This study will examine the effectiveness of the drug cyclosporine in treating hypertrophic
cardiomyopathy (HCM), a condition in which the heart muscle thickens. The thickened muscle
can impair the heart's pumping action or decrease its blood supply, or both. Various
symptoms, such as chest pain, shortness of breath, fatigue, and palpitations, may result.
In animal studies, cyclosporine prevented heart muscle from thickening in mice that had been
engineered to develop thick hearts.
Patients with HCM 18 to 75 years old are screened for this study under protocol 98-H-0102
and this protocol. Screening tests include blood tests, echocardiogram to measure heart
thickness, Holter monitor to record heartbeats, treadmill exercise test, and various imaging
tests including a thallium scan, radionuclide angiography, magnetic resonance imaging (MRI),
and cardiac catheterization to examine heart function and blood supply.
Patients admitted to the study will be randomly assigned to take either cyclosporine tablets
or a placebo (a look-alike tablet with no active ingredient) twice a day for 6 months.
During a brief hospital stay at the start of the study, blood samples will be taken to
measure cyclosporine levels. After discharge, heart rate and blood pressure will be checked
and blood tests done during follow-up visits once a week for 2 weeks and then every two
weeks until the end of the 6-month treatment period. At that time, patients will be
hospitalized a second time for repeat tests to determine the effects of the drug on the
heart condition. They include thallium scan, radionuclide angiogram, MRI, treadmill
exercise test, cardiac catheterization, and echocardiogram. An echocardiogram and MRI will
be repeated 1 year after the start of the study to evaluate long term effects of the drug,
Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease characterized by marked
increase in cardiac mass caused by proliferation/hypertrophy of several cell types
(myocytes, fibroblasts, smooth muscle cells, and endothelial cells). There is often
associated left ventricular (LV) diastolic dysfunction and myocardial ischemia. The
severity of the LV hypertrophy, diastolic dysfunction, and myocardial ischemia are important
determinants of clinical course. In several animal models of LV hypertrophy, calcineurin
has been implicated in the development of myocardial hypertrophy, leading to cardiac
dilatation and failure. Inhibitors of calcineurin (Cyclosporin A and FK506) have been shown
to prevent the development of cardiac hypertrophy in these animal models, where cardiac
hypertrophy is related to sarcomeric dysfunction. We propose to study the ability of
Cyclosporin A (CsA) to reduce LV mass, and to improve symptoms, LV diastolic function, and
myocardial perfusion in HCM caused by sarcomeric gene mutations.
Patients of either gender, aged 18-75 years, with HCM caused by sarcomeric gene mutations
determined by existing protocols.
LV wall thickness of greater than or equal to 20 mm measured in any LV segment by MRI.
Severe symptoms refractory to medical treatment (New York Heart Association functional
class III or IV).
No LV outflow tract obstruction at rest greater than 30 mm Hg as determined by cardiac
No coronary artery disease (greater than 50% arterial luminal narrowing of a major
No chronic atrial fibrillation.
No bleeding disorder (PTT greater than 35 sec, pro time greater than 14 sec, platelet
count less than 154 k/mm(3).
No anemia (Hb less than 12.7 g/dl in males and less than 11.0 g/dl in females).
No renal impairment (serum creatinine greater than 1.3 mg/dl).
No hepatitis B or C; nor unexplained abnormal LFTs.
No inability to estimate LV wall thickness.
No positive urine pregnancy test.
No pregnant or lactating female patients.
No concurrent use of immunosuppressives or steroids.
No diabetes mellitus.
No history of malignancy other than skin tumors (squamous and basal cell) in the last 5
No condition that excludes the patient from undergoing an MRI test.