A multi-modal diagnostic model improves detection of cardiac amyloidosis among patients with diagnostic confirmation by cardiac biopsy

Am Heart J. 2021 Feb:232:137-145. doi: 10.1016/j.ahj.2020.11.006. Epub 2020 Nov 17.

Abstract

Background: Timely recognition of cardiac amyloidosis is clinically important, but the diagnosis is frequently delayed.

Objectives: We sought to identify a multi-modality approach with the highest diagnostic accuracy in patients evaluated by cardiac biopsy, the diagnostic gold standard.

Methods: Consecutive patients (N = 242) who underwent cardiac biopsy for suspected amyloidosis within an 18-year period were retrospectively identified. Cardiac biomarker, ECG, and echocardiography results were examined for correlation with biopsy-proven disease. A prediction model for cardiac amyloidosis was derived using multivariable logistic regression.

Results: The overall cohort was characterized by elevated BNP (median 727 ng/mL), increased left ventricular wall thickness (IWT; median 1.7 cm), and reduced voltage-to-mass ratio (median 0.06 mm/[g/m2]). One hundred and thirteen patients (46%) had either light chain (n = 53) or transthyretin (n = 60) amyloidosis by cardiac biopsy. A prediction model including age, relative wall thickness, left atrial pressure by E/e', and low limb lead voltage (<0.5 mV) showed good discrimination for cardiac amyloidosis with an optimism-corrected c-index of 0.87 (95% CI 0.83-0.92). The diagnostic accuracy of this model (79% sensitivity, 84% specificity) surpassed that of traditional screening parameters, such as IWT in the absence of left ventricular hypertrophy on ECG (98% sensitivity, 20% specificity) and IWT with low limb lead voltage (49% sensitivity, 91% specificity).

Conclusion: Among patients with an advanced infiltrative cardiomyopathy phenotype, traditional biomarker, ECG, and echocardiography-based screening tests have limited individual diagnostic utility for cardiac amyloidosis. A prediction algorithm including age, relative wall thickness, E/e', and low limb lead voltage improves the detection of cardiac biopsy-proven disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aged
  • Amyloid Neuropathies, Familial / blood
  • Amyloid Neuropathies, Familial / diagnosis*
  • Amyloid Neuropathies, Familial / pathology
  • Amyloid Neuropathies, Familial / physiopathology
  • Amyloidosis / blood
  • Amyloidosis / diagnosis
  • Amyloidosis / pathology
  • Amyloidosis / physiopathology
  • Biopsy
  • Blood Flow Velocity
  • Cardiomyopathies / blood
  • Cardiomyopathies / diagnosis*
  • Cardiomyopathies / pathology
  • Clinical Decision Rules
  • Echocardiography
  • Electrocardiography
  • Female
  • Heart Ventricles / diagnostic imaging
  • Heart Ventricles / pathology
  • Humans
  • Immunoglobulin Light-chain Amyloidosis / blood
  • Immunoglobulin Light-chain Amyloidosis / diagnosis*
  • Immunoglobulin Light-chain Amyloidosis / pathology
  • Immunoglobulin Light-chain Amyloidosis / physiopathology
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Natriuretic Peptide, Brain / blood
  • Organ Size
  • Sex Factors
  • Troponin I / blood

Substances

  • Troponin I
  • Natriuretic Peptide, Brain

Supplementary concepts

  • Amyloidosis, Hereditary, Transthyretin-Related