Efficacy and Safety of Novel NovaCross Microcatheter for Chronic Total Occlusions: First-in-Human Study

Abstract: Objectives. The aim of this first-in-human (FIH) study was to evaluate the efficacy and safety of the novel NovaCross microcatheter system in eligible consecutive patients with chronic total occlusion (CTO). Background. CTOs remain the most challenging lesion subset in percutaneous coronary intervention (PCI). Failure to cross to the distal true lumen with the guidewire is one of the major causes of procedural failure in CTO-PCI. The NovaCross microcatheter (Nitiloop, Ltd) is designed to improve antegrade recanalization success. Methods. This study was a prospective, non-randomized, FIH investigational study. Patients with total occlusion of a coronary artery determined to be more than 3 months old and accepted for coronary CTO-PCI with an intended antegrade strategy were enrolled. Results. Twenty-four patients were enrolled in this study. Despite the high complexity of the lesions (including 80% J-CTO score ≥3 and 50% of the cases having had a previous failed CTO-PCI attempt), technical success was 81.8%. No patients reported any major adverse cardiac event up to and including 30 days post procedure. Conclusion. In this FIH study, the NovaCross microcatheter exhibited the potential to stabilize guidewires and enhance crossing of coronary CTO lesions.

J INVASIVE CARDIOL 2016;28(3):88-91

Key words: chronic total occlusion, microcatheter

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Coronary chronic total occlusions (CTOs) are commonly encountered, with complex lesions identified in 15%-30% of all patients referred for coronary angiography.^1,2 The benefits of CTO percutaneous coronary intervention (PCI) include revascularization, improved quality of life, reduced ischemia, improved left ventricular function, and potentially a survival advantage. Despite this, the attempt rates for CTO-PCI are significantly lower than attempt rates for PCI for other lesion subsets.³ Furthermore, despite a continued evolution in technical equipment and techniques, the success rate for treating CTOs by PCI remains much lower than for treating non-occluded lesions, the most common being the failure of the guidewire to cross the CTO into the distal true lumen.

The NovaCross is a novel microcatheter (Nitiloop, Ltd) that was designed to enhance recanalization success during PCI of CTO lesions. We evaluated herein for the first time the efficacy and safety of this system in a first-in-human (FIH) study on eligible consecutive patients with CTO.

Methods

Catheter system. The NovaCross is a guidewire supporting catheter with an extendable segment for additional intra-CTO support. The NovaCross is both a competent anchoring and supporting microcatheter as well as a lesion crossing catheter on its own. It gains its supportive characteristics through the use of a unique operator-controlled nitinol (nickel-titanium) scaffold and an extendable segment, both at its distal tip. Located at its distal end is an ~10 mm-long flexible nitinol element that deforms upon axial compression by outward curving of several helical struts (Figure 1). The fine loops are highly elastic, allowing gentle abutment of the distal end of the microcatheter to the vessel lumen, providing support and control over the distal tip of the coronary guidewire, potentially increasing CTO penetration success rates and intralesion wire progression and maneuverability. Once penetration of the guidewire is achieved, a 0.6 mm diameter inner portion of the NovaCross can be extended distally up to 5 cm to assist in interocclusion guidewire penetration and potentially improve channel penetration by subsequent atheroma compression and lumen preservation. Once the scaffold is collapsed, the device can be retrieved and withdrawn over the guidewire.

Study design. This study was a prospective, non-randomized, FIH investigation. The trial was approved by the Ethics Committees at all sites and all territorial Competent Authorities. All patients provided written informed consent prior to enrollment. Between March and September 2014, patients with total occlusion of a coronary artery were enrolled at 4 centers in Europe and Israel. Inclusion criteria included: >25 years of age; clinically estimated or angiographically proven occlusion age of CTO >3 months occlusion duration (showing distal Thrombosis in Myocardial Infarction [TIMI] flow 0 per the definition of the EuroCTO Club consensus⁴); reference vessel diameter ≥2 mm; and left ventricular ejection fraction (LVEF) >25%. Main exclusion criteria included: in-stent CTOs; aorto-ostial CTO location; fresh thrombus or intraluminal filling defects; history of stroke or transient ischemic attack within 1 month; and renal insufficiency. A documented or real-time 10 minute fluoroscopy time initial attempt to cross the CTO with a workhorse guidewire was required. If unsuccessful, the NovaCross system could be used. All procedures were accompanied by a Sponsor representative.

The objective of the FIH study was to evaluate the safety and performance of the NovaCross microcatheter in providing additional guidewire support to facilitate crossing of CTO lesions in coronary arteries. 

The primary safety endpoint was 30-day major adverse cardiac event (MACE) rate, with MACE defined as cardiac death, myocardial infarction (MI), or urgent target-lesion revascularization (repeat PCI within 24 hours or urgent coronary artery bypass surgery [CABG]). MI was defined as new Q-waves and/or CPK-MB >3x normal CK with positive MB component and 2x the upper limit of normal with positive MB fraction. The primary efficacy endpoint was technical success, defined as the ability of the NovaCross microcatheter to successfully facilitate placement of a guidewire beyond a native coronary CTO in the true vessel lumen. Procedural success was defined as technical success with no in-hospital MACE. Secondary endpoints included maneuverability of the NovaCross up to the occlusion and safe withdrawal, and the ability to cross the lesion with a guidewire in the true lumen, effectively dilate the CTO lesion, and place a coronary stent with residual lumen of <30% with restoration of TIMI 3 flow.

Results

Seventeen males (70.8%) and 7 females (29.1%) were treated with the NovaCross. The mean age was 67.2 ± 8.2 years and mean body mass index was 29.6 ± 4.5. Average LVEF was 53.4 ± 8.7%. Average occlusion length was 25.3 ± 10.6 mm and vessel diameter was 2.98 ± 0.46 mm. 83.3% of CTOs had a J-CTO score of 3 or more and were considered very difficult. The complete list of baseline angiographic characteristics appears in Table 1.

The NovaCross was used in 22 out of the 24 patients; in 2 patients, the landing zones were not suitable for the device as they were close to a vessel ostium and thus too short. In the 22 procedures where the NovaCross was used, the proximal cap was crossed with the guidewire in all cases (100.0%) and the primary endpoint of crossing the CTO to the true lumen was achieved in 81.8%. The complete list of intraprocedural results in the cases where the NovaCross was used appears in Table 2 and the secondary endpoints are described in Table 3.

Minor adverse events anticipated in CTO procedures and which were defined per protocol were reported in 11 patients (45.83%). These included groin pain, hematoma at the insertion site (not requiring transfusion, intervention, or surgery), leg pain, and nausea. 

Four per-protocol serious adverse events (16.7%) occurred; all were anticipated and adjudicated by the principal investigators as not device related, and none of them resulted in any clinical sequelae for the patients. Three of them occurred after the NovaCross was removed or was not used at all. In 1 patient, a coronary perforation occurred 45 minutes after the device was removed during balloon angioplasty. There was no tamponade or need for any other intervention. In 1 patient, ventricular fibrillation occurred 56 minutes after the beginning of the procedure and there was immediate cardioversion to normal sinus rhythm. In 1 patient, a myocardial hematoma occurred 60 minutes after the device was removed as a consequence of vessel injury distal to the CTO, but without vessel rupture. In 1 patient, a coronary dissection occurred 30 minutes after the device was removed. The investigator reported that the event was caused by the angioplasty guidewire. The clinical events at 30 days are summarized in Table 4. There were no MACE events up to 30 days.

Discussion

The results of this feasibility and safety study demonstrated that use of the NovaCross in CTO procedures is safe. Throughout the study, there were no MACE events, no life-threatening adverse events, and no deaths. The 30-day MACE rate was 0.0%. Four patients (16.7%) presented with serious adverse events, all of which were classified as not device related. These adverse events are considered typical of CTO procedures. Published information on 30-day MACE results in CTO alludes to higher rates ranging from 4.8%-10% for the assessment of new devices and in routine clinical practice. However, this is a small study and further validation is required in a larger series of patients.

Use of the NovaCross in CTO procedures is effective; the proximal cap was penetrated in all cases (100.0%), and in 81.8% the entire lesion was crossed, siting a guidewire in the distal true lumen. Published success rates using various mechanical guidewires or support catheter device combinations range from 53%-72% and sometimes higher.^5-11 It should be noted that one-half of the patients selected in this study had undergone prior failed attempts at crossing the CTO, and >80% of the lesions had a J-CTO score of ≥3, signifying highly challenging occlusions.¹² In this respect, NovaCross’s possible benefit to current CTO microcatheters is in its ability to provide support and control over the distal tip of the coronary guidewire, potentially increasing CTO penetration success rates and intralesion wire progression and maneuverability.

Study limitations. This is a preliminary and small study. Technical approaches were limited to antegrade wire escalation within the study due to the FIH nature of the trial. This may have limited the overall success rates obtained. In addition, the QCA analysis was conducted by local operators rather than a core laboratory and could be a potential source of bias. Also, the clinical events were not adjudicated by an independent committee. Nevertheless, a larger trial is warranted to compare the NovaCross with other technologies or techniques.

Conclusion

In this FIH study, the NovaCross microcatheter was used reliably with demonstrable feasibility and safety in patients with coronary CTOs. A total of 24 patients were enrolled and all patients completed the study with 30-day follow-up requirements. Trials in a larger series of patients are required to expand our understanding of the role of this device in clinical practice.

References

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10.    Orlic D, Stankovic G, Sangiorgi G, et al. Preliminary experience with the Frontrunner coronary catheter: novel device dedicated to mechanical revascularization of chronic total occlusions. Catheter Cardiovasc Interv. 2005;64:146-152.

11.    Whitlow PL, Burke MN, Lombardi WL, et al. Use of a novel crossing and re-entry system in coronary chronic total occlusions that have failed standard crossing techniques: results of the FAST-CTOs (Facilitated Antegrade Steering Technique in Chronic Total Occlusions) trial. JACC Cardiovasc Interv. 2012;5:393-401.

12.    Morino Y, Abe M, Morimoto T, et al. Predicting successful guidewire crossing through chronic total occlusion of native coronary lesions within 30 minutes: the J-CTO (Multicenter CTO Registry in Japan) score as a difficulty grading and time assessment tool. JACC Cardiovasc Interv. 2011;4:213-221.

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From the ¹Belfast Health & Social Care Trust, Belfast, Northern Ireland; ²Jagiellonian University Medical College, Krakow, Poland; ³Rabin Medical Center, Petach Tikva, Israel; and ⁴Hadassah Medical Center, Jerusalem, Israel.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Kornowski is co-founder of the company, has IP arrangements, and is a shareholder in Nitiloop Ltd. Israel. Dr Dannenberg is a shareholder in NitiLoop Ltd. The remaining authors report no conflicts of interest regarding the content herein. 

Manuscript submitted September 1, 2015, provisional acceptance given October 12, 2015, final version accepted November 5, 2015.

Address for correspondence: Simon Walsh, MD, Belfast Health & Social Care Trust, Cardiology, Belfast, Ireland. Email: Simon.Walsh@belfasttrust.hscni.net