BACKGROUND

There are many types of heart disease, and each one has its own symptoms and treatment. Lifestyle changes and medicine can make a huge difference in improving a subject's health. One type of heart disease is an arrhythmia (when the heart has an irregular beating pattern). Serious arrhythmias can often develop from other heart problems, but may also happen on their own.

Treatment of arrhythmia depends on the type and severity of the arrhythmia. In some cases of arrhythmia, no treatment is necessary. Treatment options can include: medications, lifestyle changes, invasive therapies, electrical devices, and/or surgery. Some anti-arrhythmic medications are extremely toxic, and thus are very infrequently used for the treatment of arrhythmias, and even then can only be used for a short time due to the toxicity. Thus, there is a need in the art to develop improved methods, compositions, and therapies for treating cardiac arrhythmias.

SUMMARY

The disclosure provides methods and compositions for treating heart conditions. In particular, the disclosure provides compositions comprising lithium, or a salt thereof, either alone or in combination with at least one additional anti-arrhythmia agent, and methods for treating heart conditions using such compositions.

In one aspect, the disclosure provides a method for treating and/or preventing a heart condition, comprising administering an effective amount of lithium, or a salt thereof, to a subject in need thereof.

In certain embodiments of this aspect, the heart condition is premature ventricular contraction (PVC), ventricular premature contraction (VPC), ventricular tachycardia, ventricular fibrillation, paroxysmal supraventricular tachycardia, accessory pathway tachycardia, AV nodal reentrant tachycardia, supraventricular tachycardia, premature atrial contractions, atrial fibrillation, atrial flutter, trigeminy, bigeminy, or Wolff-Parkinson-White (WPW) syndrome. In one embodiment, the heart condition is premature ventricular contraction (PVC) or ventricular premature contraction (VPC). In another embodiment, the heart condition is atrial fibrillation.

In some embodiments, the lithium, or salt thereof, is lithium carbonate (Li2CO3), lithium sulfate (Li2SO4), lithium citrate (Li3C6H5O7), lithium acetate (C2H3LiO2), lithium bromide (LiBr), lithium chloride (LiCl), lithium orotate (C5H3LiN2O4), or lithium gluconate (C6H11LiO7). In certain embodiments, the effective amount of lithium comprises about 5 mg to about 1800 mg per day, about 10 mg to about 1200 mg per day, about 25 mg to about 600 mg per day, about 50 mg to about 550 mg per day, about 100 mg to about 500 mg per day, about 150 mg to about 450 mg per day, about 200 mg to about 400 mg per day, or about 250 mg to about 350 mg per day. In one embodiment, the effective amount of lithium comprises about 300 mg per day.

In some embodiments, the effective amount of lithium results in a lithium serum concentration in the subject in the range of about 0.01 to about 1.2 mmol/L, about 0.02 to about 1.0 mmol/L, about 0.05 to about 0.8 mmol/L, about 0.1 to about 0.6 mmol/L, about 0.2 to about 0.5 mmol/L, about 0.25 to about 0.45 mmol/L, or about 0.1 to about 0.3 mmol/L. In one embodiment, the effective amount of lithium results in a lithium serum concentration in the subject in the range of about 0.1 to about 0.3 mmol/L.

In some embodiments, the effective amount of lithium, or salt thereof, is administered as an extended release formulation. In certain embodiments, the effective amount of lithium, or salt thereof, is administered one time per day, two times per day, three times per day, or four times per day.

In some embodiments, the effective amount of lithium, or salt thereof, is administered orally, parenterally, transdermally, topically, transmucosally, by inhalation, by suppository, by buccal delivery, by sublingual delivery, by ophthalmic delivery, or by injection (subcutaneous injection, subdermal injection, intramuscular injection, depot administration, or intravenous injection).

In some embodiments, the subject is treated for about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 7 months, about 8 months, about 9 months, about 10 months, about 11 months, about 1 year, about 2 years, or more than 2 years. In certain embodiments, the subject is treated indefinitely.

In some embodiments, the method further comprises administering an additional anti-arrhythmic agent. In certain embodiments, the additional anti-arrhythmic agent is a sodium channel blocker (Class I), a beta-blocker (Class II), a potassium channel blocker (Class III), a calcium channel blocker (Class IV), and/or another anti-arrhythmic agent.

In some embodiments, the additional anti-arrhythmic agent is a beta-blocker and the beta-blocker is Acebutolol (SECTRAL®), Atenolol (TENORMIN®), Betaxolol (KERLONE®), Bisoprolol (ZEBETA®, ZIAC®), Carteolol (CARTROL®), Carvedilol (COREG®), Labetalol (NORMODYNE®, TRANDATE®), Metoprolol (LOPRESSOR®, TOPROL-XL®), Nadolol (CORGARD®), Nebivolol (BYSTOLIC®), Penbutolol (LEVATOL®), Pindolol (VISKEN®), Propanolol (INDERAL®), Sotalol (BETAPACE®), or Timolol (BLOCADREN®).

In another aspect, the disclosure provides a composition comprising lithium, or a salt thereof, and an additional anti-arrhythmic agent.

In certain embodiments of this aspect, the lithium, or salt thereof, is lithium carbonate (Li2CO3), lithium sulfate (Li2SO4), lithium citrate (Li3C6H5O7), lithium acetate (C2H3LiO2), lithium bromide (LiBr), lithium chloride (LiCl), lithium orotate (C5H3LiN2O4), or lithium gluconate (C6H11LiO7).

In some embodiments, the additional anti-arrhythmic agent is a sodium channel blocker (Class I), a beta-blocker (Class II), a potassium channel blocker (Class III), a calcium channel blocker (Class IV), and/or another anti-arrhythmic agent.

In some embodiments, the additional anti-arrhythmic agent is a beta-blocker and the beta-blocker is Acebutolol (SECTRAL®), Atenolol (TENORMIN®), Betaxolol (KERLONE®), Bisoprolol (ZEBETA®, ZIAC®), Carteolol (CARTROL®), Carvedilol (COREG®), Labetalol (NORMODYNE®, TRANDATE®), Metoprolol (LOPRESSOR®, TOPROL-XL®), Nadolol (CORGARD®), Nebivolol (BYSTOLIC®), Penbutolol (LEVATOL®), Pindolol (VISKEN®), Propanolol (INDERAL®), Sotalol (BETAPACE®), or Timolol (BLOCADREN®).

In one embodiment, the lithium, or salt thereof, is lithium carbonate (Li2CO3), and the beta-blocker is Metoprolol (LOPRESSOR®, TOPROL-XL®). In another embodiment, the lithium, or salt thereof, is lithium sulfate (Li2SO4), and the beta-blocker is Metoprolol (LOPRESSOR®, TOPROL-XL®).

In some embodiments, the composition comprises about 50 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, about 300 mg, about 350 mg, about 400 mg, about 450 mg, about 500 mg, or about 600 mg of the lithium, or salt thereof.

In some embodiments, the composition comprises about 2.5 mg, about 3.125 mg, about 5 mg, about 6.25 mg, about 10 mg, about 12.5 mg, about 20 mg, about 25 mg, about 30 mg, about 40 mg, about 50 mg, about 60 mg, about 80 mg, about 100 mg, about 150 mg, about 200 mg, about 250 mg, or about 300 mg of the additional anti-arrhythmic agent.

In some embodiments, the compositions as disclosed herein are extended release formulations.

