The Impact of Pomegranate Extract on Chronic Cardiomyopathy Complicated by Renal Insufficiency (ImPrOVE): a Pilot Study

Heart failure (HF) is a disease of great prevalence in the U.S. with an associated high
morbidity and mortality. In individuals with concomitant chronic renal insufficiency (CRI),
outcomes are even worse due to pharmaceutical under treatment and higher baseline levels of
oxidative stress. Reactive oxygen species (ROS) are generated during mechanoenergetic
uncoupling and can cause myocardial protein, lipid, and DNA damage, leading to the
development of HF. One means of preventing the progression of HF may be through ROS
reduction or an improvement in systemic or local oxidative stress handling. In this
randomized, single blind placebo-controlled pilot study, we hypothesize that 12 weeks of
treatment with oral pomegranate extract (POMx) will lead to a reduction in oxidative stress
(as assessed by measuring thiobarbituric acid-reactive substances, F8-isoprostanes, and
glutathione) in subjects (n=30) with cardiomyopathy (LVEF ≤40%) and CRI (GFR <60 ml/hr).
Secondary aims include assessing the impact of POMx on myocardial remodeling and endothelial
dysfunction by measuring serum collagen levels and asymmetric dimethylarginine,
respectively. Findings from this study will serve as pilot data for a larger randomized
trial of longer term POMx therapy in subjects with cardiomyopathy.

Inclusion Criteria:

- Adult subjects (≥21 years of age) with cardiomyopathy (ejection fraction ≤40%) of at
least 1 year duration and CRI (GFR <60 cc/hr for at least 3 months) will be eligible
for enrollment.

- Subjects must have New York Heart Association (NYHA) functional class I-III symptoms
and be on stable doses of HF evidence-based therapies (β-blocker, ACE inhibitor or
ARBs, aldosterone inhibitor [if appropriate]) for at least 3 months or have a
documented contraindication or intolerance to such therapy

Exclusion Criteria:

- Subjects admitted to a hospital for acute myocardial infarction (defined as positive
troponins) or HF exacerbation within the last 6 months will not be eligible for
enrollment.

- Subjects on warfarin or rosuvastatin will also be excluded.

- Other exclusion criteria are as follows:

- HF that is deemed to be congenital or infiltrative in etiology

- the presence of a life-threatening illness with a projected survival ≤6 months;
ongoing infection

- pregnancy

- inability to follow-up

- end-stage renal disease requiring dialysis

- renal transplant listing

- recent (within last 6 months) POMx use or intake >8 ounces daily of pomegranate
juice

- known hypersensitivity to any fruit in the Punicaceae family

- connective tissue or collagen vascular disease