Dataset Information

Calcified plaque modification alters local drug delivery in the treatment of peripheral atherosclerosis.

ABSTRACT:

Background

Calcific atherosclerosis is a major challenge to intraluminal drug delivery in peripheral artery disease (PAD).

Objectives

We evaluated the effects of orbital atherectomy on intraluminal paclitaxel delivery to human peripheral arteries with substantial calcified plaque.

Methods

Diagnostic angiography and 3-D rotational imaging of five fresh human lower limbs revealed calcification in all main arteries. The proximal or distal segment of each artery was treated using an orbital atherectomy system (OAS) under simulated blood flow and fluoroscopy. Explanted arterial segments underwent either histomorphometric assessment of effect or tracking of ¹⁴C-labeled or fluorescent-labeled paclitaxel. Radiolabeled drug quantified bulk delivery and fluorescent label established penetration of drug over finer spatial domain in serial microscopic sections. Results were interpreted using a mathematical model of binding-diffusion mediated arterial drug distribution.

Results

Lesion composition affected paclitaxel absorption and distribution in cadaveric human peripheral arteries. Pretreatment imaging calcium scores in control femoropopliteal arterial segments correlated with a log-linear decline in the bulk absorption rate-constant of ¹⁴C-labeled, declining 5.5-fold per calcified quadrant (p=0.05, n=7). Compared to controls, OAS-treated femoropopliteal segments exhibited 180μm thinner intima (p<0.001), 45% less plaque calcification, and 2 log orders higher paclitaxel bulk absorption rate-constants. Correspondingly, fluorescent paclitaxel penetrated deeper in OAS-treated femoropopliteal segments compared to controls, due to a 70% increase in diffusivity (p<0.001).

Conclusions

These data illustrate that calcified plaque limited intravascular drug delivery, and controlled OAS treatment of calcific plaques resulted in greater drug permeability and improved adjunct drug delivery to diseased arteries.

SUBMITTER: Tzafriri AR

PROVIDER: S-EPMC5955709 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Publications

Calcified plaque modification alters local drug delivery in the treatment of peripheral atherosclerosis.

Tzafriri Abraham R AR Garcia-Polite Fernando F Zani Brett B Stanley James J Muraj Benny B Knutson Jennifer J Kohler Robert R Markham Peter P Nikanorov Alexander A Edelman Elazer R ER

Journal of controlled release : official journal of the Controlled Release Society 20170901

<h4>Background</h4>Calcific atherosclerosis is a major challenge to intraluminal drug delivery in peripheral artery disease (PAD).<h4>Objectives</h4>We evaluated the effects of orbital atherectomy on intraluminal paclitaxel delivery to human peripheral arteries with substantial calcified plaque.<h4>Methods</h4>Diagnostic angiography and 3-D rotational imaging of five fresh human lower limbs revealed calcification in all main arteries. The proximal or distal segment of each artery was treated usi ...[more]

PMID: 28867375

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Project description:BackgroundOrbital atherectomy (OA) is a known alternative to other atherectomy devices. However, some complex patient demographics (eg, left ventricular ejection fraction <25%) were excluded from the first-in-human trial (ORBIT I) and the pivotal FDA device approval trial (ORBIT II) which evaluated the safety and efficacy of OA in severely calcified de novo coronary lesions. This single-operator cohort study aimed to examine the impact of OA on a real-world complex Veterans Affairs patient subset.MethodsRetrospective analysis was completed on 40 consecutive patients with severely calcified coronary lesions who underwent OA prior to drug-eluting stent placement at the Atlanta Veterans Affairs Medical Center from January 2015 to June 2017.ResultsOrbital atherectomy plus drug-eluting stent placement was successful in all 40 cases. Chocolate focal force balloon angioplasty was the most commonly used post-atherectomy balloon (N = 34, 85%). Few complications were observed, including one case (2.5%) of perforation and one case (2.5%) of no-reflow. Neither acute stent thrombosis nor emergent coronary artery bypass grafting was observed. The intravascular ultrasound (IVUS)-determined median [IQR] pre-procedure minimum lumen area and post-procedure minimum stent area (MSA) were 2.8 [2.2, 3.0] mm2 and 8.7 [7.7, 10.0] mm2, respectively (P < 0.0001, Mann-Whitney test). Major adverse cardiovascular events, including all-cause mortality, at 30 days and at a median [IQR] follow-up of 197.5 [35.5, 461.3] days, was 5% and 10%, respectively. During that period, one target vessel revascularization (2.5%) was observed.ConclusionsThis study indicates that OA is a useful tool in performing high-risk percutaneous coronary intervention effectively in VA patients with severely calcified coronary lesions. OA plaque modification in combination with a high utilization rate of IVUS and Chocolate focal force angioplasty facilitates stent delivery and optimal stent expansion, resulting in a large MSA.

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Dataset Information

Calcified plaque modification alters local drug delivery in the treatment of peripheral atherosclerosis.

Background

Objectives

Methods

Results

Conclusions

Publications

Calcified plaque modification alters local drug delivery in the treatment of peripheral atherosclerosis.

Similar Datasets

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