2) Our expert author is Ronald Witteles MD @Ron_Witteles, @StanfordMed IM program director, Professor of Medicine, #Cardiologist, Specialist in #Amyloidosis, #Sarcoidosis, #Cardio_Oncology, and Advanced #heartfailure . . . and he's 🎯ing this program at NON-cardiologists! pic.twitter.com/SQuSfmFIVO
— cardio-met (@cardiomet_CE) October 25, 2023
4a) #ATTR #amyloid #cardiomyopathy (#ATTR_CM) has been in the news a lot the last few years. But what is this disease? Is this something the non-cardiologist really needs to know about?
— cardio-met (@cardiomet_CE) October 25, 2023
5a) “#Amyloid” comes from the Latin word amylum, which means starch, as pathologists originally thought the deposits were made up of starch. The deposits are actually made mainly from misfolded proteins which stack into tiny #fibrils, which deposit extracellularly.
— cardio-met (@cardiomet_CE) October 25, 2023
5c) And WHAT A GREAT TIME to learn about this—TOMORROW (26 October) is World Amyloidosis Day! @AmyloidosisDay pic.twitter.com/vFs1nqhDwU
— cardio-met (@cardiomet_CE) October 25, 2023
6b) Importantly, it circulates mainly as four units bound together (a ‘tetramer’), in steady state with a small number of monomers. #Thyroxine binding to TTR stabilizes the tetrameric form. pic.twitter.com/0G75Z5Ctey
— cardio-met (@cardiomet_CE) October 25, 2023
7b) For reasons we largely don’t understand, in some people the deposits occur in a normal human lifespan. When this occurs, we call it “ATTR” (for “amyloid-transthyretin”) #amyloidosis.
— cardio-met (@cardiomet_CE) October 25, 2023
8b) #ATTR_v happens in people who have inherited a pathogenic mutation in the TTR protein, making it more likely to misfold/deposit.
— cardio-met (@cardiomet_CE) October 25, 2023
9b) The orthopedic manifestations often precede the clinical cardiac manifestations by 10-15 years. For unclear reasons, ATTR-wt #amyloidosis occurs much more commonly in ♂️ than in ♀️.
— cardio-met (@cardiomet_CE) October 25, 2023
10b) A @MayoClinicautopsy study found ATTR-wt amyloid deposits in >20% and >50% of HFpEF patients in their 80s and 90s, respectively – and even in >15% of patients without heart failure! 😮 pic.twitter.com/bOwwVA5TCO
— cardio-met (@cardiomet_CE) October 25, 2023
11b) There are dozens of pathogenic mutations described, and the manifestations (#cardiomyopathy vs. #polyneuropathy dominant, age of onset, etc.) depend greatly on the specific mutation.
— cardio-met (@cardiomet_CE) October 25, 2023
12b) Population studies suggest that simply carrying the mutation results in a hazard ratio #HR for atrial fibrillation #Afib and #stroke of 1.86 and 1.58, respectively. pic.twitter.com/0K1YG8zOXw
— cardio-met (@cardiomet_CE) October 25, 2023
13b) You may remember an association with #amyloidosis & low EKG voltages. While that can be seen, it isn’t reliable, & normal (or high!) EKG voltages shouldn’t dissuade you from the diagnosis. The main clinical findings are #heartfailure, atrial #arrhythmias, & heart block 🚧.
— cardio-met (@cardiomet_CE) October 25, 2023
15) In the past, dx of #ATTR-CM could only be made by biopsy (typically of 🫀 )—very limiting! Later, it was fortuitously discovered that 🫀 w/ATTR #amyloid deposits took up nuclear tracers used in bone scans. In 🇺🇸, the tracer used is #PYP & the test is now widely available. pic.twitter.com/aIvL56nFzu
— cardio-met (@cardiomet_CE) October 25, 2023
16b) Once you have made the diagnosis, you can do genetic testing for the #TTR gene to see if your patient has #ATTR-wt or ATTR-v #amyloidosis.
— cardio-met (@cardiomet_CE) October 25, 2023
See 🔓 https://t.co/tXa5SRZBG9. pic.twitter.com/4ha9QbdXAV
18a) There are 2 main proven strategies to treat the disease – #stabilizers & #silencers. The stabilizers bind to the thyroxine binding site of #TTR and stabilize the tetrameric form.
— cardio-met (@cardiomet_CE) October 25, 2023
19) The landmark #ATTR-ACT trial tested the stabilizer #tafamidis vs. placebo in pts w/#ATTR-CM ➡️large benefits, including #survival (NNT 7.5 to prevent 1 death at 30 mos!) & CV #hospitalizations (NNT 4.5 to prevent 1 hospitalization each yr!). 😳
— cardio-met (@cardiomet_CE) October 25, 2023
🔓 https://t.co/xUc76LF7X0 pic.twitter.com/OrKkDOzG6B
21a) We now have 4⃣ agents approved or likely to be approved in #ATTR_PN (#patisiran, #vutrisirian, #inotersen, #eplontersen), and 2⃣agents approved or likely to be approved in #ATTR_CM (#tafamidis, #acoramidis).
— cardio-met (@cardiomet_CE) October 25, 2023
22a) In summary – #ATTR #amyloidosis is NOT rare, is straightforward to diagnose, and has a growing list of very effective therapies. And don't forget–#Team management of #amyloidosis is 🔑.
— cardio-met (@cardiomet_CE) October 25, 2023
22c) An important resource for #nurses who help manage patients with #ATTR is the Amyloidosis Nurse Collaborative, part of the Amyloidosis Research Consortium @Amyloidosis_ARC. See https://t.co/9qqN0qr4Zy.
— cardio-met (@cardiomet_CE) October 25, 2023
24a) So what have you learned? #ATTR_CM is most commonly suspected due to:
— cardio-met (@cardiomet_CE) October 25, 2023
a. Low voltages on the EKG
b. A ‘thick’ heart muscle on imaging
c. Persistent high #bloodpressure
d. Refractory ventricular #arrhythmias
25a) All of the following have shown benefits in #ATTR #amyloidosisclinical trials EXCEPT:
— cardio-met (@cardiomet_CE) October 25, 2023
25c) . . . have already shown large benefits in #ATTR #amyloidosis in randomized, double-blind placebo-controlled trials. The future is bright! 😎
— cardio-met (@cardiomet_CE) October 25, 2023
26) And YOUR future just became a bit brighter, too: you just earned 0.5hr 🆓 CE/#CME! Claim your certificate now at https://t.co/mh4n8cXbA8 & then click that 🖱️ just one more time & FOLLOW US for more #MedEd delivered right here on Twitter! @Ron_Witteles thanks you for joining! pic.twitter.com/XfDTnvXDyM
— cardio-met (@cardiomet_CE) October 25, 2023