2a) This program is intended for #healthcare providers and is supported by an educational grant from Bristol-Myers Squibb. Statement of accreditation and faculty disclosures at https://t.co/gvXca4GHMU. FOLLOW US for the most timely expert education in #cardiometabolic care!
— cardio-met (@cardiomet_CE) December 19, 2022
3) #HCM is common, affects 1:200 to 1:500 adults in the US, and is a pan-ethnic disease without known sexual or racial predilections. Background:
— cardio-met (@cardiomet_CE) December 19, 2022
👉🔓https://t.co/KEbWJDXj8z
👉🔓https://t.co/gq5YcBviIr
👉🔓https://t.co/24tQHQZ75p
Photo from https://t.co/igxiPydJd0 pic.twitter.com/r1yTXqK5TP
5) There are different imaging phenotypes of #HCM which can be seen on #echofirst and/or #whycmr
— cardio-met (@cardiomet_CE) December 19, 2022
Image from 🔓https://t.co/oyGNYZscOv pic.twitter.com/oQYLeqzQMY
7) However, myosin is not only bound to actin or available to bind, there is a third state called the super-relaxed state (off myosin) where the myosin head is folded inward and is not available to engage with actin.
— cardio-met (@cardiomet_CE) December 19, 2022
See 🔓https://t.co/owqrMVCpQc pic.twitter.com/0f42fzhbdj
9) This strong (or excessive) actin-myosin bound state leads not only to #hypercontractility, but also disordered relaxation (i.e. #diastole). See
— cardio-met (@cardiomet_CE) December 19, 2022
👉🔓https://t.co/9CRKnPgXht
👉🔓https://t.co/mVQCKzXGRO
11) Cardiac #myosin inhibitors were invented to address the issue of hypercontractility at the #sarcomere level without affecting calcium currents in myocytes.
— cardio-met (@cardiomet_CE) December 19, 2022
13) The first cardiac myosin inhibitor (#CMI) was #mavacamten; in an animal model of #HCM, it increases the super-relaxed state (#SRX) of myosin. See
— cardio-met (@cardiomet_CE) December 19, 2022
👉🔓https://t.co/pQ0rUwjsa7
👉🔓https://t.co/DzMao7diwB
👉🔓https://t.co/GHb02TduSL pic.twitter.com/ukKbAUXdVy
15) Tying it all together – cardiac myosin inhibitors represent the first class of medications to directly address the underlying #pathophysiology of #HCM
— cardio-met (@cardiomet_CE) December 19, 2022
👉 🔓https://t.co/LSDs7V4NXX pic.twitter.com/PLW9vAg6US
17) Another way to think about this is an imbalance between the gas and the brake mechanism. #MYH7 represents the gas (too much of it) while #MYBPC3 represents the brake (too little of it), and why those variants can cause #HCM
— cardio-met (@cardiomet_CE) December 19, 2022
🔓https://t.co/xybX3WZTVs
19) Back to disease classification: for tx decisions, #HCM is obstructive (#HOCM) or non-obstructive #HCM. This is based on having LV outflow tract (#LVOT) gradient of at least 30 mmHg as a result of systolic anterior motion of the mitral valve (#SAM).
— cardio-met (@cardiomet_CE) December 19, 2022
See https://t.co/A6cszkfF1m pic.twitter.com/BMA1N8m9eP
21) In terms of treatment, the whole therapeutic approach in #HCM relies on this classification, where it is estimated that 2/3 of #HCM patients are obstructive (at rest or with provocation)https://t.co/Rjq6llrI2r
— cardio-met (@cardiomet_CE) December 19, 2022
21) In terms of treatment, the whole therapeutic approach in #HCM relies on this classification, where it is estimated that 2/3 of #HCM patients are obstructive (at rest or with provocation)https://t.co/Rjq6llrI2r
— cardio-met (@cardiomet_CE) December 19, 2022
23) Patients are typically started on #beta_blockers or #calcium_channel_blockers, and if they remain with significant symptoms, then they are typically offered second line therapies or invasive intervention.
— cardio-met (@cardiomet_CE) December 19, 2022
25) The use of #ICDs with modern therapy in #HCM led to improvement in survival, but this meant that the lifetime risk of heart failure and arrhythmias would have ⬆️ in this populationhttps://t.co/mkhMu3Hqzl pic.twitter.com/ujxzNMrnl6
— cardio-met (@cardiomet_CE) December 19, 2022
27) With septal myectomy, ICDs and other interventions, outcomes of symptomatic obstructive #HCM appear to be favorable
— cardio-met (@cardiomet_CE) December 19, 2022
🔓https://t.co/y0FCBZFLFU pic.twitter.com/RmPikAc8tO
29) Up until recently, all therapies used in #HCM lacked any robust large multicenter trial data to support their use. #Mavacamten, a cardiac myosin inhibitor which is now approved by @US_FDA, is the first one with such data.
— cardio-met (@cardiomet_CE) December 19, 2022
31) Welcome back to our #accredited #tweetorial on #HCM! I am @MasriAhmadMD and you are earning 1⃣ hour 🆓CE/#CME credit! Follow @cardiomet_ce to address your CE needs with expert-authored programs delivered entirely on Twitter!
— cardio-met (@cardiomet_CE) December 20, 2022
33) So yesterday we started talking about #mavacamten, which was approved on the basis of the #EXPLORER_HCM trial ➡️20% difference in a co-primary endpoint (PVO2 and NYHA class) between the mavacamten arm and placebo over a 30 week treatment period
— cardio-met (@cardiomet_CE) December 20, 2022
See https://t.co/FaGw0Pljs0 pic.twitter.com/Qcm7pknIev
35) #Mavacamten also showed marked improvement in patient reported outcomes (by #KCCQ, available at 🔓https://t.co/hK4TwOXSzb).
— cardio-met (@cardiomet_CE) December 20, 2022
See https://t.co/Y1mN8KcvHC pic.twitter.com/LVudLUeMzK
37) #Mavacamten was associated with some events of low #LVEF, for which the majority were asymptomatic and are reversible with reducing the dose/withdrawal of treatment. LVEF decrease is discrepant with other markers. pic.twitter.com/UV2xUXSQgX
— cardio-met (@cardiomet_CE) December 20, 2022
39) @US_FDA approved #mavacamten on the basis of #EXPLORER_HCM trial. However, due to the risk of LV systolic dysfunction, narrow therapeutic window, and potential drug-drug interactions, the FDA mandated a sophisticated REMS program
— cardio-met (@cardiomet_CE) December 20, 2022
41) As part of the #REMS program, prescriber, patient and pharmacy have to enroll, and the drug can be dispensed only if all the established rules are satisfied
— cardio-met (@cardiomet_CE) December 20, 2022
Read more here if interested: https://t.co/doP4G9Q1E1
43) Patients must stay on the same dose for 12 weeks, & have 3 echo’s during this time, before up-titration can occur. If they had 2 echo’s with Valsalva LVOT gradient < 20 mm Hg, then the drug should be withheld.
— cardio-met (@cardiomet_CE) December 20, 2022
45) Patients must be reminded of drug-drug interactions, and the medications need to be reconciled when #mavacamten is dispensed. Some of the medications that interact are #OTC (omeprazole) but some are Rx for acute treatment (Paxlovid).
— cardio-met (@cardiomet_CE) December 20, 2022
47) #Mavacamten has only been approved for patients with obstructive #HCM, #NYHA class II-III, on standard background first line medical therapy for obstructive #HCM. It is not approved for asymptomatic or non-obstructive HCM.
— cardio-met (@cardiomet_CE) December 20, 2022
49) So . . . back to the #mavacamten trial data. In #EXPLORER, 2/3 of patients were #NYHA class II, and if patients require septal reduction therapy within the trial duration, they were excluded.
— cardio-met (@cardiomet_CE) December 20, 2022
51) VALOR-HCM recruited 112 patients referred for septal reduction therapy, with placebo controlled trial for 16 weeks followed by dose blinded cross over from placebo to #mavacamten. pic.twitter.com/n4qfMv4ykq
— cardio-met (@cardiomet_CE) December 20, 2022
53) The primary outcome was met as shown with 82% of patients on mavacamten being guideline-ineligible for septal reduction therapy at week 16.
— cardio-met (@cardiomet_CE) December 20, 2022
See https://t.co/6q566MGxEl. pic.twitter.com/sGmQLsoK6A
55) The Week 32 data were presented at #AHA22 and published as well, showing similar efficacy profile, but a high rate of low LVEF events (12.5% in the #mavacamten group and 5.7% in the placebo-mava group).
— cardio-met (@cardiomet_CE) December 20, 2022
See abstract 🔓https://t.co/EWd8ShPVg0 pic.twitter.com/9UPWobH3iV
57) #Mavacamten was also evaluated for safety and dose finding in non-obstructive HCM (#nHCM) in the phase II #MAVERICK_HCM trial.
— cardio-met (@cardiomet_CE) December 20, 2022
See 👉https://t.co/kUWqc9sWsL. pic.twitter.com/u8I7LPnmGP
59) The incidence of low LVEF was 12.8% in the study. This is generally reversible and not known to be associated with long term adverse outcomes.
— cardio-met (@cardiomet_CE) December 20, 2022
61) Finally, patients who received #mavacamten as part of #EXPLORER and #MAVERICK were enrolled in the #MAVA_LTE trial, which is a 5 year long term open-label extension study. Overall, mavacamten continued to have a similar efficacy profile to those seen in the parent studies. pic.twitter.com/4IHI5tj0xP
— cardio-met (@cardiomet_CE) December 20, 2022
63) Aside from #mavacamten, another cardiac myosin inhibitor is in development & undergoing clinical trials. #Aficamten has a similar therapeutic MoA but different binding site.
— cardio-met (@cardiomet_CE) December 20, 2022
See 🔓 https://t.co/tdUPigqUxT
🔓 https://t.co/Fr8twihXss
65) Welcome back! You are > 2/3 done earning 1⃣ full hour of 🆓CE/#CME right here on Twitter, at your best source for #cardiometabolic education! Expert faculty @MasriAhmadMD is teaching us all about the course of #HCM and new/evolving medical mgt options.
— cardio-met (@cardiomet_CE) December 21, 2022
67) The first phase II trial of #aficamten was in obstructive #HCM patients and called the #REDWOOD_HCM trial (Cohorts 1 and 2). In Cohort 1, dose was 5-15 mg, and 10-30 mg in Cohort 2.
— cardio-met (@cardiomet_CE) December 21, 2022
See nonaccredited 📽️at https://t.co/ZazlPfq4jo pic.twitter.com/gGGKDDwf21
69) There were 2 events of low #LVEF. Both happened with the higher dose rapid titration strategy(going from 10 to 20 mg aficamten). This informed the design of the ongoing phase III SEQUOIA-HCM trial.https://t.co/fc111Dw7oO
— cardio-met (@cardiomet_CE) December 21, 2022
71) Back to #REDWOOD, there was a 3rd Cohort of patients with obstructive #HCM refractory to an AV nodal blocking agent + #disopyramide.
— cardio-met (@cardiomet_CE) December 21, 2022
Abstract 🔓https://t.co/YEoTqQDwQM pic.twitter.com/lAhpEJxchW
73) Currently there is a 4th Cohort of #REDWOOD_HCM which enrolled non-obstructive #HCM patients pic.twitter.com/KiXPHZJHo4
— cardio-met (@cardiomet_CE) December 21, 2022
75) (Same ref) FOREST-HCM continued to show safety and efficacy of #aficamten pic.twitter.com/3UrgkRL7a1
— cardio-met (@cardiomet_CE) December 21, 2022
77) This is a summary of the confirmed low LVEF events in REDWOOD-HCM and REDWOOD-OLE (FOREST-HCM) pic.twitter.com/6fF6knvsoR
— cardio-met (@cardiomet_CE) December 21, 2022
79) Currently, a 2nd phase III trial of aficamten in #HOCM is planned to start soon: aficamten vs metoprolol, head to head, using #CPET. This would be the first evaluation of metoprolol using CPET in a large multicenter trial in obstructive #HCM. The trial is called MAPLE-HCM. pic.twitter.com/TOjFv1x3ZV
— cardio-met (@cardiomet_CE) December 21, 2022
81) This trial showed improvement in symptoms and #LVOT gradients but no difference in pVO2, #NTproBNP, and only a 3 point difference in #KCCQ. See https://t.co/P5eLU40KCz. pic.twitter.com/ZWOiMTex47
— cardio-met (@cardiomet_CE) December 21, 2022
83a) And here is the follow up video at Week 144. Evidence of the reverse #remodeling seen with improved #LVOT gradient and markers of diastolic function, indicating both reverse remodeling and improved cardiac structure. pic.twitter.com/pSl8Ec5jXm
— cardio-met (@cardiomet_CE) December 21, 2022
84) And here is an example of using #aficamten as part of a clinical trial in someone with significant #SAM but without severe hypertrophy (15 mm), and symptoms refractory to medical therapy:https://t.co/jQGuCxfQcy
— cardio-met (@cardiomet_CE) December 21, 2022
85b) The correct Answer is B – the treatment goal is to relieve symptoms
— cardio-met (@cardiomet_CE) December 21, 2022
(cont–mark your response below)
— cardio-met (@cardiomet_CE) December 21, 2022
C) Symptomatic obstructive HCM with 5 mmHg LVOT gradient at rest which increases to 83 mmHg with Valsalva
D) Symptomatic HCM with an LVEF of 48%
87) Finally, treatment of patients with obstructive #HCM is rapidly evolving. Evidence-based medicine is transforming HCM, and randomized clinical trials should be considered in every patient. Shared decision making is central in the treatment of patients with HCM! pic.twitter.com/G9jHfRn2XZ
— cardio-met (@cardiomet_CE) December 21, 2022
88) And you have just completed 1⃣ hour of CE/#CME! Claim your certificate 🇺🇸🇨🇦🇪🇺🇬🇧 at https://t.co/264JutFue0 and FOLLOW US for more expert education on #HCM and other #cardiometabolic disease! I am @MasriAhmadMD.#FOAMed #cardiotwitter #MedTwitter @MedTweetorials
— cardio-met (@cardiomet_CE) December 21, 2022