title: Left atrial enlargement increases the risk of major adverse cardiac events independent of coronary vasodilator capacity.
abstract: OBJECTIVE
  Longstanding uncontrolled atherogenic risk factors may contribute to left atrial (LA) hypertension, LA enlargement (LAE) and coronary vascular dysfunction. Together they may better identify risk of major adverse cardiac events (MACE). The aim of this study was to test the hypothesis that chronic LA hypertension as assessed by LAE modifies the relationship between coronary vascular function and MACE.
  
  
  METHODS
  In 508 unselected subjects with a normal clinical (82)Rb PET/CT, ejection fraction ≥40 %, no prior coronary artery disease, valve disease or atrial fibrillation, LAE was determined based on LA volumes estimated from the hybrid perfusion and CT transmission scan images and indexed to body surface area. Absolute myocardial blood flow and global coronary flow reserve (CFR) were calculated. Subjects were systematically followed-up for the primary end-point - MACE - a composite of all-cause death, myocardial infarction, hospitalization for heart failure, stroke, coronary artery disease progression or revascularization.
  
  
  RESULTS
  During a median follow-up of 862 days, 65 of the subjects experienced a composite event. Compared with subjects with normal LA size, subjects with LAE showed significantly lower CFR (2.25 ± 0.83 vs. 1.95 ± 0.80, p = 0.01). LAE independently and incrementally predicted MACE even after accounting for clinical risk factors, medication use, stress left ventricular ejection fraction, stress left ventricular end-diastolic volume index and CFR (chi-squared statistic increased from 30.9 to 48.3; p = 0.001). Among subjects with normal CFR, those with LAE had significantly worse event-free survival (risk adjusted HR 5.4, 95 % CI 2.3 - 12.8, p < 0.0001).
  
  
  CONCLUSIONS
  LAE and reduced CFR are related but distinct cardiovascular adaptations to atherogenic risk factors. LAE is a risk marker for MACE independent of clinical factors and left ventricular volumes; individuals with LAE may be at risk of MACE despite normal coronary vascular function.
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Angela S
authors.initials: AS
authors.lastname: Koh
authors.forename: Venkatesh L
authors.initials: VL
authors.lastname: Murthy
authors.forename: Arkadiusz
authors.initials: A
authors.lastname: Sitek
authors.forename: Peter
authors.initials: P
authors.lastname: Gayed
authors.forename: John
authors.initials: J
authors.lastname: Bruyere
authors.forename: Justina
authors.initials: J
authors.lastname: Wu
authors.forename: Marcelo F
authors.initials: MF
authors.lastname: Di Carli
authors.forename: Sharmila
authors.initials: S
authors.lastname: Dorbala
mesh_terms: D000368:Aged; D001900:Boston / Q000453:epidemiology; D015984:Causality; D015897:Comorbidity; D003324:Coronary Artery Disease / Q000175:diagnosis* / Q000401:mortality*; D018572:Disease-Free Survival; D005080:Exercise Test / Q000706:statistics & numerical data; D005260:Female; D006325:Heart Atria / Q000000981:diagnostic imaging*; D006333:Heart Failure / Q000401:mortality*; D006801:Humans; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging / Q000706:statistics & numerical data; D009203:Myocardial Infarction / Q000401:mortality*; D049268:Positron-Emission Tomography / Q000706:statistics & numerical data; D015203:Reproducibility of Results; D012307:Risk Factors; D012680:Sensitivity and Specificity; D015996:Survival Rate; D014057:Tomography, X-Ray Computed / Q000706:statistics & numerical data; D014665:Vasodilator Agents
chemical_list: D014665:Vasodilator Agents