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Ahmad Masri Profile picture
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19 Dec, 4 tweets, 3 min read
Preclinical and phase I data for $AKCA-TTR-LRx (second generation inotersen, ASO conjugated with GalNAc), currently being tested in CARDIO-TTRansform, the largest #ATTR #Amyloidosis trial to date. Tafamidis allowed without restrictions.

onlinelibrary.wiley.com/doi/epdf/10.10…

#cardiotwitter
Cojugation with GalNAc increased potency by 20-30x, allowing lower dose, lower frequency, less AE
more about the trial here

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Ahmad Masri Profile picture
20 Jun
Thread/

There are many new exciting trials in transthyretin #amyloidosis – as we continue to enroll patients in the CARDIO-TTRansform trial, I thought I would highlight some of these trials in ATTR-CM

clinicaltrials.gov/ct2/show/NCT04…

#cardiotwitter Image
If you recall, 2 main approaches to treating ATTR #amyloidosis with approved drugs (figure credit @frederickruberg @maz_hanna )
1)Stabilizers: bind to the TTR tetramer to stabilize it. #tafamidis , AG-10, diflunisal
2)Silencers: Inotersen and Patisiran Image
tafamidis is prescribed to ATTR-CM pts & inotersen/patisiran for those with hATTR polyneuropathy
But – 2 main questions in ATTR-CM
1)Which is associated with better outcomes – silencer or stabilizer?
2)Is the combination of silencer+stabilizer superior to stabilizer only?
Read 13 tweets
Ahmad Masri Profile picture
23 Dec 18
A thread.
So the @US_FDA @SGottliebFDA issued a warning re: Fluoroquinolones (FLQ) and aortic dissection (AD) or aneurysm (AA). Do FLQs cause AD/AA? Not really. Is there an association? Maybe. Let’s go throw the evidence and you can decide for yourself.
#CardioTwitter #MedEd
1/ Why was this association even studied? FLQ are known to be associated with Achilles tendon rupture, tendinopathy, retinal detachment. How? 1)decrease collagen synthesis and increase MMP (especially 2, 9) activity (among others). Aorta is affected by these processes
2/First study was published in 2015 using a national database in Taiwan. 1477 cases (662 AD, 850 AA) matched to 147 700 controls. There was signal of the association of FLQ and AD; rate ratio ranging 1.37 - 2.11 with any FLQ use (tinyurl.com/ybhcpexz)
Read 13 tweets
Ahmad Masri Profile picture
29 Nov 18
A great case of bicuspid-associated aortopathy.
How common is aortic dissection in BAV? To date, many surgeons operate on patients with dilated aortas in the 4.5-5.0 cm range without concomitant severe valve disease. But, how about the evidence so far?
#cardiotwitter #MedEd
1) IRAD had 1.9% BAV patients in a 2006 report (out of 303 type A dissections)
ncbi.nlm.nih.gov/pubmed/16820599
2) GenTAC registry had 2 dissections / 772 BAV (follow-up 3.6 years, outcome ascertained in 88%)
ncbi.nlm.nih.gov/pubmed/27282895
Read 8 tweets
Ahmad Masri Profile picture
27 Sep 18
1/ A long thread on LifeVest. I promise it will be entertaining. If you find any inaccuracies please let me know.

Paper of VEST published here - will discuss background to WCD and #VEST but not the trial itself nejm.org/doi/full/10.10…
2/ In 2001, FDA gave approval to Lifecor for the first WCD. Later Lifecor was acquired by Zoll (2004 agreement, 2006 acquisition). Zoll maintains a registry for prescribed LifeVests. But lets go back to the FDA approval process.
3/ Lifecor presented 2 separate prospective studies to the FDA; WEARIT and BIROAD. FDA asked for both to be combined into 1 study, and each study representing a subgroup. A total of 289 patients were included.
Read 18 tweets

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