1b) We are honoured to have as our guest expert faculty Fausto Pinto MD PhD @fjpinto1960, Diretor do Serviço de Cardiologia do @ulssanta_maria; Past-President, #WHF, Past-President @escardio, from Lisbon 🇵🇹. As you might have noticed ⤴️, he is the senior author of this document! pic.twitter.com/reXzaa1CRF
— cardio-met (@cardiomet_CE) March 6, 2024
4a) This is an absolutely essential document in your #cardiology library. #Transthyretin #amyloid #cardiomyopathy (#ATTR_CM) is a progressive & fatal condition requiring early dx, careful management, & specific tx. Recent ⬆️in interest because of 🆕disease-modifying therapies.
— cardio-met (@cardiomet_CE) March 6, 2024
5a) #ATTR_CM can be age-related (wild-type form #wt) or due to mutations in the #TTR gene (genetic, #hereditary forms). Though systemic, a predominant #cardiac #phenotype is often present. This document focuses on 🫀 involvement, which is the most critical factor for prognosis.
— cardio-met (@cardiomet_CE) March 6, 2024
6) So for context: ~50% of pts with #HF have #HFpEF, ie, their #LVEF is preserved. Then half of THOSE pts have increased #LV wall thickness (for #MedEd on another disease associated with ⬆️LV wall thickness, see https://t.co/7KtfmhxiaX.
— cardio-met (@cardiomet_CE) March 6, 2024
And see https://t.co/P4u6PQTPff
8a) #ATTR_CM was considered a rare disease in the past, but as graph ⤴️shows, it is not an uncommon cause of #HF. Also in the past it has been considered progressive & fatal if not diagnosed early.
— cardio-met (@cardiomet_CE) March 6, 2024
🔓 https://t.co/YpCmdy7cg8
🔓 https://t.co/fhROyVOVeh
👉https://t.co/iNmjTRB38r pic.twitter.com/81xJj0UK3A
8c) Early & accurate dx (it's often mis- and under-diagnosed) are also more important than ever because there are now approved & emerging specific treatments for #ATTR_CM.
— cardio-met (@cardiomet_CE) March 6, 2024
🫀 https://t.co/iNmjTRB38r
🔓 https://t.co/g8qGOXDeKc
🫀 https://t.co/BhPQH06w2K
🔓 https://t.co/SgwZoCz68V pic.twitter.com/HZTd94rBzs
9b) Conditions are named for their amyloidogenic precursor protein; eg, in #transthyretin #amyloidosis (#ATTR) the #amyloid (A) fibril is formed by transthyretin (#TTR), a tetrameric transport protein synthesized in liver, in choroid plexus, & by retinal pigment epithelial cells pic.twitter.com/B0h6cq8LUi
— cardio-met (@cardiomet_CE) March 6, 2024
10a) Cardiac #amyloidosis occurs when fibrils accumulate in the 🫀, often evolving to #restrictive #cardiomyopathy.https://t.co/ykpmCu4qgb
— cardio-met (@cardiomet_CE) March 6, 2024
10c) … that deposit in tissues, including the heart in ~50% of cases. Amyloid light-chain (#AL) is a rare hematologic disease. While the amyloid fibril deposition in AL-CM and ATTR-CM can manifest systemically, 🫀 involvement determines prognosis. pic.twitter.com/mj11vqHFQK
— cardio-met (@cardiomet_CE) March 6, 2024
12) Hereditary #ATTR_CM has a more heterogeneous multisystem presentation vs #ATTRwt; deposition of ATTR can occur in multiple organs: 🫀, peripheral nervous system (ATTR polyneuropathy [#ATTR_PN]), musculoskeletal system, 👁️, 🫘, & GI tract.
— cardio-met (@cardiomet_CE) March 6, 2024
🔓 https://t.co/xTmhQjPf7h
14) #CMR is ⬆️used in dx; in #ATTR_CM usually shows expansion of extracellular volume, abnormal #gadolinium contrast kinetics, & diffuse late gadolinium enhancement #LGE. Note CMR alone cannot establish dx of 🫀 amyloidosis & cannot distinguish ATTR-CM vs AL-CM. pic.twitter.com/ho18E3Lgd9
— cardio-met (@cardiomet_CE) March 6, 2024
16) #PET scans with #amyloid-specific tracers detect cardiac #ATTR & #AL amyloidosis. PET results have been shown to correlate to findings on echo, CMR, & cardiac scintigraphy.
— cardio-met (@cardiomet_CE) March 6, 2024
🧪Cardiac #biomarkers #NT_proBNP & #hs_cTnT are included in ATTR-CM staging systems.
17b) 2⃣ #LVH + #HFpEF
— cardio-met (@cardiomet_CE) March 6, 2024
3⃣ aortic stenosis
4⃣ carpal tunnel syndrome, spinal stenosis, or spontaneous biceps tendon rupture
5⃣ #echo red flags, esp pts w/ #HF and unexplained #LVH
18) So, suspicion is there–how do we make the dx?
— cardio-met (@cardiomet_CE) March 6, 2024
Here from the consensus doc is an overall approach. Imaging with #echo and/or #CMR is critical. pic.twitter.com/dCwdyWu0wk
19b) If any 1 abnl, a non-invasive dx pathway is not an option & biopsy of involved organ is needed.
— cardio-met (@cardiomet_CE) March 6, 2024
👉If #AL is excluded, ➡️bone avid tracer #scintigraphy for #ATTR_CM. If ➡️ grade 2/3, dx ✅made, & genetic testing (#TTR gene) must follow.
19d) But
— cardio-met (@cardiomet_CE) March 6, 2024
👉if scintigraphy is grade 0/1 ➡️echo, CMR, & poss biopsy if there is ongoing clinical suspicion of cardiac amyloidosis.
🫀 #Endomyocardial biopsy #EMB should be performed in any of these 3 scenarios:
🔓 https://t.co/YajsZNZif7https://t.co/AITMe9LX4g
20) And NOW we treat
— cardio-met (@cardiomet_CE) March 6, 2024
1⃣ symptomatic therapy, inc tx of comorbidities
2⃣ disease-modifying therapy #DMT with the aim of changing the natural history of the disease
3⃣ general supportive therapeutic measures to help the pt achieve a better quality of life pic.twitter.com/eoKgODIhTC
21b) Rhythm:
— cardio-met (@cardiomet_CE) March 6, 2024
👉if #AAD needed, #amiodarone has most support in the lit
👉 consider #anticoagulation even in #NSR b/c of ⬆️risk of intracardiac #thrombus
👉 if #pacemaker needed, #bivent pacing is best
👉 role for #ICD is unclear
👉 🫀 transplant is an option & #LVAD may help
22) As for the fast-developing area of #DMT for #ATTR_CM, there are #TTR #stabilizers, TTR #silencers, & TTR #degraders. Stabilizers aim to maintain the native structure of TTR #tetramers, thus preventing #amyloid aggregation. Only approved agent to date is #tafamidis.
— cardio-met (@cardiomet_CE) March 6, 2024
24a) Other #TTR #stabilizers in development:
— cardio-met (@cardiomet_CE) March 6, 2024
🫀 #Acoramidis (#AG10) in an ongoing phase 3 trial (#ATTRibute-CM trial, NCT03860935) looks to be well tolerated in patients with #ATTR_CM + symptomatic #HF.
See 🔓 https://t.co/mGfMC7E703.
25) #TTR silencers work by inhibiting TTR production in the liver. The consensus doc addresses #patisiran, #vutrisiran, #inotersen, & #eplontersen in this class. All now approved in #ATTR_PN & all are under study for #ATTR_CM.#CRISPR/Cas9 gene editing may silence #TTR as well. pic.twitter.com/EYcUGCLV7C
— cardio-met (@cardiomet_CE) March 6, 2024
27) #Vutrisiran: SubQ 2nd-gen #siRNA approved for #ATTR_PN with promising results in an exploratory 🫀investigation (NT-proBNP, echocardiography, scintigraphy). Trial underway (NCT04153149).
— cardio-met (@cardiomet_CE) March 6, 2024
See 🔓https://t.co/NgF4v25L8w
29) #Eplontersen: SubQ 2nd-gen #ASO aimed at improving safety of inotersen. Newest approval for #ATTRv_PN; in phase 3 trial (🔓 https://t.co/p7ttvHhFjU), 28% of pts also had #ATTRv_CM & results were promising. Dedicated study now underway, expected complete 2025 (NCT04136171). pic.twitter.com/H5HvvbVE4f
— cardio-met (@cardiomet_CE) March 6, 2024
31) Obviously much going on! These complex patients require #multidisciplinary care. There is often overlap between #neurologic & #cardiac manifestations.
— cardio-met (@cardiomet_CE) March 6, 2024
See 🔓 https://t.co/e1RBVx4LjW.
🔑When accessible, specialized centers provide optimal care, listed https://t.co/7FlfeIoewk pic.twitter.com/CfDHWg2n45
33a) In summary, #ATTR_CM has been increasingly recognized in various clinical settings. Its apparent higher prevalence is attributed to a growing interest, as it can be diagnosed non-invasively in most cases.
— cardio-met (@cardiomet_CE) March 6, 2024
34a) So what have we learned?
— cardio-met (@cardiomet_CE) March 6, 2024
The most common clinical presentation of #ATTR_CM is
34c) It's d, #TTR #stabilizers & #silencers, & we could add #degraders. Careful volume management with loop #diuretics + #MRA is part of symptomatic management of #ATTR_CM but is not disease modifying.
— cardio-met (@cardiomet_CE) March 6, 2024
34e) It's d, eplontersen, so recently approved that the consensus doc is now not fully up to date. A dedicated Ph 3 study for #eplontersen in #ATTR_CM is underway. See methodology at https://t.co/ZQtuk3mMjA.
— cardio-met (@cardiomet_CE) March 6, 2024
35) And YOU just earned ONE FULL HOUR 🆓CE/#CME! Claim your certificate now at https://t.co/7EFcrxOom7, and then one more click of the 🖱️ means you can FOLLOW US for more expert-led #MedEd! Thanks again to our expert author @fjpinto1960 !
— cardio-met (@cardiomet_CE) March 6, 2024