2) Follow this 🧵for 0.75h 🆓CE/#CME! See prior programs on #HCM, still available for even more 🆓credit, at https://t.co/7KtfmhxQ0v, where you’ll find #tweetorials from @GiuseppeGalati_ and @MasriAhmadMD.
— cardio-met (@cardiomet_CE) January 31, 2023
🫀 @cardiomet_ce is your ONLY 🏠 for CE/CME delivered wholly on Twitter!
4) Hypertrophic cardiomyopathy (#HCM) is the most common inherited #cardiomyopathy w/ a general population prevalence of 1:500.
— cardio-met (@cardiomet_CE) January 31, 2023
🫀 Defined by otherwise unexplained left ventricular (#LV) hypertrophy + a maximal end-diastolic wall thickness of ≥15 mm (≥13 mm in familial cases).
6) The main complications include #LV outflow tract or midventricular obstruction (#LVOTO), #heartfailure, #atrialfibrillation (#AF), ventricular #arrhythmias and sudden cardiac death (#SCD)
— cardio-met (@cardiomet_CE) January 31, 2023
8) Current treatment for obstructive #HCM (#oHCM or #HOCM) rests on septal reduction therapies (#SRT), and the use of drugs developed for other purposes, such as beta-blockers (BB), calcium antagonists (#CCBs), and #disopyramide.
— cardio-met (@cardiomet_CE) January 31, 2023
10) #Myosins are molecular propellers converting the chemical energy of ATP hydrolysis into mechanical force necessary for muscle contraction. Each myosin dimer consists of two globular heads and a coiled-coil tail.
— cardio-met (@cardiomet_CE) January 31, 2023
See https://t.co/BXFhgH1Mgn pic.twitter.com/EdXqdU7oy7
11b) Therefore generated force depends on the amount of open-headed myosins.
— cardio-met (@cardiomet_CE) January 31, 2023
See 🔓https://t.co/GHb02TduSL pic.twitter.com/zv8oWjYQPF
13) #Mavacamten (#Mava) shifts the on-off state equilibrium toward the off-folded state causing a dose-dependent reduction in contractilityhttps://t.co/uZuqhumr3U pic.twitter.com/HNlay2Ml68
— cardio-met (@cardiomet_CE) January 31, 2023
15) In the Ph 2 #PIONEER_HCM trial, treatment with #Mava in #oHCM led to dose-dependent (cohort A 10 to 20 mg/d vs cohort B 2 to 5 mg/d) improvements in post-exercise #LVOT gradients, exercise capacity and symptoms, and was generally well toleratedhttps://t.co/SqV1cNH9tX pic.twitter.com/Ur4Ted3zp5
— cardio-met (@cardiomet_CE) January 31, 2023
17) Primary endpoint: composite evaluating functional capacity by cardiopulmonary exercise testing #CPET and symptoms : ≥1.5 mL/kg/min increase in pVO2 with ≥1 NYHA class improvement or ≥3.0 mL/kg/min increase in pVO2 with no worsening of NYHA class https://t.co/uZuqhumr3U
— cardio-met (@cardiomet_CE) January 31, 2023
19) #pVO2 is a direct, objective, and reproducible measure of exercise capacity which has been shown to correlate with NYHA functional class, PROs, and quality of life #QoL in #HCM.
— cardio-met (@cardiomet_CE) January 31, 2023
See https://t.co/wKMnHz5j2A. pic.twitter.com/xxHvzY0mPR
21) Patient reported outcomes (#PROs): Kansas City Cardiomyopathy Questionnaire (#KCCQ) and the new disease-specific #HCM Symptom Questionnaire (#HCMSQ) have been used.
— cardio-met (@cardiomet_CE) January 31, 2023
23) And now let’s dive into the results pic.twitter.com/8TrRaEMexg
— cardio-met (@cardiomet_CE) January 31, 2023
25) Twice as many patients on #Mavacamten met the primary endpoint (37% vs. 17%, p = 0.0005). pic.twitter.com/DYYhJSkJLy
— cardio-met (@cardiomet_CE) January 31, 2023
27) #PROs: quality of life evaluated by #KCCQ and HCM shortness of breath subscore improved in Mava vs Pbo pic.twitter.com/7Zynhry9xn
— cardio-met (@cardiomet_CE) January 31, 2023
29) Clinical improvement was associated with marked reduction in serum levels of N-terminal pro-brain natriuretic peptide (#NTproBNP) and troponin I, two predictors of long-term outcome in #HCM. pic.twitter.com/zGUBdd9tCe
— cardio-met (@cardiomet_CE) January 31, 2023
31) Treatment-emergent adverse events #TEAEs were generally mild.
— cardio-met (@cardiomet_CE) January 31, 2023
🫀 11 serious adverse events were reported by ten (8%) patients on Mava versus 20 events reported by 11 (9%) on Pbo pic.twitter.com/tahchho1Y6
33) Benefit from #mavacamten was consistent across most prespecified subgroups. Patients on BB had a lower response, but we will evaluate this data later… pic.twitter.com/Y4Zs5X44Zs
— cardio-met (@cardiomet_CE) January 31, 2023
35) Welcome back! @IacopoOlivotto and @AlessiaArgiro 🇮🇹 are taking through a review of the pathophys and optimal contemporary med mgt of #HCM. And YOU 🫵 are earning 🆓CE/#CME!#FOAMed #cardiotwitter #cardiomyopathy @MedTweetorials #MedEd
— cardio-met (@cardiomet_CE) February 1, 2023
37) #ECHO substudy:#Mavacamten determined a complete resolution of #SAM in 81% of patients (vs 34%, difference 48.8, p<0.01), improved measures of diastolic function including left atrial volume index, lateral E/e’, & reduction in #NTproBNPhttps://t.co/VscXPKcN78 pic.twitter.com/rs0Sr1TkUD
— cardio-met (@cardiomet_CE) February 1, 2023
39) Cardiac magnetic resonance (#whyCMR) substudy: positive remodeling of chambers’ geometry with a reduction of LV mass index, maximal LV wall thickness and reduction of left atrial volumehttps://t.co/eHAFGuBOyQ pic.twitter.com/0HvOTpkAPd
— cardio-met (@cardiomet_CE) February 1, 2023
40b) Notably, the majority of patients on #BB had #chronotropic incompetence, affecting heart-rate dependent measures (pVO2, peak exercise time, peak METS). See https://t.co/RX3xG3NKf5 pic.twitter.com/Q79UHa569Y
— cardio-met (@cardiomet_CE) February 1, 2023
42) But also, a significant improvement in nonpeak-exercise #CPET parameters: VE/VCO2 slope and ventilatory power pic.twitter.com/TOAHdxROJW
— cardio-met (@cardiomet_CE) February 1, 2023
44) Long-term extension (#EXPLORER_LTE): substantial and sustained improvement in resting and Valsalva #LVOT gradients, LV filling pressures, #NTproBNP and #NYHA class at 84 weeks, confirming a favorable safety profilehttps://t.co/FwlYmevs0F pic.twitter.com/8H6Bp07Bpq
— cardio-met (@cardiomet_CE) February 1, 2023
46) #VALOR_HCM trial (Mavacamten in Adults with Symptomatic Obstructive #HCM Who Are Eligible for #SRT): 112 pts with severe symptoms despite maximal medical therapy (BB/CCB ± disopyramide) were randomized to Mava or Pbo
— cardio-met (@cardiomet_CE) February 1, 2023
See 🔓 https://t.co/5DIfYsB5Ix pic.twitter.com/RFAUKIJqO4
48) Secondary endpoints: mean differences in post-exercise peak #LVOT gradient -37.2 mm Hg; ≥1 #NYHA functional class improvement 41.1%; improvement in patient-reported outcome 9.4 points; and improvement in #NTproBNP & TnI. pic.twitter.com/BRVX9aUwB0
— cardio-met (@cardiomet_CE) February 1, 2023
50) More definite answers for symptomatic nonobstructive #HCM patients will hopefully originate from the ongoing Ph 3 #ODYSSEY_HCM trial, https://t.co/EgUWX1bxgl
— cardio-met (@cardiomet_CE) February 1, 2023
52a) Now that we acknowledge all the data on #Mavacamten let’s do a poll.
— cardio-met (@cardiomet_CE) February 1, 2023
52c) Have you been paying attention? The correct answer (ie the FALSE statement) is D.
— cardio-met (@cardiomet_CE) February 1, 2023
53b) achieving steady state concentration within 2wks vs 6 wks Mava ➡️ potentially easier titration https://t.co/7bWeB5wV65 pic.twitter.com/AHjBdMLjFF
— cardio-met (@cardiomet_CE) February 1, 2023
55) Clinical trial population: Median age treatment arm 57 ys, 54% women, 39% NYHA III, 75% on BB, 25% CCB. pic.twitter.com/LfxvcTINN9
— cardio-met (@cardiomet_CE) February 1, 2023
57) Symptomatic improvement in ≥1 New York Heart Association functional class was observed in 31% on placebo, 43% and 64% on #Aficamten in Cohorts 1 and 2. pic.twitter.com/04PRtWkEOj
— cardio-met (@cardiomet_CE) February 1, 2023
59) #Aficamten was well tolerated with no SAEs that led to early termination of the drug and most events were mild/moderate. pic.twitter.com/Q1lPVM66Ef
— cardio-met (@cardiomet_CE) February 1, 2023
61) Cohort 3: 13 pt on #disopyramide (+ 11/13 BB). 3 escalating doses (5, 10, 15 mg): reduction in resting (-28 ± 3.2 mmHg p < 0.0001) & Valsalva LVOT-G (-27 ± 5.9 mmHg p = 0.0002) + modest reduction in LVEF (-4.8 ± 1.9% p = 0.018). None had LVEF < 50%. https://t.co/X5hqrcpe1Z pic.twitter.com/MHrYpASjJN
— cardio-met (@cardiomet_CE) February 1, 2023
63a) Within 2 weeks saw sustained reduction in #LVOT gradients that improved with up-titration through 24 weeks (resting LVOT-G = -32.6 (28) mmHg, p<0.0001 at 12 weeks, -32.8 (32.3) mmHg, p=0.0003 at 24 weeks . . .
— cardio-met (@cardiomet_CE) February 1, 2023
64) At 12 weeks, 72% of patients improved 1 #NYHA class & 7% improved two classes; at 24 weeks 61% of patients improved by one class and 17% improved by two classes.
— cardio-met (@cardiomet_CE) February 1, 2023
There was also a 70% and 20% reduction in #NTproBNP and #troponin I, respectively. pic.twitter.com/Apy3aTA8V9
66) #KCCQ-OS and all sub-domains improved. At 12 and 24 wks, the change in KCCQ-OSS was 16.5 [16.7] (p<0.0001) and 17.6 [24.7] (p=0.0015). There was a very large clinical improvement (≥20 points) in 36% of patients at Week 12 & 40% at wk 24.https://t.co/AUg9h47tRu pic.twitter.com/1E6Mv24kIo
— cardio-met (@cardiomet_CE) February 1, 2023
68) One more poll. Which of the following is FALSE?
— cardio-met (@cardiomet_CE) February 1, 2023
a. Aficamten is a myosin inhibitor
b. Aficamten has a shorter half-life compared to Mavacamten
c. Aficamten reaches steady state conc in 2wks compared to 6wks for Mavacamten
d. Aficamten has not been studied in obstructive HCM
70) And so you have just earned 0.75hr 🆓CE/#CME! Just point your 🖱️ to https://t.co/U7ZXiESDBO to claim your certificate. And FOLLOW US for more expert-led education. @IacopoOlivotto and @AlessiaArgiro 🙏for joining us!#FOAMed #cardiotwitter
— cardio-met (@cardiomet_CE) February 1, 2023