Mazen A. Hanna, MD

RX Review: Future Directions, Changing Landscape of ATTR-CM 

Understanding ATTR-CM's New Era of Management

Impact of New, Upcoming Therapies for ATTR-CM

Future Directions, Changing Landscape of ATTR-CM

With such a rapid rate of advancement for diagnostic and treatment capabilities within the management of transthyretin amyloid 

 (ATTR-CM), many are playing catch-up with the sheer amount of information. However, many are also already looking to the future for what’s next for the field.

In the fourth and final part of our RX Review on updates and unmet needs in ATTR-CM, Mazen Hanna, MD, director of the Heart Failure Intensive Care Unit and codirector of the Amyloid Program at Cleveland Clinic, leads a discussion with Marian Vandyck-Acquah, MD, director of Education and Quality-Noninvasive Cardiology at Hackensack Meridian Health Heart and Vascular Hospital, and Jesus Almendral, MD, director of the Advanced Heart Failure Center at the Jersey Shore University Medical Center, on what the ever-changing landscape could hold in the near future.

Vandyck-Acquah highlights AI's potential in detecting ATTR cardiomyopathy (ATTR-CM) by analyzing EMRs for early signs like spinal stenosis and carpal tunnel syndrome. AI-driven imaging may also improve echocardiographic differentiation of hypertrophic cardiomyopathy (HCM) and amyloidosis. However, careful data interpretation is crucial.

Almendral discusses treatment complexities in elderly patients with comorbidities like renal disease and diabetes. Since ATTR-CM therapies take months to show benefits, determining when to start treatment is challenging, with high costs and insurance coverage further impacting treatment choices.

Future Therapies: Gene Editing & Antibodies

Hanna and Vandyck-Acquah explore upcoming therapies, including gene editing (CRISPR-Cas9) and amyloid-targeting antibodies. These may enable earlier intervention, with treatments tailored to disease stage:

 Antibody therapies for amyloid clearance.

The panelists conclude the series with a discussion on what unanswered questions remain about monitoring treatment response, genetic screening, and long-term follow-up for asymptomatic carriers. Cost remains a major barrier, and insurance coverage often dictates treatment choices. However, growing treatment options provide hope for earlier diagnosis and improved patient outcomes.

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.

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.

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.

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

 (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

Videos

In this video, the last in a 4-part series, panelists discuss how ongoing research and efforts could shape the future of ATTR-CM management.

RX Review: Future Directions, Changing Landscape of ATTR-CM

RX Review: Impact of New, Upcoming Therapies for ATTR-CM

After more than half a decade with tafamidis (Vyndamax) as the only FDA-approved therapy for transthyretin amyloid 

 (ATTR-CM), the December 2024 and March 2025 approvals of disease-modifying therapies in acoramidis (Attruby) and vutrisiran (Amvuttra) have left clinicians better equipped than ever to meet the needs of this growing patient population.

In part 3 of our 4-part RX Review on updates and unmet needs in ATTR-CM, Mazen Hanna, MD, director of the Heart Failure Intensive Care Unit and codirector of the Amyloid Program at Cleveland Clinic, leads a discussion with Marian Vandyck-Acquah, MD, director of Education and Quality-Noninvasive Cardiology at Hackensack Meridian Health Heart and Vascular Hospital, and Jesus Almendral, MD, director of the Advanced Heart Failure Center at the Jersey Shore University Medical Center, on how recent FDA approvals for ATTR-CM therapies have influenced clinical decision-making.

Vandyck-Acquah outlines the evolving treatment landscape since 2018, highlighting a growing arsenal of therapeutic options. Initial treatments, such as tafamidis, provided the first disease-modifying approach, but subsequent trials, including ATTR-ACT, ATTRibute-CM, and ongoing gene-editing studies, have expanded possibilities. She notes that vutrisiran, originally approved for hereditary polyneuropathy, has now received FDA approval for cardiomyopathy, offering an alternative to stabilizers. However, she raises key questions: Which therapy should be used for which patient? When should combination therapy be considered? And how do these new agents fit into clinical practice?

Beyond approved therapies, the panel discuses gene-editing and fibril-removal strategies, which remain in experimental phases. Hanna emphasizes the lack of head-to-head data comparing tafamidis and acoramidis, making direct comparisons challenging. Differences in study populations—ATTRibute-CM included less severely ill patients than ATTR-ACT—further complicate cross-trial comparisons.

The discussion shifts to the question of combination therapy. Almendral notes that no current data definitively support its use. While the HELIOS-B study allowed tafamidis use in some patients receiving vutrisiran, no significant differences emerged between monotherapy and combination therapy groups. He acknowledges that, mechanistically, combining stabilizers and silencers may seem logical, but without direct evidence, routine combination therapy cannot be recommended.

Hanna concurs, referencing the HELIOS-B trial, where combination therapy showed only a nonsignificant trend toward mortality benefit. Given the high cost of these therapies, financial toxicity remains a critical concern. Until more data emerge, Hanna suggests most clinicians are likely to reserve combination therapy for cases of disease progression rather than as an initial strategy.

In this video, part 3 of a 4-part series, panelists discuss the impact of recent approvals and pipeline developments on the outlook for ATTR-CM management. 

RX Review: ATTR-CM Diagnosis

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 

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.

In this video, part 2 of a 4-part series, panelists discuss on recent advancements in imaging and biomarker-based diagnostics for ATTR-CM

RX Review: Advances in Diagnosis of ATTR-CM

ATTR-CM RX Review Part 1

 (ATTR-CM), once considered a rare disease, is now recognized as a more prevalent and underdiagnosed cause of cardiomyopathy, heart failure, and increased hospitalization. Advances in diagnostic strategies, including non-biopsy methods, as well as pharmacological breakthroughs, have contributed to earlier detection and a shift in disease management.

In the first of this 4-part RX Review series celebrating advancement in ATTR-CM, our panel of experts introduces the topic and dives into how these advances have influenced the unmet need within the disease state. After opening the conversation, Mazen Hanna, MD, director of the Heart Failure Intensive Care Unit and codirector of the Amyloid Program at Cleveland Clinic, turns to Marian Vandyck-Acquah, MD, director of Education and Quality-Noninvasive Cardiology at Hackensack Meridian Health Heart and Vascular Hospital, who notes that ATTR-CM is no longer “hidden in plain sight” but is increasingly identified due to heightened clinical awareness and the availability of targeted therapies.

Later, Jesus Almendral, MD, director of the Advanced Heart Failure Center at the Jersey Shore University Medical Center, highlights the growing recognition of ATTR-CM in clinical practice, with seemingly unrelated symptoms—such as carpal tunnel syndrome, spinal stenosis, and polyneuropathy—now understood as potential indicators of systemic disease. He attributes this shift to increased awareness from professional organizations, updated screening guidelines, and direct-to-consumer campaigns that prompt patients to seek evaluation. Hanna emphasizes the ongoing need for improved detection, citing data indicating that approximately 10% of older patients with heart failure with preserved ejection fraction and increased wall thickness may have ATTR-CM. Additionally, a notable proportion of elderly patients undergoing transcatheter aortic valve replacement for severe aortic stenosis have been diagnosed with ATTR-CM, further underscoring the importance of early identification.

In this video, part 1 of a 4-part series, panelists discuss recent advancements in ATTR-CM management.

Mazen A. Hanna, MD

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