Noninvasive Imaging of Heart Failure: A Pilot Study

More than 9% of American men and close to 5% of women ages 60 to 79 years report a diagnosis
of heart failure, where above the age of 80 years these figures increase to 13.8% and 12.2%,
respectively. Projection into the middle part of this century suggests that, as the
population ages, the prevalence and cost of heart failure will continue to rise. The primary
aim of this proposal is to investigate noninvasive imaging methods for quantifying diffuse
myocardial fibrosis with cardiac magnetic resonance imaging (CMR) in heart failure patients.
The secondary aims are to investigate the association between diffuse fibrosis detected by
CMR with left ventricular function, and examine the utility of multi-detector CT (MDCT) in
detecting diffusion myocardial fibrosis.

- INCLUSION CRITERIA:

The common inclusion criteria between patients and controls are:

A. Able to understand and sign informed consent.

B. Able to complete a MRI or CT scan.

C. Age greater than or equal to 18 years old.

Heart Failure subject:

D. Men and women with a clinical diagnosis of heart failure.

E. New York Heart Association functional class II or worse.

F. For the normal ejection fraction arm.

1. Preserved left ventricular ejection fraction (EF >50%)

2. Diastolic dysfunction defined one or more of the following

1. LVEDP > 16 mm Hg

2. PCW > 12 mm Hg

3. E/E ratio >15

4. E/E ratio >8 AND NT-proBNP >220 pg/mL

For the systolic dysfunction arm:

3. Left ventricular ejection fraction <40%

Normal Control:

G. Men and women without a clinical diagnosis of heart failure.

H. NIH employees may be involved and NIH requirements will be followed as laid out in
NIH Policy Manual 2300-630-3 - Leave Policy For NIH Employees Participating In NIH
Medical Research Studies.

EXCLUSION CRITERIA:

Individuals will be excluded from the study if they are discovered to have coexistent
conditions that may contribute to structural or functional cardiac abnormalities,
which may confound interpretation of results, are ineligible for MRI or if they are at
increased risk for Nephrogenic Systemic Fibrosis (NSF) including:

A. Contra indications for gadiolinium-based contrast agent:

1. eGFR < 30ml/min/1.73m(2)

2. Acute renal failure, renal transplantation, current dialysis treatment or
hepatorenal syndrome

3. History of liver transplantation or severe liver disease

4. Severe Asthma

5. Hemoglobinopathies, sickle cell anemia and thalassemias major

6. History of multiple myeloma

7. History of significant allergic reaction to gadolinium-based contrast agents

B. Coronary artery disease with unstable symptoms or acute coronary syndrome within
the last six months.

C. Medical conditions associated with increased collagen turnover which may confound
interpretation of biomarkers of collagen synthesis. Examples include systemic amyloid
disease, cirrhosis, liver, pulmonary, or renal fibrosis, inflammatory states, cancer,
recent trauma or surgery;

D. Pregnant or lactating women;

E. Mental, neurologic or social condition preventing understanding of the rationale,
procedures, risks and potential benefits associated with the trial;

F. Any other conditions that precludes safety for MRI or MDCT per the researcher s
evaluation.

G. Patients otherwise eligible but with any of the following contraindications for
iodine-based CT contrast agent will be excluded from contrast CT angiography but may
undergo all other study procedures:

1. Renal dysfunction (defined as eGFR <45 mL/min/m(2))

2. Current clinical diagnosis of renal failure

3. Prior hypersensitivity to iodine containing substances (shellfish, iodine, and or
previous contrast reactions to contrast agents.