Author + information
- Received June 21, 2016
- Revision received July 5, 2016
- Accepted July 14, 2016
- Published online October 10, 2016.
- Samir B. Pancholy, MDa,∗ (, )
- Ivo Bernat, MD, PhDb,
- Olivier F. Bertrand, MD, PhDc and
- Tejas M. Patel, MD, DMd
- aThe Wright Center for Graduate Medical Education, The Commonwealth Medical College, Scranton, Pennsylvania
- bUniversity Hospital and Faculty of Medicine Pilsen, Pilsen, Czech Republic
- cQuebec Heart and Lung Institute, Quebec City, Quebec, Canada
- dApex Heart Institute, Ahmedabad, India
- ↵∗Reprint requests and correspondence:
Dr. Samir B. Pancholy, The Wright Center for Graduate Medical Education and The Commonwealth Medical College, 401 North State Street, Clarks Summit, Pennsylvania 18411.
Objectives The study sought to evaluate whether prophylactic ipsilateral ulnar artery compression during radial artery hemostasis could reduce the risk of radial artery occlusion (RAO).
Background RAO after transradial access (TRA) is a structural complication of TRA. It limits future ipsilateral TRA and may cause transient pain. Maintaining radial artery flow during hemostasis reduces the incidence of acute RAO. Ipsilateral ulnar compression increases radial artery flow and could impact the incidence of RAO.
Methods Three thousand patients undergoing diagnostic cardiac catheterization using TRA were randomized to receive either standard patent hemostasis protocol (Group I) or prophylactic ipsilateral ulnar compression in addition to patent hemostasis (Group II). Using plethysmography, radial artery patency was evaluated at the time of removal of the compression device as well as 24 h and 30 days after the procedure. The primary study endpoint was 30-day RAO.
Results The primary endpoint, 30-day RAO, was significantly reduced in patients with patent hemostasis and prophylactic ulnar compression compared with standard patent hemostasis (0.9% vs. 3.0%; p = 0.0001). Baseline patient and procedural characteristics were similar between the 2 groups. RAO was significantly reduced by prophylactic ulnar compression at all time intervals (p < 0.0001).
Conclusions Prophylactic ipsilateral ulnar compression during radial artery hemostasis is an effective, simple, and inexpensive technique that lowers the risk of RAO after TRA.
Transradial access (TRA) has been increasingly adopted for diagnostic and interventional cardiovascular procedures (1). This is largely driven by the evidence supporting an unequivocal reduction in access site–related complications associated with TRA compared with transfemoral access (2–4), as well as reduction in cost (5) and increased patient comfort (6,7), with resultant guideline recommendation (8).
Patients undergoing percutaneous coronary procedures frequently require repeat procedures as a result of staging, restenosis, and progression of coronary artery disease. In a recent analysis of repeat TRA, each entry into the radial artery was associated with a 5% reduction in the probability of successful future ipsilateral TRA in the hands of highly experienced radial operators (9). Radial access failures were attributed to chronic radial artery occlusion (RAO) likely resulting from previous TRA. RAO is the most common structural complication of TRA (10). It is a result of acute thrombosis caused likely by intimal abrasion and vessel injury in conjunction with flow cessation (11). A sizeable fraction of these patients develop permanent obliteration of the radial artery lumen. Although clinically silent from a standpoint of resting ischemia, it leads to inability to use the ipsilateral radial artery for future TRA. Several pharmacologic and nonpharmacologic strategies including a low sheath to artery size ratio (12), use of intraprocedural heparin (13), and maintenance of radial artery patency during hemostasis after TRA (14,15) have been shown to lower the risk of RAO and have been termed best practices (16). Despite these recommendations, the contemporary “real-world” incidence of acute RAO reported from institutions with expertise in performing TRA continues to reach 10% (17). Ipsilateral ulnar artery compression has been demonstrated as an effective, safe, and inexpensive technique to facilitate radial artery recanalization in patients who developed acute RAO after TRA (18,19).
We sought to evaluate the effect of prophylactic ipsilateral ulnar artery compression on 30-day RAO in patients undergoing transradial cardiac catheterization.
The PROPHET-II (PROPhylactic Hyperperfusion Evaluation Trial) trial was performed at 2 large tertiary care centers, 1 in India and the other in the Czech Republic. Patients referred for coronary angiography using TRA were enrolled (Figure 1). Pre-procedural Barbeau test was performed as previously described (20) on all patients. Patients excluded from the trial included those: 1) undergoing ad-hoc percutaneous coronary intervention; 2) with history of previous ipsilateral TRA; 3) with scleroderma; 4) undergoing warfarin therapy; 5) with inability to tolerate heparin; and 6) with Barbeau type D response or nonpalpable ulnar pulse at distal forearm. Randomization (1:1) was performed after written informed consent using SNOSE (Sequentially Numbered Opaque Sealed Envelopes) method (21). Patients were randomized to Group I (patent hemostasis group) or Group II (ulnar compression with patent hemostasis group). A total of 5 operators performed all the procedures.
After sterile preparation and 2% preservative free lidocaine infiltration, using a Teflon-sheathed needle, the radial artery was accessed using the counterpuncture technique as described earlier (22). Eleven-centimeter-long 5-F hydrophilic introducer sheath (Terumo Interventional Systems, Tokyo, Japan) was inserted into the radial artery lumen over a 0.021-inch guidewire. All patients received 200 μg of nitroglycerin, 2.5 mg of verapamil, and 5000 international units of unfractionated heparin intra-arterially through the introducer sheath. Diagnostic coronary angiography was performed using 5-F catheters. Choice of catheter shape and number of catheters was left up to the operator’s discretion.
After completion of the diagnostic procedure, hemostasis was achieved as follows: for Group I, the standard “patent hemostasis protocol” was used as previously described (14). Briefly, an inflatable band (TR band, Terumo Interventional Systems) was applied at the arterial puncture site, the bladder was inflated, and the introducer sheath was removed from under the band. The bladder was then decompressed to lower the compression pressure until some bleeding was visible, to purge the pre-thrombotic and thrombotic material and establish radial artery flow as evidenced by mild bleeding at the site. The bladder was then reinflated with 1 to 2 ml of additional air to re-establish hemostasis. Transient manual compression of the ulnar artery was performed to evaluate the status of radial artery patency by plethysmography, and if antegrade flow in radial artery was absent (lack of signal), the process of deflation and reinflation was repeated over the next 15 min to attempt re-establishment of antegrade radial artery flow without sacrificing hemostasis. After 2 h of continuous compression at the puncture site, the band was gradually deflated and then removed, and a light dressing was applied. The patients were monitored for at least 30 min after band removal. If bleeding reoccurred, the band was reapplied and the process was repeated.
For Group II, after applying the inflatable band (TR band, Terumo Interventional Systems) at the sheath entry site, the ipsilateral ulnar artery was compressed at the Guyon’s canal by placing a cylindrical composite made by wrapping 4 inch × 4 inch gauze around a 1-inch plastic needle cap, or the barrel of a 3 ml plastic syringe, and compressing it using a circumferentially applied Hemoband (Hemoband Corporation, Portland, Oregon). After occlusive compression of ulnar artery was confirmed using plethysmography, the radial artery introducer sheath was removed and “patent hemostasis protocol” was used for radial artery hemostasis as described previously.
Evaluation of radial artery patency
Radial artery patency was evaluated using digital plethysmography using the reverse Barbeau test, where after placement of a digital sensor on the index finger or the thumb both radial and ulnar arteries are compressed transiently, with loss of plethysmographic signal, after which the radial artery was released and return of plethysmographic signal with maintenance of ulnar compression was considered evidence of radial artery patency. In those patients where compression of both radial and ulnar arteries did not result in total loss of plethysmographic signal, and in those where RAO was detected by digital plethysmography, duplex ultrasonography was performed to confirm patency status. Patency evaluation was performed at the time of removal of the radial compression band, 24 h after the procedure, and 30 days following the procedure. The primary endpoint was the 30-day rate of RAO using pulse plethysmography or oximetry.
Demographic data and procedural data were recorded. Furthermore, post-procedural ipsilateral upper extremity pain, need to remove ulnar or radial band because of any attributable symptoms or signs, and hematoma formation using EASY (Early Discharge After Transradial Stenting of Coronary Arteries Study) hematoma scale (23) were also assessed.
A total of 101 random patients from Group I (n = 50) and Group II (n = 51) underwent duplex ultrasound of both radial and ulnar arteries before TRA and 30 days after the TRA procedure. Lumen size and wall thickness of the arteries were measured in a standard fashion. Status of antegrade radial artery flow was also recorded.
All variables were analyzed to characterize the type of distribution. Analyses were performed with patients assigned to their original randomization group, on an intention-to-treat basis. Differences among normally distributed continuous variables were evaluated using Student t test, and those not normally distributed were evaluated using the Mann-Whitney U test. Differences among categorical variables were evaluated using the chi-square test or Fisher exact test. Binary logistic regression was used to perform multivariable analysis, to identify the effect of all relevant variables on the primary endpoint using forward selection. Receiver-operating characteristic (ROC) analysis–derived area under the curve was used to assess the goodness of fit of the model. A 2-tailed p value of ≤0.05 was considered statistically significant. Analyses were performed using SPSS version 20 (IBM, Armonk, New York).
The sample size calculation was performed using a superiority design with assumed incidence of primary endpoint of 30-day RAO of 2.5% in Group I (reference data derived from local registry) and 0.8% (18) in Group II. Overall, 1,452 patients per group (total = 2,904) were deemed adequate to achieve 90% power considering an alpha error of 0.05, assuming a 10% rate of crossover from Group II to Group I due to intolerance (24).
The trial protocol was approved by the local institutional review boards. The trial was registered on NCT01564888. All patients provided written informed consent prior to procedures.
From 4,238 screened patients, a total of 3,000 patients were randomized, 1,497 in Group I and 1,503 in Group II (Figure 1). Baseline and procedural characteristics of patients were similar in both groups (Table 1).
The primary endpoint, 30-day rate of RAO, was significantly lower in Group II compared with Group I (0.9% vs. 3.0%; p = 0.0001). The incidence of RAO immediately post-hemostasis (1.5% vs. 13.9%; p < 0.0001) and 24 h later (4.3% vs. 1%; p < 0.0001) were also significantly lower in Group II compared with Group I, respectively (Figure 2). Patent hemostasis was achieved at the outset in 74% of patients in Group I compared with 96% of patients in Group II (p = 0.0001). No significant difference between groups was noted in hematoma formation at access site (Table 2).
Univariate predictors of 30-day RAO are shown in Table 3, which included female patients (p < 0.0001), patients with diabetes (p < 0.0001), older patients (p < 0.0001), and patients with pain during compression (p < 0.021). By multivariable analysis, age (odds ratio [OR]: 1.1; 95% confidence interval [CI]: 1.03 to 1.09; p = 0.0001), female gender (OR: 4.0; 95% CI: 2.3 to 7.2; p = 0.0001), history of diabetes mellitus (OR: 4.1; 95% CI: 2.2 to 7.5; p = 0.0001), and prophylactic ulnar compression or randomization to Group II (OR: 0.3; 95% CI: 0.16 to 0.57; p = 0.0001) and pain during compression (OR: 3.9; 95% CI: 1.0 to 14.9; p = 0.049) were significant independent predictors of 30-day RAO. Area under the curve derived by performing a ROC analysis with predicted probabilities and the dependent variable of 30-day RAO was 0.82. In a second multivariate model, when patent hemostasis was entered as an independent variable in addition to the previously mentioned variables, age, prophylactic ulnar compression and pain during compression lost its significance, and diabetes mellitus (OR: 2.6; 95% CI: 1.3 to 4.9; p = 0.004), female gender (OR: 3; 95% CI: 1.7 to 5.7; p = 0.0001), and patent hemostasis were identified as independent predictors of 30-day RAO (OR: 0.006; 95% CI: 0.001 to 0.25; p = 0.0001). The C-index derived by the ROC analysis of this second model was 0.96, corroborating a well-fitted model.
Prior to TRA, radial artery lumen diameter (1.9 [interquartile range [IQR]: 1.7 to 2.1] mm vs. 1.9 [IQR: 1.7 to 2.0] mm; p = 0.53), baseline ipsilateral ulnar artery diameter (2.0 [IQR: 1.8 to 2.0] mm vs. 2.0 [IQR: 1.8 to 2.1] mm; p = 0.51), and baseline ipsilateral ulnar artery wall thickness (0.80 [IQR: 0.77 to 0.90] mm vs. 0.80 [IQR: 0.80 to 0.90] mm; p = 0.15) were comparable between Group I and Group II. No significant difference was found in ipsilateral ulnar artery wall thickness between Group I and Group II (0.80 [IQR: 0.80 to 0.90] mm vs. 0.80 [IQR: 0.80 to 0.90] mm; p = 0.92) at 30-day follow-up. However, radial artery wall thickness increased significantly at 30-day follow-up compared with baseline (0.8 [IQR: 0.75 to 0.9] mm vs. 1.0 [IQR: 0.9 to 1.0] mm; p = 0.005).
Our results demonstrate a statistically significant and clinically relevant reduction in the incidence of 30-day RAO using prophylactic ipsilateral ulnar artery compression while compressing the radial artery for hemostasis after TRA. In fact, using that prophylactic technique, RAO was significantly reduced at all time intervals. With a rapidly growing adoption of TRA worldwide with a large mix of operators at several stages of the learning curve and increasing patient as well as procedural complexity, RAO prevention should take center stage to preserve the safest access site in a patient with a chronic recurrent illness such as atherosclerotic vascular disease.
Presence of radial artery patency during hemostatic compression has been shown to be associated with a lower incidence of RAO (25). Patent hemostasis, defined as persistence of antegrade flow in the radial artery during hemostatic compression, has been shown to significantly lower the incidence of RAO (14). However, it is achieved in 70% to 80% of patients after TRA, exposing the remaining 20% to 30% of patients to a high risk of RAO, in a facility where careful implementation of patent hemostasis protocol is practiced. A bigger challenge has been the adoption of the practice of paying attention to radial artery patency during hemostasis. As observed by Sanmartin et al. (25), if patency is not monitored during hemostasis, hemostatic compression occludes radial flow in 80% to 90% of patients, exposing them to the risk of RAO. The patent hemostasis protocol has had limited operational adoption in catheterization laboratories around the world despite high cognitive adoption. This has largely been driven by the need for larger involvement of post-procedural care team with repeated point-of-care evaluation of radial flow, making a rather simplistic and inexpensive process of hemostatic compression significantly more complex.
Extensive microcollateralization and macrocollateralization of forearm and palmar arterial circulation creates hemodynamic interdependence between radial and ulnar arteries. Alteration of flow in 1 limb of this circuit has been shown to alter flow dynamics in the other limb (26). Increase in radial artery flow, and possibly other less recognized subsequent hydrodynamic changes caused by “radial artery hyperperfusion” induced by ipsilateral ulnar artery compression (26), may create a milieu conducive to lowering the risk of radial artery thrombosis, hence acute and chronic RAO. Administration of additional vasodilators before removal of introducer sheath has also been shown to lower the risk of RAO (27). It is plausible that an abrupt increase in radial artery flow due to ulnar flow interruption might lead to flow mediated vasodilation of the radial artery, hence nonpharmacologically ameliorating residual spasm and lowering the risk of RAO. Occlusive compression of ulnar artery allows the operator and staff to continuously monitor radial artery patency using continuous plethysmographic monitoring of the ipsilateral index finger or thumb with automated alarms, eliminating the need for routine repeated evaluation by the staff. Prompt recognition of loss of radial artery patency anytime during the process of hemostatic compression, indicated by the plethysmographic alarms, with subsequent adjustment in radial compression pressure and re-establishment of patent hemostasis, may improve the adoption of this strategy by the post-procedural staff with successful prevention of RAO.
The physiologic relationship between ulnar compression and radial flow, hence patent hemostasis, and their temporal relationship as well as the previously observed findings of the multivariable analyses suggest that patent hemostasis may be the main mediator variable responsible for the significant preventive effect of prophylactic ulnar compression on 30-day RAO.
The 2 primary concerns associated with ipsilateral ulnar artery compression, hand ischemia and ulnar artery trauma, were also alleviated to a large extent by our findings. In our cohort, none of the patients developed symptoms or clinical signs of digital ischemia. This is consistent with prior findings which demonstrated the efficacy and safety of 1-h ulnar artery compression to recanalize radial artery after post-catheterization RAO (18,19). Furthermore, the findings of the ultrasound substudy did not reveal any detectable signs of acute or delayed ulnar artery trauma as evident by a lack of significant change in ulnar artery wall thickness and absence of ulnar artery stenosis formation or occlusion at 30-day follow-up. The ulnar compression cohort had a very high likelihood of achieving patent hemostasis. Even the small minority of patients who did not achieve patent hemostasis did not report symptoms of resting digital ischemia, likely due to presence of interosseous and other forearm collateral channels providing some flow to the hand, corroborating previous reports supporting their functional role (28).
The simplicity and safety of the maneuver of ipsilateral ulnar artery compression, with lack of need for complex equipment, combined with its highly significant efficacy and safety in lowering the incidence of RAO, should encourage most radial operators and staff to embrace the technique as default protocol, in addition to the previously established best practices of intraprocedural anticoagulation and strategies to minimize radial artery trauma caused by hardware, to obtain safe hemostasis and long-term radial artery patency after TRA.
Although adequately powered, our results were derived from 2 highly experienced radial centers dedicated to meticulous radial artery patent hemostasis protocol. Hence, these results will need to be corroborated in a larger cohort of centers with a broader spread of expertise in TRA. The simplicity of the proposed technique should not represent a major burden for adoption, although in this trial a dedicated device was not used, requiring the operators to manage 2 separate compression devices, which may be perceived as increasing procedural complexity. With hopeful emergence of dedicated devices capable of dual compression, wide application will be likely achievable. Despite the lack of symptoms of resting ischemia, biochemical evaluation of digital ischemia was not performed and hence the risk of digital ischemia should be individually assessed and the technique used accordingly. We excluded patients with Barbeau type D pattern and those without palpable ulnar pulse in the distal forearm, in view of expected lack of macrocirculatory interdependence, and hence our findings cannot be extrapolated to those patients. Efficacy of ipsilateral ulnar compression for shorter durations in lowering RAO needs to be evaluated. In our trial, plethysmography was used to detect radial artery patency, with a very rigorous protocol supported by liberal use of ultrasound, hence likely mitigating any potential unknown limitations posed by plethysmography.
Prophylactic ipsilateral ulnar artery compression during radial artery hemostasis is an effective, safe, and inexpensive technique to lower the risks of RAO post-transradial catheterization.
WHAT IS KNOWN? RAO is the most frequent structural complication of radial access. The burden of occluded radial arteries is likely to increase as TRA adoption increases.
WHAT IS NEW? Maintenance of radial artery patency during hemostatic compression after radial access is a recommended best practice, although has limited adoption. Prophylactic ipsilateral ulnar artery compression during radial artery hemostatic compression may improve patent hemostasis and lower RAO.
WHAT IS NEXT? Future trials evaluating efficacy of the technique in a broader array of centers preferably using devices capable of dual compression are needed to corroborate its efficacy in general use.
Dr. Pancholy has served as a consultant for Terumo Medical Corporation; and has reported equity interest in VasoInnovations Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- confidence interval
- interquartile range
- odds ratio
- radial artery occlusion
- receiver-operating characteristic
- transradial access
- Received June 21, 2016.
- Revision received July 5, 2016.
- Accepted July 14, 2016.
- American College of Cardiology Foundation
- Feldman D.N.,
- Swaminathan R.V.,
- Kaltenbach L.A.,
- et al.
- Amin A.P.,
- House J.A.,
- Safley D.M.,
- et al.
- Hess C.N.,
- Krucoff M.W.,
- Sheng S.,
- et al.
- Roffi M.,
- Patrono C.,
- Collet J.P.,
- et al.
- Kotowycz M.A.,
- Dzavík V.
- Pancholy S.,
- Coppola J.,
- Patel T.,
- et al.
- Rao S.V.,
- Tremmel J.A.,
- Gilchrist I.C.,
- et al.
- Bertrand O.F.,
- De Larochellière R.,
- Rodés-Cabau J.,
- et al.,
- Early Discharge After Transradial Stenting of Coronary Arteries Study Investigators
- Pocock S.J.