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Quiz

Genetics and Genomics

Heart Failure, Neuropathy, and Spinal Stenosis

Educational Objective
Based on this clinical scenario and the accompanying image, understand how to arrive at a correct diagnosis.

1 Credit CME

JAMA

Published Online: June 22, 2023

JAMA Clinical Challenge

Article Information and Disclosures

Omar A. Welleman, MD¹;

Yvonne C. Schrama, MD, PhD¹;

Henk-Jan Boiten, MD, PhD¹

Author Affiliations

¹Department of Internal Medicine, Franciscus Gasthuis and Vlietland Hospital, Rotterdam/Schiedam, the Netherlands

Read article on JAMA Network

Research Letter

Association of RBT With Wild-Type Transthyretin Cardiac Amyloidosis

Hallie I. Geller, BA; Avinainder Singh, MBBS; Kevin M. Alexander, MD; Tara M. Mirto, BA; Rodney H. Falk, MD
Original Investigation

Association of TTR V122I With Heart Failure Among Individuals of African or Hispanic/Latino Ancestry

Scott M. Damrauer, MD; Kumardeep Chaudhary, PhD; Judy H. Cho, MD; Lusha W. Liang, MD; Edgar Argulian, MD; Lili Chan, MD; Amanda Dobbyn, PhD; Marie A. Guerraty, MD, PhD; Renae Judy, MS; Jenna Kay, MD; Rachel L. Kember, PhD; Michael G. Levin, MD; Aparna Saha, MD; Tielman Van Vleck, PhD; Shefali S. Verma, PhD; JoEllen Weaver, BS; Noura S. Abul-Husn, MD, PhD; Aris Baras, MD; Julio A. Chirinos, MD; Brian Drachman, MD; Eimear E. Kenny, PhD; Ruth J. F. Loos, PhD; Jagat Narula, MD, PhD; John Overton, PhD; Jeffrey Reid, PhD; Marylyn Ritchie, PhD; Giorgio Sirugo, MD, PhD; Girish Nadkarni, MD; Daniel J. Rader, MD; Ron Do, PhD
Review

Systemic Amyloidosis Recognition, Prognosis, and Therapy

Morie A. Gertz, MD; Angela Dispenzieri, MD
Original Investigation

Identification of Transthyretin Cardiac Amyloidosis

Marios Arvanitis, MD; Clarissa M. Koch, PhD; Gloria G. Chan, MS; Celia Torres-Arancivia, PhD; Michael P. LaValley, PhD; Daniel R. Jacobson, MD; John L. Berk, MD; Lawreen H. Connors, PhD; Frederick L. Ruberg, MD
Brief Report

Association of Patisiran With Regional Left Ventricular Myocardial Strain in Hereditary Transthyretin Amyloidosis

Masatoshi Minamisawa, MD, PhD; Brian Claggett, PhD; David Adams, MD; Arnt V. Kristen, MD; Giampaolo Merlini, MD; Michel S. Slama, MD; Angela Dispenzieri, MD; Amil M. Shah, MD, MPH; Rodney H. Falk, MD; Verena Karsten, PhD; Marianne T. Sweetser, MD, PhD; Jihong Chen, PhD; Richard Riese, MD; John Vest, MD; Scott D. Solomon, MD
Brief Report

V122I Transthyretin Amyloidosis Genetic Variant and Cardiac Structure and Function in Middle-aged Black Adults

Arjun Sinha, MD; Yinan Zheng, PhD; Drew Nannini, PhD; Yishu Qu, MPH; Lifang Hou, MD, PhD; Sanjiv J. Shah, MD; Clyde W. Yancy, MD; Elizabeth M. McNally, MD, PhD; Myriam Fornage, PhD; Joao Lima, MD; Donald M. Lloyd-Jones, MD; Laura J. Rasmussen-Torvik, PhD; Sadiya S. Khan, MD, MS

Read Case Take Quiz Answer

A 60-year-old Black patient presented to the emergency department with a 2-month history of chest pain and shortness of breath with exertion, 3 months of toe numbness, and unintended weight loss of 8 kg over 6 months. The patient also had a history of lumbar spinal stenosis. On presentation, blood pressure was 104/73 mm Hg; heart rate, 91/min; respiratory rate, 16/min; and oxygen saturation, 96% on room air. Physical examination revealed edema to the mid-calf bilaterally, hypoesthesia below the knees, and ankle plantar flexion strength of 3 of 5 based on the Medical Research Council Scale for muscle strength. Laboratory testing revealed a high-sensitivity troponin level of 52 ng/L (reference, <34 ng/L); brain-type natriuretic peptide, 112 pmol/L (reference, <30 pmol/L); aspartate aminotransferase, 51 U/L (0.85 μkat/L) (reference, 0-35 U/L [0-0.58 μkat/L]); and alanine aminotransferase, 76 U/L (1.27 μkat/L) (reference, 0-45 U/L [0-0.75 μkat/L]). A chest radiograph showed cardiomegaly without pulmonary vascular redistribution or pulmonary edema.

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A 60-year-old Black patient presented to the emergency department with a 2-month history of chest pain and shortness of breath with exertion, 3 months of toe numbness, and unintended weight loss of 8 kg over 6 months. The patient also had a history of lumbar spinal stenosis. On presentation, blood pressure was 104/73 mm Hg; heart rate, 91/min; respiratory rate, 16/min; and oxygen saturation, 96% on room air. Physical examination revealed edema to the mid-calf bilaterally, hypoesthesia below the knees, and ankle plantar flexion strength of 3 of 5 based on the Medical Research Council Scale for muscle strength. Laboratory testing revealed a high-sensitivity troponin level of 52 ng/L (reference, <34 ng/L); brain-type natriuretic peptide, 112 pmol/L (reference, <30 pmol/L); aspartate aminotransferase, 51 U/L (0.85 μkat/L) (reference, 0-35 U/L [0-0.58 μkat/L]); and alanine aminotransferase, 76 U/L (1.27 μkat/L) (reference, 0-45 U/L [0-0.75 μkat/L]). A chest radiograph showed cardiomegaly without pulmonary vascular redistribution or pulmonary edema.

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Article Information

Corresponding Author: Henk-Jan Boiten, MD, PhD, Department of Internal Medicine, Franciscus Gasthuis and Vlietland, Vlietlandplein 2, 3118 JH Schiedam, the Netherlands (henkjan_boiten@hotmail.com).

Published Online: June 22, 2023. doi:10.1001/jama.2023.8977

Conflict of Interest Disclosures: None reported.

Additional Information: We thank the patient for providing permission to share his information.

References

Gertz MA , Dispenzieri A . Systemic amyloidosis recognition, prognosis, and therapy: a systematic review. JAMA. 2020;324(1):79-89. doi:10.1001/jama.2020.5493 PubMed Google Scholar Crossref

Buxbaum JN , Ruberg FL . Transthyretin V122I (pV142I)* cardiac amyloidosis: an age-dependent autosomal dominant cardiomyopathy too common to be overlooked as a cause of significant heart disease in elderly African Americans. Genet Med. 2017;19(7):733-742. doi:10.1038/gim.2016.200 PubMed Google Scholar Crossref

Muchtar E , Dispenzieri A , Magen H , et al. Systemic amyloidosis from A (AA) to T (ATTR): a review. J Intern Med. 2021;289(3):268-292. doi:10.1111/joim.13169 PubMed Google Scholar Crossref

Dispenzieri A , Coelho T , Conceição I , et al; THAOS Investigators. Clinical and genetic profile of patients enrolled in the Transthyretin Amyloidosis Outcomes Survey (THAOS): 14-year update. Orphanet J Rare Dis. 2022;17(1):236. doi:10.1186/s13023-022-02359-w PubMed Google Scholar Crossref

Parcha V , Malla G , Irvin MR , et al. Association of transthyretin Val122Ile variant with incident heart failure among Black individuals. JAMA. 2022;327(14):1368-1378. doi:10.1001/jama.2022.2896 PubMed Google Scholar Crossref

Damrauer SM , Chaudhary K , Cho JH , et al. Association of the V122I hereditary transthyretin amyloidosis genetic variant with heart failure among individuals of African or Hispanic/Latino Ancestry. JAMA. 2019;322(22):2191-2202. doi:10.1001/jama.2019.17935 PubMed Google Scholar Crossref

Yanagisawa A , Ueda M , Sueyoshi T , et al. Amyloid deposits derived from transthyretin in the ligamentum flavum as related to lumbar spinal canal stenosis. Mod Pathol. 2015;28(2):201-207. doi:10.1038/modpathol.2014.102 PubMed Google Scholar Crossref

Gillmore JD , Maurer MS , Falk RH , et al. Nonbiopsy diagnosis of cardiac transthyretin amyloidosis. Circulation. 2016;133(24):2404-2412. doi:10.1161/CIRCULATIONAHA.116.021612 PubMed Google Scholar Crossref

Redfield MM , Borlaug BA . Heart failure with preserved ejection fraction: a review. JAMA. 2023;329(10):827-838. doi:10.1001/jama.2023.2020 PubMed Google Scholar Crossref

Adams D , Gonzalez-Duarte A , O'Riordan WD , et al Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis. N Engl J Med. 2018;379(1):11-21. doi:10.1056/NEJMoa1716153 PubMed Google Scholar Crossref

AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
1.00 credit toward the CME of the American Board of Surgery’s Continuous Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.