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Pittsburgh B Compound Positron Emission Tomography in Patients With AL Cardiac Amyloidosis
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To examine the use of 11C-Pittsburgh B compound positron emission tomography (11C-PiB PET) as a noninvasive method of imaging myocardial light-chain (AL) cardiac amyloidosis for prognostic purposes, this prospective proof-of-concept study examined imaging from 41 chemotherapy-naive AL cardiac amyloidosis patients who were followed for a median of 423 days. Compared with control subjects, patients had a significantly higher degree of myocardial 11C-PiB PET uptake. Additionally, there was a correlation between the degree of amyloid deposit on histology and the amount of uptake. The primary composite endpoint (all-cause death, acute decompensated heart failure, and heart transplantation) was met by 24 patients. Clinical event-free survival was lowest in patients in the highest tertile of myocardial 11C-PiB PET uptake, and a multivariate analysis found that myocardial 11C-PiB PET uptake independently predicted clinical outcome.
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These data suggest that 11C-PiB PET may be a useful noninvasive method of assessing prognosis in patients with AL cardiac amyloidosis, but clinical studies are needed to test the use of 11C-PiB PET for this purpose.
abstract
This abstract is available on the publisher's site.
Access this abstract now Full Text Available for ClinicalKey SubscribersBACKGROUND
It remains unknown whether the noninvasive evaluation of the degree of amyloid deposition in the myocardium can predict the prognosis of patients with light chain (AL) cardiac amyloidosis.
OBJECTIVES
The purpose of this study was to demonstrate that 11C-Pittsburgh B compound positron emission tomography (11C-PiB PET) is useful for prognostication of AL cardiac amyloidosis by noninvasively imaging the myocardial AL amyloid deposition.
METHODS
This study consecutively enrolled 41 chemotherapy-naïve AL cardiac amyloidosis patients. The amyloid deposit was quantitatively assessed with amyloid P immunohistochemistry in endomyocardial biopsy specimens and was compared with the degree of myocardial 11C-PiB uptake on PET. The primary endpoint was a composite of all-cause death, heart transplantation, and acute decompensated heart failure.
RESULTS
The degree of myocardial 11C-PiB PET uptake was significantly higher in the cardiac amyloidosis patients compared with normal subjects and correlated well with the degree of amyloid deposit on histology (R2 = 0.343, p < 0.001). During follow-up (median: 423 days, interquartile range: 93 to 1,222 days), 24 patients experienced the primary endpoint. When the cardiac amyloidosis patients were divided into tertiles by the degree of myocardial 11C-PiB PET uptake, patients with the highest PiB uptake experienced the worst clinical event-free survival (log-rank p = 0.014). The degree of myocardial PiB PET uptake was a significant predictor of clinical outcome on multivariate Cox regression analysis (adjusted hazard ratio: 1.185; 95% confidence interval: 1.054 to 1.332; p = 0.005).
CONCLUSIONS
These proof-of-concept results show that noninvasive evaluation of myocardial amyloid load by 11C-PiB PET reflects the degree of amyloid deposit and is an independent predictor of clinical outcome in AL cardiac amyloidosis patients.
Additional Info
Disclosure statements are available on the authors' profiles:
Pittsburgh B Compound Positron Emission Tomography in Patients With AL Cardiac Amyloidosis
J Am Coll Cardiol 2020 Feb 04;75(4)380-390, SP Lee, HY Suh, S Park, S Oh, SG Kwak, HM Kim, Y Koh, JB Park, HK Kim, HJ Cho, YJ Kim, I Kim, SS Yoon, JW Seo, JC Paeng, DW SohnFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Light-chain (AL) cardiac amyloidosis is a rare disease that, if unrecognized and untreated, can prove fatal. Advances in chemotherapeutic regimens that have dramatically extended survival in AL amyloidosis are most effective when administered in early-stage disease. In this proof-of-concept study, Lee et al demonstrate the utility of the positron emission tomography (PET) radiotracer 11C-Pittsburgh B compound (11C-PiB) to both noninvasively quantify the degree of light-chain deposition in AL cardiac amyloidosis and predict prognosis. A total of 41 patients with endomyocardial biopsy–proven AL amyloidosis naïve to chemotherapy were imaged by 11C-PiB PET and followed for a median of 423 days for clinical outcomes. 11C-PiB uptake was quantified and divided into tertiles (low, medium, and high) by standard uptake values (SUV).
The authors found that the degree of uptake correlated to adverse clinical outcomes (primarily all-cause mortality). Furthermore, they showed by autoradiography that the PET signal seen in biopsy specimens correlated spatially to histologically defined amyloid deposits. Interestingly, differences in standard echocardiographic variables were not observed among the SUV tertiles, although the analysis was limited by under-powering from the small subgroup sample size. It is notable that nearly 50% of the cohort died (21 deaths; mostly in the high-uptake group), most within the first 6 months, suggestive of either advanced disease, treatment-related toxicity, or poor hematological/organ-specific response (only 3 patients are cited as having a cardiac response). In that context, standardized risk-stratification schemes that utilize plasma troponins or natriuretic peptides (Mayo or BU staging) are not presented, importantly limiting the capacity to place these findings into the context of current practice. That being said, is it clear that 11C-PiB PET imaging has the capacity to image AL amyloid deposits with a high degree of specificity, thus affording the potential for utility in the management of cardiac amyloidosis.