title: Mechanisms of coronary microcirculatory dysfunction in patients with aortic stenosis and angiographically normal coronary arteries.
abstract: BACKGROUND
  Development of left ventricular hypertrophy in aortic stenosis (AS) is accompanied by coronary microcirculatory dysfunction, demonstrated by an impaired coronary vasodilator reserve (CVR). However, evidence for regional abnormalities in myocardial blood flow (MBF) and the potential mechanisms is limited. The aims of this study were to quantitatively demonstrate differences in subendocardial and subepicardial microcirculation and to investigate the relative contribution of myocyte hypertrophy, hemodynamic load, severity of AS, and coronary perfusion to impairment in microcirculatory function.
  
  
  RESULTS
  Twenty patients with isolated moderate to severe AS were studied using echocardiography to assess severity of AS, cardiovascular magnetic resonance to measure left ventricular mass (LVM), and PET to quantify resting and hyperemic (dipyridamole 0.56 mg/kg) MBF and CVR in both the subendocardium and subepicardium. In the patients with most severe AS (n=15), the subendocardial to subepicardial MBF ratio decreased from 1.14+/-7 at rest to 0.92+/-7 during hyperemia (P<0.005), and subendocardial CVR (1.43+/-3) was lower than subepicardial CVR (1.78+/-35; P=0.01). Resting total LV blood flow was linearly related to LVM, whereas CVR was not. Increase of total LV blood flow during hyperemia (mean value, 89.6+/-6%; range, 17% to 233%) was linearly related to aortic valve area. The decrease in CVR was related to severity of AS, increase in hemodynamic load, and reduction in diastolic perfusion time, particularly in the subendocardium.
  
  
  CONCLUSIONS
  CVR was more severely impaired in the subendocardium in patients with LVH attributable to severe AS. Severity of impairment was related to aortic valve area, hemodynamic load imposed, and diastolic perfusion rather than to LVM.
authors.affiliation: Medical Research Council Clinical Sciences Centre, Hammersmith Hospital, London, UK.
authors.forename: Kim
authors.initials: K
authors.lastname: Rajappan
authors.forename: Ornella E
authors.initials: OE
authors.lastname: Rimoldi
authors.forename: David P
authors.initials: DP
authors.lastname: Dutka
authors.forename: Ben
authors.initials: B
authors.lastname: Ariff
authors.forename: Dudley J
authors.initials: DJ
authors.lastname: Pennell
authors.forename: Desmond J
authors.initials: DJ
authors.lastname: Sheridan
authors.forename: Paolo G
authors.initials: PG
authors.lastname: Camici
mesh_terms: D000328:Adult; D000368:Aged; D001021:Aortic Valve / Q000000981:diagnostic imaging; D001024:Aortic Valve Stenosis / Q000000981:diagnostic imaging / Q000503:physiopathology*; D017023:Coronary Angiography; D003326:Coronary Circulation; D005260:Female; D006439:Hemodynamics; D006801:Humans; D006940:Hyperemia / Q000139:chemically induced / Q000000981:diagnostic imaging; D017379:Hypertrophy, Left Ventricular / Q000175:diagnosis / Q000503:physiopathology; D018810:Magnetic Resonance Angiography; D008297:Male; D008833:Microcirculation / Q000000981:diagnostic imaging / Q000503:physiopathology; D008875:Middle Aged; D010496:Pericardium; D012039:Regional Blood Flow; D014055:Tomography, Emission-Computed / Q000379:methods; D014463:Ultrasonography