title: Synergistic prognostic values of cardiac sympathetic innervation with left ventricular hypertrophy and left atrial size in heart failure patients without reduced left ventricular ejection fraction: a cohort study.
abstract: OBJECTIVE
  This study tested whether cardiac sympathetic innervation assessed by metaiodobenzylguanidine (MIBG) activity has long-term prognostic value in combination with left ventricular hypertrophy (LVH) and left atrial size in heart failure (HF) patients without reduced left ventricular ejection fraction (LVEF).
  
  
  METHODS
  A single-centre prospective cohort study.
  
  
  METHODS
  With primary endpoints of cardiac death and rehospitalisation due to HF progression, 178 consecutive symptomatic HF patients with 74% men, mean age of 56 years and mean LVEF of 64.5% were followed up for 80 months. The entry criteria consisted of LVEF more than 50%, completion of predischarge clinical evaluations including cardiac MIBG and echocardiographic studies and at least more than 1-year follow-up when survived.
  
  
  RESULTS
  Thirty-four patients with cardiac evens had larger left atrial dimension (LAD), increased LV mass index, reduced MIBG activity quantified as heart-to-mediastinum ratio (HMR) than did the others. Multivariable Cox analysis showed that LAD and HMR were significant predictors (HR of 1.080 (95% CI 1.00 to 1.16, p=0.044) and 0.107 (95% CI 0.01 to 0.61, p=0.012, respectively). Thresholds of HMR (1.65) and LAD (37 mm) were closely related to identification of high-risk patients. In particular, HMR was a significant determinant of cardiac events in both patients with and without LV hypertrophy. Reduced HMR with enlarged LAD or LV hypertrophy identified patients at most increased risk; overall log-rank value, 11.5, p=0.0032 for LAD and 17.5, p=0.0002, respectively.
  
  
  CONCLUSIONS
  In HF patients without reduced LV ejection fraction, impairment of cardiac sympathetic innervation is related to cardiac outcomes independently and synergistically with LA size and LV hypertrophy. Cardiac sympathetic innervation assessment can contribute to better risk-stratification in combination with evaluation of LA size and LV mass but is needed to be evaluated for establishing aetiology-based risk assessment in HF patients at increased risk.
authors.affiliation: Second Department of Internal Medicine (Cardiology),  Sapporo Medical University School of Medicine, Sapporo,  Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Doi
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Nakata
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Hashimoto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yuda
authors.forename: Takeru
authors.initials: T
authors.lastname: Wakabayashi
authors.forename: Hidemichi
authors.initials: H
authors.lastname: Kouzu
authors.forename: Naofumi
authors.initials: N
authors.lastname: Kaneko
authors.forename: Mamoru
authors.initials: M
authors.lastname: Hase
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Tsuchihashi
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Miura