Targeting Central Pulsatile Hemodynamics in Chronic Kidney Disease

Exclusion Criteria

• •A clinically- indicated stress test demonstrating significant myocardial ischemia within 1 year of enrollment, not followed by coronary revascularization
• •Rhythm other than sinus (i.e., atrial fibrillation)
• •Non-cardiac condition limiting life expectancy to \<1 year
• •Current or anticipated future need for long acting organic nitrate therapy
• •Severe aortic or mitral valve disease
• •Hypertrophic cardiomyopathy
• •Known infiltrative or inflammatory myocardial disease (amyloid, sarcoid)
• •Pericardial disease
• •Primary pulmonary arteriopathy
• •History of myocardial infarction, unstable angina, percutaneous transluminal coronary angiography (PTCA) or coronary artery bypass grafting (CABG) within 60 days, or requirement for either PTCA or CABG at the time of consent
• •Resting heart rate (HR) \>100 bpm
• •A reduced LV ejection fraction (EF\<50%)
• •Known severe liver disease (AST \>3x normal, alkaline phosphatase or bilirubin \>2x normal)
• •Allergy to ISMN
• •Current therapy with phosphodiesterase inhibitors, such as sildenafil, vardanafil or tadalafil
• •Therapy with rosiglitazone
• •Current pregnancy or a positive urine pregnancy test; women who become pregnant during the study will be discontinued from the trial
• •Therapy with warfarin
• •History of kidney stones
• •History of glucose-6-phosphate dehydrogenase (G6PD) deficiency
• •Systolic blood pressure \<110 mmHg or diastolic blood pressure \<40 mmHg;
• •Contraindications to a cardiac MRI: (a) Central nervous system aneurysm clips; (b) Implanted neural stimulators; (c) Implanted cardiac pacemaker or defibrillator; (d) Cochlear implant; (e) Ocular foreign body (e.g. metal shavings); (f) Other implanted medical devices: (e.g. drug infusion ports); (g) Insulin pump; (h) Metal shrapnel or bullet; (i) Claustrophobia; (j) Extreme obesity rendering the patient unable to fit into narrow-bore scanners; (k) Unwillingness of the patient to undergo a cardiac MRI.