Transradial Intervention in Patients With Non-ST Elevation Acute Coronary Syndrome Using One 4.0 Fr Sheath and One Sheathless Guide Catheter Via a Single Puncture Site: The 1-1-1 Strategy

Abstract: Objectives. The optimal primary transradial intervention (TRI) technique has not been established in non-ST segment elevation acute coronary syndrome (NSTEACS) patients, because they often, but not always, undergo immediate revascularization after coronary angiography (CAG). Moreover, TRI failure has been reported in 5%-10% of cases. We investigated whether a newly designed strategy of immediate TRI using one sheathless hydrophilic-coated guiding catheter (SH-GC) after diagnostic CAG with one 4.0 Fr sheath via a single access site (the 1-1-1 strategy) could be beneficial for NSTEACS patients. Methods. We performed immediate TRI prospectively using SH-GC in consecutive NSTEACS patients in our hospital and compared the procedural success rate with that of conventional TRI performed before this study. Results. Between 2015 and 2017, immediate TRI using SH-GC was performed in 330 consecutive NSTEACS patients after CAG using a 4.0 Fr sheath. Compared with the conventional TRI group (n = 330), the procedural success rate was significantly higher in the SH-GC group (P<.01), as SH-GC prevented TRI failure due to radial spasm (P<.01). SH-GC use was also significantly associated with completion of both diagnostic CAG and immediate TRI using only one sheath (P<.001) and one guiding catheter (P=.02). Multivariate analysis revealed that SH-GC use was an independent predictor of successful TRI (P<.01). The rates of major adverse cardiac events were comparable; however, rates of major access-site bleeding (P<.01) and blood transfusion (P=.02) were significantly lower in the SH-GC group. Conclusions. The 1-1-1 strategy using SH-GC may offer better TRI treatment than conventional systems for NSTEACS patients and simultaneously prevent access-site bleeding.

J INVASIVE CARDIOL 2018;30(9):316-323.

Key words: access-site management, acute MI, radial artery access

Numerous studies have shown that a transradial approach (TRA) can reduce the incidence of serious vascular complications when compared with a transfemoral approach (TFA).^1-4 However, inherent potential complications of TRA include procedural failure because of radial artery spasm (RAS) and postprocedural radial artery occlusion (RAO), which appears to be a barrier to the adoption of TRA. The sheathless Eaucath hydrophilic-coated guiding catheter (SH-GC) (Asahi Intecc) was developed as a therapeutic catheter to overcome these complications. This catheter has a small equipment diameter and a hydrophilic coating, which allow direct insertion into the radial artery without an introducer sheath (Figures 1A and 1B).^5-8 The external diameter of a 6.5 Fr SH-GC (2.16 mm) is smaller than a conventional 5 Fr sheath (2.29 mm). Similarly, the external diameter of a 7.5 Fr SH-GC (2.49 mm) is smaller than a conventional 6 Fr sheath (2.62 mm). It has been shown that the SH-GC was feasible for primary transradial coronary intervention (TRI) in consecutive patients with ST-segment elevation myocardial infarction (STEMI) and that there were few incidences of RAS and RAO.⁹ 

Primary percutaneous coronary intervention (PCI) is a standard treatment in patients with acute coronary syndrome (ACS); however, an optimal primary TRA system has not yet been established in patients with non-ST segment elevation acute coronary syndrome (NSTEACS). NSTEACS patients do not always undergo immediate PCI after diagnostic angiography, and primary medical management with elective revascularization is often preferred.^10,11 We hypothesized that we could perform immediate TRI using SH-GC after coronary angiography (CAG) without an additional large sheath. Moreover, initial CAG could be conducted using a small sheath system if the SH-GC was chosen. The primary purpose of the present interventional trial was therefore to prospectively investigate whether immediate TRI with one SH-GC via a single puncture site could be successfully performed after diagnostic CAG using one 4.0 Fr sheath (the “1-1-1” strategy) to prevent access-site complications in NSTEACS patients.

Methods 

Study design and participants. This open-label, prospective, single-center, non-randomized study was performed in consecutive patients who were suspected to suffer from NSTEACS between January 2015 and June 2017. Patients whose radial arteries were not palpable because of cardiogenic shock, those with a previous history of coronary artery bypass graft (CABG) surgery involving both radial arteries, those with STEMI, and those with end-stage renal disease on hemodialysis were excluded. We compared the procedural and clinical outcomes between NSTEACS patients treated with TRI using the SH-GC and those treated with a conventional sheath system in our hospital before the start of this trial. The study was approved by the institutional review board of our hospital, and written informed consent was obtained from all patients.

Procedures. After achieving local anesthesia of the skin with 2.0% xylocaine, the radial artery was punctured with an 18.0 gauge needle and a 4 Fr introducer sheath was inserted. CAG was performed with 4 Fr diagnostic catheters. At the start of CAG, 2000 IU unfractionated heparin (UFH) was intravenously administered after cannulation with a 4 Fr sheath. In patients where the operator decided that immediate TRI was not appropriate, catheterization was completed after CAG. If it was found that the culprit lesion should be treated with immediate revascularization, the 4 Fr sheath was replaced with a SH-GC and a central dilator over a standard 220 cm J-tipped 0.035˝ wire (Figures 1C and 1D). The size and shape of the SH-GC were left to the discretion of the operator. The SH-GC was advanced to the ascending thoracic aorta, and both the central dilator and the 0.035˝ wire were removed (Figure 1E). Additional UFH (5000 IU) was infused when immediate TRI was successively performed. On completion of TRI, the SH-GC was removed over the 0.035˝ wire, and the puncture site was sealed using a compression device (Tometa Kun; Zeon Medical). Anticoagulation was not routinely reversed after TRI. None of the patients received fibrinolysis agents.

Before the study, we performed transradial CAG using a 4 Fr or 6 Fr conventional sheath and decided to perform immediate TRI according to the operator’s decision in NSTEACS patients in our hospital from 2004 to 2014. If a 4.0 Fr sheath was inserted initially, it was replaced with a 6 Fr or 7 Fr sheath for immediate TRI. We included these NSTEACS patients in the conventional TRI group to compare the procedural and clinical outcomes. The anesthesia approach, UFH injection protocol, and hemostasis approach were similar to those in the current cohort study using SH-GC. 

Study endpoints and definitions. The primary endpoint was the procedural success rate of TRI, which was defined as achieving postprocedural residual stenosis of <20% and Thrombolysis in Myocardial Infarction (TIMI) grade 2 or 3 angiographic flow without access-site crossover.¹² The choice of crossover to other sheath systems or to other access sites was left to the operator’s discretion. The secondary endpoints were procedure time, onset of major adverse cardiac event (MACE), and occurrence of access-site complications. MACE included cardiac death, definite stent thrombosis, and target-lesion revascularization within 30 days after TRI. Access-site complications included RAS, RAO, pseudoaneurysm, arteriovenous fistula, and access-site hemorrhage. RAS was defined as severe pain perceived by the patient and/or procedural difficulty perceived by the operator during TRI.¹²RAS severity was classified from mild (grade 1) to very severe (grade 4) as previously described.¹² In this study, symptomatic RAS was defined as moderate to very severe (grade 2-4). RAO was defined as the absence of antegrade flow as evaluated on Doppler ultrasound 2-4 days after immediate TRI.¹³ Ultrasound was also used to evaluate pseudoaneurysms and arteriovenous fistulas. The internal lumen diameter of the radial artery was defined as the furthest distance between the two inner walls, where the radial artery was punctured.¹⁴Major access-site hemorrhage was defined as hemoglobin loss of >3.0 g/dL, blood transfusion, or vascular repair.¹⁵

Statistical analysis. This trial was powered to test the superiority of the primary outcome. We expected a success rate of 97.5% with the 1-1-1 strategy⁹ and 92.4% with the conventional TRI strategy.² A total of 327 patients per group were selected to provide >80.0% power, and a two-sided α of 5.0% was selected to detect a significant difference in the primary outcome. Categorical variables are reported as percentages, and they were compared using the chi-square or Fisher’s exact test. Continuous variables are reported as mean ± standard deviation, and they were compared using the t-test. In order to identify the independent predictors of procedural failure, all baseline values and procedural characteristics were prescreened using a univariate logistic regression analysis. Four univariate predictors were included in a multivariate logistic regression analysis with stepwise procedures where potential predictors were entered and retained in the model at P<.20. A subsequent multivariate model, including all significant variables, was established to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). A P-value <.05 was considered to indicate statistical significance. All statistical analyses were performed using JMP statistical software (version 11; SAS Institute).

Results

Patient characteristics. A total of 901 Asian patients underwent transradial diagnostic CAG using a 4.0 Fr sheath for clinically suspicious NSTEACS (Figure 2), and significant coronary lesions were ruled out in 393 patients. The diagnoses of these patients without significant coronary lesions have been summarized in Figure 3. Of 508 NSTEACS patients, 178 did not receive immediate TRI, but underwent medical treatment (n = 65), elective PCI (n = 97), or CABG (n = 16) at the discretion of the operator (Figure 2). Immediate TRI using SH-GC was conducted in 330 patients with non-ST segment elevation myocardial infarction (NSTEMI; n = 158) or unstable angina pectoris (UAP; n = 172). The conventional TRI group included 330 consecutive Asian patients (NSTEMI, 155 patients; UAP, 175 patients) who underwent immediate TRI using a standard sheath system after CAG in our hospital between May 2004 and December 2014. The comparison of baseline characteristics between the SH-GC and conventional TRI groups is shown in Table 1. The SH-GC group included patients with a higher prevalence of dyslipidemia and multivessel disease compared with the conventional TRI group. There were fewer current smokers in the SH-GC group. The baseline lesion characteristics were similar in both groups (Table 2). 

Primary and secondary outcomes. Although the clinical success rate was comparable in the SH-GC and conventional TRI groups (97.9% vs 96.4%; P=.35), the procedural success rate was significantly higher in the SH-GC group (97.6% vs 92.1%; P<.01) because insertion failure due to RAS could be prevented by using the SH-GC (0.0% vs 2.7%; P<.01) (Table 3). Moreover, two sheaths were used in only 1 patient in the SH-GC group, while the 4 Fr sheath was used at the start of CAG and was switched to a larger sheath in more than half the patients in the conventional TRI group (0.3% vs 59.7%; P<.001). Moreover, the rate of patients treated with one guiding catheter (GC) was significantly higher in the SH-GC group (91.2% vs 85.2%; P=.02). A 7 Fr compatible catheter was used in the majority of patients in the SH-GC group (88.2% vs 14.2%; P<.001). Thrombus aspiration (15.5% vs 31.8%; P<.001) and intraaortic balloon pump (IABP) (4.6% vs 10.6%; P<.01) were used less frequently in the SH-GC group. Multivariate regression analysis showed that SH-GC use was independently associated with a reduction in failed TRI (OR, 0.27; 95% CI, 0.11-0.59; P<.01) and that a heavily calcified lesion was a predictor of failed TRI (OR, 4.06; 95% CI, 1.72-9.07; P<.001) (Table 4). 

The comparison of clinical outcomes is summarized in Table 5. The incidence rate of MACE within 30 days after TRI was similar in both groups. However, the incidence rate of major access-site hemorrhage was significantly lower in the SH-GC group than in the conventional TRI group (1.0% vs 4.2%; P<.01); thus, blood transfusion for access-site complications was performed in no patients of the SH-GC group (0.0% vs 2.1%; P=.02). Postprocedural ultrasound assessment of the radial artery was performed in 312 patients from the SH-GC group (94.5%), and it detected RAO in 5 patients (1.6%) and arteriovenous fistulas in 4 patients (1.2%) (Table 6). None of the patients required surgery for arm ischemia or pseudoaneurysm enlargement after TRI using the SH-GC.

Discussion 

The present study had four main findings for this newly designed 1-1-1 strategy. First, the procedural success rate was significantly higher in NSTEACS patients treated with the SH-GC than in those treated with a conventional sheath system because of preventing insertion failure owing to RAS. Moreover, multivariate analysis demonstrated that SH-GC use was an independent predictor of successful TRI. Second, the feasibility outcomes, including MACE, were not different between both groups; however, major access-site hemorrhage and blood transfusion were less frequent in the SH-GC group. Third, access-site complications, including RAO, arteriovenous fistula, and pseudoaneurysm, occurred at a low rate after TRI using the SH-GC, as assessed on ultrasound. Fourth, the 1-1-1 strategy safely identified patients who did not require immediate PCI after CAG using a 4.0 Fr sheath system.

This study presented the newly designated method to start CAG with a 4.0 Fr sheath in all patients who were suspected of having NSTEACS and to perform immediate TRI via the same access site using the SH-GC. The advantage of this strategy is that operators can initiate CAG using a 4.0 Fr sheath and identify the patients who should not undergo immediate revascularization. In this study, we ruled out significant coronary stenosis in 393 patients. Moreover, a total of 178 patients were diagnosed with NSTEACS and were treated with medical therapy, elective PCI, or CABG and not immediate TRI. Compared to STEMI patients, the timing of revascularization is variable in NSTEACS patients;^10,11 therefore, we propose that a smaller sheath might be appropriate for diagnostic CAG in order to reduce radial complications. Thus, the use of SH-GC made it possible to initiate diagnostic CAG using a 4 Fr system. As another advantage, operators could conduct immediate TRI using SH-GC without taking care of insertion failure, RAS, and postprocedural access-site complications. In the conventional TRI group, two or more sheaths were required for CAG and immediate TRI in most of the patients, and it was of concern that symptomatic RAS occurred in 8.8% of patients and access-site crossover owing to RAS was required in 2.7%. We confirmed that TRI using the SH-GC could be safely performed in NSTEACS patients with a high procedural success rate and low incidence of vascular complications. 

Previous studies reported that the rates of TRI failure requiring access-site crossover ranged between 3.8% and 7.6% using conventional sheaths and GCs in ACS patients.^2,16,17 Our study demonstrated that the rate of access-site crossover was remarkably low at 0.3% in patients treated with TRI using the SH-GC. It should be noted that the SH-GC could resolve the inherent limitation of emergent TRI. There are several possible reasons for this low crossover rate. The SH-GC has a hydrophilic coating to minimize friction between the catheter and surrounding tissues of the radial arteries,^5-8 which could prevent RAS and facilitate smooth cannulation. Additionally, the small external diameters of 6.5 Fr (2.16 mm) and 7. Fr (2.49 mm) SH-GCs might contribute to the prevention of RAS. The mismatch between the sheath diameter and radial artery size was shown to be a strong predictor of radial complications.^5,12,13 Although previous studies have demonstrated that the mean inner diameter of adult radial arteries ranged from 2.21 to 2.60 mm as measured by ultrasound,^5,13,18 our study included Asian patients and the mean diameter of their radial arteries was small at 2.30 mm (Table 6). It is remarkable that the SH-GC could reduce the incidence of fatal access-site complications in such patients with small radial arteries. The mean sheath to radial artery (S:RA) ratio was 1.16 in our present study and we consider that this ratio might be feasible enough to prevent RAO and access-site crossover due to RAS. This interpretation is based on our previous report that TRI devices with hydrophilic coating could prevent postprocedural RAO (1.7%) and symptomatic RAS (2.3%) substantially in patients where the mean S:RA ratio was 1.17.⁵ 

Our study demonstrated the feasibility of the SH-GC for immediate TRI; however, several shortcomings of this GC have been reported.^6-11 To braid the skin and arterial wall, the SH-GC has a stiffer tip than a conventional GC, and there is the possibility of coronary ostium injury. To avoid this complication, it was ensured that the SH-GC was coaxial to the coronary artery, particularly at contrast medium injection. Another shortcoming is a possibility of limited back-up support because of the hydrophilic coating. A previous study reported that even experienced radialists had difficulty in performing TRI with a 6.5 Fr SH-GC in complex lesions, such as bifurcations, tortuous arteries, and calcified lesions.^19,20 We consider that the 7.5 Fr SH-GC provides better back-up support than the 6.5 Fr SH-GC and has sufficient intraluminal area for kissing-balloon inflation, rotational atherectomy, and a thrombectomy catheter with a large aspiration lumen. Although use of the 7.5 Fr SH-GC makes the S:RA ratio increase, this catheter has a smaller external diameter than in a 6 Fr introducer sheath (2.62 mm) and our study showed the low incidence rates of radial complications, as mentioned above. The TRI system should balance potentially improved safety with the theoretical concern of compromised performance in emergent PCI for ACS patients. Therefore, we used a 7.5 Fr SH-GC for most patients in this study.

Study limitations. The present study has several limitations. First, this study was not designed as a randomized controlled trial. Second, this was a single-center study with a small cohort, even though the sample size was adequate to compare the primary outcome of the study groups. Third, the conventional TRI group included NSTEACS patients treated during the past decade. There were differences in the procedure such as use of IABP and thrombus aspiration between the groups. Because large randomized control trials did not prove the efficacy of these devices,^21,22 operators might tend to avoid using them in the current cohort. However, we believe that it was reasonable to compare the clinical outcomes in the conventional TRI group with the 1-1-1 strategy group, as we did not change the TRI procedure between 2004 and 2014. Moreover, we attempted TRI in ACS patients since 1996 and reported the experience.⁶ Fourth, as ultrasound examinations were not conducted before this study in our hospital, the incidence rates of access-site complications could not be compared between the SH-GC and conventional TRI groups.

Conclusion

Here, the newly designed 1-1-1 strategy using a SH-GC was feasible as an initial TRA technique for NSTEACS patients undergoing immediate TRI after diagnostic CAG, with a high procedural success rate and a low incidence of radial complications. Therefore, the 1-1-1 strategy may offer better TRI treatment than the conventional approach in NSTEACS patients. 

Acknowledgments. The authors are very grateful for Manami Kumagai, Ai Saito, and Shizuka Ito for their support in data collection and analysis of catheterization findings. 

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From the ¹Department of Cardiovascular Medicine, Sendai Kousei Hospital, Sendai, Miyagi, Japan; and ²Department of Biostatics, Yokohama City University School of Medicine, Yokohama, Kanagawa, Japan.

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 January 4 2018, provisional acceptance given March 8, 2018, final version accepted June 6, 2018.

Address for correspondence: Kazunori Horie, MD, Division of Cardiovascular Medicine, Sendai Kousei Hospital, 4-15 Hirose-cho, Aoba-ku, Sendai, Miyagi 980-0873, Japan. Email: horihori1015@gmail.com