Russell M. Jones

Paired Comparison of Vascular Wall Reactions to Palmaz Stents, Strecker Tantalum Stents, and Wallstents in Canine Iliac and Femoral Arteries

BACKGROUND Palmaz stents, Strecker stents, and Wallstents, all used clinically, differ substantially in their physical characteristics, yet how differently the vascular wall reacts to them has not been demonstrated conclusively. We therefore undertook a side-by-side comparison. METHODS AND RESULTS One stent was implanted into each canine external iliac and/or the flexing portion of the proximal femoral artery. In 9 dogs, Palmaz stents were placed vis-à-vis Strecker stents, with follow-up of 2 and 4 months. In 7 dogs, Palmaz stents were placed vis-à-vis Wallstents, with 4 months of follow-up. Angiographic midstent luminal diameters immediately after placement and at follow-up as well as midstent cross-sectional areas of neointima were compared for significant differences. In addition, neointimal maturation, medial atrophy, and stent-related trauma were assessed. Angiographically, all arteries remained open. The degree of luminal narrowing by recoil and neointima never reached 50% and was modest for Palmaz stents and Wallstents (P = .33) but significantly higher for Strecker stents (P < .0001 compared with Palmaz stents). This corresponded histologically to a significantly thicker neointima (P = .003) over Strecker than over Palmaz stents but not between Palmaz stents and Wallstents (P = .18). Neointimal buildup was generally more pronounced in the femoral artery segments than in the iliac segments. Maturation of the neointima over Palmaz stents was much further advanced than over Strecker stents and slightly more advanced than over Wallstents. Pressure-related atrophy of the tunica media was least for Strecker stents and more pronounced but similar for Wallstents and Palmaz stents. Wallstent wire ends caused some wall trauma; several femoral Palmaz stent struts protruded through the media. CONCLUSIONS The lower-hoop-strength, higher-profile tantalum Strecker stent is affected by vascular wall recoil and evokes a greater degree of neointima formation than the lower-profile, higher-hoop-strength Palmaz stent and Wallstent. Medial atrophy is pronounced outside the latter two stents. The rigid Palmaz stent can penetrate through the vascular wall in flexing arteries.

Pathological Healing Response of Explanted MitraClip Devices

Background— The safety and effectiveness of the MitraClip device (Abbott Vascular, Menlo Park, CA) is being evaluated in the Endovascular Valve Edge-to-Edge Repair Study (EVEREST) clinical studies. The healing response after device implantation has not previously been characterized in humans. Methods and Results— A total of 67 explanted devices (implantation duration, 1 to 1878 days) from 50 patients were submitted for histological evaluation. Explants were analyzed in 4 implantation intervals: acute (⩽30 days; n=7), subacute (31 to 90 days; n=23), chronic (91 to 300 days; n=18), and long term (>300 days; n=19). The acute healing response consisted of platelet/fibrin deposition. The subacute response exhibited granulation tissue with early fibrous encapsulation (pannus). The chronic response was characterized by various degrees of tissue bridging between the device arms. The long-term healing response demonstrated collagen-rich matrix (by type I collagen), incorporating the device components with complete encapsulation by organized, fibrous growth. In long-term devices with minimal surgical disruption, a fibrous tissue bridge (mean area, 7.39±4.3 mm2) was observed over and between the device arms, resulting in atrial tissue continuity between the 2 valve leaflets. Devices demonstrated no evidence of endocarditis, mechanical wear, component fracture, or corrosion up to the time of explantation (median, 119 days; first and third quartiles, 42 and 365 days). Conclusions— In all patients, device mechanical integrity was maintained up to the time of explantation. Four phases of physiological healing were observed: platelet and fibrin deposition, inflammation, granulation tissue, and finally, fibrous encapsulation. Long-term device fibrous encapsulation with extension over adjacent mitral leaflets and tissue bridge formation adds structural stability. Clinical Trial Registration— URL: http://clinicaltrials.gov/show/NCT00209274. Unique identifiers: NCT00209339 and NCT00209274.

Left atrial appendage obliteration: mechanisms of healing and intracardiac integration.

OBJECTIVES The objectives of this study were: 1) to delineate the temporal course of histopathologic healing as the left atrial appendage (LAA) is obliterated by a mechanical device; and 2) to compare this process with other intravascular and intracardiac implanted technologies. BACKGROUND Intracardiac device healing is incompletely understood. We thus studied the histopathology of device-based LAA obliteration. METHODS Nine dog hearts were examined over time after LAA device placement and results were compared with human hearts with prior LAA obliteration using the same device. RESULTS At 3 days in dogs, atrial surfaces were covered by fibrin, which sealed gaps between the LA wall and the device and filled the LA appendage cavity. At 45 days, endothelial cells covered the endocardial surface with underlying smooth muscle cells that sealed the device-LA interface. Regions with prior thrombus were replaced by endocardium surrounding the device membrane. Disorganized thrombus remained in the LAA body and at the periphery near the appendage walls. Mild inflammation was observed as thrombus resorbed. By 90 days, a complete endocardial lining covered the former LAA ostium. Organizing thrombus had become connective tissue, with no residual inflammation. The human necropsy hearts had similar findings. In these 4 hearts (139, 200, 480, and 852 days after implant), the ostial fabric membrane was covered with endocardium. The appendage surface contained organizing thrombus with minimal inflammation. Organizing fibrous tissue was inside the LAA cavity, prominent near the atrial wall. The LAA interior contained organizing thrombus. CONCLUSIONS This intracardiac device integration study delineated healing stages of early thrombus deposition, thrombus organization, inflammation and granulation tissue, final healing by connective tissue, and endocardialization without inflammation. These observations may yield insight into cellular healing processes in other cardiac devices.

Reperfusion injury in the ischemic myocardium

Myocardial reperfusion injury is defined as the conversion of reversibly injured myocytes to irreversibly injured cells following temporary coronary artery occlusion. Although not universally accepted, the concept of lethal reperfusion injury is strongly supported by studies that temporally link an interventional therapy administered in the perireperfusion period to myocardial salvage. Myocardial reperfusion may be due to the deleterious consequences of cellular edema, calcium overload, free-radical generation, neutrophil infiltration, and microvascular damage. Current studies suggest that perfluorochemicals and adenosine (agents that preserve endothelium and attenuate neutrophil chemotaxis) are the most promising compounds that reduce infarct size in experimental animal models and may warrant clinical trials in man.

A comparison of experimental aneurysm occlusion determination by angiography, scanning electron microscopy, MICROFIL® perfusion, and histology

In clinical practice, occlusion of embolized, intracerebral aneurysms is evaluated using angiography. Standard, two-dimensional digital subtract angiography (DSA) is unable to quantify irregular aneurysm remnants, and even three-dimensional rotational angiography cannot quantify the degree of occlusion. To better understand occlusion at the aneurysm neck, we compared angiographic results with MICROFIL perfusion, histology, and scanning electron microscopy (SEM) results in 20 elastase-induced saccular aneurysms in rabbits. Aneurysms were embolized with HydroCoil devices (n = 12) or platinum coils (n = 8). Aneurysm follow-up occurred at 2 (n = 10) and 6 (n = 10) weeks. Aneurysm occlusion was evaluated using DSA, MICROFIL perfusion, histological ground sections, and SEM. Groups were compared statistically using ANOVA and chi(2) tests. The MICROFIL perfusion results were not concordant with the angiographic results for the HydroCoil and platinum coil groups. Both increased and decreased occlusion was observed on the MICROFIL-perfused aneurysms when compared with angiography. The histologic occlusion results of the HydroCoil group were concordant with the angiographic results; however, unoccluded areas not visible on angiography were routinely observed on the ground sections in the platinum coil group. SEM imaging of the aneurysm neck consistently showed decreased occlusion than angiographic results for both the HydroCoil and platinum coil groups. Although histology and MICROFIL-perfusion analyses provided additional details of aneurysm occlusion when compared with angiography, complete visualization of the entire neck of the aneurysm and accurate assessment of aneurysm occlusion was possible only with SEM.