Noninvasive risk stratification of patients with transthyretin amyloidosis

JACC Cardiovasc Imaging. 2014 May;7(5):502-10. doi: 10.1016/j.jcmg.2014.03.002. Epub 2014 Apr 9.

Abstract

Objectives: We sought to evaluate noninvasive parameters by electrocardiography, echocardiography, technetium-99m-3,3-diphosphono-1,2-propanodicarboxylic acid ((99m)Tc-DPD) scintigraphy, and cardiac magnetic resonance for the prediction of all-cause mortality in patients with cardiac transthyretin amyloidosis (ATTR).

Background: ATTR may present with highly variable symptoms, including polyneuropathy and cardiomyopathy, the latter being associated with a poor outcome. However, data on noninvasive risk stratification of ATTR are limited.

Methods: A total of 70 patients with ATTR were evaluated by echocardiography, cardiac biomarkers, and (99m)Tc-DPD scintigraphy. Cardiac magnetic resonance was performed in 30 patients. Echocardiographic findings and plasma levels of biomarkers were correlated with results of quantitative analysis of scintigraphy using a region-of-interest technique (whole-body as well as heart tracer retention). Receiver-operating characteristic (ROC) analysis was performed to calculate a cutoff value of (99m)Tc-DPD scintigraphy for heart retention for the diagnosis of cardiac amyloid involvement with the highest sensitivity and specificity. Univariate and multivariate analyses were performed in patients with cardiac involvement (n = 60) to determine noninvasive predictors of all-cause mortality.

Results: Scintigraphy findings correlated with morphological (interventricular septum thickness, left ventricular hypertrophy index) as well as functional (mitral annular systolic velocity, mitral/tricuspid annular plane systolic excursion) findings, cardiac biomarkers, renal function, and late gadolinium enhancement. The ROC-derived cutoff for the detection of cardiac amyloidosis by scintigraphic heart tracer retention was 4.8%. Univariate Cox regression revealed N-terminal pro-B-type natriuretic peptide, troponin T, mitral annular plane systolic excursion, and left ventricular hypertrophy index as predictors of all-cause mortality. However, on multivariate analysis, troponin T remained the only independent predictor of survival. The ROC-derived cutoff value of troponin T predicting all-cause mortality with the highest sensitivity (80.0%) and specificity (68.7%) was 0.0375 ng/l.

Conclusions: Quantitative analysis of tracer retention is capable of characterizing the severity of cardiac involvement in ATTR. By multivariate analysis, troponin T remained the only independent predictor of survival.

Keywords: cardiac magnetic resonance; echocardiography; skeletal scintigraphy; survival; transthyretin amyloidosis.

MeSH terms

  • Aged
  • Amyloid Neuropathies, Familial / complications
  • Amyloid Neuropathies, Familial / diagnosis
  • Amyloid Neuropathies, Familial / mortality*
  • Biopsy
  • Cardiomyopathies / diagnosis
  • Cardiomyopathies / etiology
  • Cardiomyopathies / mortality*
  • Cause of Death / trends
  • Diagnosis, Differential
  • Echocardiography, Doppler
  • Electrocardiography
  • Female
  • Follow-Up Studies
  • Germany / epidemiology
  • Humans
  • Magnetic Resonance Imaging, Cine
  • Male
  • Middle Aged
  • Prealbumin / metabolism*
  • ROC Curve
  • Retrospective Studies
  • Risk Assessment / methods*
  • Risk Factors
  • Survival Rate / trends
  • Tomography, Emission-Computed, Single-Photon

Substances

  • Prealbumin

Supplementary concepts

  • Amyloidosis, Hereditary, Transthyretin-Related