2) Our expert first-time @cardiomet_ve author is Dra. Lucía Galán Dávila @lucia_galan, Especialista de área Neurologiaat Hospital Clinico San Carlos de Madrid 🇪🇸! @IIS_IdISSC#neurotwitter #attrpn #amyloidosis pic.twitter.com/kpAgVCtVZe
— cardio-met (@cardiomet_CE) February 21, 2024
4) In prior #tweetorials, you have learned about #ATTR_CM from @Ron_Witteles at https://t.co/mh4n8cXbA8 & from @BrettSperryMD at https://t.co/YwNJ0yMOJH. BTW, you can still earn 🆓C#/#CME from those programs!
— cardio-met (@cardiomet_CE) February 21, 2024
5b) You learned that the 2 most common types are lightchain amyloidosis (#AL) & transthyretin amyloidosis (#ATTR); ATTR may present as a hereditary or variant ATTR (#hATTR or #ATTRv) or wild-type ATTR (#wtATTR) with normal transthyretin (TTR) genotype.https://t.co/TQtawscGG9
— cardio-met (@cardiomet_CE) February 21, 2024
5d) #wtATTR is thought to be a aging-related phenomenon similar to #Aβ deposition in the brain, & manifests primarily as #cardiomyopathy, although wtATTR deposits can be found in connective and musculoskeletal tissue as well.
— cardio-met (@cardiomet_CE) February 21, 2024
🔓 https://t.co/bZ1nX5AjQb
6a) #ATTR #amyloidosis with #PN is the most progressive hereditary #polyneuropathy of adult onset. Early recognition & diagnosis are 🔑 because treatments are available to help slow the progression of #neuropathy. Not always easy: presentation varies; #FHx not always known.
— cardio-met (@cardiomet_CE) February 21, 2024
6c) In endemic countries 🇵🇹🇯🇵🇧🇷🇸🇪suspect #ATTR_PN in any patient who has length-dependent small-fiber PN with autonomic dysfunction + FHx #amyloidosis, unexplained weight loss, 🫀 rhythm disorders, vitreous opacities, or 🫘 abnormalities.
— cardio-met (@cardiomet_CE) February 21, 2024
6e) In nonendemic areas, dx likely to be missed; 50-75% have no FHx, presentation is variable; #ATTR_PN reported to be suspected in only 26–38% of 1st evaluations in these areas. Multiple misdiagnoses before correct dx reported in 20–40% of cases.
— cardio-met (@cardiomet_CE) February 21, 2024
🔓 https://t.co/sF87RUOamz pic.twitter.com/ElcqVFGd9M
6g) #EarlyDetection: #Orthopedic symptoms like carpal tunnel syndrome #CTS can precede #ATTR diagnosis by years, serving as early warning signs.
— cardio-met (@cardiomet_CE) February 21, 2024
6i) Recent reviews found no clear difference in #orthopedic manifestations between #vATTR and #wtATTR, but they’re especially frequent in cardiac phenotypes.https://t.co/eJYWuEcBqD
— cardio-met (@cardiomet_CE) February 21, 2024
6k) The timeline from disease onset to orthopedic symptoms varies (2-14 years) but is often shorter in #wtATTR. Recognizing these signs early is key. #EarlyDetection
— cardio-met (@cardiomet_CE) February 21, 2024
7a) So you & your patient are fortunate: you have made an early dx of #ATTR_PN. What are management options? #Neuropathic pain can often be managed by typical neuropathic oral agents (#gabapentin #pregabalin #duloxetine #venlafaxine) +/- topical agents (#lidocaine #capsaicin) pic.twitter.com/tk5FS0gPuV
— cardio-met (@cardiomet_CE) February 21, 2024
7c) Other nonspecific tx may be helpful, eg wrist splints or carpal tunnel release for #CTS, occupational therapy for #orthostasis, change in diet for nausea, vomiting, early satiety, constipation, etc. But let's consider targeted 🎯therapy: disease-modifying therapies (#DMT)
— cardio-met (@cardiomet_CE) February 21, 2024
8b) Reduction of circulating #TTR limits the building blocks for amyloid production while stabilization of TTR tetramer reduces dissociation into monomeric TTR, which is prone to #misfolding and #amyloid aggregation.
— cardio-met (@cardiomet_CE) February 21, 2024
8d) Development of “gene silencers” selectively targeting the production of #TTR in hepatocytes allowed suppression of circulating levels of both variant and wild-type TTR. See 🔓https://t.co/kfGN9T2Mb0 pic.twitter.com/uif1aWy4Ub
— cardio-met (@cardiomet_CE) February 21, 2024
8f) #Patisiran is a first-generation #siRNA drug that is formulated into lipid nanoparticles to allow delivery into hepatocytes for targeting TTR. It may also have some effectiveness for #ATTR_CM.
— cardio-met (@cardiomet_CE) February 21, 2024
🔓 https://t.co/ZfuGv4xIsk
8g) #Inotersen is an antisense oligonucleotide #ASO that inhibits hepatic production of #transthyretin. The #NeuroTTR trial showed inotersen had favorable effects on #ATTR_PN disease progression and #QoL.
— cardio-met (@cardiomet_CE) February 21, 2024
See 🔓 https://t.co/AqE1bIvAbg pic.twitter.com/m6IxoXer1g
8i) Following the #NeuroTTR trial, inotersen was approved by @US_FDA and @EMA_news for treatment of #ATTR_PN, under frequent platelet and renal function monitoring. It is no longer being evaluated for #ATTR_CM.
— cardio-met (@cardiomet_CE) February 21, 2024
8k) #HELIOS_A enrolled 164 pts (122 on #vutrisiran, 42 on #patisiran, 77 on historical placebo (APOLLO). Vutrisiran met primary EP of change from baseline in modified Neuropathy Impairment Score #mNIS +7 at 9 months & all secondary efficacy endpoints.https://t.co/HyrjKrs1P1 pic.twitter.com/04JCB8fWdE
— cardio-met (@cardiomet_CE) February 21, 2024
8m) #Vutrisiran is now approved by @US_FDA and @EMA_news for #ATTR_PN and is being studied (#HELIOS_B, NCT04153149) in #ATTR_CM.
— cardio-met (@cardiomet_CE) February 21, 2024
🔓https://t.co/enJkT1kOSX
9b) Approval from #NEUROTTRansform trial, an open-label, single-group, Ph 3 study to eval safety & efficacy of eplontersen vs historical placebo from the #NEURO_TTR trial of #inotersen, an earlier #ASO ⤴️, use of which is now limited by a #REMS program.https://t.co/p7ttvHhFjU
— cardio-met (@cardiomet_CE) February 21, 2024
9d) The #eplontersen group showed changes consistent w/ significantly ⬇️ serum #transthyretin concentration, less neuropathy impairment, & better #QoL compared with historical placebo. Longer-term safety/tolerability is being assessed in an ongoing open-label extension study. pic.twitter.com/qrPzsau5vb
— cardio-met (@cardiomet_CE) February 21, 2024
9f) #TEAEs in pts on #eplontersen were consistent w/ integrated class safety analysis of data from 7 Ph 2 studies for 6 GalNAc-conjugated #ASOs. TEAEs mild in 51% of pts; rate of tx d/c was low. No ⬆️risk of severe #thrombocytopenia or #renal impairment vs historical placebo. pic.twitter.com/qKIya7gpD1
— cardio-met (@cardiomet_CE) February 21, 2024
10) Other approaches to treating #ATTR_PN may emerge over the next few years, including gene editing with #CRISPR, new #TTR #stabilizers including #acoramidis & #tolcapone. For more info see:
— cardio-met (@cardiomet_CE) February 21, 2024
👉🔓 https://t.co/fRx8p5pwDt
👉🔓 https://t.co/mGfMC7E703
👉🔓 https://t.co/MjozLKZiLE
12a) #ATTR has been historically underdiagnosed. With advances in diagnostic methods and the advent of new #DMT, early diagnosis and initiation of treatment is revolutionizing management of this disease. While much attention is focused on #cardiomyopathy . . .
— cardio-met (@cardiomet_CE) February 21, 2024
13a) Currently @US_FDA-approved therapies for #ATTR_PN include all but which ONE of the following?
— cardio-met (@cardiomet_CE) February 21, 2024
13c) It’s d; #Eplontersen is an antisense oligonucleotide (#ASO) that acts as a gene silencer in #ATTR disease. Good job!
— cardio-met (@cardiomet_CE) February 21, 2024
14) YOU have not been silenced! You just earned 0.5hr 🆓 CE/#CME! Claim your certificate now at https://t.co/rewBDylm58 & then click that 🖱️ just one more time & FOLLOW US for more #MedEd delivered right here on Twitter! @lucia_galan thanks you for joining!
— cardio-met (@cardiomet_CE) February 21, 2024