A First-Visit Clinical Score to Distinguish Immunoglobulin Light-Chain from Wild-Type Transthyretin Cardiac Amyloidosis: Derivation and Internal Validation

@misc{matsumoto2026firstvisit,
  title = {{A First-Visit Clinical Score to Distinguish Immunoglobulin Light-Chain from Wild-Type Transthyretin Cardiac Amyloidosis: Derivation and Internal Validation}},
  author = {Y. Matsumoto and Y. Izumiya and Y. Kawano and N. Kuyama and K. Morikawa and A. Tabira and M. Yamamoto and K. Hirakawa and M. Ishii and S. Hanatani and Y. Matsuzawa and H. Usuku and E. Yamamoto and H. Soejima and K. Tsujita},
  howpublished = {medRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.10.26362801},
  url = {https://www.medrxiv.org/content/10.64898/2026.09.10.26362801v1},
  note = {CC BY-NC-ND},
}

TY  - UNPB
TI  - A First-Visit Clinical Score to Distinguish Immunoglobulin Light-Chain from Wild-Type Transthyretin Cardiac Amyloidosis: Derivation and Internal Validation
AU  - Y. Matsumoto
AU  - Y. Izumiya
AU  - Y. Kawano
AU  - N. Kuyama
AU  - K. Morikawa
AU  - A. Tabira
AU  - M. Yamamoto
AU  - K. Hirakawa
AU  - M. Ishii
AU  - S. Hanatani
AU  - Y. Matsuzawa
AU  - H. Usuku
AU  - E. Yamamoto
AU  - H. Soejima
AU  - K. Tsujita
PY  - 2026
DA  - 2026/09/10
PB  - medRxiv
DO  - 10.64898/2026.09.10.26362801
UR  - https://www.medrxiv.org/content/10.64898/2026.09.10.26362801v1
AB  - BackgroundDelayed diagnosis of immunoglobulin light-chain cardiac amyloidosis (AL-CA) worsens prognosis, partly because AL-CA and wild-type transthyretin cardiac amyloidosis (ATTRwt-CA) are difficult to distinguish at the initial cardiology visit. We developed and validated a practical score to triage AL-CA from ATTRwt-CA.  MethodsWe retrospectively analyzed 541 consecutive patients with cardiac amyloidosis (91 AL-CA, 450 ATTRwt-CA) at our institutions amyloidosis center, randomly divided into derivation (n=378) and validation (n=163) cohorts. Candidate first-visit variables underwent LASSO selection after multiple imputation, with estimates pooled by Rubins rules. Performance was assessed by bootstrap validation, calibration, and decision curve analysis. The model was converted into a simplified point-based score.  ResultsSeven variables were retained: age, absence of atrial fibrillation, absence of carpal tunnel syndrome, low serum albumin, proteinuria ([≥]1+), low voltage, and thinner left ventricular posterior wall thickness. Areas under the curve (AUC) were 0.97 in the derivation cohort and 0.99 in the validation cohort; the bootstrap optimism-corrected AUC was 0.96. The model provided net benefit across threshold probabilities of 0.01- 0.50. Risk tiering categorized the validation cohort into low (0-5 points; AL-CA 0%), intermediate (6-9 points; 26%), and high (10-13 points; 95%) probability groups. Discrimination remained high for AL-CA versus monoclonal protein-positive ATTRwt-CA at a cutoff of [≥]8 points (AUC 0.90). Adding this score to monoclonal protein testing significantly improved diagnostic performance compared with monoclonal protein testing alone.  ConclusionsThis simple first-visit score may help cardiologists rapidly triage suspected AL-CA and prioritize urgent hematology referral and subtype-specific confirmatory testing.  Clinical Perspective1) What Is New?O_LIA 7-variable score using age, history of atrial fibrillation and carpal tunnel syndrome, serum albumin, dipstick proteinuria, low QRS voltage, and left ventricular posterior wall thickness distinguished AL-CA from ATTRwt-CA using information available at the first cardiology visit. C_LIO_LIThe score retained high discrimination in the challenging subgroup comprising patients with AL-CA or monoclonal protein-positive ATTRwt-CA. C_LI  2) What Are the Clinical Implications?O_LIThe score may complement--not replace--standard monoclonal protein testing and definitive amyloid typing by helping prioritize the urgency of hematology assessment and subtype-specific confirmatory evaluation. C_LI
ER  -