Effects of Focused Force Angioplasty: Pre-clinical Experience and Clinical Confirmation

Conventional balloon angioplasty aims to reduce or eliminate coronary arterial stenoses. This is achieved by a combination of plaque compression and fracture, creation of intimal flaps and localized medial dissection, as well as stretching and remodeling of the arterial wall. Depending upon the specific forces applied to the vessel wall and the physical and biological characteristics of the atherosclerotic lesion, differing degrees of each of these mechanisms will take place. The effect of the application of concentric pressure to the vessel wall will depend, therefore, on the physical characteristics of the lesion. If the pressure is applied eccentrically allowing for the balloon force to be focused along a specified line or lines, the reduction in vessel resistance will allow for an improved or equivalent result at a lower pressure.^1,2 The FX miniRAIL™ (Guidant Corporation, Indianapolis, Indiana) is a novel balloon angioplasty catheter equipped with two external wires that are compressed by the inflating balloon into the vessel wall. This may be referred to as “focused force angioplasty,” as there is a focused application of the force from the expanding balloon, much akin to other devices currently available³ or to the buddy wire technique, where the balloon is inflated alongside an adjacent guidewire.^2,4 This technique not only results in the application of the force along the balloon in the cross sectional plane, but also by splinting the balloon, concentrates the balloon force at resistant sites in the longitudinal plane. This concentrated application of force along the adjacent wire or wires will often result in a limited dissection or intimal/medial injury, increasing vessel compliance to allow for equivalent luminal expansion at lower pressures, and with significantly reduced vessel wall disruption than conventional balloon angioplasty. Although metallic stents have become the standard of care for the percutaneous treatment of coronary artery disease due to their proven acute^5,6 and long-term benefits,^7,8 balloon angioplasty still plays an important role. The objectives of this study were to assess the safety of the use of the FX miniRAIL catheter in a porcine coronary model, and to compare the effect of FX balloon inflation to that of a conventional PTCA balloon catheter on the coronary artery as determined by post-inflation angiography and pathological examination. Methods FX miniRAIL balloon. The FX miniRAIL balloon (Figure 1) features a semi-compliant balloon that is designed to expand to a specified diameter at a nominal pressure of 8 atmospheres. It is similar in maximum inflation pressure and balloon compliance to other PTCA balloons. The balloon is connected to a distal tip which houses a short guidewire lumen. The proximal end of the balloon is connected to an inflation channel which floats freely inside a stainless steel hypotube. A pull wire connects the hypotube to the distal tip. The FX miniRAIL possesses dual markers on the pull wire rather than a central marker band. This facilitates fluoroscopic visualization of the balloon during use. Initial clinical results have recently been reported.⁹Animal study protocol. Five Yorkshire male swine (Animal Biotech Industries, Danboro, Pennsylvania) underwent balloon inflation with a conventional PTCA balloon in the left anterior descending (LAD) or the left circumflex (LCX) arteries, and received an FX miniRAIL balloon in the other left coronary artery in a randomized manner. All procedures and care of animals were in accordance with Cornell University institutional guidelines. All animals were kept from food the night before the intervention and were pre-treated with oral aspirin 325 mg and verapamil 120 mg to minimize vessel spasm. On the day of the procedure, the animals were sedated with an intramuscular injection of Telazol [tiletamine and zolazepam (4.4–8.8 mg/kg)], xylazine (2.2–4.4 mg/kg), and atropine (0.06 mg/kg). The pigs were intubated and ventilation was started using a mixture of 20 vol% of pure oxygen and 80 vol% of room air. The animal was then maintained at 0.5–2.0% isoflurane and supplemental oxygen. The neck area was shaved, prepped, and draped in a sterile fashion. An external carotid artery was surgically exposed, and a 6 Fr intra-arterial sheath was inserted over a 0.035 inch guidewire. Heparin (100 units/kg intra-arterial) was administered as a bolus. The left coronary arteries were visualized using a 6 Fr Judkins 3.5 L catheter. Following coronary angiography, a 0.014 inch guidewire was advanced to the distal end of the coronary artery and balloon inflation was performed in a randomized manner with balloon/artery at 1.0–1.2, using Phillips online QCA software. The LAD and CX arteries were used in each animal, with each vessel being used alternatively for the FX catheter and the POBA catheter in subsequent animals. The balloon inflations were performed at a nominal pressure for 60 seconds. Coronary angiography [after intracoronary administration of nitroglycerin (100 mg) if coronary artery spasm was present and blood pressure was normal] confirmed vessel patency in all animals. Next, the animals were euthanized with intravenous Beuthanasia D-special solution (1 ml/5 kg). The hearts were perfusion-fixed with 10% formaldehyde and sent to the study pathologist. Quantitative coronary angiography (QCA). The baseline angiograms were analyzed quantitatively by using the Philips online QCA system. The reference vessel size was obtained by measuring the mean vessel size where the balloon angioplasty was subsequently performed. The balloon-to-artery ratio was obtained by dividing the balloon diameter during inflation by the reference vessel size. Histology. The hearts were examined externally for any lesions along the length of the LAD and LCX arteries. These arteries were dissected off the heart with a portion of the myocardium still attached. The arteries were serially sectioned, tagged with tattoo ink, and submitted for H&E, Elastic, and PAS staining. The average length of the LAD arteries was 80 mm, and an average of 27 sections were analyzed. For the LCX, these values were 58 and 19, respectively. The sections were taken at about 3 mm intervals. Both the elastic and the H&E-stained preparations were examined to evaluate for mural injuries. The PAS stain was used to evaluate for loss of glycogen granules in acute myocardial injury. A score of “1” was given for breakage of the internal elastic membrane, “2A” for less than full thickness disruption of the tunica media, “2B” for full thickness injury to the media, “2D” for dissection, and “3” for adventitial perforation. Clinical correlations. In sample clinical cases immediately following the use of the FX miniRail for relief of significant coronary stenoses, intracoronary imaging studies were performed. IVUS studies were performed with the CVIS imaging system (Sunnyvale, California) equipped with a 2.9 Fr catheter and 30 mHz, using motorized automatic pullback at a speed of 0.5 mm/sec, and recorded on super VHS video tape. Optical coherence tomography was performed using the Light Labs system (Westford, Massachusetts). Results Angiographic result. Overall, the angiographic results were similar between the two groups, including reference vessel size (2.81 ± 0.25 versus 2.77 ± 0.5), balloon diameter (2.95 ± 0.32 versus 3.01 ± 0.47), and balloon-to-artery ratio (1.05 ± 0.13 versus 1.1 ± 0.13). There were no angiographic dissections in either group. Histologic results. There were no significant gross epicardial hemorrhages noted along the length of the arteries. The arteries had sloughing of endothelial cells through most of the sections examined. The length of injury found in the two vessel sets were similar, with 8.4 ± 7.4 mm found in the the FX miniRAIL-treated vessls, and 8.4 ± 7.7 mm in the conventional balloon angioplasty-treated vessels. The injury score is presented in Table 1, with no clear difference observed between the two groups. However, the FX miniRAIL balloon seemed to cause “controlled” dissection with a focal “nick” (Figure 2 A and B), with the regular balloon resulting in uncontrolled, mural disruption (Figure 3 A and B). The findings of a localized scoring of the vessel wall appeared to be reproduced in the sample imaging studies performed following FX miniRail angioplasty in patients who underwent both IVUS (Figure 4) and OCT (Figure 5). Discussion The results of this preliminary study suggest that the FX miniRAIL balloon performs similarly to a regular angioplasty balloon, although the mechanism of action appears to be a more limited, controlled dissection of the vessel wall. Although the effect of such a device in healthy juvenile pig coronary arteries could be postulated to be different to those in atherosclerotic lesions in human coronary arteries, IVUS and OCT studies represent anecdotal support that these findings can be translated to diseased human stenoses. As there were no stenoses in these normal vessels, there could be no assessment of the effect of this device on relieving stenosis pressure. Nonetheless, it appears reasonable that the limited dissection noted with the FX miniRAIL would result in an increase in vessel compliance, enabling stenosis resolution at lower balloon pressures. Furthermore, the lack of vessel injury proximal to the balloon inflation and the similarity of injury length and depth when compared to conventional balloon angioplasty, support the safety and feasibility of this novel device. It seems likely, based upon these results, that the mechanism of action of this device is similar to that of the Cutting Balloon (Boston Scientific, IVT, Ireland), with a localized cut along the length of the balloon, as we have previously reported.¹⁰Potential advantages and niches. As the histology revealed, the FX miniRAIL balloon causes a controlled dissection, rather than uncontrolled barotrauma and tear. Due to a unique design, the balloon is as flexible as regular balloons in contradistinction to other technologies aimed at causing controlled vessel scoring. It also is a simpler option than performing a buddy wire procedure, saving the expense, complexity, and complications of introducing an additional wire. Furthermore, with the advent of drug-eluting stents and their widespread introduction to catheterization laboratories, improved vessel preparation may play a greater role, and the ability to achieve this with limited vessel wall disruption promises to be a significant advantage. The device could also potentially treat bifurcation lesions, however, due to its construct, the passage to a side branch through a stent should probably be advised against initially to avoid catching on inadequately apposed stent struts. Limitations. This study was performed in healthy animals in the absence of stenotic lesions. Nonetheless, the presence of similar findings with OCT and IVUS seem to support the presence of the identified effect in human stenotic vessels. Conclusions Balloon injury performed with the FX miniRAIL balloon, when compared to BA, results in equivalent depth and length injury to normal porcine coronary arteries, with apparent reduction of circumferential damage due to a characteristic localized injury to the vessel. This finding was anecdotally confirmed in diseased coronary arteries using IVUS and OCT.

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