Methods and compositions for treatment of acute heart failure
The present disclosure provides methods and compositions for treating acute heart failure, by administering to a subject in need thereof a therapeutically effective amount of an AICA riboside analog or a pharmaceutically acceptable salt or prodrug thereof.
1. A method of treating acute decompensated heart failure in a patient in need thereof, comprising administering to the patient an effective amount of a compound of Formula V:
or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 , wherein the patient has non-ischemic cardiomyopathy.
3. The method of claim 1 , whereby the administering step results in an improvement in global cardiac function in the patient.
4. The method of claim 1 , wherein global cardiac function comprises left ventricular function, left ventricular systolic function, left ventricular diastolic function, and/or efficiency of cardiac contraction.
5. The method of claim 4 , wherein left ventricular systolic function comprises one or more of left ventricular ejection fraction, cardiac output, or stroke volume.
6. The method of claim 1 , whereby the administering step does not produce a statistically significant increase in any one or more of blood pressure, myocardial oxygen consumption, or heart rate in the patient.
7. The method of claim 1 , whereby the administering step does not cause hypotension, tachycardia, or arrhythmia in the patient.
8. The method of claim 1 , whereby the administering step causes a reduction in plasma levels of NT-Pro-BNP and TnI in the patient.
9. The method of claim 1 , wherein the patient has a left ventricular ejection fraction of less than 35% prior to the administering step.
10. The method of claim 1 , wherein the patient has a left ventricular ejection fraction of greater than 40% prior to the administering step.
11. The method of claim 1 , wherein the compound of Formula V or a pharmaceutically acceptable salt thereof is:
or a pharmaceutically acceptable salt thereof.
12. The method of claim 1 , wherein the compound of Formula V or pharmaceutically acceptable salt thereof is administered for between about 1 hour and about 24 hours.
13. The method of claim 1 , wherein the administering step is not accompanied by administration of an increased dose of a diuretic, an inotrope, or a vasodilator to the patient.
14. The method of claim 1 , wherein the compound of Formula V or pharmaceutically acceptable salt thereof is administered at a rate in the range of about 3 μg/kg/min to about 300 μg/kg/min.
15. The method of claim 14 , wherein the administration rate is less than 100 μg/kg/min.
16. A method of treating decompensation of cardiac function associated with acute decompensated heart failure in a patient in need thereof, comprising administering to the patient an effective amount of a compound of Formula V:
or a pharmaceutically acceptable salt thereof.
17. The method of claim 16 , wherein an improvement in global cardiac function of the patient occurs within three hours of initiation of the administering step.
18. The method of claim 16 , wherein an improvement in global cardiac function of the patient occurs within one hour of initiation of the administering step.
19. A method of improving global cardiac function in a patient with acute decompensated heart failure, comprising administering to the patient an effective amount of a compound of Formula V:
or a pharmaceutically acceptable salt thereof.
20. The method of claim 19 , wherein improving global cardiac function comprises improving left ventricular function.
21. The method of claim 19 , wherein left ventricular function comprises left ventricular systolic function and left ventricular diastolic function.
22. The method of claim 21 , wherein left ventricular systolic function comprises one or more of left ventricular ejection fraction, cardiac output, or stroke volume.
23. The method of claim 19 , wherein improving global cardiac function comprises improving efficiency of cardiac contraction in the patient.
24. The method of claim 19 , whereby the administering step does not produce a statistically significant increase in any one or more of blood pressure, myocardial oxygen consumption, or heart rate in the patient.
25. The method of claim 19 , whereby the administering step does not cause hypotension, tachycardia, or arrhythmia in the patient.
26. The method of claim 19 , whereby the administering step causes a reduction in plasma levels of NT-Pro-BNP and TnI in the patient.
27. The method of claim 19 , wherein the patient has non-ischemic cardiomyopathy.
28. The method of claim 19 , wherein the patient has a left ventricular ejection fraction of less than 35% prior to the administering step.
29. The method of claim 19 , wherein the patient has a left ventricular ejection fraction of greater than 40% prior to the administering step.
30. The method of claim 19 , wherein the improvement in global cardiac function occurs within six hours of initiation of the administering step.
31. The method of claim 30 , wherein the improvement in global cardiac function occurs within three hours of initiation of the administering step.
32. The method of claim 30 , wherein the improvement in global cardiac function occurs within one hour of initiation of the administering step.
33. The method of claim 19 , wherein the compound of Formula V or a pharmaceutically acceptable salt thereof is:
or a pharmaceutically acceptable salt thereof.