Method of treating heart failure with preserved ejection fraction by administering milrinone
The present invention relates to methods of treating subjects having heart failure with preserved ejection fraction (HFpEF) with a sustained-delivery formulation of cardiotonic 5-(pyridinyl)-2(1H)-pyridinone compounds.
1. A method of treating a patient having heart failure with preserved ejection fraction (HFpEF) comprising administering to the patient milrinone, or a pharmaceutically acceptable salt thereof;
wherein the formulation permits delivery of milrinone in an amount to achieve steady state plasma levels effective to alleviate the symptoms of HFpEF;
wherein delivery of milrinone is in the range of between 0.1 μg/kg body weight per minute to 20 μg/kg body weight per minute; and
wherein the patient shows an abnormal measured exercise pulmonary artery pressure or an abnormal measured exercise pulmonary capillary wedge pressure.
2. The method of claim 1 , wherein the patient shows an abnormal measured exercise pulmonary artery pressure.
3. The method of claim 2 , wherein the patient shows an abnormal measured exercise pulmonary artery pressure of about 41 mmHg to about 49 mmHg.
4. The method of claim 1 , wherein the patient shows an abnormal measured exercise pulmonary capillary wedge pressure.
5. The method of claim 4 , wherein the patient shows an abnormal measured exercise pulmonary capillary wedge pressure of about 30 mmHg to about 33 mmHg.
6. The method of claim 1 , wherein the patient shows a normal measured resting pulmonary artery pressure or a normal measured resting pulmonary capillary wedge pressure.
7. The method of claim 1 , wherein after the administration of milrinone a measured pulmonary artery pressure or a measured pulmonary capillary wedge pressure of the patient is reduced.
8. The method of claim 7 , wherein the measured pulmonary artery pressure is a resting pulmonary artery pressure.
9. The method of claim 8 , wherein the resting pulmonary artery pressure is reduced about 29%.
10. The method of claim 7 , wherein the measured pulmonary artery pressure is an exercise pulmonary artery pressure.
11. The method of claim 10 , wherein the exercise pulmonary artery pressure is reduced about 35%.
12. The method of claim 7 , wherein the measured pulmonary capillary wedge pressure is a resting pulmonary capillary wedge pressure.
13. The method of claim 12 , wherein the resting pulmonary capillary wedge pressure is reduced about 64%.
14. The method of claim 7 , wherein the measured pulmonary capillary wedge pressure is an exercise pulmonary capillary wedge pressure.
15. The method of claim 14 , wherein the exercise pulmonary capillary wedge pressure is reduced about 42%.
16. The method of claim 1 , wherein the patient shows symptoms of left ventricular diastolic dysfunction.
17. The method of claim 1 , wherein the patient does not show symptoms of renal disease or cardiovascular disease.
18. The method of claim 17 , wherein the patient does not show symptoms of renal disease.
19. The method of claim 17 , wherein the patient does not show symptoms of cardiovascular disease.
20. The method according to claim 1 , wherein the administration achieves a plasma concentration of milrinone in the range of 100 to 400 ng/mL.
21. The method of claim 1 , wherein the patient has not been diagnosed with renal disease or cardiovascular disease.
22. The method of claim 21 , wherein the patient has not been diagnosed with renal disease.
23. The method of claim 21 , wherein the patient has not been diagnosed with cardiovascular disease.
24. A method of treating a patient having heart failure with preserved ejection fraction (HFpEF) comprising administering to the patient milrinone, or a pharmaceutically acceptable salt thereof;
wherein the formulation permits delivery of milrinone in an amount to achieve steady state plasma levels effective to alleviate the symptoms of HFpEF;
wherein delivery of milrinone is in the range of between 0.1 μg/kg body weight per minute to 20 μg/kg body weight per minute;
wherein the patient shows an abnormal measured exercise pulmonary artery pressure of about 41 mmHg to about 49 mmHg or an abnormal measured exercise pulmonary capillary wedge pressure of about 30 mmHg to about 33 mmHg; and
wherein the patient shows a normal measured resting pulmonary artery pressure or a normal measured resting pulmonary capillary wedge pressure.