The DIAMOND Study: Distensibility Improvement And Remodeling in Diastolic Heart Failure
The DIAMOND Study: Distensibility Improvement And Remodeling in Diastolic Heart Failure
The purpose of this study is to test the hypothesis that treatment with oral ALT-711 twice
 daily for 16 weeks will improve aortic distensibility, exercise tolerance, and quality of
 life in elderly patients with isolated diastolic heart failure (DHF), and that the
 improvements in exercise tolerance will correlate with the improvements in aortic
 distensibility.
Inclusion Criteria

 1. Men or women ≥ 60 years of age.

 2. Diagnosis of congestive heart failure with one or both of the following criteria: a
 Heart Failure Clinical Score ≥ 3 based on the NHANES-I criteria and/or a history of
 either acute pulmonary edema or the occurrence of 2 or more of the following with
 subsequent improvement with diuretic therapy and with no other identifiable cause:
 dyspnea on exertion, paroxysmal nocturnal dyspnea, orthopnea, systemic edema,
 exertional fatigue.

 3. Left ventricular ejection fraction ≥ 50% based on the baseline Doppler
 echocardiography test.

 4. Ability to provide written informed consent.

 5. Ability to comply with procedures specified in the study protocol.

 Exclusion Criteria

 1. Valvular heart disease as the primary etiology of congestive heart failure.

 2. Significant change in cardiovascular medication(s) <3 weeks prior to the baseline
 visit.

 3. Uncontrolled hypertension.

 4. History of stroke, or any sequelae of a transient ischemic attack (TIA), reversible
 ischemic neurologic defect (RIND), or stroke, within the last 12 months prior to entry
 into the study.

 5. Cancer or other noncardiovascular conditions with life expectancy less than 2 years.

 6. Significant anemia defined as a hemoglobin <11 gm/dL.

 7. Significant renal insufficiency defined as a serum creatinine >2.5 mg/dL.

 8. Significant hepatic insufficiency defined as an SGPT (ALT) or SGOT (AST) >2.5 times
 the upper limit of normal.

 9. Psychiatric disease (including uncontrolled major psychoses, depression, dementia, or
 personality disorder) or any additional condition(s) which, in the investigator's
 opinion, would prohibit the patient from completing the study, or not be in the best
 interest of the patient.

 10. Presence or history of drug or alcohol abuse.

 11. Prior exposure to ALT-711 or use of any other investigational drugs within 30 days
 prior to screening.

 12. Known seropositivity for HIV or hepatitis C, or presence of hepatitis B surface
 antigen.

 13. Severe COPD requiring recurrent oral steroids, oxygen at home or more than one
 inhaler.

 14. Baseline echocardiogram demonstrating the presence of left ventricular ejection
 fraction <50%.

 15. Unstable or uncontrolled myocardial ischemia, with no wall abnormality.

 16. Screening Familiarization Exercise Test demonstrating the presence of any of the
 following findings: evidence of significant ischemia (consisting of ECG finding of > 1
 mm flat ST depression confirmed with echocardiogram wall motion, or wall motion
 abnormality or decrease in global contractility on echocardiogram, or inability to
 continue exercising due to significant chest or leg pain or any reason other than
 exhaustion/fatigue/dyspnea, exercise SBP >240 mm Hg, DBP >110 mmHg, unstable
 hemodynamics or rhythm, or unwilling or unable to complete test adequately.

 17. Any contraindications to magnetic resonance imaging including but not limited to
 indwelling metal-containing prosthesis (orthopedic, valvular, other), pacemaker or
 defibrillator, history of welding occupation (ocular metal debris), or uncontrollable
 claustrophobia.