Methodological Standardization for the Pre-Clinical Evaluation of Renal Sympathetic Denervation

Transcatheter ablation of renal autonomic nerves is a viable option for the treatment of resistant arterial hypertension; however, structured pre-clinical evaluation with standardization of analytical procedures remains a clear gap in this field. Here we discuss the topics relevant to the pre-clinical model for the evaluation of renal denervation (RDN) devices and report methodologies and criteria toward standardization of the safety and efficacy assessment, including histopathological evaluations of the renal artery, periarterial nerves, and associated periadventitial tissues. The pre-clinical swine renal artery model can be used effectively to assess both the safety and efficacy of RDN technologies. Assessment of the efficacy of RDN modalities primarily focuses on the determination of the depth of penetration of treatment-related injury (e.g., necrosis) of the periarterial tissues and its relationship (i.e., location and distance) and the effect on the associated renal nerves and the correlation thereof with proxy biomarkers including renal norepinephrine concentrations and nerve-specific immunohistochemical stains (e.g., tyrosine hydroxylase). The safety evaluation of RDN technologies involves assessing for adverse effects on tissues local to the site of treatment (i.e., on the arterial wall) as well as tissues at a distance (e.g., soft tissue, veins, arterial branches, skeletal muscle, adrenal gland, ureters). Increasing experience will help to create a standardized means of examining all arterial beds subject to ablative energy and in doing so enable us to proceed to optimize the development and assessment of these emerging technologies

Acute Thrombogenicity of a Durable Polymer Everolimus-Eluting Stent Relative to Contemporary Drug-Eluting Stents With Biodegradable Polymer Coatings Assessed Ex Vivo in a Swine Shunt Model

AbstractObjectivesThis study sought to evaluate whether the permanent fluoropolymer-coated Xience Xpedition everolimus-eluting stent (Xience-EES) exhibits lower acute thrombogenicity compared with contemporary drug-eluting stents (DES) with biodegradable polymer coatings in an acute swine shunt model.BackgroundPrevious pre-clinical and clinical experience suggests that several factors may influence the predisposition for acute thrombus formation of polymer-coated DES, including stent design and the polymer coating technology. It remains unclear whether relevant differences exist with respect to acute thrombogenicity, particularly between current commercial stent designs using permanent polymers and those using biodegradable polymers.MethodsAn ex vivo carotid to jugular arteriovenous porcine shunt model involving a test circuit of 3 in-line stents, was used to test acute thrombogenicity, where Xience-EES (n = 24) was compared with 4 CE-marked DES with biodegradable polymer coatings (BioMatrix Flex, Synergy, Nobori, and Orsiro [n = 6 each]). After 1 h of circulation, platelet aggregation in whole mount stents was evaluated by confocal microscopy with immunofluorescent staining against dual platelet markers (CD61/CD42b) along with scanning electron microscopy.ResultsXience-EES showed the least percentage of thrombus-occupied area as compared with the biodegradable polymer-coated DES, with a significant difference compared with BioMatrix Flex and Synergy (mean differences: [BioMatrix Flex: 15.54, 95% confidence interval [CI]: 11.34 to 19.75, p < 0.001; Synergy: 8.64, 95% CI: 4.43 to 12.84, p < 0.001; Nobori: 4.22, 95% CI: -0.06 to 8.49, p = 0.055; Orsiro: 2.95, 95% CI: -1.26 to 7.15, p = 0.286). The number of cell nuclei on strut surfaces was also the least in Xience-EES, with a significant difference relative to BioMatrix Flex, Nobori, and Orsiro (mean ratios: BioMatrix Flex: 4.73, 95% CI: 2.46 to 9.08, p < 0.001; Synergy: 1.44, 95% CI: 0.75 to 2.76, p = 0.51; Nobori: 5.97, 95% CI: 3.11 to 11.44, p < 0.001; Orsiro: 5.16, 95% CI: 2.69 to 9.91, p < 0.001).ConclusionsXience-EES’s overall design confers acute thromboresistance relative to contemporary DES with biodegradable coatings, with less platelet aggregation versus BioMatrix Flex and Synergy, and less inflammatory cell attachment versus BioMatrix Flex, Nobori, and Orsiro, in an ex vivo swine shunt model, which lends support to reported clinical findings of lower early stent thrombosis

Rapid Switch from Intra-Aortic Balloon Pumping to Percutaneous Cardiopulmonary Support Using Perclose ProGlide

We present a case of a patient who needed rapid switch from intra-aortic balloon pumping (IABP) to percutaneous cardiopulmonary support (PCPS)/venoarterial extracorporeal membrane oxygenation. It is difficult to switch from IABP to PCPS, because 0.035-inch guidewires cannot pass the IABP guidewire lumen (0.025-inch compatible), and the IABP sheath needs to be removed together with the IABP catheter. First, a 0.025-inch guidewire was inserted into the IABP wire lumen, and then the IABP catheter together with the 8 Fr IABP sheath was removed, leaving the 0.025-inch guidewire in place. We used the Perclose ProGlide for safe and rapid exchange of the 0.025-inch guidewire for a 0.035-inch guidewire. This allowed insertion of a PCPS cannula and the prompt initiation of PCPS

Halfway rotational atherectomy for calcified lesions: Comparison with conventional rotational atherectomy in a propensity-score matched analysis.

BackgroundThe incidence of severe complications such as burr entrapment or perforation is considerable with rotational atherectomy (RA). Halfway RA is a novel strategy, in which an operator does not advance the burr to the end of a continuous calcified lesion, and performs balloon dilatation to treat the remaining part of the calcified lesion. The purpose of this study was to compare complications after halfway and conventional RA.MethodsWe included 307 consecutive lesions that were divided into a conventional RA group (n = 244) and halfway RA group (n = 63). In analysis 1, the incidence of complications was compared between the conventional RA and halfway RA groups. Propensity-score matching was used to match the intentional halfway RA and conventional RA. In analysis 2, the incidence of complications was compared between the matched conventional RA and intentional halfway RA groups.ResultsBurr entrapment (0.4%) and major perforation (0.8%) were observed in the conventional RA group, whereas there was no burr entrapment or perforation in the halfway RA group. The success rate of halfway RA was 90.5%, which required switching from halfway RA to conventional RA. The incidences of slow flow and periprocedural myocardial infarction with slow flow were similar between the intentional halfway RA and matched conventional RA groups.ConclusionsThere was no burr entrapment or vessel perforation following halfway RA. The incidences of slow flow and periprocedural myocardial infarction were similar between the intentional halfway RA and the matched conventional RA, indicating the safety of halfway RA