Feasibility and Safety of the Novel Vivolight Frequency Domain Optical Coherence Tomography System: A Multicenter Study

Abstract: Objective. The study sought to assess the effectiveness and safety of the novel P60 Vivolight frequency-domain optical coherence tomography (OCT) system (Shenzhen Vivolight Medical Device & Technology). Methods. A total of 90 patients were enrolled from 3 institutions. The pullbacks were performed with both the P60 Vivolight OCT system and the Ilumien Optis OCT system (Abbott Vascular). The primary endpoint was the clear stent length (CSL). Device safety was assessed by the record of serious procedure-related or postprocedure adverse events. The secondary endpoints were the average lumen area of stent, clear image length (CIL), system stability, and imaging catheter operability. Results. The mean relative errors of CSL were 3.30% (95% confidence interval [CI], -0.71 to 7.31) in the full analysis set (FAS) and 0.83% (95% CI, -1.79 to 3.45) in the per-protocol set (PPS). The mean relative errors of the average lumen area of stent were 2.20% (95% CI, 0.70 to 3.80) in the FAS and 1.55% (95% CI, 0.30 to 2.80) in the PPS. No difference was observed in the percentage of obtaining >24 mm of CIL (93.18% in the P60 Vivolight group vs 95.45% in the Ilumien Optis group; P=.48). There were no serious procedure-related or postprocedure adverse events. Conclusions. The feasibility and safety of the novel Vivolight OCT system is equivalent to that of the Ilumien Optis OCT system.

J INVASIVE CARDIOL 2021;33(6):E412-E416. Epub 2021 April 8.

Key words: coronary artery disease, feasibility, optical coherence tomography, safety

Coronary angiography is considered the “gold standard” for the diagnosis of coronary artery disease, but it has many limitations in clinical application; the resulting two-dimensional images aren’t optimal for judging the degree of stenosis, measuring the lumen area, or assessing lesion characteristics.¹ Intravascular ultrasound (IVUS) displays cross-sectional images of the vessel and provides detailed imaging of coronary artery lesions. A large number of clinical studies and systematic meta-analyses have confirmed that IVUS-guided percutaneous coronary intervention (PCI) is superior to coronary angiography alone.^2-4

The most prominent advantage of optical coherence tomography (OCT) compared with other technologies is its resolution, which is 10 times higher than IVUS.^5-9 OCT can identify different plaque types and thrombus, measure the size of vascular lesions accurately, optimize stent implantation, and assess the effectiveness of stenting.^10,11 As a result, OCT can explore the pathogenesis of acute coronary syndrome (ACS), reduce the related complications, improve clinical benefit of PCI, evaluate the effectiveness of new interventional medical devices, and more.^3,4,12-15 Despite compelling evidence and recommendations, the use of OCT is not frequent in the real world. Cost is a factor that influences the use of OCT; therefore, it is necessary to develop more economical OCT systems. This multicenter Chinese study evaluated the safety and feasibility of the novel  P60 Vivolight frequency domain OCT system (Shenzhen Vivolight Medical Device & Technology).

Methods

Study population. This study utilized a prospective, multicenter, randomized, blind evaluation, and paired-control design. From November 2017 to May 2018, a total of 90 patients were enrolled from 3 centers (The General Hospital of the People’s Liberation Army, Beijing Anzhen Hospital of Capital Medical University, and Zhongshan Hospital Fudan University).

The study inclusion criteria were: (1) male or non-pregnant female (age, 18-80 years old); (2) patients who required PCI with a single stent; and (3) vessel diameter of stented segment measuring 2.0-3.5 mm.

The clinical exclusion criteria were: (1) lesions in the left main and ostia; (2) large thrombosis or severe calcification or highly tortuous target vessels; (3) ACS within 24 hours; (4) the target vessel has undergone coronary artery bypass surgery; (5) New York Heart Association class III or IV heart failure; (6) preoperative renal impairment (serum creatinine >2.0 mg/dL); (7) unstable arrhythmias, such as ventricular tachycardia; (8) platelet count <100×10⁹/L or >700×10⁹/L and white blood cell <3×10⁹/L; and (9) the researcher judged that the patient had poor compliance.

This study complied with the Declaration of Helsinki. The study protocol was approved by the institutional review board and ethics committee at each participating institution, and written informed consent was obtained from all participating patients.

Image acquisition and analysis. Heparin injection (100 U/kg) was given for anticoagulation. After the placement of a 6 Fr guiding catheter, 100-200 μg of nitroglycerin were injected to prevent coronary vasospasm. After the placement of a drug-eluting stent, OCT imaging was performed.

OCT images were acquired by both the Ilumien Optis OCT system (Abbott Vascular) and the P60 Vivolight OCT system. The imaging catheter was advanced approximately 10 mm beyond the stent into the distal vessel. After the imaging catheter was placed, contrast was manually injected through the guiding catheter at a rate of 4 mL/s. To exclude the possible influence of the sequence of 2 different OCT machines, the examination sequence was determined randomly.

Images were analyzed at the core laboratory of the General Hospital of the People’s Liberation Army, which was not privy to interventional procedure and patient information. Each OCT segment was analyzed at 1 mm intervals to measure clear stent length (CSL), average lumen area of stent, and clear imaging length (CIL). CSL is defined as the accumulation of clear imaging frames within the stent area and is reported in millimeters. CIL is defined as the cumulative sum of clear imaging frames within the length of an OCT pullback and is reported in millimeters. Average lumen area of stent segment was defined as the mean lumen area measured per 1 mm of the stent segment, and is reported in millimeters squared. Clear image frame was defined as an OCT cross-sectional image frame with a visible boundary between the lumen and vessel wall along a continuous arc of at least 270° around the center of the lumen. The presence of stent edge dissection, malapposition, and tissue prolapse were also recorded during analysis.

Primary endpoint. The primary endpoint was the relative error of CSL. The measure result of the Ilumien Optis OCT system was considered as standard. The 95% confidence interval (CI) of the relative error was in the range of -10% to approximately +10%.

Safety endpoints were assessed by the incidence of intraoperative or postoperative adverse events (AEs) and severe adverse events (SAEs). AEs included chest tightness, angina pectoris, hypotension, and infectious endarteritis; coronary artery dissection, acute occlusion, perforation, thrombosis, and continuous arterial spasm after treatment during OCT operation; and electrocardiographic changes, including ST-segment elevation, T-wave changes, etc. SAEs included malignant arrhythmias (ventricular flutter, ventricular fibrillation, etc), acute heart failure, ST-segment elevation myocardial infarction, or death during surgery.

Secondary endpoints. Secondary endpoints included: (1) mean lumen area of stent segment: (2) CIL; and (3) the stability of the system, which includes: (a) software operation stability (ie, the system did not crash or stop during OCT examination; (b) image clarity (whether the target area can be clearly identified during OCT examination); (c) ease of use (the machine operation is convenient ); (d) the machine interface is friendly; (e) the machine storage is safe and reliable; (f) the output data of the machine is complete and can be diagnosed and analyzed; and (g) imaging catheter maneuverability (the catheter could pass lesions smoothly and without damage).

Statistical analysis. Statistical analysis was performed using SAS 9.4 statistical software. Continuous variables were reported as mean ± standard deviation or median and interquartile range (IQR) based on their normal distribution. Categorical variables were expressed as the number or frequency of occurrence. Statistical analysis was performed at a level of .05 (consistency test level, .10).

Results

A total of 90 participants were enrolled in this study, with 2 incomplete analyses. Of the 88 cases enrolled and completed, 64 (72.73%) were male and 24 (27.27%) were female. There were no differences of gender distribution among the test centers (Chi²=0.843; P=.66). Mean age of the 88 patients was 59.54 ± 9.92 years. No difference in age was found between gender (P=.09), and there was no difference in age distribution among test centers (P=.13).

Primary endpoint. The analyses of the relative error of CSL of the full analysis set (FAS) and per-protocol set (PPS) are shown in Table 1. The relative error of the FAS is 3.30% (bilateral 95% CI, -0.71 to 7.31). The relative error of the PPS is 0.83% (bilateral 95% CI, -1.79 to 3.45).

According to the experimental design, intraclass correlation coefficient (ICC) estimation used 2-way random/mixed, single absolute model of the agreement. ICC of the CSL measurement was 0.965 (95% CI, 0.950 to 0.976). Pearson’s relative coefficient was 0.965, suggesting a high degree of consistency between the 2 measurement methods.

Table 2 shows the difference and mean value of relative error percentage between the test group and the control group, as well as the limit of agreement (LOA) and LOA 95% CI. If LOA or LOA 95% CI meets the clinical requirement and no more than 5% of the cases are outside of LOA or LOA 95% CI, the 2 measures can be considered fungible. Figures 1 and 2 display the Bland-Altman consistency distribution map of difference value and relative error percentage, respectively.

Safety endpoint. Of the 90 enrolled patients, a total of 12 subjects had AEs, with an incidence of 13.3%. All AEs occurred post operatively rather than during OCT operation and were treated accordingly. Only 1 AE was judged to be possibly related to device (contrast agent allergy). There were no SAEs.

Secondary endpoint. The relative errors of the average lumen area in the stented segment for the FAS and PPS are shown in Table 3. The relative error of the FAS is 2.20% (bilateral 95% CI, 0.70 to 3.80).The relative error of the PPS is 1.55% (bilateral 95% CI, 0.30 to 2.80).

The second endpoint was CIL. If the CIL was >24 mm, it was considered qualified. The qualified rates for the P60 vs Ilumien Optis groups in the FAS were 93.18% vs 95.45%, respectively (P=.48). The qualified rates for the P60 vs Ilumien Optis groups in the PPS were 96.43% vs 95.24%, respectively (P=.66). In both groups, additional features such as stent edge dissection, malapposition, and tissue prolapse were observed at the same position (Figure 3).

There were no significant differences in the evaluated indexes of stability of system and imaging catheter between the P60 group and the Ilumien Optis group (P>.05).

Discussion

Due to the limitations of coronary angiography in assessing vessel size, plaque characteristics, and stenting outcomes, the role of intravascular imaging in PCI has become increasingly important. OCT, as the highest resolution intravascular imaging technology, has been increasingly recommended in the PCI guidelines as the evidence has grown in the literature. The recommendations for OCT-optimized stent implantation in the 2018 European Society of Cardiology/European Association for Cardio-Thoracic Surgery guidelines on myocardial revascularization were upgraded to class IIa.¹² OCT provides unique advantages in clinical applications, such as identifying red and white thrombus and vulnerable plaques, accurately measuring the size of vascular lesions, and assessing the effect of stent implantation (underexpansion, stent edge dissection, malapposition, tissue prolapse, etc). These advantages are helpful for understanding the pathogenesis of ACS, reducing the related complications, and guiding PCIs with bioresorbable vascular scaffold implantation, in-stent restenosis, and bifurcation lesions. Advances in OCT technology, including smaller imaging catheters and better delivery capacity, OCT-angio coregistration, imaging and functional integration (such as OCT-based fractional flow reserve), and more intelligent software evaluation during stent treatment will continue to promote the use of OCT in clinical applications.

OCT has been widely recognized for its clinical value in guiding PCI, but it should be noted that OCT is not widely used in clinical practice. The reasons may include the need for additional contrast agents, longer operation time, and additional costs.³ With continuing improvements in imaging catheter technology, complications related to imaging catheters have become very rare. In a study of 3618 cases, OCT complications occurred in only 0.6%, with no serious adverse cardiovascular events. Too much information in OCT images and lack of experience cause prolonged operation times. However, adequate training in the ability to acquire and interpret images can effectively improve the efficient use of OCT. Although OCT is already considered a routine examination in Japan, it is an optional examination in most countries. The absence of medical reimbursement and high OCT catheter costs contribute to the problem. At present, there are 2 OCT systems in the OCT market. The lack of competition between OCT manufacturers is an important reason for the high cost of OCT exams and restricts the popularity of OCT in clinical application.

In this multicenter clinical study, the statistical analysis results of primary and secondary endpoints proved that P60 and Ilumien Optis had no difference in image acquisition, measurement, and analysis. In terms of safety, all AEs in this study occurred after surgery, and most were transient. Only 1 case of contrast agent allergy was related to the examination equipment, and no serious AEs occurred. Therefore, the OCT equipment in this study was safe. The P60 OCT system is equipped with unique three-dimensional postprocessing software, which can be used to conduct 3D reconstruction analysis of blood vessels and help guide the treatment of complex anatomy, such as bifurcation lesions.

Study limitations. The first limitation was the small number of patients in this study. Despite the limited population, the sample number of this clinical study was calculated statistically according to the study protocol. The second limitation was that patients with complex coronary arteries (especially those with severely calcified or highly convoluted vessels) were excluded. However, these exclusions were intended to minimize the potential risk of participants.

Conclusion

This clinical study confirmed that P60 and Ilumien Optis are equal in feasibility and safety. With the standardization and popularization of OCT technology in the clinical application of PCI, the Vivolight OCT system can provide an additional option for interventional doctors and reduce the medical economic burden for more patients.

From the ¹Department of Cardiology, The General Hospital of the People’s Liberation Army, Beijing, China; ²Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China; and ³Department of Cardiology, Beijing Anzhen Hospital of Capital Medical University, Beijing, China.

This study was a pre-approval study for China Food and Drug Administration (CFDA) clearance for clinical use in China, and has been registered on local CFDA (20170410).

Funding: This study was sponsored by Vivolight through an institutional research grant. The executive committee, together with the sponsor, designed this trial. The sponsor had no role in data collection, data analysis, data interpretation, writing the manuscript, or the decision to submit the manuscript for publication.

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 accepted August 24, 2020.

Address for correspondence: Yundai Chen, MD, Department of Cardiology, The General Hospital of the People’s Liberation Army, 28 Fuxing Road, Beijing (Wukesong), China. Email: cyundai@vip.163.com

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