Physiological Effects of Grape Seed Extract in Diastolic Heart Failure

• grape seed extract (MegaNatural BP, Polyphenolics, Inc.) (Drug), also known as grapes, wine, polyphenols, resveratrol, quercetin, anthocyanins, flavonoids, flavanols, flavonols, antioxidants: Subjects will be randomized in double-blind fashion to either grape seed extract (GSE) or maltodextrin placebo capsules for for 6 weeks. Patient will take 300 mg GSE/placebo twice a day for 6 weeks. Patient will have a 2 week washout period and then cross over to the opposite group for an additional 6 weeks.

Primary outcomes

• Brachial artery flow-mediated dilation (FMD) [Pre-six weeks of investigational drug and placebo intervention]: Ultrasound measure of conduit artery endothelial function
• Brachial artery flow-mediated dilation (FMD) [Post-six weeks of investigational drug and placebo intervention]: Ultrasound measure of conduit artery endothelial function

Secondary outcomes

• 24-hour blood pressure [Pre-six weeks of investigational drug and placebo intervention]: Mean and diurnal variation
• EndoPAT arterial endothelial function [Pre-six weeks of investigational drug and placebo intervention]: Plethysmographic measure of resistance arterial endothelial function
• Carotid-femoral pulse wave velocity [Pre-six weeks of investigational drug and placebo intervention]
• Maximal exercise capacity and oxygen consumption [Pre-six weeks of investigational drug and placebo intervention]
• Resting and post-exercise ventricular systolic and diastolic function [Pre-six weeks of investigational drug and placebo intervention]: Standard and novel echocardiographic measures including strain/strain rate
• Urinary 8-isoprostanes [Pre-six weeks of investigational drug and placebo intervention]: Measure of oxidative stress
• Heart failure related quality of life [Pre-six weeks of investigational drug and placebo intervention]: Minnesota Living With Heart Failure Questionnaire
• 24-hour blood pressure [Post-six weeks of investigational drug and placebo intervention]: Mean and diurnal variation
• EndoPAT arterial endothelial function [Post-six weeks of investigational drug and placebo intervention]: Plethysmographic measure of resistance arterial endothelial function
• Carotid-femoral pulse wave velocity [Post-six weeks of investigational drug and placebo intervention]
• Maximal exercise capacity and oxygen consumption [Post-six weeks of investigational drug and placebo intervention]
• Resting and post-exercise ventricular systolic and diastolic function [Post-six weeks of investigational drug and placebo intervention]: Standard and novel echocardiographic measures including strain/strain rate
• Urinary 8-isoprostanes [Post-six weeks of investigational drug and placebo intervention]: Measure of oxidative stress
• Heart failure related quality of life [Post-six weeks of investigational drug and placebo intervention]: Minnesota Living With Heart Failure Questionnaire

Sex: All, ages: 50 Years to any

Inclusion Criteria:

Inclusion:

* Signs and symptoms of heart failure
* Left ventricular ejection fraction ≥ 50% (contrast ventriculography, echocardiography, nuclear scintigraphy, MRI or CT imaging)
* Diastolic dysfunction on previous echocardiogram/catheterization, or indeterminate diastolic function with supporting evidence of heart failure (HF) (as per European Society of Cardiology guidelines)
* History of systemic hypertension
* Age ≥ 50 years
* Willing to adhere to prescribed course of supplementation
* Informed consent

Exclusion Criteria:

* Daily intake of antioxidant supplements or vitamins beyond that provided in a standard daily multivitamin (e.g. high-dose vitamin E or vitamin C)
* NYHA Class IV heart failure symptoms (except during previous hospitalization)
* Hospitalization for decompensated heart failure within past one month
* Severely uncontrolled hypertension (SBP ≥ 180 and.or DBP ≥ 100 at rest, on current antihypertensive regimen
* Uncontrolled diabetes mellitus (hemoglobin A1C > 9%)
* Severe renal (estimated GFR < 30 ml/min) or hepatic disease/failure
* Severe anemia (Hgb < 9)
* Primary exercise limitation due to severe pulmonary disease
* Unacceptably poor echocardiographic images for analysis
* Worse than moderate mitral or aortic stenosis or insufficiency.
* Non-hypertensive cause of HFpEF (e.g. valvular disease, congenital heart disease, amyloidosis, sarcoidosis, constrictive pericardial syndromes)
* Myocardial infarction or unstable angina, including new or worsening anginal syndrome, within the past three months
* Uncontrolled arrhythmia (including non rate-controlled atrial fibrillation)
* Terminal illness expected to result in death within six months or active solid-organ cancer
* Psychiatric disorder (or dementia) with potential to compromise adherence
* Changes in medical regimen for heart disease or hypertension within past 1 month (except diuretic dose adjustment)

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• Scott L Hummel, MD, MS, Principal investigator, University of Michigan