The main objective is to test the effect of prolonged therapy (24 weeks) with isosorbide dinitrate ± hydralazine on arterial wave reflections (primary endpoint). Secondary endpoints include left ventricular (LV) mass, fibrosis and diastolic function) and exercise capacity (assessed via the 6-minute walk test) in patients with Heart Failure and Preserved Ejection Fraction (HFPEF). We will also test the hypothesis that the reduction in arterial wave reflections induced by vasoactive therapy will correlate with the improvement in exercise capacity, LV mass, fibrosis and diastolic function. Finally, we will assess whether the hemodynamic response to an acute dose of sublingual nitroglycerin (NTG) can predict the sustained changes in the reflected wave and other hemodynamic parameters in response to chronic vasodilator therapy.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
44
Enrolled subjects will be randomized in a blinded fashion to 1 isosorbide dinitrate capsule TID + 1 placebo capsule TID. In addition, all subjects will receive a single in-lab dose of 0.4 mg of sublingual nitroglycerine (open label) before randomization to the blinded study drugs. Subjects receiving isosorbide dinitrate will be given 20mg PO q8am, 2pm, and 8pm and will be titrated up to 40mg PO q8am, 2pm, and 8pm.
Enrolled subjects will be randomized in a blinded fashion to 1 isosorbide dinitrate capsule TID + 1 hydralazine capsule TID. In addition, all subjects will receive a single in-lab dose of 0.4 mg of sublingual nitroglycerine (open label) before randomization to the blinded study drugs. Subjects receiving isosorbide dinitrate will be given 20mg PO q8am, 2pm, and 8pm and will be titrated up to 40mg PO q8am, 2pm, and 8pm. Subjects receiving hydralazine will be given 37.5mg PO q8am, 2pm, and 8pm and will be titrated up to 75mg PO q8am, 2pm, and 8pm.
Enrolled subjects will be randomized in a blinded fashion to 2 placebo capsules TID. In addition, all subjects will receive a single in-lab dose of 0.4 mg of sublingual nitroglycerine (open label) before randomization to the blinded study drugs.
Philadelphia VA Medical Center
Philadelphia, Pennsylvania, United States
Wave Reflection Magnitude
The dimensionless ratio of backward (reflected) to forward wave amplitude. Higher values imply more wave reflection.
Time frame: 24 weeks
LV Mass
LV mass measured by MRI, in grams normalized to height in meters raised to the 1.7 power (m\^1.7)
Time frame: 24 weeks
Quality of Life (Kansas City Cardiomyopathy Questionnaire Score)
Quality of life, assessed with the Kansas City cardiomyopathy questionnaire (overall summary score, which ranges from 0 to 100). Higher values imply better quality of life.
Time frame: 24 weeks
Early Diastolic Mitral Annular Velocity
Diastolic mitral annular velocity measured at the basal septal mitral annulus
Time frame: 24 weeks
Myocardial Extracellular Volume Fraction
Myocardial extracellular volume, expressed as percent of total tissue volume, measured by MRI (T1 mapping pre and post-gadolinium administration)
Time frame: 24 weeks
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