were similar to the recent findings seen with mavacamten.

Takeaway: SEQUOIA-HCM challenges the status quo in HCM treatment and presents a novel option that is shown to provide symptomatic benefit to patients. Will aficamten become the standard of care? Will these results impact your practice? #CardsJC

Have you changed your HCM treatment strategy based on any recent trials? Share your experiences and thoughts! 💬❤️👇 #CardsJC

And thats a wrap! Thanks for all the help from our incredible panel of experts #CardsJC Martin Maron, MD Srihari S. Naidu, MD Christopher Kramer MD W. H. Wilson Tang, MD Sonu Abraham Dr. Purvi Parwani Milind Desai MD MBA Vincent Chen

Thank you to our incredible 🤩CardioNerds team and academy fellows! shout out to Anna Radakrishnan, MD, MBA Akiva Rosenzveig Apoorva Gangavelli, MD, MSc Shazli Khan

Stay tuned for more updates and deep dives into the latest cardiology trials. Thanks for joining and sharing your insight! 🫀🩺 CardioNerds Journal Club #CardsJC

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