title: Multicenter Study of Planar Technetium 99m Pyrophosphate Cardiac Imaging: Predicting Survival for Patients With ATTR Cardiac Amyloidosis.
abstract: Transthyretin cardiac amyloidosis (also known as ATTR cardiac amyloidosis) is an increasingly recognized cause of heart failure with preserved ejection fraction. In single-center studies, technetium 99m pyrophosphate (Tc 99m PYP) cardiac imaging noninvasively detects ATTR cardiac amyloidosis, but the accuracy of this technique in a multicenter study and the association of Tc 99m PYP myocardial uptake with survival are unknown.
  
  
  
  To assess Tc 99m PYP cardiac imaging as a diagnostic tool for ATTR cardiac amyloidosis and its association with survival in a multicenter study.
  
  
  
  Retrospective cohort study performed at 3 academic specialty centers for cardiac amyloidosis in the United States in which 229 participants were evaluated for cardiac amyloidosis and also underwent Tc 99m PYP cardiac imaging. The date of analysis and final confirmation from the statistician was May 4, 2016.
  
  
  
  Tc 99m PYP cardiac imaging for detection of ATTR cardiac amyloidosis.
  
  
  
  Retention of Tc 99m PYP in the heart was assessed using both a semiquantitative visual score (range, 0 [no uptake] to 3 [uptake greater than bone]) and a quantitative heart to contralateral (H/CL) ratio. The H/CL ratio was calculated as total counts in a region of interest over the heart divided by background counts in an identical size region of interest over the contralateral chest. The outcome measured was time to death after Tc 99m PYP imaging.
  
  
  
  Tc 99m PYP imaging of 171 participants (121 with ATTR cardiac amyloidosis and 50 with non-ATTR cardiac amyloidosis [34 with AL amyloidosis and 16 with nonamyloid heart failure with preserved ejection fraction]; 86% male; median [IQR] age, 73 years [65-79 years]) demonstrated 91% sensitivity and 92% specificity for detecting ATTR cardiac amyloidosis with an area under the curve of 0.960 (95% CI, 0.930-0.981). Univariable and multivariable Cox proportional hazards regression analyses among participants with ATTR cardiac amyloidosis showed that an H/CL ratio of 1.6 or greater predicted worse survival (hazard ratio, 3.911 [95% CI, 1.155-13.247]; P = .03 for univariable analysis and 7.913 [95% CI, 1.679-37.296]; P = .01 for multivariable analysis). In Kaplan-Meier analysis over a 5-year follow-up period, survival was significantly worse if the H/CL ratio was 1.6 or greater rather than less than 1.6 (log-rank P = .02).
  
  
  
  In this multicenter study, Tc 99m PYP cardiac imaging conferred a high level of sensitivity and specificity for differentiation of patients with ATTR cardiac amyloidosis (irrespective of genotype) from patients with AL cardiac amyloidosis and patients with nonamyloid heart failure with preserved ejection fraction. An H/CL ratio of 1.6 or greater was associated with worse survival among patients with ATTR cardiac amyloidosis. Among patients for whom there is a high clinical suspicion of cardiac amyloidosis, Tc 99m PYP may be of diagnostic and prognostic importance.
authors.affiliation: Division of Cardiology, Department of Medicine, Center for Advanced Cardiac Care, Columbia University Medical Center, New York, New York.
authors.forename: Adam
authors.initials: A
authors.lastname: Castano
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Haq
authors.affiliation: Division of Cardiology, Department of Medicine, Center for Advanced Cardiac Care, Columbia University Medical Center, New York, New York.
authors.forename: David L
authors.initials: DL
authors.lastname: Narotsky
authors.affiliation: Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, New York.
authors.forename: Jeff
authors.initials: J
authors.lastname: Goldsmith
authors.affiliation: Nuclear Cardiology Laboratory, Columbia University, New York, New York.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Weinberg
authors.affiliation: Nuclear Cardiology Laboratory, Columbia University, New York, New York.
authors.forename: Rachelle
authors.initials: R
authors.lastname: Morgenstern
authors.affiliation: Nuclear Cardiology Laboratory, Columbia University, New York, New York.
authors.forename: Ted
authors.initials: T
authors.lastname: Pozniakoff
authors.affiliation: Amyloidosis Center, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Frederick L
authors.initials: FL
authors.lastname: Ruberg
authors.affiliation: Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Miller
authors.affiliation: Amyloidosis Center, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: John L
authors.initials: JL
authors.lastname: Berk
authors.affiliation: Department of Hematology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Angela
authors.initials: A
authors.lastname: Dispenzieri
authors.affiliation: Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota.
authors.forename: Martha
authors.initials: M
authors.lastname: Grogan
authors.affiliation: Department of Radiology and Immunology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Johnson
authors.affiliation: Nuclear Cardiology Laboratory, Columbia University, New York, New York.
authors.forename: Sabahat
authors.initials: S
authors.lastname: Bokhari
authors.affiliation: Division of Cardiology, Department of Medicine, Center for Advanced Cardiac Care, Columbia University Medical Center, New York, New York.
authors.forename: Mathew S
authors.initials: MS
authors.lastname: Maurer
mesh_terms: D000368:Aged; D000686:Amyloidosis / Q000000981:diagnostic imaging / Q000401:mortality*; D009202:Cardiomyopathies / Q000000981:diagnostic imaging / Q000401:mortality*; D011756:Diphosphates; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging; D006801:Humans; D008297:Male; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D012189:Retrospective Studies; D013667:Technetium
chemical_list: D011756:Diphosphates; D019275:Radiopharmaceuticals; D013667:Technetium