Study to Evaluate Sex Differences in the Acute Effects of PL-3994 in Heart Failure Subjects

Exclusion Criteria

• •1. Orthostatic hypotension, systolic blood pressure \<100 mm Hg, diastolic blood pressure \< 50 mmHg.
• •2. Any prior echocardiogram with LVEF \< 40%
• •3. Hemoglobin \< 9 g/dl
• •4. eGFR \< 30 mL/min/1.73 m2
• •5. Hemodynamically significant arrhythmias within prior 4 weeks
• •6. Acute coronary syndrome, cardiac surgery, or percutaneous coronary intervention within prior 3 months
• •7. Any of the following cardiac diagnoses: active myocarditis, hypertrophic cardiomyopathy, \> moderate regurgitant valvular disease, any valvular stenosis, restrictive cardiomyopathy (including amyloid, sarcoid, or hemochromatosis), constrictive pericarditis, complex congenital heart disease, or pulmonary arterial hypertension
• •8. Current need for IV inotropic medication
• •9. Currently taking nitrates or having stopped nitrates within 24 hours of visit
• •10. Currently taking antihistamines, antipsychotics, tri-cyclic antidepressants, catecholamines/related compounds, monoamine oxidase inhibitors, stimulants (including caffeine and nicotine), sympathomimetics, dopamine agonists. Additionally, medications that inhibit PDE activity will be prohibited during the study and for 5 half- lives prior to Day 1 so that cGMP measurements will not be affected
• •11. Currently hospitalized for HF
• •12. Any prior need for mechanical circulatory support
• •13. Previous adverse reaction to the study drug
• •14. Inability to comply with planned study procedures
• •15. Pregnant or nursing mothers
• •16. Participation in another study with an investigational drug or device within 30 days or a biologic study within 90 days prior to signing consent.
• •17. Study participants must use method of birth control that has been approved by the Study Doctor and males must not donate sperm during the study and for 30 days after the last dose of study drug.