title: Enhanced pulmonary vasodilator reserve and abnormal right ventricular: pulmonary artery coupling in heart failure with preserved ejection fraction.
abstract: BACKGROUND
  Pulmonary hypertension and right ventricular (RV) dysfunction are common in patients with advanced heart failure with preserved ejection fraction (HFpEF), yet their underlying mechanisms remain poorly understood. We sought to examine RV-pulmonary artery (PA) functional reserve responses and RV-PA coupling at rest and during β-adrenergic stimulation in subjects with earlier stage HFpEF.
  
  
  RESULTS
  In a prospective trial, subjects with HFpEF (n=39) and controls (n=18) underwent comprehensive invasive and noninvasive hemodynamic assessment using high fidelity micromanometer catheters, echocardiography, and expired gas analysis at rest and during dobutamine infusion. HFpEF subjects displayed similar RV structure but significantly impaired RV systolic (lower RV dP/dtmax/IP and s') and diastolic function (higher RV τ) coupled with more severe pulmonary vascular disease, manifest by higher PA pressures, higher PA resistance, and lower PA compliance compared with controls. Dobutamine infusion caused greater pulmonary vasodilation in HFpEF compared with controls, with enhanced reductions in PA resistance, greater increase in PA compliance, and a more negative slope in the PA pressure-flow relationship when compared with controls (all P<0.001). RV-PA coupling analysis revealed that dobutamine improved RV ejection in HFpEF subjects through afterload reduction alone, rather than through enhanced contractility, indicating RV systolic reserve dysfunction.
  
  
  CONCLUSIONS
  Pulmonary hypertension in early stage HFpEF is related to partially reversible pulmonary vasoconstriction coupled with RV systolic and diastolic dysfunction, even in the absence of RV structural remodeling. Pulmonary vascular tone is more favorably responsive to β-adrenergic stimulation in HFpEF than controls, suggesting a potential role for β-agonists in the treatment of patients with HFpEF and pulmonary hypertension.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT01418248.
authors: From the Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic Rochester, MN (M.J.A., S.-J.H., G.C.K., V.M., T.P.O., K.F., B.A.B.); The Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark (M.A.J.); The Division of Cardiology, Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Korea (S.-J.H.); and Department of Cardiology, Institute of Clinical and Experimental Medicine-IKEM, Prague, Czech Republic (V.M.).
authors: Mads J
authors: MJ
authors: Andersen
authors: From the Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic Rochester, MN (M.J.A., S.-J.H., G.C.K., V.M., T.P.O., K.F., B.A.B.); The Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark (M.A.J.); The Division of Cardiology, Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Korea (S.-J.H.); and Department of Cardiology, Institute of Clinical and Experimental Medicine-IKEM, Prague, Czech Republic (V.M.).
authors: Seok-Jae
authors: SJ
authors: Hwang
authors: From the Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic Rochester, MN (M.J.A., S.-J.H., G.C.K., V.M., T.P.O., K.F., B.A.B.); The Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark (M.A.J.); The Division of Cardiology, Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Korea (S.-J.H.); and Department of Cardiology, Institute of Clinical and Experimental Medicine-IKEM, Prague, Czech Republic (V.M.).
authors: Garvan C
authors: GC
authors: Kane
authors: From the Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic Rochester, MN (M.J.A., S.-J.H., G.C.K., V.M., T.P.O., K.F., B.A.B.); The Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark (M.A.J.); The Division of Cardiology, Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Korea (S.-J.H.); and Department of Cardiology, Institute of Clinical and Experimental Medicine-IKEM, Prague, Czech Republic (V.M.).
authors: Vojtech
authors: V
authors: Melenovsky
authors: From the Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic Rochester, MN (M.J.A., S.-J.H., G.C.K., V.M., T.P.O., K.F., B.A.B.); The Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark (M.A.J.); The Division of Cardiology, Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Korea (S.-J.H.); and Department of Cardiology, Institute of Clinical and Experimental Medicine-IKEM, Prague, Czech Republic (V.M.).
authors: Thomas P
authors: TP
authors: Olson
authors: From the Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic Rochester, MN (M.J.A., S.-J.H., G.C.K., V.M., T.P.O., K.F., B.A.B.); The Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark (M.A.J.); The Division of Cardiology, Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Korea (S.-J.H.); and Department of Cardiology, Institute of Clinical and Experimental Medicine-IKEM, Prague, Czech Republic (V.M.).
authors: Kenneth
authors: K
authors: Fetterly
authors: From the Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic Rochester, MN (M.J.A., S.-J.H., G.C.K., V.M., T.P.O., K.F., B.A.B.); The Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark (M.A.J.); The Division of Cardiology, Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Korea (S.-J.H.); and Department of Cardiology, Institute of Clinical and Experimental Medicine-IKEM, Prague, Czech Republic (V.M.). borlaug.barry@mayo.edu.
authors: Barry A
authors: BA
authors: Borlaug
mesh_terms: D058665:Adrenergic beta-1 Receptor Agonists / Q000008:administration & dosage; D000368:Aged; D000369:Aged, 80 and over; D062186:Arterial Pressure / Q000187:drug effects; D003935:Diagnostic Techniques, Cardiovascular; D004280:Dobutamine / Q000008:administration & dosage; D005260:Female; D006333:Heart Failure / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology; D007263:Infusions, Parenteral; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology*; D013318:Stroke Volume / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D018497:Ventricular Dysfunction, Right / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000187:drug effects; D016278:Ventricular Function, Right / Q000187:drug effects
chemical_list: D058665:Adrenergic beta-1 Receptor Agonists; D004280:Dobutamine
keywords: heart failure; heart failure, diastolic; hypertension, pulmonary; pulmonary circulation; ventricular function, right