The study is designed to define the underlying vascular abnormalities present in patients
with diastolic heart failure and test the effect of a therapy aimed at vascular
abnormalities. This study is designed to investigate the effects of therapy with
atorvastatin in subjects with diastolic heart failure to improve abnormalities of vascular
and myocardial structure and function, with particular emphasis on arterial stiffness and
Forty subjects will be given either drug (atorvastatin 40 mg) or placebo in a randomized
fashion once daily for six months. Using echocardiography, tonometry, and flow mediated
dilation of conduit arteries and arterioles, baseline cardiovascular anatomy and physiology
will be defined. Subjects that enroll in the study will be required to come in for 5 study
visits. The initial visit is a screening visit; subject consent is obtained and an
echocardiogram is performed as well as blood tests. At the randomization visit (4-14 days
following screening), the subject will be provided with drug or placebo in a blinded
fashion.Also at this visit, subjects will be asked to do a 6 minute walk, QOL questionnaire,
and vascular function testing. There will be follow-up study visits at 1 and 3 months
following randomization. At each follow-up visit a medical history, pill count and brief
physical examination will be performed, a repeat QOL questionnaire administered, and blood
tests to assess safety of the statin therapy. At 6 months, the final study visit will occur.
At this visit a full history and detailed physical examination will be performed. Repeat
echocardiogram, 6 minute walk test, QOL questionnaire, and vascular function examinations
will be performed.
- Signed informed consent,
- Age > 18,
- Ejection fraction ≥ 50%,
- hospitalization for heart failure in the last 6 months and
- current NYHA Class II-IV symptoms, OR
- current NYHA Class III-IV symptoms and one of the following:
1. ECG or echocardiographic evidence of moderate/severe left ventricular
2. chest x-ray evidence of pulmonary congestion
- Probable alternative cause of symptoms (pulmonary disease, severe anemia, etc.)
- Prior documented LVEF < 40% or qualitative moderate or greater LV systolic
- Current indication for statin therapy
- Intolerance to statin therapy.
- Documented ischemic heart disease requiring lipid-lowering therapy (i.e. CAD,
myocardial infarction, stroke)
- Evidence of significant myocardial ischemia on stress testing at screening visit.
- Evidence of hepatic abnormality (defined as liver enzymes > 2 times the upper limit
of normal values).
- Uncontrolled hypertension (BP > 150/100)
- Significant valvular disease.
- Atrial fibrillation
- Known familial hypertrophic cardiomyopathy or obstructive hypertrophic
- Restrictive cardiomyopathy or systemic illness known to be associated with
infiltrative heart disease (i.e. amyloidosis, sarcoidosis, hemochromatosis).
- Cor pulmonale or other cause of right heart failure not related to LV dysfunction.
- Clinically significant pulmonary disease.
- Pericardial constriction or hemodynamically significant pleural effusion.
- Uncontrolled arrhythmia.
- Any systemic condition other than heart failure that may limit survival to less than
- Advance renal disease (serum creatinine > 3.0 mg/dl or on dialysis)
- Known intolerance or allergy to HMG CoA reductase inhibitors
- Uncontrolled hyper- or hypothyroidism.
- Any subject characteristic that may interfere with study compliance, such as baseline
dementia, substance abuse, history of non-compliance with medications or
- Prisoners or other vulnerable populations.
- Any woman of child-bearing age with a documented positive pregnancy test.
- Subject is receiving therapy with other investigational therapy or is participating
in any other clinical trial.