Dedicated Closure Device for Transcaval Access Closure: From Concept to First-in-Human Testing

Abstract

Objectives: This study sought to test safety and exploratory effectiveness of a dedicated transcaval closure device (TCD).

Background: Transcaval access enables delivery of large-caliber devices to the aorta in patients ineligible for transfemoral arterial access. Closure of aortocaval fistulae using off-label nitinol cardiac occluders has been shown to be safe, but persistent aortocaval fistulae at exit from the catheterization lab and bleeding complications were common in a prospective study.

Methods: Preclinical testing of the TCD was performed in 24 Yorkshire swine, including 10 under good laboratory practice conditions. Subsequently, subjects undergoing transcatheter aortic valve replacement for symptomatic severe aortic stenosis, ineligible for transfemoral arterial access, were enrolled in a U.S. Food and Drug Administration-approved early feasibility study of the TCD (Transmural Systems, Andover, Massachusetts). Independently adjudicated endpoints included technical, device, and procedural success, incorporating in-hospital and 30-day clinical and imaging follow-up.

Results: Transcaval access and closure in swine confirmed that at 30 days, TCDs were almost entirely endothelialized. Subsequently, 12 subjects were enrolled in the early feasibility study. Transcaval access, transcatheter aortic valve replacement, and aortocaval fistula closure was successful in all 12 subjects. The primary endpoint of technical success was met in 100% of subjects. Complete closure of the transcaval access tract was achieved in 75% of subjects at exit from the catheterization lab and in 100% of subjects at 30 days. There were zero modified Valve Academic Research Consortium-2 major vascular complications and zero Valve Academic Research Consortium-2 life-threatening or major bleeding complications related to transcaval access or the TCD.

Conclusions: The TCD achieved complete closure of the transcaval access tract in most subjects at exit from the catheterization lab and essentially eliminated transcaval-related bleeding. Dedicated devices for transcaval access and closure could enable more widespread adoption of transcaval techniques without fear of bleeding complications. (Transmural Systems Transcaval Closure Device for Transcaval Access Ports During Transcatheter Aortic Valve Replacement; NCT03432494).

Keywords: early feasibility study; first-in-human; transcatheter aortic valve replacement; transcaval access and closure.

Conflict of interest statement

No other author has a financial conflict of interest related to this research.

Published by Elsevier Inc.

Figures

Figure 1 -. Preclinical findings

Angiography (A) immediately post-deployment and (B) after 90 days. Gross pathology of (C) IVC surface and (D) aorta surface after 90 days shows endothelialization of the TCD. Micro-CT images (E-M) confirms structural integrity of the TCD and lack of nitinol wire braid fracture. Hematoxylin and Eosin (H&E) stains: (N) low power view shows the central hub of the TCD with the aorta at the top of the image. (O) and (P) correspond to the green and red boxes in (N) respectively. The central guidewire lumen is completely filled with fibrous tissue in (P). Low power (Q) and (R) and corresponding higher power (q) and (r) views of the aortic surface show the TCD fully incorporated by a smooth muscle cell and proteoglycan rich neointima with polyester material surrounded by fibrous tissue, scattered lymphocytic infiltrates, giant cells, and golden-brown hemosiderin pigment. (S) corresponds to the gray box in (N), with giant cells incorporated by fibrous tissue and scattered lymphocytes at high power (s). Low power (T) and corresponding high power (t) of the central hub on the IVC surface shows the TCD fully incorporated by a smooth muscle cell and proteoglycan rich neointima. (T) corresponds to the blue box in (S). (U) and (V) and corresponding high power (u) and (v) views of the IVC surface show polyester material surrounded by fibrous tissue, with giant cells and a few scattered lymphocytes. Scale bar in (N) and (S) = 1mm; low power = 200μm; high power = 100μm.

Figure 2 -. Confirmed 100% aorto-caval tract closure at 30 days

Final digital subtraction angiogram at the end of the TAVR procedure (subject 1) and contrast-enhanced arterial-phase CT scans at 30 days (subjects 2–12). CT: computed tomography; TAVR: transcatheter aortic valve replacement.

Central illustration -. Transmural Systems Transcaval Closure Device (TCD)

(A) The TCD has a braided nitinol double-disc design with an interconnecting spring to flatten the intravascular disc and a retention paddle to prevent inadvertent pull through the aortic wall during deployment. The TCD is delivered on a flexible cable through a beveled catheter and over a central guidewire. (B) Deployment of the TCD in the transcaval tract. The TCD is delivered on a flexible cable through a beveled delivery catheter over a central guidewire. (C) Digital subtraction angiography confirms complete closure of the transcaval tract. (D) 30-day CT scan shows the TCD (highlighted in green) in the wall of the abdominal aorta. (E) Transcaval outcomes comparing the TCD and the Amplatzer cardiac occluder from the NHLBI sponsored prospective transcaval trial(1).