The learning curve of the distal radial access for coronary intervention

Recently, coronary angiography (CAG) and percutaneous coronary intervention (PCI) via the distal radial access (DRA), are gaining attention owing to fewer complications. Despite the advantages of the DRA, there is difficulty to initiate this new vascular approach. The data from 1000 patients who underwent CAG and PCI via the DRA by a single experienced radial operator were retrospectively analyzed. The primary outcome was the success rate of the DRA per 100 cases. Moreover, the predictors of the failed DRA were analyzed. Overall, 952 (95.2%) of the total 1,000 patients underwent a successful DRA. After experiencing 200 cases, the DRA success rate was well maintained at > 94%, and there was no difference in success rate per 100 cases (Ptrend = 0.216). The predictors of failure were female sex [odds ratio (OR) 1.84, 95% confidence interval (CI) 1.01–3.39, P = 0.049] and systolic blood pressure (SBP) of < 120 mmHg (OR 1.87, 95% CI 1.04–3.36, P = 0.036). For achieving a stable DRA with the success rate of > 94%, 200 procedures would be needed. Moreover, this new approach could fail in women and patients with low SBP. Trial registration: https://cris.nih.go.kr/cris/index/index.do (Unique identifier: KCT0005349).

www.nature.com/scientificreports/ Process of the DRA. Puncture was performed using a 20-gauge two-piece needle with the through-andthrough puncture technique or a 21-gauge open needle with the anterior wall puncture technique. After a successful puncture, a 0.025-inch straight wire or 0.018-inch hair wire was inserted, followed by the insertion of a 4-Fr to 7-Fr radial sheath (Radiofocus Introducer II; TERUMO Corporation, Tokyo, Japan or Prelude Radial; MERIT MEDICAL, UT, USA). The selection of the sheath size was made at the physician's discretion. After successful sheath cannulation, a combination of 2.5 mg of verapamil, 0.2 mg of nitroglycerine, and 3000 units of unfractionated heparin diluted in 10 mL of saline solution was administered in all patients except those planned to undergo the ergonovine provocation test. Hemostasis was achieved using compression bandage with gauze.
Study endpoints and definitions. The primary endpoint was the success rate of the DRA per 100 cases.
Furthermore, the predictors of DRA failure were analyzed. Secondary endpoints were puncture attempts and median DRA time per 100 cases. Puncture success refers to the case of blood pumping after puncture with a needle. The successful wiring with the sheath insertion after a puncture was called cannulation success and was also defined as DRA success. Puncture attempts was defined as the number of attempts to puncture with the needle at a completely different position until cannulation. DRA time was defined as the time interval between local anesthesia and complete sheath insertion. Forearm or distal radial artery occlusion was evaluated using palpation of pulse manually during hospitalization. Local numbness was also evaluated by the description of patients of a tingling sensation. Hematoma was divided to hand and forearm hematoma. Hand hematoma was classified as ≤ 5 cm diameter, 5-10 cm diameter, and > 10 cm diameter.
Statistical analyses. Continuous variables were expressed as means with standard deviations or medians with interquartile ranges and were compared using the unpaired t-test. All categorical variables were represented as numbers with percentages and were analyzed using a χ 2 test or Fisher's exact test. Trends were analyzed using the Mantel-Haenszel test. The predictors of DRA failure were analyzed using the multivariable logistic regression model using factors with a p value of < 0.1 in the univariate model. Statistical analyses were conducted using R version 3.5.0 (The R Foundation for Statistical Computing, Vienna, Austria) and SPSS 25.0 for Windows (SPSS-PC, Chicago, IL, USA).

Results
Overall, 1000 consecutive patients who underwent CAG and PCI via the DRA were analyzed in this study. The mean age was 66.3 ± 10.9 years, and 733 patients (73.3%) were men. Among 1,000 patients, 372 patients were performed PCI via the DRA and had a success rate of 98.4% (366/372). The details of PCI via the DRA were described in supplementary Table 1.
Outcomes. Overall, 952 (95.2%) of the 1,000 patients underwent a successful DRA (Table 1). Among the 48 (4.8%) patients with a failed DRA, 27 (2.7%) patients had failed wiring and cannulation, and 21 (2.1%) patients had failed puncture. Trend analysis showed that the success rate gradually increased (P trend < 0.001). After experience with 200 cases, the success rate was well maintained at > 94%, and there was no difference in the success rate per 100 cases (P trend = 0.216) (Fig. 1). All cases with the failed DRA succeeded by switching to the conventional radial approach and none of the cases were switched to the femoral approach. The average puncture attempts were 1.27 ± 0.61 for all DRA success patients ( Table 1). The puncture attempts decreased gradually from 1.52 to 1.14 (P trend < 0.001) (Fig. 2). The median DRA time was 117.5 [81.0-203.3] s. Moreover, DRA time decreased gradually when analyzing the trend per 100 cases (P trend < 0.001) (Fig. 3).

Hemostasis duration and access-site complications.
Among the DRA success group, the left DRA was 94.5% (900/952). For hemostasis duration, it was approximately 2 h (144.6 ± 91.3 min) for CAG (n = 580) and 3.5 h (217.3 ± 121.3 min) for PCI (n = 372). For access-site complications, there was no forearm and distal radial artery occlusion during hospitalization. Puncture-related local numbness was observed in two cases (0.2%), and local hematoma occurred in 29 (3.0%) cases without major bleeding complications requiring surgery or transfusion (Table 1).
Factors associated with the failed DRA. Baseline clinical characteristics of our study population were divided into two groups: the DRA success (n = 952) and the failed DRA (n = 48) groups. The failed group had less hypertension and lower proportion of men than the success group ( Table 2). The multivariable analysis revealed female sex [odds ratio (OR) 1.84, 95% confidential interval (CI) 1.01-3.39, P = 0.049] and systolic blood pressure (SBP) < 120 mmHg (OR 1.87, 95% CI 1.04-3.36, P = 0.036) as independent predictors of the failed DRA (Table 3).

Discussion
In our learning curve study of the DRA, we found that 200 cases of the DRA were required to maintain a consistently high success rate of > 94.0%. Moreover, puncture attempts and DRA time decreased gradually as the operator's experience with the new vascular approach increased. Female sex and SBP < 120 mmHg were significant and independent predictors of the failed DRA (Fig. 4). To our knowledge, this is the first study to report the learning curve of the DRA for coronary intervention.
The concept of a learning curve for vascular intervention has been observed for many procedures, including the trans-radial intervention, although no studies have attempted to quantify this relationship for the DRA 7-9 .  6 . There was no random study conducted for investigating the success rates between distal www.nature.com/scientificreports/ and conventional radial approaches, but the smaller diameter of the distal radial artery, when compared to the conventional radial artery, suggested that it takes more time to overcome the learning curve of the DRA 14 .
Additionally, there are no reports of failure factors of the DRA despite the importance of choosing appropriate patients to shorten the learning curve. Our study showed that female sex and SBP < 120 mmHg were significant factors associated with the failed DRA. This could be because women have a smaller distal radial artery diameter than men: 2.40 ± 0.53 mm versus 2.65 ± 0.46 mm (P < 0.016) on angiography, and 2.5 ± 0.5 mm versus 2.6 ± 0.5 mm on ultrasonography (P < 0.08), respectively 13,14 . For SBP < 120 mmHg, there is no related study, but it can be assumed that there would be difficulties to perform puncture if the pulse was weakly palpable owing to low blood pressure at the point of the distal radial artery. It is expected that it could be easier to overcome the learning curve if operators who want to perform DRA for the first time select a male patient with a high SBP. There are several interesting results in our study. Firstly, in all patients in whom the DRA failed, the procedure was converted to the conventional radial approach: 83.3% in the ipsilateral and 16.7% in the contralateral access-site. It is possible to change quickly and easily to the ipsilateral radial, even if the operator fails the DRA. Secondly, access-site complications, including local numbness and major hematoma, were rare, and there was no forearm and distal radial artery occlusion. In a systemic review and meta-analysis for the DRA, the overall rate of complications was 2.4% in a total of 4,209 cases, and the radial artery occlusion was only 1.7% among the 2,003 cases of the DRA 15 . Therefore, this study observed the potential benefits of the DRA with less access-site complications, including forearm and distal radial artery occlusions as described in previous study.
The limitations of this study are as follows. First, this study has the inherent limitation owing to its retrospective nature. Second, since it involves data from a single operator, it is difficult to generalize our findings for all operators performing CAG and PCI. In contrast, our study can confirm the consistent improving trend of the DRA success rate, puncture attempts, and time in a large sample of 1,000 patients because it was performed by a single operator. Third, the occurrence of both forearm and distal radial artery occlusion was investigated during only hospitalization and was not evaluated using ultrasonography, although a reduction in the risk of radial artery occlusion is a potential benefit of the DRA.  www.nature.com/scientificreports/

Conclusions
Two hundred cases of DRA for CAG and PCI were required to be performed to overcome the learning curve with consistently high success rates, and the puncture attempts and DRA time also gradually improved as the number of cases increased. Moreover, female sex and SBP < 120 mmHg were factors associated with the failed DRA. Regarding access-site complications, low incidence of minor hematoma was observed without forearm and distal radial artery occlusion. Prospective studies are needed to further confirm the learning curve period and predictors of the failed DRA.