Methods, compositions, and devices for the occlusion of cavities and passageways
Provided herein are methods, compositions, and devices for occluding cavities or passageways in a patient, in particular cavities or passageways in the cardiovascular system of a patient, such as the LAA of a patient's heart. The methods, compositions, and devices can be used to percutaneously occlude the LAA, decreasing the risk of thromboembolic events associated with AF.
1. A method of occluding a left atrial appendage (LAA) of a patient comprising:
(a) providing a delivery catheter comprising:
a proximal region;
a distal region comprising a distal tip;
a first lumen extending from the proximal region to the distal region; and
an occluding element positioned in proximity to the distal tip;
(b) advancing the delivery catheter percutaneously through vasculature of the patient such that the distal tip of the delivery catheter reaches a left atrium of the patient;
(c) advancing the distal tip of the delivery catheter into the LAA of the patient, such that the occluding element transitorily occludes the LAA;
(d) withdrawing blood from the patient's LAA;
(e) measuring a volume of the blood withdrawn from the patient's LAA to determine an amount of a crosslinkable biomaterial to be injected into the LAA of the patient; and
(f) injecting the amount of the crosslinkable biomaterial into the LAA of the patient, wherein the crosslinkable biomaterial comprises a first precursor molecule and a second precursor molecule; and
wherein the first precursor molecule and the second precursor molecule crosslink in situ in the LAA to form a biocompatible polymeric matrix that occupies a cavity in the LAA of the patient, thereby preventing stagnation of blood within the cavity in the LAA of the patient.
2. The method of claim 1 , wherein the first precursor molecule comprises an oligomer or polymer having one or more nucleophilic groups, and the second precursor molecule comprises an oligomer or polymer having one or more conjugated unsaturated groups.
3. The method of claim 2 , wherein the first precursor molecule comprises a poly(alkylene oxide)-based oligomer or polymer having x nucleophilic groups, wherein x is an integer of from 2 to 6.
4. The method of claim 3 , wherein the first precursor molecule comprises pentaerythritol poly(ethylene glycol)ether tetrasulfhydryl.
5. The method of claim 2 , wherein the second precursor molecule comprises a biomacromolecule having y conjugated unsaturated groups, wherein y is an integer of from 2 to 25.
6. The method of claim 5 , wherein the second precursor molecule comprises dextran vinyl sulfone.
7. The method of claim 1 , wherein the crosslinkable biomaterial has a cure time of less than about 5 minutes.
8. The method of claim 1 , wherein the biocompatible polymeric matrix has a degradation rate such that about 70% or less by weight of the biocompatible polymeric matrix degrades within 90 days of curing.
9. The method of claim 1 , wherein the biocompatible polymeric matrix exhibits an equilibrium swelling ratio of from about 2 to about 8.
10. The method of claim 1 , wherein the biocompatible polymeric matrix has an elastic modulus of from about 8 kPa to about 12 kPa.
11. The method of claim 1 , wherein the occluding element comprises an inflatable balloon configured to substantially seal the LAA when inflated.
12. The method of claim 11 , wherein step (b) comprises (i) advancing the distal tip of the delivery catheter into the LAA, and (ii) inflating the balloon to seal the LAA.
13. The method of claim 1 , wherein the patient has a CHA 2 DS 2 -VASc score of 2 or more.
14. The method of claim 1 , wherein the patient is contraindicated for anticoagulation therapy.
15. The method of claim 1 , wherein the crosslinkable biomaterial has a cure time, and wherein the method further comprises maintaining the delivery catheter in the LAA following injection of the crosslinkable biomaterial, such that the occluding element is configured to seal the LAA for a period of time greater than the cure time of the crosslinkable biomaterial.
16. The method of claim 1 , further comprising positioning the patient at an angle relative to the ground which is effective to facilitate injection of the crosslinkable biomaterial into the LAA of the patient.
17. The method of claim 1 , wherein the biocompatible polymeric matrix reaches equilibrium swelling within about 24 hours.
18. The method of claim 1 , wherein the biocompatible polymeric matrix has a cure time of less than about 20 minutes.
19. The method of claim 1 , wherein step (f) comprises injecting from about 2 cc to about 8 cc of the crosslinkable biomaterial into the LAA of the patient.
20. The method of claim 1 , wherein the biocompatible polymeric matrix is not biodegradable.