RX Review: Understanding ATTR-CM's New Era of Management - Episode null
RX Review: Advances in Diagnosis of ATTR-CM
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In this video, part 2 of a 4-part series, panelists discuss on recent advancements in imaging and biomarker-based diagnostics for ATTR-CM
With recent advances in pharmacotherapy, including the approvals of acoramidis (Attruby) and vutrisiran (Amvuttra), which boast different mechanisms of action, a new impetus has been placed on early diagnosis and testing for transthyretin amyloid cardiomyopathy (ATTR-CM).
Part 2 of our 4-part RX Review on updates and unmet needs in ATTR-CM focuses on advances in imaging and biomarker-based diagnostics for ATTR-CM. In this segment, Hanna Mazen, MD, director of the Heart Failure Intensive Care Unit and codirector of the Amyloid Program at Cleveland Clinic, opens the conversation by asking “how have recent advances in particularly imaging and biomarker-based diagnostics improved our ability to diagnose this condition at earlier stages instead of more advanced stages?”.
Marian Vandyck-Acquah, MD, director of Education and Quality-Noninvasive Cardiology at Hackensack Meridian Health Heart and Vascular Hospital, highlights the shift from reliance on endomyocardial biopsy to noninvasive diagnostic tools, particularly cardiac amyloid radionuclide imaging using technetium pyrophosphate (99mTc-PYP) scans. When applied correctly, this approach achieves near-perfect sensitivity and specificity for ATTR-CM, provided AL amyloidosis is ruled out. Additional advancements, such as apical sparing strain patterns and expanded access to genetic testing, have further enhanced early detection. However, the increasing detection of early-stage disease raises new questions regarding treatment initiation in asymptomatic or minimally symptomatic patients.
Jesus Almendral, MD, director of the Advanced Heart Failure Center at the Jersey Shore University Medical Center, emphasizes the transformative impact of 99mTc-PYP scans, which have enabled general cardiologists to diagnose ATTR-CM with greater confidence. Previously, suspected cases were often referred to specialists due to the need for invasive biopsy. Now, adherence to established diagnostic algorithms, including ruling out AL amyloidosis, allows for accurate diagnoses in standard cardiology practice.
Hanna underscores the importance of correct testing protocols, citing common pitfalls such as failure to order serum free light chain assay and immunofixation to exclude AL amyloidosis. He also addresses false positives associated with planar imaging alone, which can misinterpret blood pool uptake as myocardial deposition.
The panel concludes by discussing the future of amyloid imaging, including the development of PET-based tracers with high specificity for amyloid fibrils. Unlike technetium-based scans, whose exact binding mechanism remains uncertain, these PET agents offer potential improvements in diagnostic accuracy.
Our Panelists:
Mazen Hanna, MD, is a cardiologist at the Cleveland Clinic's Vascular & Thoracic Institute. Hanna is also director of the Heart Failure Intensive Care Unit and codirector of the Amyloid Program at Cleveland Clinic and serves as the moderator for this panel discussion.
Marian Vandyck-Acquah, MD, is an assistant professor of medicine in the cardiology department at the Hackensack Meridian School of Medicine. Vandyck-Acquah is also the director of Education and Quality-Noninvasive Cardiology at Hackensack Meridian Health Heart and Vascular Hospital.
Jesus Almendral, MD, is a cardiovascular disease specialist board-certified in advanced heart failure and heart transplant, cardiovascular disease and internal medicine at the Jersey Shore University Medical Center. He is the director of the Advanced Heart Failure Center at the center and serves as the third panelist for our discussion.
Relevant disclosures for Hanna include Pfizer, Alnylam, Ionis, and Eidos. Almendral and Vandyck-Acquah have no relevant disclosures to report.
References:
Office of the Commissioner. FDA approves new treatments for heart disease caused by a serious rare disease, transthyretin mediated amyloidosis. FDA. Published May 6, 2019. Accessed March 28, 2025. https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatments-heart-disease-caused-serious-rare-disease-transthyretin-mediated.
BridgeBio. AttrubyTM (acoramidis), a Near Complete TTR Stabilizer (≥90%), approved by FDA to Reduce Cardiovascular Death and Cardiovascular-related Hospitalization in ATTR-CM Patients - BridgeBio. BridgeBio. Published November 22, 2024. Accessed March 28, 2025. https://bridgebio.com/news/attruby-acoramidis-a-near-complete-ttr-stabilizer-%E2%89%A590-approved-by-fda-to-reduce-cardiovascular-death-and-cardiovascular-related-hospitalization-in-attr-cm-patients/.
Alnylam. Alnylam Announces FDA Approval of AMVUTTRA® (vutrisiran), the First RNAi Therapeutic to Reduce Cardiovascular. Investor Relations | Alnylam Pharmaceuticals, Inc. Published March 20, 2025. Accessed March 28, 2025. https://investors.alnylam.com/press-release?id=28831.
