• Mads J Andersen, Seok-Jae Hwang, Garvan C Kane, Vojtech Melenovsky, Thomas P Olson, Kenneth Fetterly, and Barry A Borlaug.
• 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.).
• Circ Heart Fail. 2015 May 1;8(3):542-50.

BackgroundPulmonary 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.Methods And ResultsIn 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.ConclusionsPulmonary 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.Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT01418248.© 2015 American Heart Association, Inc.

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