This webinar will guide participants in learning the signs and symptoms of heart failure in patients at risk for Cardiac Amyloidosis as well as the latest updates in diagnosis treatment and management options.

• Recognize the barriers to ATTR-CM identification and diagnosis for underdiagnosed populations
• Identify red flags and other markers that should prompt testing for ATTR-CM
• Leverage multimodality imaging to diagnose ATTR-CM
• Incorporate bone scintigraphy protocols for SPECT and SPECT/CT imaging, interpretation, and reporting
• Discuss the importance of genetic testing and counseling with patients and their families
• Manage treatment of heart failure where the underlying cause is ATTR-CM.

Transthyretin cardiomyopathy (ATTR-CM) is a debilitating and deadly disease. Cardiac amyloidosis (CA) is an underdiagnosed cause of heart failure (HF), both in patients with preserved ejection fraction (HFpEF) [Ruberg 2019] and with reduced ejection fraction. [Asif 2020; Aimo 2022] Amyloid fibril deposition seen in ATTR-CM leads to increased ventricular wall thickness with the potential for ventricular stiffening and left ventricular dysfunction. These deposits may also account for underlying conduction abnormalities and atrial and ventricular arrhythmias. Prognosis of ATTR- CA is dependent on age of onset, diagnostic delays, amyloidogenic mutation and phenotype. The presence and severity of cardiac involvement is the leading predictor both in hereditary (hATTR) and wildtype (wtATTR)amyloidosis.[ Martinez-Naharro 2020; Porcari 2020] Early diagnosis is a critical component to achieving better outcomes in these patients as treatments are more effective. [Ioannou 2022]  

Transthyretin CA (ATTR) has 2 main subtypes, hATTR caused by a hereditary amino acid mutation in the transthyretin molecule and senile or wild type, wtATTR, seen mostly in patients with advancing age. [Ruberg 2019 Falk 2011] Lack of awareness and suspicion of CA, and the fact that the clinical presentation often overlaps with other more common cardiovascular diseases including hypertrophic cardiomyopathy, hypertensive heart disease, aortic stenosis, leads to missed and/or delayed diagnosis. [White 2016] Fragmented knowledge and awareness among different specialists and subspecialists, lack of specialized treatment centers, and perception that ATTR-CM is a rare disease contribute to delays in diagnosis.

Cardiomyopathy is predominant in patients with wtATTR, but they may also show symptoms consistent with neuropathy.[Maurer 2019] Symptom presentation in hATTR differs with the underlying disease-causing mutation (polyneuropathy for Val30Met, cardiomyopathy for Val122Ile and Leu111Met, and mixed for Glu89Gln).  Val122Ile is common in individuals with African ancestry. Being a carrier of this variant is significantly associated with an increased risk of HF among Black individuals living in the US.[Parcha 2022] Black female Val122Ile carriers have been shown to have a higher risk of cardiovascular disease and death compared to non-carriers. [Haring 2023] If clinical suspicion for CA is high, even in Black middle-aged adults, these patients need to be screened to ensure early treatment to prevent or postpone HF. [Sinha 2021]

Non-invasive imaging and new therapies have the potential to improve the long-term prognosis of patients with ATTR-CM. Distinguishing the signs and symptoms of CA from other cardiovascular diseases, providing early and accurate diagnosis differentiating the CA subtype, and understanding treatments to optimize patient care and limit organ damage is critical. In addition, the trans-generational impact of hATTR-CM may remain underappreciated by the patient and their family members, further limiting early diagnosis of the disease or the identification of those at risk of developing it in the future.  Understanding the need for genetic testing is a critical aspect of evaluation of patients with ATTR-CM/  [Ruberg 2012; Maurer 2017] Accurate diagnosis of ATTR-CM is confounded by other co-morbidities and delays in diagnosis and treatment can impact patient outcomes. Clinicians need to suspect ATTR-CM, and understand the diagnostic algorithm, and the use of laboratory and non-invasive testing.

References

Ruberg FL, Grogan M, Hanna M, Kelly WS, Maurer MS.  Berk JL. Transthyretin amyloid cardiomyopathy. JACC State-of-the-Art review. J Am Coll Cardiol. 2019;73:2872-2891.

Asif T, Aruago T, Singh V, Malhotra S. High prevalence of heart failure with reduced ejection fraction in patients with transthyretin cardiac amyloidosis. J Nucl Cardiol. 2020;27(3):1044-1046.

Aimo A, Merlo M, Porcari A, Georgiopoulos G, Pagura L, Vergaro G, et al. Redefining the epidemiology of cardiac amyloidosis. A systematic review and meta-analysis of screening studies. Eur J Heart Fail. 2022;24(12):2342-2351.

Martinez-Naharro A, Baksi AJ, Hawkins PN, Fontana M. Diagnostic imaging of cardiac amyloidosis. Nat Rev Cardiol 2020;17:413–426.

Porcari A, Merlo M, Rapezzi C, Sinagra G. Transthyretin amyloid cardiomyopathy: an uncharted territory awaiting discovery. Eur J Intern Med. 2020;82:7–15.

Ioannou A, Patel RK, Razvi Y, Porcari A, Sinagra G, Venneri L, et al. Impact of earlier diagnosis in cardiac ATTR amyloidosis over the course of 20 years. Circulation. 2022;146:1657-1670.

Maurer MS, Bokhari S, Damy T, et al. Expert consensus recommendations for the suspicion and diagnosis of transthyretin cardiac amyloidosis. Circ Heart Fail. 2019 Sep:12(9):e006075. doi: 10.1161/CIRCHEARTFAILURE.119.006075

Parcha V, Malla G, Ivin MR, Armstrong NC, Judd SE, Lange LA, et al. Association of transthyretin Val122Ile variant with incident heart failure among Black individuals. JAMA.2022;327:1368-1378.

Haring B, Hunt RP, Shadyab A, Eaton C, Kaplan R, Martin LW, et al. Cardiovascular disease and mortality in Black women carrying the amyloidogenic V122I transthyretin gene variant. JACC Heart Fail. 2023;11(9):1189-1199.

Sinha A, Zheng Y, Nannini D, Qu Y, Hou L, Shah AJ, et al. Association of the V122I transthyretin amyloidosis genetic variant with cardiac structure and function in middle-aged Black adults. JAMA Cardiol. 2021;6:1-5.

Physicians: The American Society of Nuclear Cardiology designates this internet live activity for a maximum of 2.5 AMA PRA Category 1 Credits^TM. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Technologists: The American Society of Nuclear Cardiology is a recognized provider of continuing education credit for technologists. ASNC’s Continuing Education (CE) credit is accepted by both NMTCB and ARRT. This internet live activity has been approved for a maximum of 2.5 ARRT Category A credits for Technologists.

As an accredited provider of the Accreditation Council for Continuing Medical Education (ACCME), The American Society of Nuclear Cardiology (ASNC) adheres to the ACCME’s Standards for Integrity and Independence in Accredited Continuing Education.  In compliance with these standards, it is ASNC’s policy to ensure balance, independence, objectivity, and scientific merit in all of its educational activities through the disclosure of all financial relationships with ineligible companies and mitigation of conflicts of interest.  The financial interest or relationships requiring disclosure are outlined in ASNC’s CME Conflict of Interest Policy.  All persons who influenced the content of this activity are required to disclose all financial relationships.  The American Society of Nuclear Cardiology has reviewed these disclosures and mitigated or managed all identified conflicts of interest through a peer review process.

The following faculty, reviewers and ASNC staff who were involved in the planning and development of this activity reported no financial relationships:

Matthew Harinstein, MD
Tawfiq Al Lahham, MD
J. Clay Hays, Jr., MD
Pawel Pomianowski, MD
Linda Giering, PhD (ASNC Staff)
Wendy Passerell (ASNC Staff)

The following faculty, reviewers and ASNC staff who were involved in the planning and development of this activity reported the following financial relationships:

Sharmila Dorbala, MD, MPH: Research Grants – Pfizer, Attralus, Siemens, Phillips; Consultant: Pfizer, Novo Nordisk, Alexion, Astra Zeneca
Charles Moore, MD: Speaker’s Bureau – Pfizer
Frederick Ruberg, MD: Research Grants – Pfizer, Alnylam, Akcea; Consultant – AstraZeneca, Attralus; Advisory Board – AstraZeneca
Prem Soman, MD, PhD: Research grants – Pfizer; Consultant – Alnylam, Spectrum Dynamics, Eidos, Pfizer