2) Our expert author is again Sergio Kaiser MD PhD FACC FESC 🇧🇷🇮🇱 @pabeda1, cardiologist 🫀, Professor 🎓 of #InternalMedicine, Rio de Janeiro State University. He brings the general cardiologist's perspective to our #HCM discussions. Read and learn!#FOAMed #CardioTwitter pic.twitter.com/dX56lsBgib— cardio-met (@cardiomet_CE) April 10, 2023
4a) So we promised at the end of Part 1 to talk about advances in #medical therapy for #HCM, and we alluded to the mechanism of #myosin inhibition in that regard.— cardio-met (@cardiomet_CE) April 10, 2023
The first report of a small molecule capable of preventing development of #HCM in a 🐁model dates back to 2016.
7b) Biomarkers of ventricular wall stress (#NT_proBNP and cardiac #troponin I) were significantly ⬇️ in both groups. Serious adverse events occurred in 10% of participants on mavacamten and in 21% participants on placebo.— cardio-met (@cardiomet_CE) April 10, 2023
(Group 1=200mg dose, Group 2=500mg dose) pic.twitter.com/hK3BslI4tD
8b) #Mavacamten doses 2.5, 5, 10, or 15mg given PO to ➡️target ⬇️in #LVOT gradient < 30mm Hg + mavacamten plasma concentration 350-700ng/mL. 75% of pts taking beta-blockers & 18.7% taking #CCBs at enrollment. pic.twitter.com/9pGHmrRAZv— cardio-met (@cardiomet_CE) April 10, 2023
8d) Pts on #mavacamten had— cardio-met (@cardiomet_CE) April 10, 2023
🫀 greater ⬇️ vs placebo in post-exercise #LVOT gradient
🫀 greater ⬆️in pVO2
🫀 improved symptom scores
Improvement by at least 1⃣NYHA class in 34% more patients in the mavacamten group. pic.twitter.com/42oXlwVu94
8f) #symptom relief? per Kansas City Cardiomyopathy Score #KCCS— cardio-met (@cardiomet_CE) April 10, 2023
👉 At 30wks, change in #KCCQ_OS (overall score) sig greater w/#mavacamtenvs placebo, & % pts w/ a very large change = 36% vs 15% ➡️#NNT=5.
👉 Gains returned to baseline after tx interrupted.https://t.co/Y1mN8KbXS4
9a) We talked in Part 1 about "classic" therapy for #HCM, eg beta-blockers. An interesting analysis of pts from #EXPLORER_HCM & #MAVA_LTE (ongoing Ph 2/3 extension study of long-term #mavacamten (252 weeks) after completion of EXPLORER or MAVERICK.— cardio-met (@cardiomet_CE) April 10, 2023
12b) Mark your best answer and RETURN TOMORROW for the correct response, more education, an intro to @aficamten, and a link to your 🆓CE/#CME!— cardio-met (@cardiomet_CE) April 10, 2023
👍 @alexariasmx20 @KemalogluOz @Sarah_Moharem @DrCCaroli @vitorborin_ @omendiz @VerwerftJan @bcaramelli @rmourilhe @EzequielZaidel
14a) Yesterday's quiz? The correct answer is C: #echocardiograms. A Risk Evaluation and Mitigation Strategy #REMS is a drug safety program that @US_FDA can require for certain medicines to ensure they are used safely.— cardio-met (@cardiomet_CE) April 11, 2023
16b (cont)— cardio-met (@cardiomet_CE) April 11, 2023
🫀 resting or provoked #LVOT gradient ≥ 50 mmHg
🫀 LVEF ≥ 60%
In this trial, use of disopyramide at baseline allowed. Pts randomized to an escalating dose of #mavacamtenor placebo, followed 16 weeks:
🔓 https://t.co/5DIfYsAxSZ pic.twitter.com/2t4lTxxwrW
16d) No patient had a dangerous drop in #LVEF. Two patients on mavacamten experienced a >50% ⤵️in EF, but returned to baseline values after transient drug discontinuation.— cardio-met (@cardiomet_CE) April 11, 2023
17b) At 32 weeks, 10.7% in original #mavacamten group & 13.5% in the placebo cross-over group met #SRT guideline criteria or elected to undergo SRT. The mava group showed sustained ⬇️in resting #LVOT gradient and Valsalva LVOT gradient pic.twitter.com/M4W23Qft4O— cardio-met (@cardiomet_CE) April 11, 2023
18b) #REDWOOD_HCMwas Ph 2 dose-finding #RPCT of #aficamten.— cardio-met (@cardiomet_CE) April 11, 2023
👉enrolled 2 sequential cohorts of pts w/ symptomatic #oHCM
👉1 tx'd w/ 3 escalating doses of 5 to 15 mg vs placebo, 1 tx'd w/ 3 escalating doses of 10 to 30 mg vs placebo
19b) 85% of pts achieved max 15 mg dose & no pt had #LVEF drop <50%. In this trial, 54% of patients improved by at least one functional class. There were also significant drops in NT-proBNP and hs-TNI over time. Trial medication was withheld after 10 weeks pic.twitter.com/BPqJ5z9Gw5— cardio-met (@cardiomet_CE) April 11, 2023
22a) Where do cardiac #myosin inhibitors fit into management of #oHCM? A suggested decision flow for use of #macavamten from— cardio-met (@cardiomet_CE) April 11, 2023
📖 Ommen SR #ACC22 oral presentation
📖 🔓 https://t.co/5DIfYsAxSZ
📖 Lakdawala 2023
📖#mavacamten PI: https://t.co/qTufMimRpY pic.twitter.com/13MEFxxfxp
23a) So as we summarize, let's see what you learned. Which of the following re #HCM is FALSE?— cardio-met (@cardiomet_CE) April 11, 2023
a. genetic testing is not required for diagnosis.
b. echo and #CMR are complementary imaging methods
c. mavacamten is approved for #oHCM
d. mavacamten is approved for non-oHCM
24a) On to take-🏡messages:— cardio-met (@cardiomet_CE) April 11, 2023
1⃣ Hypertrophic cardiomyopathy #HCM is now compatible w/ longevity & good quality of life, thanks to advances in assessment & tx of its phenotypic expressions. But, periodic reassessment will be a companion over the life course of a patient with HCM. pic.twitter.com/UVkR3wBMXR
24c)— cardio-met (@cardiomet_CE) April 11, 2023
3⃣Genetic testing is recommended for famílial screening, though probands harboring a sarcomeric mutation may never develop the clinical and morphological spectrum of HCM. Indeed, phenotypic features of HCM cannot be fully explained by genetics.
24d)— cardio-met (@cardiomet_CE) April 11, 2023
4⃣Echocardiography and cardiac MR are complementary methods for assessing hypertrophy patterns, cardiac systolic and diastolic function, and features of prognostic importance, like apical aneurisms, myocardial fibrosis and massive hypertrophy.
24h)— cardio-met (@cardiomet_CE) April 11, 2023
8⃣ #Macavamtenis already approved in the U.S. for the treatment of adults with symptomatic #NYHA class II-III obstructive #HCM to improve functional capacity and symptoms. #Aficamten is under study.