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1926 Diagnostic Test Accuracy of Cardiac Biomarkers for Light Chain Amyloidosis: A Systematic Review and Meta-Analysis

Program: Oral and Poster Abstracts
Session: 652. MGUS, Amyloidosis, and Other Non-Myeloma Plasma Cell Dyscrasias: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Research, Clinical Research
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Hassan Kawtharany1*, Muayad Azzam, MD2*, Jamil Nazzal, MD1*, Vishal Kukreti, MD, MSc3, Matthew D. Seftel, MD, FRCP, FRCPC, MPH4, Qais Hamarsha, MD1*, Aseel Alkhader, MD1*, Tala Khraise, MD5*, Mohammad Mahmoud AlMasri, MD6*, Hadi Khaled Abou Zeid, MD7*, Iktimal Alwan, MD8*, Mhd Amin Alzabibi, MD9*, Noor Jaber1*, Alfredo H. De La Torre, MD10, Noel Dasgupta, MD11*, Nitasha Sarswat, MD12*, Faizi Jamal, MD13*, Maria Adela Aguirre, MD, PhD14*, Deborah Boedicker15*, Naresh Bumma, MD16, Antonia Carroll, MD17*, Raymond Comenzo, MD18, Joselle Cook, MBBS19, Angela Dispenzieri, MD19, Jack Khouri, MD20, Maria M. Picken, MD, PhD21*, Shahzad Raza, MD20, Nelson Leung, MD19, Vaishali Sanchorawala22, Hira Shaikh, MD23, Daulath Singh, MD24* and Reem A Mustafa, MD, PhD, MPH25*

1Evidence-Based Practice and Impact Center, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS
2Evidence-Based Practice and Impact Center, Department of Internal Medicine, University of Kansas Medical Center, Overland Park, KS
3Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada
4Department of Medicine, University of British Columbia, Vancouver, CAN
5Northwest Health, Porter County, IN
6King Hussein Cancer Center, Amman, Jordan
7University of Balamand, Balamand, Lebanon
8AdventHealth, Tampa
9Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden
10QEII Health Sciences Centre, Halifax, NS, CAN
11Indiana University School of Medicine, Indianapolis, IN
12Advanced Heart Failure, Mechanical Circulatory Support and Transplantation, Division of Cardiology, The University of Chicago, Chicago, IL
13Division of Cardiology, Department of Medicine, City of Hope National Medical Center, Duarte, CA
14Internal Medicine Department, Hospital Italiano de Buenos Aires, BUENOS AIRES, AL, ARG
15Mackenzie’s Mission, Great Falls, VA
16The Ohio State University Comprehensive Cancer Center, COLUMBUS, OH
17Department of Neurology and Neurophysiology, St Vincent’s Hospital, Sydney, AUS
18Tufts Medical Center, Boston, MA
19Division of Hematology, Mayo Clinic, Rochester, MN
20Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH
21Loyola University Medical Center, Maywood, IL
22Section of Hematology and Medical Oncology, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine and Boston Medical Center, Boston, MA
23Division of Hematology, Oncology and Bone Marrow Transplantation, University of Iowa, Coralville, IA
24Mission Cancer + Blood, Des Moines, IA
25Division of Nephrology and Hypertension, Department of Internal Medicine, University of Kansas Medical Centre, Kansas City, KS

Introduction: In patients with systemic light-chain amyloidosis, cardiac involvement is common. Cardiac involvement (presence and severity) is the most important predictor of mortality in patients with AL amyloidosis. Endomyocardial biopsy remains the gold standard, but it is a costly and invasive test. Consequently, cardiac biomarkers are used for screening for cardiac involvement and have significant prognostic value. In this systematic review, we aim to estimate the diagnostic test accuracy (DTA) of Nt-proBNP, BNP, and high sensitivity troponin for cardiac amyloidosis.

Methods: As part of the American Society of Hematology guidelines on the diagnosis of Amyloidosis, we searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials from inception till January 2024 for relevant studies. Two reviewers independently performed title and abstract screening and full-text article screening on LASER Al and extracted relevant data using piloted Excel sheets. The panel judged whether the reference test is acceptable or not. Acceptable reference test is EMB alone or a combination of extracardiac biopsy plus cardiac imaging (CMR or echocardiography) with or without positive cardiac biomarkers (troponin or BNP or NT-proBNP). For statistical analysis, we only included studies reporting on both the sensitivity and specificity of the cardiac biomarker. We used Stata 18.0 software for meta-analysis. We evaluated risk of bias using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) and used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of the evidence. We report diagnostic test accuracy as sensitivity (95% confidence interval) and specificity (95% confidence interval).

Results: After screening 29,237 studies, a total of 10 studies addressed DTA of Nt-proBNP for cardiac amyloidosis. These studies used a wide variety of cutoffs for diagnosis of cardiac involvement, ranging from 150 to 5000 ng/L and a cutoff of 332 ng/L was the most studied and reported. The pooled estimates for sensitivity and specificity of Nt-proBNP using 332 as cutoffs are 0.99 ( 0.97, 1) and 0.53 (0.3, 0.75), respectively. The pooled estimates were based on 4 studies (n=645) with moderate certainty in the evidence.

For BNP, DTA was assessed in 3 studies (n= 257). Each study used a different cutoff for BNP (73, 100, and 412 ng/L). The sensitivity and specificity of BNP in each study were comparable and not significantly affected by the cutoff variation. Pooled sensitivity and specificity across studies, were 0.87 (0.80, 0.92), and 0.79 (0.71, 0.85), respectively. The certainty in evidence for the DTA of BNP was low.

Eight studies reported on DTA of high sensitivity troponin, with cutoffs ranging from 14 to 86 ng/L. Meta-analysis of studies reporting on cutoff 14 ng/L yielded sensitivity of 0.94 (0.87, 0.97) and specificity of 0.11 (0.08, 0.16) with moderate certainty evidence. Increasing the cutoff to 35 ng/l led to a decrease in sensitivity to 0.82 (0.66, 0.92) and an increase in specificity to 0.86 (0.74, 0.93) with low certainty evidence.

Conclusion: Cardiac biomarkers are highly sensitive, valuable initial tests for increasing suspicion of cardiac involvement in patients with AL amyloidosis. However, they lack specificity and, on their own, are insufficient for a definitive diagnosis of cardiac involvement. These biomarkers may be used in conjunction with other diagnostic tests to accurately identify and assess the extent of cardiac involvement.

Disclosures: Seftel: Astrazeneca: Other: Meal at CME event; Novartis: Other: Meal at CME event. Dasgupta: Siemens: Other: Adjudicator; Alnylam: Other: Advisory Board; NovoNordisk: Other: Advisory Board; Eidos: Other: Advisory Board; Astra Zeneca: Other: Advisory Board; Intellia: Other: Advisory Board. Sarswat: Alnylam: Consultancy, Membership on an entity's Board of Directors or advisory committees; Eidos: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees. Jamal: Janssen: Consultancy. Aguirre: Pfizer: Honoraria; PTC Bio: Honoraria. Bumma: Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Carroll: Alnylam: Other: Advisory Committee; Janssen: Other: Travel Support; CSL Behring: Honoraria. Cook: Geron Corp: Other: Held $600 Geron Stock for one week and sold without profit . Dispenzieri: Pfizer: Research Funding; Janssen: Research Funding; Alnylam: Research Funding; Alexion: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; HaemaloiX: Research Funding. Khouri: Prothena: Honoraria; GPCR Therapeutics, Inc.: Honoraria; Legend: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consultant. Raza: Pfizer: Consultancy, Honoraria; Prothena Biosciences: Consultancy; Kite Pharma: Consultancy. Leung: AbbVie: Current holder of stock options in a privately-held company; Checkpoint Therapeutics: Current holder of stock options in a privately-held company. Sanchorawala: Celgene, Millennium-Takeda, Janssen, Prothena, Sorrento, Karyopharm, Oncopeptide, Caelum, Alexion: Research Funding; Proclara, Caelum, Abbvie, Janssen, Regeneron, Protego, Pharmatrace, Telix, Prothena, AstraZeneca, Nexcella: Membership on an entity's Board of Directors or advisory committees; Pfizer, Janssen, Attralus, GateBio, Abbvie, BridgeBio: Consultancy.

*signifies non-member of ASH