title: Noninvasive risk stratification of patients with transthyretin amyloidosis.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Cardiology, Angiology, and Respiratory Medicine, University Hospital Heidelberg, Heidelberg, Germany. Electronic address: Arnt.Kristen@med.uni-heidelberg.de.
authors.forename: Arnt V
authors.initials: AV
authors.lastname: Kristen
authors.affiliation: Department of Cardiology, Angiology, and Respiratory Medicine, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Scherer
authors.affiliation: Department of Cardiology, Angiology, and Respiratory Medicine, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Buss
authors.affiliation: Department of Cardiology, Angiology, and Respiratory Medicine, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: aus dem Siepen
authors.affiliation: Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Haufe
authors.affiliation: Department of Cardiology, Angiology, and Respiratory Medicine, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Bauer
authors.affiliation: Institute of Human Genetics, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Hinderhofer
authors.affiliation: Department of Cardiology, Angiology, and Respiratory Medicine, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Giannitsis
authors.affiliation: Department of Cardiology, Angiology, and Respiratory Medicine, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hardt
authors.affiliation: Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Haberkorn
authors.affiliation: Department of Cardiology, Angiology, and Respiratory Medicine, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Katus
authors.affiliation: Department of Cardiology, Angiology, and Respiratory Medicine, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Steen
mesh_terms: D000368:Aged; D028227:Amyloid Neuropathies, Familial / Q000150:complications / Q000175:diagnosis / Q000401:mortality*; D001706:Biopsy; D009202:Cardiomyopathies / Q000175:diagnosis / Q000209:etiology / Q000401:mortality*; D002423:Cause of Death / Q000639:trends; D003937:Diagnosis, Differential; D015150:Echocardiography, Doppler; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D005858:Germany / Q000453:epidemiology; D006801:Humans; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D008875:Middle Aged; D011228:Prealbumin / Q000378:metabolism*; D012372:ROC Curve; D012189:Retrospective Studies; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D015996:Survival Rate / Q000639:trends; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D011228:Prealbumin
keywords: cardiac magnetic resonance; echocardiography; skeletal scintigraphy; survival; transthyretin amyloidosis