A Prospective Multicenter Study Using a Virtual 3 Fr Percutaneous Coronary Intervention System: The V3 Registry

Abstract: Objectives. To evaluate the safety and feasibility of virtual 3 Fr (V3), sheathless 5 Fr percutaneous coronary intervention (PCI). Background. A small-diameter guiding catheter (GC) makes less-invasive PCI possible. The V3 is an extremely slender PCI system; however, the outcome of using this system has not yet been determined. Methods. The V3 registry is a prospective, multicenter, non-randomized study that enrolled patients who underwent elective V3-PCI. The primary endpoint was clinical success rate, and the secondary endpoints were PCI success rate in all cases, major adverse cardiac and cerebrovascular event (MACCE) at 30 days, and access-site complications. Results. A total of 260 patients with 321 lesions were enrolled. Of this group, 70% were male and the mean age was 70.8 ± 10.0 years. Type B2/C lesions comprised 50.7% of the total. The clinical success rate was 95.8%, and the PCI success rate was 99.2%. PCI failure was reported in 2 chronic total occlusion cases. No MACCE was reported. Although there was no major bleeding, hematoma occurred at the puncture site in 12.7% of cases. There was a single radial artery occlusion (0.4%) without symptoms. Conclusions. PCI with the V3 was safe and feasible. Radial artery occlusion and major bleeding complications were extremely low. However, access-site hematoma frequently complicated catheter exchange.

J INVASIVE CARDIOL 2017;29(1):16-23. Epub 2016 June 15.

Key words: virtual 3 Fr guiding catheter, sheathless, slender PCI, transradial intervention 

Percutaneous coronary intervention (PCI) has been developed as a revascularization modality that is less invasive than bypass surgery. The approach has evolved from a transfemoral approach to a transradial approach, with the latter causing fewer bleeding complications and less patient discomfort.^1-3 Furthermore, reducing catheter size has several additional benefits such as lower radial occlusion rates^4-7 and shorter hospital stays.⁸ 

The use of a sheathless system has been re-examined as a possible means of reducing puncture size by approximately 2 Fr compared with a sheathed system. On the other hand, the risk for arterial injury and spasm could be increased because vascular walls and puncture sites are directly stimulated by the movement of catheters, including their insertion and removal. The virtual 3 Fr system (V3) is an extremely small-diameter PCI system, which is equivalent to a sheathless 5 Fr guiding catheter (GC) (Figure 1). It makes the smallest vascular puncture site among commercially available systems.^9-11 However, the safety and effectiveness of PCI with the V3 system is still unknown. The objective of this study was to test this system as a primary device for use in routine PCI. 

Methods

Study design. A multicenter V3 registry study was conducted using a prospective non-randomized design to confirm the safety and effectiveness of V3 as a primary routine PCI system. The study period was from January 1, 2011 to December 31, 2012. The study was approved by the patient registry institutional review board. All patients provided informed consent.

Patients. Patients who underwent elective V3-PCI were enrolled prospectively. Inclusion criteria were as follows: ischemic disease that needed to be treated and had significant coronary artery stenosis. Reference diameters were between 1.5 and 4.0 mm, and the lesions were deemed treatable by elective PCI in the native coronary arteries or bypass grafts and included chronic total occlusion (CTO) lesions. Exclusion criteria included patients without indications for PCI, age <21 years, female gender with the possibility of pregnancy, lack of informed consent, and individuals thought by a physician to be unsuitable for this study.

Virtual 3 Fr and Works systems. Initially, a 100 cm, 3 Fr-long sheath with flexible multipurpose-type tip was used with a 3 Fr diagnostic catheter. If significant stenosis was observed on angiography with the 3 Fr diagnostic catheter, the long sheath was advanced along the diagnostic catheter. A 3 Fr-long sheath was used as GC with an inner diameter equal to a 5 Fr GC. This configuration is the original V3 system (Figures 2 and 3).

Because easy engagement was required without a 3 Fr diagnostic catheter, Judkins-type or Amplatzer-type GCs were requested. Common 5 Fr GCs were used instead of a multipurpose-type long sheath. In this way, the size of the GC was 5 Fr, but trauma to the puncture site is the same as with a 3 Fr sheath. This is the concept behind the V3 system.

The Works (Medikit Co, Ltd) is an all-in-one V3 kit. The kit consists of a puncture needle, a 0.025˝ guidewire used when puncturing the vessel, a predilator, a GC (multipurpose, Amplatz, Judkins, Extra Back-up; inner diameter 0.059˝), and a dilator for the GC. There is no large size difference between the GC dilator and the GC, a design which enables smooth insertion at the puncture site and prevents the razor effect, which means the sharp edge of a GC tip shaves the inner vessel when advancing the GC (Figures 4 and 5). The Works GC has a 0.059˝ inner lumen, and less razor effect was expected than if the physician selected a conventional 5 Fr GC with a 0.059˝ inner lumen.

PCI procedure. The study required the use of a sheathless 5 Fr device, which as noted earlier is equivalent to a V3 system. The approach site was determined by each physician. Patients were required to take dual-antiplatelet drugs preoperatively. Puncture and guidewire insertion were performed, and then a conventional 3 Fr sheath or Works dilator was used for predilation before system insertion.

Study physicians selected either a conventional GC or a catheter in the Works kit. The GC and dilator of the Works system were integrated and advanced along a 0.025˝ guidewire that had been previously placed. The long dilator itself is soft and flexible, with an acute tapered tip to insert at the approach site. The dilator is easy to advance through the radial, subclavian, and brachiocephalic arteries. The dilator was then advanced from the puncture site to the ascending aorta in order to prevent the razor effect. Wetting the outer surface of the GC is needed to prevent intravascular resistance when advancing the catheter. The dilator was removed, and the GC was then inserted into a diseased coronary artery, where PCI was performed. Heparin was administered to maintain blood clotting time ≥250 seconds, which was felt to be suitable for PCI based on the criteria of each institution. Details of the PCI technique were based on the strategy pursued by individual physicians. When the GC was deemed unsuitable for PCI, the system was altered in an attempt to achieve clinical success. The decision to change the GC or employ a larger sheathless system or sheath system was left to operator discretion.

Endpoints. The primary endpoint was V3 success, which was defined as completion of the PCI procedure for the target lesion using the V3 system alone, regardless of whether there was a change of puncture site or use of a different catheter. The secondary endpoints were: PCI success rate of all entered cases; major adverse cardiac and cerebrovascular event (MACCE) rate, which included all-cause mortality, cardiac death, myocardial infarction, cerebral bleeding, cerebral infarction, and acute revascularization due to PCI at 30 days; and access-site complications. Access-site complication was defined as hematoma, compartment syndrome, radial artery spasm, and radial artery occlusion. The definition of major bleeding was fatal bleeding and/or symptomatic bleeding in a critical area or organ, and/or bleeding causing a fall in hemoglobin level of ≥2.0 g/L (1.24 mmol/L), or leading to transfusion of ≥2 units of whole blood or red cells.¹²Radial artery occlusion was defined as no pulsation as checked by the physician after removal of all hemostasis devices.

Results

Clinical characteristics of all patients are shown in Table 1. A total of 260 patients with 321 lesions, 70% male, were enrolled in this registry. Mean patient age was 70.8 ± 10.0 years and mean body mass index was 24.1 ± 3.3 kg/m². All patients received dual-antiplatelet therapy. Lesion characteristics are shown in Table 2. Of all lesions, 50.8% were American College of Cardiology/American Heart Association type B2/C, 2.8% were chronic total occlusions (CTOs), and 10.6% were bifurcation lesions. Procedural characteristics are shown in Table 3. The transradial approach was used in 90.4% of patients. For predilation at the puncture site before GC insertion, a 3 Fr sheath was used in 38.5% of cases, and a Works predilator was used in 50.4% of cases. A Works GC was used in 83.3% of cases, and other 5 Fr GCs were used in 16.2% of cases. Intravascular ultrasound was used in 68.1% of cases, and optical coherence tomography was used in 4.2% of cases. For hemostasis, an inflatable hemostasis device was used in 90.3% of cases. Manual compression was performed only for the femoral approach and brachial approach.

The V3-PCI results are shown in Table 4 and Figure 6. V3 success was achieved in 95.8% of the patients, of whom 6.9% had changed to the preshaped V3 from the GC that was initially used. In contrast, 3.4% of the procedures were V3 failures but had successful PCI performed (ie, cases in which a sheath was used and cases in which the sheathless catheter was upsized). 

However, V3 usage in acute coronary syndrome was not formally excluded in this registry; there were no cases of acute myocardial infarction in this study. Because of difficulty of getting informed consent for this registry and incompatibility with aspiration catheters, the V3 system was not regularly used on acute coronary syndrome in Japan. 

The total PCI success rate was 99.2%, with PCI failure in only 2 cases (0.8%). One failed case was a patient with CTO in whom the V3 was used, but the procedure had to be discontinued due to coronary perforation. The other was a patient with CTO in whom transradial approach with the V3 was initially used; however, due to inability to achieve guidewire passage, the system was exchanged to a 6 Fr sheath and then to the femoral approach using an 8 Fr sheath. Unfortunately, the guidewire failed to pass even with the 8 Fr femoral approach. In this study, 13.1% of the cases had bifurcation areas with side branches of ≥2 mm, 10.4% required guidewire insertion into side branches, 4.2% had side-branch dilation, and 2.3% had stent insertion. A mother-and-child technique was used in 6.1% of cases and rotational atherectomy was used in 1.5% of cases.

Complications are shown in Table 5. No MACCE was reported. Two patients (0.8%) had hematomas of ≥5 cm but did not require blood transfusion; both patients were successful V3 cases in which there was a change of catheter. A hematoma <5 cm was found in 31 patients (11.9%). Five of these 31 patients had a change of catheter, but the procedure was completed using the V3 system; 2 patients required the catheter and sheath sizes to be increased from the V3 size, 2 patients were treated using the brachial approach, and 1 patient was treated using the femoral approach.

Radial spasm was seen in 1 patient (0.4%). Radial artery occlusion was seen in 1 patient (0.4%) without symptoms or functional disorder, which proved enough blood flow was supplied from the ulnar artery. Swelling and hematoma of <5 cm were seen after intervention in 1 patient. In this patient, the brachial approach was used and the procedure was completed using the V3 system. This patient was also diagnosed with compartment syndrome, and these symptoms improved without functional disorder using conservative treatment. Functional disorder, defined as continuation of numbing or pain, paralysis, or disturbance of mobility, was not observed in any of the patients. Although there were no major bleeding complications that resulted in blood transfusion or functional disorder, 12.7% of the patients had hematomas, particularly when catheter exchange was performed (Table 6). 

Discussion

This multicenter prospective registry study showed the current status of sheathless, 5 Fr, V3-PCI in a real-world population. PCI success was achieved in 99.2% of patients studied, except for 2 CTO cases. No major adverse events were reported, including death, myocardial infarction, stroke, or major bleeding. However, access-site hematoma was observed in 12.7% of cases, occurring most often when catheter exchange was performed.

The 5 Fr GC^13-15 used in V3-PCI has a narrow inner lumen, and some physicians may be concerned about limited ability to treat severely calcified lesions or to utilize the kissing-balloon technique for bifurcation lesions, as well as concern about weak GC back-up force for complex lesions. For severely calcified lesions, a small 1.25 mm or 1.5 mm rotational atherectomy burr can be used in a 5 Fr GC. Also, the kissing-balloon technique may be feasible in a 5 Fr GC system using small devices such as a 0.010˝ wire and compatible balloons.^16,17 When there is insufficient back-up force, the mother-and-child technique can be carried out in a 5 Fr GC using a 4 Fr straight-type GC such as iWorks or Heartrail 4 Fr ST 01 (Terumo Medical Corporation). Although CTO may impose limitations,¹⁸ the failed cases in this registry were not caused by the small catheter diameters.

The V3 system is extremely slender, and consequently injuries to vessels are markedly decreased. The reported incidence of radial artery spasm during transradial intervention with 6 Fr GC ranges from 2%-20% in the literature,^19-21 and the reported incidence of radial artery occlusion varies widely from 0.8%-30.0%.^2,4-7 In another report, 5% of radial artery occlusions at 7 days and 2.5% of those at 30 days were observed with use of a 7 Fr sheathless GC.²² Major bleeding ranged from 1.8%-2.4% and blood transfusion from 1.0%-3.2%.²³ However, there was no major bleeding and no blood transfusion in the V3 registry. Radial artery occlusion occurred in only 1 of 253 cases of transradial intervention, and spasm occurred in only 1 patient. This extremely low complication rate suggests that the slender outer diameter of the V3-PCI catheter system is an important factor in reducing arterial injury. To use this system, the learning curve for manipulating slender catheters, using transradial intervention, and appropriate lesion selection were important. 

Complications were primarily focused on more contact of the GC against the radial artery wall, more manipulation, more dilator damage, and more manipulation in catheter exchange with the sheathless system. However, we saw fewer of these complications except bleeding; the superiority of the V3 system has not been proven in this patient population because there was no direct comparison with a conventional sheath system.

A high incidence of bleeding (12.7%) was observed. It seemed that bleeding happened during the exchange from the predilator to the GC because it is difficult for a single physician to exchange the long system alone. In order to decrease the likelihood of this incident, the operator should compress the access site during the GC exchange, with another operator managing the GC and guidewire. This action seems likely to prevent hematoma and leaking around the GC. Bleeding was sometimes observed after manipulating the GC to engage the coronary artery or to make a deep engagement; the physical stimulus by the GC as it approached the site was a possible cause.

Study results showed that operators should avoid catheter exchange in a sheathless system to prevent hematoma. Also rediscovered was the role of a sheath device in preventing bleeding during the catheter exchange despite making a larger entry site. These results show that careful selection of an optimal GC is important to prevent exchanging GC as well as multiple and/or heavy manipulation of the GC to ensure power position and deep engagement. In cases where use of the initial GC is ineffective, aggressive “child” catheter deployment may be attempted before catheter exchange.²⁴

The Works system is a good all-in-one V3 package. However, the GC in Works has only four preshaped types, ie, the multipurpose, Amplatz, Judkins, and Extra Back-up. Extended use led to softening of the GC as it was warmed by the patient’s body temperature, and it required additional back-up support to use, unlike other 5 Fr GCs. These circumstances led to hesitation in physicians who typically use a 6 Fr GC with a sheath.

Study limitations. There are several limitations to this study. Many cases were performed via transradial approach, and <10% were performed via transfemoral approach. It seems reasonable to use a sheathless system for the transfemoral approach, although further studies are needed to investigate the safety and feasibility of such an approach. The transradial approach results in fewer bleeding complications than the transfemoral approach, although this may change with the use of slender catheters for transfemoral intervention. In this study, specific slender devices such as a 4 Fr straight GC employed as a “child” catheter (when catheterizing via the mother-and-child technique) or 0.010˝ guidewires and balloon systems could be used; however, these devices are not universally available. In spite of multicenter registration, only 260 cases were registered over 2 years. One reason is the limitation of using a 5 Fr GC, which is not compatible with the kissing-balloon technique and has less back-up support. It is sometimes difficult to complete PCI using a 5 Fr GC. The percentage of cases using a 5 Fr GC may be <5% in Japan. Another reason is the sheathless system itself; physicians worry about the effort of exchanging the catheter and they worry about the sheathless system injuring the artery during long catheter insertion and removal. The percentage of sheathless system use in Japan may be <5%. There were 260 cases in the registry where the V3 system was used, and this seems like a small series with multicenter collection of patients over 2 years. The total number of PCI cases in all hospitals was about 10,400 over 2 years, including emergency cases. The percentage of V3 usage was about 2.5%. This number of cases was small, but seemed a reasonable real-world percentage for Japanese patients with an indication for use of the V3 system. We need larger randomized case-controlled studies in order to produce real evidence. Also, hemostasis was performed per each hospital’s methods and protocols. In order to recognize the advantages of a small-diameter catheter, we need another trial to evaluate the shortening of hemostasis time. It is desirable to check radial artery occlusion not only after removal of all hemostasis devices, but also in the chronic phase (eg, 1 month later). It was difficult to confirm radial artery occlusion in the same chronic phase at each hospital, because each hospital that participated in this registry has a different system for follow-up at their outpatient clinic. 

Although it is not impossible to treat complex lesion with the V3 system, for maximizing performance we should select simple lesions, such as those with no bifurcation, no CTO, and less calcification.

Conclusion

The V3 registry data suggested that the V3 system is safe and feasible with a high PCI success rate and a low major complication rate. However, minor bleeding at access sites related to catheter exchange may be a problem.

Acknowledgments. We wish to thank the V3 registry investigators, and all members of Slender Club Japan for inventing the Virtual 3 Fr system.

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From the ¹Department of Cardiology, Tokai University School of Medicine, Shimokasuya, Japan; ²Department of Cardiology, Otaru General Hospital, Otaru, Japan; ³Department of Cardiology, Kanazawa Cardiovascular Hospital, Kanazawa, Japan; ⁴Department of Cardiology, Takahashi Hospital, Kobe, Japan; ⁵Department of Cardiology, Shiroyama Hospital, Habikino, Japan; ⁶Department of Cardiology, Japanese Red Cross Koga Hospital, Koga, Japan; ⁷Department of Cardiology, Kamagaya General Hospital, Kamagaya, Japan; ⁸Department of Cardiology, Toyama University School of Medicine, Toyama, Japan; ⁹Department of Cardiology, Kawasaki Hospital, Osaka, Japan; ¹⁰Department of Cardiology, Tsuchiya General Hospital, Hiroshima, Japan; ¹¹Department of Cardiology, Bando Hospital, Shimoshinkawa, Japan; ¹²Department of Cardiology, Takeda Hospital, Kyoto, Japan; ¹³Department of Cardiology, Kumamoto Saishunso National Hospital, Kumamoto, Japan; ¹⁴Department of Cardiology, Tosei General Hospital, Seto, Japan; ¹⁵Department of Cardiology, Nagasaki Harbor Medical Center City Hospital, Nagasaki, Japan; ¹⁶Department of Cardiology, Chitose City Hospital, Chitose, Japan; ¹⁷Department of Cardiology, Higashi-kani Hospital, Kani, Japan; ¹⁸Department of Cardiology, Amagasaki New Town Hospital, Amagasaki, Japan; ¹⁹Department of Cardiology, Tokai University Hachioji Hospital, Hachioji, Japan; ²⁰Department of Cardiology, Shonan Kamakura General Hospital, Kamakura, Japan.

Funding: This study was supported by Medikit Co. The authors received no consulting fees.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.

Manuscript submitted February 1, 2016, provisional acceptance given March 22, 2016, final version accepted April 25, 2016.

Address for correspondence: Fuminobu Yoshimachi, MD, PhD, Department of Cardiology, Tokai University School of Medicine, 143 Shimo Kasuya, Isehara, Kanagawa 259-1193, Japan. Email: yoshimachi-circ@umin.ne.jp