title: A pooled analysis of multicenter cohort studies of (123)I-mIBG imaging of sympathetic innervation for assessment of long-term prognosis in heart failure.
abstract: OBJECTIVE
  The study objectives were to create a cardiac metaiodobenzylguanidine (mIBG) database using multiple prospective cohort studies and to determine the quantitative iodine-123-labeled mIBG indices for identifying patients with chronic heart failure (HF) at greatest and lowest risk of lethal events.
  
  
  BACKGROUND
  Although the prognostic value of cardiac mIBG imaging in patients with HF has been shown, clinical use of this procedure has been limited. It is required to define universally accepted quantitative thresholds for high and low risk that could be used as an aid to therapeutic decision-making using a large cohort database.
  
  
  METHODS
  Six prospective HF cohort studies were updated, and the individual datasets were combined for the present patient-level analysis. The database consisted of 1,322 patients with HF followed up for a mean interval of 78 months. Heart-to-mediastinum ratio (HMR) and washout rate of cardiac mIBG activity were the primary cardiac innervation markers. The primary outcome analyzed was all-cause death.
  
  
  RESULTS
  Lethal events were observed in 326 patients, and the population mortality rate was 5.6%, 11.3%, and 19.7% at 1, 2, and 5 years, respectively. Multivariate Cox proportional hazard model analysis for all-cause mortality identified age (p < 0.0001), New York Heart Association (NYHA) functional class (p < 0.0001), late HMR of cardiac mIBG activity (p < 0.0001), and left ventricular ejection fraction (LVEF) (p = 0.0029) as significant independent predictors. Analysis of the 512-patient subpopulation with B-type natriuretic peptide (BNP) results showed BNP (p < 0.0001), greater NYHA functional class (p = 0.0002), and late HMR (p = 0.0011) as significant predictors, but LVEF was not. The receiver-operating characteristic-determined threshold of HMR (1.68) identified patients at significantly increased risk in any LVEF category. Survival rates decreased progressively with decreasing HMR, with 5-year all-cause mortality rates >7% annually for HMR <1.25, and <2% annually for HMR ≥1.95. Addition of HMR to clinical information resulted in a significant net reclassification improvement of 0.175 (p < 0.0001).
  
  
  CONCLUSIONS
  Pooled analyses of independent cohort studies confirmed the long-term prognostic value of cardiac mIBG uptake in patients with HF independently of other markers, such as NYHA functional class, BNP, and LVEF, and demonstrated that categoric assessments could be used to define meaningful thresholds for lethal event risk.
authors.affiliation: Second (Cardiology) Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan. tnakata@sapmed.ac.jp
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Nakata
authors.forename: Kenichi
authors.initials: K
authors.lastname: Nakajima
authors.forename: Shohei
authors.initials: S
authors.lastname: Yamashina
authors.forename: Takahisa
authors.initials: T
authors.lastname: Yamada
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Momose
authors.forename: Shu
authors.initials: S
authors.lastname: Kasama
authors.forename: Toshiki
authors.initials: T
authors.lastname: Matsui
authors.forename: Shinro
authors.initials: S
authors.lastname: Matsuo
authors.forename: Mark I
authors.initials: MI
authors.lastname: Travin
authors.forename: Arnold F
authors.initials: AF
authors.lastname: Jacobson
mesh_terms: D019797:3-Iodobenzylguanidine; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D019992:Databases as Topic; D018450:Disease Progression; D019317:Evidence-Based Medicine; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging* / Q000294:innervation*; D006333:Heart Failure / Q000097:blood / Q000000981:diagnostic imaging* / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D007564:Japan; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D015999:Multivariate Analysis; D020097:Natriuretic Peptide, Brain / Q000097:blood; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D012307:Risk Factors; D013318:Stroke Volume; D013564:Sympathetic Nervous System / Q000000981:diagnostic imaging*; D013997:Time Factors; D016277:Ventricular Function, Left
chemical_list: D015415:Biomarkers; D019275:Radiopharmaceuticals; D020097:Natriuretic Peptide, Brain; D019797:3-Iodobenzylguanidine