
Brian Lilleness
@BLilleness
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Director of Nuclear Cardiology and non-invasive cardiologist @bidmcCVI
Boston, MA
Joined September 2018
So in the end, here's the way to stage patients with BNP with the resulting survival curves seen in @vsanchorawala recent post. #amyloidosisJC
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To determine stage IIIb, we did ROC analysis for 1 year survival on the patients who were in stage III (i.e. TnI > 0.1 and BNP >81), and we found a "IIIb" BNP cutoff of >700 pg/mL #amyloidosisJC.
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So in our validation cohort, 151 patients were assigned to stage I, 259 patients were assigned to stage II, and 88 patients wereassigned to stage III, and 94 were assigned to stage IIIb. #amyloidosisJC.
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So once we had shown that a BNP >81 cutoff closely mimic'd an NT-proBNP cutoff of >332, we had to validate the system, which we did using a cohort of 1073 patients (592 of which had BNP drawn and could be used) seen for 1st visits between 2004-2014 #amyloidosisJC.
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Interestingly, NT-proBNP had better specificity in patients with NO CKD and then in all comers there was no difference. This would suggest towards BNP's superiority in CKD IV-V; however, we didn't have enough patients to prove this. #amyloidosisJC.
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We also thought that since BNP isn't as affected by renal clearance, it may be better in patients with ESRD. Unfortunately, this didn't pan out; however, it did approach significance in having a higher specificity in patients with CKD stage IV #amyloidosisJC
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We also looked at what BNP threshold would best predict cardiac involvement (based on a combination of endomyocardial biopsy, MRI, and echo criteria) and it turns out that a BNP of 81 pg/mL also best predicted cardiac involvment (BNP is left, NT-proBNP is right) #amyloidosisJC
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Out of the 250 patients, 249 had both biomarkers drawn and we derived a BNP cutoff (which turned out to be 81pg/mL) that most closely mimic'd the Mayo 2004 system. It turns out, by using a cutoff of 81, just over 89% of people will be given the same stage. #amyloidosisJC
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So to create a system, we used 250 consecutive patients who had both BNP and NT-proBNP drawn at the same visit so we could directly compare them. Unfortunately, NT-proBNP was only available to us after 2016, so we didn't have long follow up on that cohort. #amyloidosisJC.
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Since all the current AL literature essentially relies on Mayo staging, we thought it was important to create a system that would closely mimic Mayo 2004 + IIIb so that places with only access to BNP could have a way to stratify their patients appropriately. #amyloidosisJC.
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Since both NT-proBNP and BNP are released from cardiac myocytes in AL amyloid through direct toxicity and infiltration, it would make sense that BNP would also predict survival. Unfortunately, there isn't any way to directly convert them due to clearance rates #amyloidosisJC.
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This was then updated in 2012 by the European Group with a "stage IIIb" that had much worse survival when NT-proBNP >8500 and is the most commonly used staging system to this day. #amyloidosisJC
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The original staging system was designed by the Mayo clinic in 2004 and used a combination of NT-proBNP and Toponin I (TnI) or Troponin T (TnT) to stratify patients into 3 groups with good stratification between them #amyloidosisJC
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For some background on why this was important, cardiac involvement was the leading cause of death in amyloidosis and until our paper, all staging systems relied primarily on NT-proBNP and not BNP #amyloidosisJC.
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Should we get this started? Tonight we are going to discuss our recent paper in @BloodJournal in which we developed a new staging system for AL amyloidosis. #amyloidosisJC.
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I am a chief medical resident @BMCimRES and will be a cardiology fellow at BMC next year. I have the pleasure of leading this #amyloidosisJC with @vsanchorawala. No COI.
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