Hemodynamic Response to Exercise in HFpEF Patients After Upregulation of SERCA2a
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Cardiology |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 60 - 85 |
| Updated: | 12/22/2018 |
| Start Date: | September 2015 |
| End Date: | December 2018 |
Hemodynamic Response to Exercise in Heart Failure With Preserved Ejection Fraction (HFpEF) Patients After Upregulation of SERCA2a
Heart failure with preserved ejection fraction or HFpEF, represents nearly 50% of all heart
failure cases and is particularly common in the elderly. The disease has no current treatment
options. Symptoms typically occur during exertion or exercise and is likely the result of
increased cardiac and pulmonary congestion as a result of impaired diastolic function.
Istaroxime is a novel activator of SERCA2a, an important regulator of calcium uptake within
the myocyte. We will test the hypothesis that Istaroxime will improve diastolic function
during exercise in HFpEF patients which in turn will reduce cardiac and pulmonary congestion.
failure cases and is particularly common in the elderly. The disease has no current treatment
options. Symptoms typically occur during exertion or exercise and is likely the result of
increased cardiac and pulmonary congestion as a result of impaired diastolic function.
Istaroxime is a novel activator of SERCA2a, an important regulator of calcium uptake within
the myocyte. We will test the hypothesis that Istaroxime will improve diastolic function
during exercise in HFpEF patients which in turn will reduce cardiac and pulmonary congestion.
About half of all elderly patients with a diagnosis of congestive heart failure have
apparently normal systolic function, so called "heart failure with a preserved ejection
fraction" or HFpEF. To date, no effective therapy for HFpEF has been found, in part because
of failure to discern key pathophysiologic pathways.
An extensive amount of pre-clinical work has identified that altered sarcoplasmic reticulum
(SR) Ca2+ uptake, storage, and release play a major role in the changes in cardiac relaxation
associated with aging, especially regarding sequestration of Ca++ by the sarcoplasmic
reticular Ca++-ATPase (SERCA2a), which causes cardiac muscle relaxation by reducing cytosolic
Ca++. Istaroxime is a relatively new drug that augments lusitropic function by upregulating
SERCA2a activity in the heart.
Because of the clear importance of slowed relaxation in HFpEF, and the evidence that
depressed SERCA2a activity contributes to the slowed relaxation with aging, the proposed
study may be establish the "impairment of SERCA2a" hypothesis as a mechanism of impaired
relaxation in HFpEF subjects.
apparently normal systolic function, so called "heart failure with a preserved ejection
fraction" or HFpEF. To date, no effective therapy for HFpEF has been found, in part because
of failure to discern key pathophysiologic pathways.
An extensive amount of pre-clinical work has identified that altered sarcoplasmic reticulum
(SR) Ca2+ uptake, storage, and release play a major role in the changes in cardiac relaxation
associated with aging, especially regarding sequestration of Ca++ by the sarcoplasmic
reticular Ca++-ATPase (SERCA2a), which causes cardiac muscle relaxation by reducing cytosolic
Ca++. Istaroxime is a relatively new drug that augments lusitropic function by upregulating
SERCA2a activity in the heart.
Because of the clear importance of slowed relaxation in HFpEF, and the evidence that
depressed SERCA2a activity contributes to the slowed relaxation with aging, the proposed
study may be establish the "impairment of SERCA2a" hypothesis as a mechanism of impaired
relaxation in HFpEF subjects.
Healthy Senior Controls
Inclusion Criteria:
- age > 60 years
Exclusion Criteria:
- Coronary Ischemia
- No chronic medical problems
- BMI > 30 kg/m2
HFpEF Subjects
Inclusion Criteria:
- age > 60 years
- signs and symptoms of heart failure
- ejection fraction > 50%
- objective evidence of diastolic dysfunction
Exclusion Criteria:
- Coronary Ischemia
- Chronic Kidney Disease, stage 4 or greater
- Persistent atrial fibrillation
- Severe valvular disease
- BMI > 40 kg/m2
We found this trial at
1
site
Dallas, Texas 75231
Principal Investigator: Benjamin D Levine, M.D.
Phone: 214-345-6459
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