title: Impaired myocardial oxygen availability contributes to abnormal exercise hemodynamics in heart failure with preserved ejection fraction.
abstract: BACKGROUND
  Hypertension is a frequent risk factor for the development of heart failure with preserved ejection fraction (HFPEF). Progressive extracellular matrix accumulation has been presumed to be the fundamental pathophysiologic mechanism that leads to the transition to impaired diastolic reserve. However, the contribution of other mechanisms affecting active and passive components of diastolic function has not been comprehensively assessed. In this study, we investigated the potential role of impaired myocardial oxygen delivery in the pathophysiology of HFPEF.
  
  
  RESULTS
  Patients with HFPEF, those with controlled hypertension, and healthy controls underwent simultaneous right-heart catheterization, echocardiography, and paired arterial and coronary sinus blood gas sampling at rest and during supine-cycle ergometry. Despite a lower workload (HFPEF vs control, hypertension: 43±8 versus 114±12, 87±14 W; P<0.001 and P<0.05, respectively), peak exercise pulmonary capillary wedge pressure was markedly higher in HFPEF patients compared with healthy and hypertensive controls (32±2 versus 16±1 and 17±1 mm Hg, both P<0.001). During exercise, the transcardiac oxygen gradient increased significantly in all groups; however, the peak transcardiac oxygen gradient was significantly lower in HFPEF patients (P<0.05). In addition, the left ventricular-work corrected transcardiac oxygen gradient remained significantly lower in HFPEF patients compared with controls (P<0.001).
  
  
  CONCLUSIONS
  The current study provides unique data suggesting that the abnormal diastolic reserve observed during exertion in HFPEF patients may, in part, be explained by impaired myocardial oxygen delivery due possibly to microvascular dysfunction. Further studies are required to confirm the structural and functional basis of these findings and to investigate the influence of potential therapies on this abnormality.
authors.affiliation: Heart Failure Research Group, Baker IDI Heart and Diabetes Institute, Melbourne, Australia (V.M.E., J.M., D.M.K.) Department of Cardiovascular Medicine, Alfred Hospital, Melbourne, Australia (V.M.E., J.M., D.M.K.) Department of Cardiology, Maastricht University Medical Center, Maastricht, The Netherlands (V.M.E.).
authors.forename: Vanessa P M
authors.initials: VP
authors.lastname: van Empel
authors.affiliation: Heart Failure Research Group, Baker IDI Heart and Diabetes Institute, Melbourne, Australia (V.M.E., J.M., D.M.K.) Department of Cardiovascular Medicine, Alfred Hospital, Melbourne, Australia (V.M.E., J.M., D.M.K.).
authors.forename: Justin
authors.initials: J
authors.lastname: Mariani
authors.affiliation: Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic and Foundation, Rochester, MN (B.A.B.).
authors.forename: Barry A
authors.initials: BA
authors.lastname: Borlaug
authors.affiliation: Heart Failure Research Group, Baker IDI Heart and Diabetes Institute, Melbourne, Australia (V.M.E., J.M., D.M.K.) Department of Cardiovascular Medicine, Alfred Hospital, Melbourne, Australia (V.M.E., J.M., D.M.K.).
authors.forename: David M
authors.initials: DM
authors.lastname: Kaye
mesh_terms: D000368:Aged; D001642:Bicycling; D001784:Blood Gas Analysis; D006328:Cardiac Catheterization; D016022:Case-Control Studies; D003971:Diastole; D015150:Echocardiography, Doppler; D015444:Exercise; D005080:Exercise Test; D017079:Exercise Tolerance; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000175:diagnosis / Q000503:physiopathology*; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D010100:Oxygen / Q000097:blood*; D010101:Oxygen Consumption; D011669:Pulmonary Wedge Pressure; D013318:Stroke Volume; D013997:Time Factors; D016277:Ventricular Function, Left
chemical_list: D010100:Oxygen
keywords: exercise; heart failure; hemodynamics; myocardial oxygenation; preserved ejection fraction