**4. Specific complications of transradial approach**

Despite a proven safety profile leading to a drastic reduction of vascular access site bleeding, the transradial approach is not totally free of complications. Catheterizers must be aware of some rare complications, which are often minor and localized if recognized without any delay.

#### **4.1 Post procedural radial artery thrombosis: The main pitfall of transradial approach?**

Although radial artery thrombosis is still a matter of concern after a transradial approach, this complication is usually benign because of the double blood supply to the hand insured by the two forearm arteries inter-connected at the level of the palmar arch. Moreover, handthreatening ischemia, with necrosis or clinical sequelae, has not been reported after a transradial procedure to this day.

As shown by studies that have planned post catheterization Doppler ultrasound examinations, the incidence of radial artery thrombosis ranges, in general, from 3% to 6% but one study reports a rate of 9.5% (34,56,68-71). A loss of radial pulse is reported in up to 9% of patients in other studies.

The occlusion rate increases with the size of catheters used for the procedure (54,72) and is more precisely related to the ratio between the inner radial artery diameter and the sheath outer diameter (73) . The incidence of occlusion is 4% if the ratio is higher than 1 and rises dramatically to 13% in patients with a ratio of less than 1.

Transradial Approach

**4.3 Forearm hematoma** 

same initial access.

training.

antiplatelet therapies (85).

**4.4 Miscellaneous complications** 

and with gentle manipulations.

for Coronary Interventions: The New Gold Standard for Vascular Access? 13

impaired, but generally recovers as early as 1 month after the procedure (82). Edmunson et al. have also demonstrated that the vessel vasoreactivity was maintained despite the fact that post procedural non occlusive radial artery injury was a quiet common observation after transradial interventions (80). Therefore, the main underlying process of this

Radial artery perforation, if not early recognized and managed, can lead to severe forearm hematoma and compartment syndrome. Prompt detection of the complication and precise localization of the bleeding source are of prime importance to adequately manage the problem with a pressure bandage dressing or a blood pressure sphygmomanometer inflated just over systolic pressure and placed over the bleeding area (83,84). In the great majority of cases this maneuver permits an easy, rapid and effective hemostasis. Afterwards, a careful observation of the forearm is required especially if the procedure is completed with the

The most common etiology of hematoma is radial or small side branch perforation by the guidewire during sheath insertion or loops crossing especially in patients receiving multiple

Inadequate catheter manipulations or forceful maneuvers during guidewire or catheter advancement can also cause small radial side branch avulsions or dissections leading to hematomas. Hydrophilic guidewires easily entering these small arteries should always be

Delayed recognition of a quiet but prolonged bleeding may lead to a large hematoma formation and sometimes to a compartment syndrome by pressure induced occlusion of the two major forearm arteries (ulnar and radial) (83,86).This severe complication must be treated by urgent fasciotomy and hematoma drainage to prevent ischemic injuries (Fig. 4). Fortunately, this very infrequent complication more often occurs during the learning curve of the technique and can be partially avoided by adequate nursing staff education and

Radial artery eversion or rupture during sheath removal or when catheters are drawing back, are due to a severe and refractory spasm of the radial artery blocking material retrieval (87). This complication should never occur by using hydrophilic-coated sheaths/catheters

Extremely rare cases of axillary, infraclavicular or even mediastinal hematomas due to perforation of a small arterial branch have also been reported (88).Late rebleeding occurring several hours or days after the procedure, as well as pseudo-aneurysms and arterio-venous

Causalgia (uncommon) is secondary to nerve injury during arterial puncture or sometimes secondary to aggressive haemostatic compression (50). Residual pain is often transient but may be permanent. Similarly, but with a more severe clinical pattern, instances of chronic

fistula are quiet rare after transradial approach (see below paragraph 2.2).

regional pain syndrome are described at the whole arm level (89).

permanent arterial wall injury is certainly catheter-based.

advanced carefully because of their high perforation risk profiles.

Other factors have been found to affect occlusion rate. Repeat cannulation (74) and older age are known to be predisposing factors but heparinization is effective in reducing its occurrence as well as the use of hydrophilic materials. For transradial procedure, adequate anticoagulation is extremely important and should be immediately started in all patients after sheath insertion; at least 5000 units of intra-arterial heparin are recommended. In patients receiving only 1000 units for a diagnostic coronary angiography, the incidence of radial occlusion climbs up to 30% (34). Intra-arterial or intravenous heparin administration provide comparable efficacy in preventing radial artery occlusion (75).

Nearly 50% of the patients in whom the radial artery is shown occluded at hospital discharge may expect a spontaneous recanalization of the vessel in the first month after procedure. Therefore, the true definitive incidence of radial artery thrombosis is probably between 2 and 3% (34).

Short procedure duration and immediate sheath removal at the end of the procedure, whatever the dose of heparin or the use of GP IIbIIa inhibitors, also contribute in maintaining radial permeability. In the same way, it seems to be relevant to avoid prolonged post-procedure compression times, especially if a mechanical device applying high pressures is used. Moreover, with some of these compression devices, a fine pressure adjustment, in order to always maintain blood flow in the radial artery during the compression, is feasible and may contribute to radial artery protection (76). In the PROPHET trial, guided compression that allowed antegrade flow, using the Barbeau's test to document radial artery patency at time of hemostasis, was shown to be highly effective in preventing radial artery occlusion (incidence decreased by 75% at 30 days after radial access) when compared to usual care (1.8% versus 7%, p<0.05) (77).

Nevertheless, even if radial occlusion is a fairly infrequent outcome of transradial approach, the radial artery patency should be checked in all patients after the procedure. Bernat et al. have shown recently that an early and short (1-hour) ipsilateral ulnar artery compression using TR band™ (Terumo corp.) could be an effective and safe non-pharmacologic method for the treatment of acute radial artery occlusion (78).

#### **4.2 Post-procedural non-occlusive radial artery injury**

As demonstrated by several studies, permanent radial artery damage without occlusion may sometimes follow transradial procedure.

In a first study, ultrasound examinations of the radial artery showed no significant difference in the mean radial artery internal diameter between pre and early post-procedure measurements (at 1 day). Conversely, after a mean follow up of 4.5 months, internal diameter significantly decreased from 2.63 ± 0.35 to 2.51 ± 0.29 mm (p = 0.01). Moreover the mean radial artery diameter was smaller and the radial occlusion rate higher (2.6% versus 0%; p = 0.01) in patients undergoing repeat transradial approach as compared to a first-time procedure (79).

Further intravascular ultrasound (IVUS) studies have explained that this progressive narrowing is secondary to an intima-media thickening (hyperplasia), especially in the distal radial artery, presumably induced by trauma from sheath or catheter insertion (80,81). Sanmartin et al. reported that soon after a transradial catheterization the vasoreactivity is impaired, but generally recovers as early as 1 month after the procedure (82). Edmunson et al. have also demonstrated that the vessel vasoreactivity was maintained despite the fact that post procedural non occlusive radial artery injury was a quiet common observation after transradial interventions (80). Therefore, the main underlying process of this permanent arterial wall injury is certainly catheter-based.

#### **4.3 Forearm hematoma**

12 Coronary Interventions

Other factors have been found to affect occlusion rate. Repeat cannulation (74) and older age are known to be predisposing factors but heparinization is effective in reducing its occurrence as well as the use of hydrophilic materials. For transradial procedure, adequate anticoagulation is extremely important and should be immediately started in all patients after sheath insertion; at least 5000 units of intra-arterial heparin are recommended. In patients receiving only 1000 units for a diagnostic coronary angiography, the incidence of radial occlusion climbs up to 30% (34). Intra-arterial or intravenous heparin administration

Nearly 50% of the patients in whom the radial artery is shown occluded at hospital discharge may expect a spontaneous recanalization of the vessel in the first month after procedure. Therefore, the true definitive incidence of radial artery thrombosis is probably

Short procedure duration and immediate sheath removal at the end of the procedure, whatever the dose of heparin or the use of GP IIbIIa inhibitors, also contribute in maintaining radial permeability. In the same way, it seems to be relevant to avoid prolonged post-procedure compression times, especially if a mechanical device applying high pressures is used. Moreover, with some of these compression devices, a fine pressure adjustment, in order to always maintain blood flow in the radial artery during the compression, is feasible and may contribute to radial artery protection (76). In the PROPHET trial, guided compression that allowed antegrade flow, using the Barbeau's test to document radial artery patency at time of hemostasis, was shown to be highly effective in preventing radial artery occlusion (incidence decreased by 75% at 30 days after radial access) when

Nevertheless, even if radial occlusion is a fairly infrequent outcome of transradial approach, the radial artery patency should be checked in all patients after the procedure. Bernat et al. have shown recently that an early and short (1-hour) ipsilateral ulnar artery compression using TR band™ (Terumo corp.) could be an effective and safe non-pharmacologic method

As demonstrated by several studies, permanent radial artery damage without occlusion

In a first study, ultrasound examinations of the radial artery showed no significant difference in the mean radial artery internal diameter between pre and early post-procedure measurements (at 1 day). Conversely, after a mean follow up of 4.5 months, internal diameter significantly decreased from 2.63 ± 0.35 to 2.51 ± 0.29 mm (p = 0.01). Moreover the mean radial artery diameter was smaller and the radial occlusion rate higher (2.6% versus 0%; p = 0.01) in patients undergoing repeat transradial approach as compared to a first-time

Further intravascular ultrasound (IVUS) studies have explained that this progressive narrowing is secondary to an intima-media thickening (hyperplasia), especially in the distal radial artery, presumably induced by trauma from sheath or catheter insertion (80,81). Sanmartin et al. reported that soon after a transradial catheterization the vasoreactivity is

provide comparable efficacy in preventing radial artery occlusion (75).

compared to usual care (1.8% versus 7%, p<0.05) (77).

for the treatment of acute radial artery occlusion (78).

may sometimes follow transradial procedure.

procedure (79).

**4.2 Post-procedural non-occlusive radial artery injury** 

between 2 and 3% (34).

Radial artery perforation, if not early recognized and managed, can lead to severe forearm hematoma and compartment syndrome. Prompt detection of the complication and precise localization of the bleeding source are of prime importance to adequately manage the problem with a pressure bandage dressing or a blood pressure sphygmomanometer inflated just over systolic pressure and placed over the bleeding area (83,84). In the great majority of cases this maneuver permits an easy, rapid and effective hemostasis. Afterwards, a careful observation of the forearm is required especially if the procedure is completed with the same initial access.

The most common etiology of hematoma is radial or small side branch perforation by the guidewire during sheath insertion or loops crossing especially in patients receiving multiple antiplatelet therapies (85).

Inadequate catheter manipulations or forceful maneuvers during guidewire or catheter advancement can also cause small radial side branch avulsions or dissections leading to hematomas. Hydrophilic guidewires easily entering these small arteries should always be advanced carefully because of their high perforation risk profiles.

Delayed recognition of a quiet but prolonged bleeding may lead to a large hematoma formation and sometimes to a compartment syndrome by pressure induced occlusion of the two major forearm arteries (ulnar and radial) (83,86).This severe complication must be treated by urgent fasciotomy and hematoma drainage to prevent ischemic injuries (Fig. 4). Fortunately, this very infrequent complication more often occurs during the learning curve of the technique and can be partially avoided by adequate nursing staff education and training.

#### **4.4 Miscellaneous complications**

Radial artery eversion or rupture during sheath removal or when catheters are drawing back, are due to a severe and refractory spasm of the radial artery blocking material retrieval (87). This complication should never occur by using hydrophilic-coated sheaths/catheters and with gentle manipulations.

Extremely rare cases of axillary, infraclavicular or even mediastinal hematomas due to perforation of a small arterial branch have also been reported (88).Late rebleeding occurring several hours or days after the procedure, as well as pseudo-aneurysms and arterio-venous fistula are quiet rare after transradial approach (see below paragraph 2.2).

Causalgia (uncommon) is secondary to nerve injury during arterial puncture or sometimes secondary to aggressive haemostatic compression (50). Residual pain is often transient but may be permanent. Similarly, but with a more severe clinical pattern, instances of chronic regional pain syndrome are described at the whole arm level (89).

Transradial Approach

anticoagulant strategy (92).

PCI.

for Coronary Interventions: The New Gold Standard for Vascular Access? 15

lack of severe access site bleeding when compared to transfemoral approach are now supported by large registries (22), several meta-analyses (11,24) and more recently by a large, randomized and multicenter trial (2). According to these data, when compared with the transfemoral approach, a 27% (2) to 80% (11) reduction of entry-site bleeding

As a result of these observations and of the progressive widespread endorsement of guidelines related to antithrombotic therapies for coronary procedures, attention has progressively turned to periprocedural bleeding complications and how to reduce the risk. If post-PCI bleeding events not related to the arterial access site are more difficult to anticipate, current literature, as Rao et al. have written, provides more and more data suggesting that the choice of the radial rather than the femoral access is associated with comparatively larger reductions in bleeding risk than those ever achieved with any

In parallel, according to several important studies, major bleeding events occurring after percutaneous coronary interventions have been shown to be independently associated with a marked increased risk of death and recurrent ischemic events in patients with an acute coronary syndrome or undergoing an elective revascularization (13,15,17,21,24,93). More precisely, bleeding in the 30 days after a percutaneous coronary intervention is strongly associated with mortality as late as 1 year after the procedure. This bleeding in the first 30 days after the procedure is comparatively as strong as the 30-day occurrence of other events such as post-procedural myocardial infarction and the need for an urgent revascularization. Not only major but also minor bleedings have been shown to be associated with late mortality (15). Before these observations, the composite endpoint of efficacy and safety used to assess PCI procedures was, traditionally, the combined incidence of death, myocardial infarction and urgent repeat revascularization of the target vessel at 30-days. To take into account post PCI bleeding impact on mortality, the "quadruple endpoint" that includes 30 days incidence of death, myocardial infarction, urgent revascularization and major bleeding has been recently introduced and should be promoted for the assessment of outcome after

Finally, as expected, a link between the reduction of bleeding complications with transradial interventions and a potential mortality reduction had recently emerged from data analysis. In the MORTAL study, Chase et al. found, by data linkage of three databases collecting clinical and procedural outcomes of 38,872 PCI patients of the British Columbia Cardiac Registry, that patients treated by transradial approach had a significantly lower rate of postprocedural blood transfusions (1.4% versus 2.8% for femoral, p<0.01) and a significant reduction in 30-day and 1-year mortality, odds ratio = 0.71 [95% CI 0.61 to 0.82] and 0.83 [95% CI 0.71 to 0.98], respectively (all p<0.001). In this study, the absolute increase in risk of death at 1 year associated with receiving a transfusion was 6.78% and the number needed to treat was 14.74 (prevention of 15 transfusions required to "avoid" one death). Therefore, transradial approach could potentially save one life for one thousand percutaneous coronary interventions performed by this way rather than by transfemoral approach (22). A large international registry provided similar results and demonstrated that transradial approach was independently associated with a lower risk of death or myocardial infarction

complications may be expected with transradial approach.

Fig. 4. Rare case of compartment syndrome (The same patient before and after urgent fasciotomy)

#### **4.5 Conclusions**

Long term consequences of radial artery occlusion or injury have to be further investigated, not only in patients requiring repeated percutaneous coronary interventions but also for patients in whom a radial conduit may be used for a surgical myocardial revascularization or the creation of an arterio-venous fistula.

To defend the use of radial access for coronary interventions, the conclusions of some recent major trials do not advocate the superiority of the radial artery over venous conduits for CABG surgery in terms of usefulness as well as for short or long-term patency (90). Nevertheless a retrospective study has shown a reduced early graft patency (77% versus 98%, p=0.017) in patients who had experienced a previous radial procedure before radial artery harvesting but without early clinical impact (91).

#### **5. Clinical results and outcomes with transradial approach**

#### **5.1 Drastic reduction of periprocedural bleeding complications with transradial approach potentially drives reduction in mortality**

Initially based on limited observational studies, followed by small single center or limited multicenter randomized studies, data concerning the safety of transradial approach and the

Fig. 4. Rare case of compartment syndrome (The same patient before and after urgent

Long term consequences of radial artery occlusion or injury have to be further investigated, not only in patients requiring repeated percutaneous coronary interventions but also for patients in whom a radial conduit may be used for a surgical myocardial revascularization

To defend the use of radial access for coronary interventions, the conclusions of some recent major trials do not advocate the superiority of the radial artery over venous conduits for CABG surgery in terms of usefulness as well as for short or long-term patency (90). Nevertheless a retrospective study has shown a reduced early graft patency (77% versus 98%, p=0.017) in patients who had experienced a previous radial procedure before radial

fasciotomy)

**4.5 Conclusions** 

or the creation of an arterio-venous fistula.

artery harvesting but without early clinical impact (91).

**approach potentially drives reduction in mortality** 

**5. Clinical results and outcomes with transradial approach** 

**5.1 Drastic reduction of periprocedural bleeding complications with transradial** 

Initially based on limited observational studies, followed by small single center or limited multicenter randomized studies, data concerning the safety of transradial approach and the lack of severe access site bleeding when compared to transfemoral approach are now supported by large registries (22), several meta-analyses (11,24) and more recently by a large, randomized and multicenter trial (2). According to these data, when compared with the transfemoral approach, a 27% (2) to 80% (11) reduction of entry-site bleeding complications may be expected with transradial approach.

As a result of these observations and of the progressive widespread endorsement of guidelines related to antithrombotic therapies for coronary procedures, attention has progressively turned to periprocedural bleeding complications and how to reduce the risk. If post-PCI bleeding events not related to the arterial access site are more difficult to anticipate, current literature, as Rao et al. have written, provides more and more data suggesting that the choice of the radial rather than the femoral access is associated with comparatively larger reductions in bleeding risk than those ever achieved with any anticoagulant strategy (92).

In parallel, according to several important studies, major bleeding events occurring after percutaneous coronary interventions have been shown to be independently associated with a marked increased risk of death and recurrent ischemic events in patients with an acute coronary syndrome or undergoing an elective revascularization (13,15,17,21,24,93). More precisely, bleeding in the 30 days after a percutaneous coronary intervention is strongly associated with mortality as late as 1 year after the procedure. This bleeding in the first 30 days after the procedure is comparatively as strong as the 30-day occurrence of other events such as post-procedural myocardial infarction and the need for an urgent revascularization. Not only major but also minor bleedings have been shown to be associated with late mortality (15). Before these observations, the composite endpoint of efficacy and safety used to assess PCI procedures was, traditionally, the combined incidence of death, myocardial infarction and urgent repeat revascularization of the target vessel at 30-days. To take into account post PCI bleeding impact on mortality, the "quadruple endpoint" that includes 30 days incidence of death, myocardial infarction, urgent revascularization and major bleeding has been recently introduced and should be promoted for the assessment of outcome after PCI.

Finally, as expected, a link between the reduction of bleeding complications with transradial interventions and a potential mortality reduction had recently emerged from data analysis. In the MORTAL study, Chase et al. found, by data linkage of three databases collecting clinical and procedural outcomes of 38,872 PCI patients of the British Columbia Cardiac Registry, that patients treated by transradial approach had a significantly lower rate of postprocedural blood transfusions (1.4% versus 2.8% for femoral, p<0.01) and a significant reduction in 30-day and 1-year mortality, odds ratio = 0.71 [95% CI 0.61 to 0.82] and 0.83 [95% CI 0.71 to 0.98], respectively (all p<0.001). In this study, the absolute increase in risk of death at 1 year associated with receiving a transfusion was 6.78% and the number needed to treat was 14.74 (prevention of 15 transfusions required to "avoid" one death). Therefore, transradial approach could potentially save one life for one thousand percutaneous coronary interventions performed by this way rather than by transfemoral approach (22). A large international registry provided similar results and demonstrated that transradial approach was independently associated with a lower risk of death or myocardial infarction

Transradial Approach

minimize radiation exposure.

factors have to be discussed.

femoral approach in terms of radiation exposure.

**approach?** 

for Coronary Interventions: The New Gold Standard for Vascular Access? 17

Interventional cardiology is known to be one of the professions with the greatest exposure to radiation. This is currently a growing problem for the cardiologist's health. Therefore,

When interventional cardiologists, or fellows during their training, are dealing with a new technique they are often confronted with a higher level of radiation. When skills improve, catheter manipulations are more efficient and procedures are shortened which finally helps

For the transradial approach the problem is the same but, being technically more demanding, this technique is associated with a longer learning curve. However, in current literature, radial access is consistently associated, when compared to femoral, with longer procedural and fluoroscopic times which slightly but significantly increase occupational radiation exposure for operators but also irradiation for patients (1,2,11,24,99). In the RIVAL study, median fluoroscopy time was higher in the radial group than in the femoral group (9.8 min versus 8.0 min, p<0.0001) and these results were similar to those reported by Agostoni et al. (8.9 min versus 7.8 min, p< 0.001) or Rao et al. (13.5 versus 11.3 min, p<0.01).Jolly et al. have reported a mean difference of 0.4 minutes of fluoroscopy between the two techniques ([95% CI 0.3-0.5], p<0.001). The main limitation of previous observations is the significant variability among operators' performances. Some other confounding

First of all, fluoroscopy time does not always correlate well with radiation dose received by operators (100). Secondly, many centers used classic catheter curves (Judkins, Amplatz, etc) for either diagnosis or intervention but the use of a dedicated radial catheter (Optitorque TIG™ catheter, Terumo corp.) may have influenced total fluoroscopic time. Indeed, radial operators have to take advantage of the possibility to complete a full coronary and left ventricular study with only one catheter to reduce radiation exposure (which is a significant difference compared to the femoral technique). Third, the exact puncture site is not always clearly reported in these trials. As mentioned before, a recent randomized trial, designed to evaluate safety and efficacy of left radial approach compared with right radial approach for coronary diagnostic and interventional procedures, showed that the left side was associated with slight but significantly lower fluoroscopy time and radiation dose adsorbed by patients. The left radial access advantages were particularly seen in older patients and for operators in training (66). These results are encouraging and future trials may further explore the potential advantages of a systematic left radial approach with the use of dedicated radial catheters to reduce the amount of fluoroscopy and finally the gap with

In addition, impact of operator ability in catheters or X-Ray tube manipulations (beam collimation, adequate tube angulations and operator position), as well as the use of radiation protection devices (low leaded flaps, upper mobile leaded glass, lead shields, lead aprons) are not often evaluated. The procedural setting (coronary angiography versus angioplasty, ad-hoc versus staged or urgent coronary interventions) may also influence measurements. Moreover many of these studies have been performed in centers (or by operators) with

**5.3 What about operator and patient radiation exposure during a transradial** 

data regarding transradial technique are of great interest.

after PCI (odds ratio = 0.52 [95% CI 0.31 to 0.89]) (94). Subsequently, the PRESTO ACS vascular substudy, including patients with non-ST-elevation acute coronary syndromes, also showed significant reduction in bleedings with the radial approach (0.7% versus 2.4% for femoral, p=0.05) and for the combined endpoint of 1-year mortality or re-infarction (4.9% versus 8.3%, p=0.05)(95). In patients suffering ST-segment elevation myocardial infarction (STEMI), the meta-analysis conducted by Vorobcsuk demonstrated a significant mortality reduction with transradial PCI (2.04% versus 3.06% for femoral, odds ratio= 0.54 [95% CI 0.33-0.86], p=0.01) (96). In the meta-analysis conducted by Jolly et al., despite the confirmation of a dramatic reduction of major access site bleedings with the transradial approach (0.05% versus 2.3% for femoral, odds ratio= 0.27 [95% CI 0.16, 0.45], p < 0.001), no significant association between this approach and a reduced 1-year mortality was found (24). In the same way, in the RIVAL study including patients with acute coronary syndromes, radial access did not reduce the primary outcome of death, myocardial infarction, stroke or non-CABG-related major bleeding compared with femoral approach even if radial access significantly reduced vascular access complications and insured similar procedural success rates (but patients presented with cardiogenic shock, known severe peripheral vascular disease precluding a femoral approach or previous coronary bypass surgery using the two internal mammary artery were ineligible for this trial). Nevertheless when the results of the RIVAL study ,restricted to centers with the highest radial tertile in this study, are included in an updated meta-analysis of all randomized trials conducted by known radial experts, the composite of death, myocardial infarction, or stroke was lower in the radial group than in the femoral group (2.3% versus 3.5%, p=0.005) (2). These observations suggest that the effectiveness of radial access might be linked to operator's or center's expertise in transradial PCI.

#### **5.2 Does transradial approach influence the occurrence of silent cerebral injuries or post-procedural strokes?**

Stroke is also a subject that people are worried about with the radial approach but previous studies have never demonstrated higher rates of TIAs or strokes with this technique even if used in higher risk subgroups of patients, such as the octogenarians (2,24,27).

Lund et al. and more recently Jurga et al. raised concern about the possibility that transradial access may induce subclinical solid cerebral microemboli at a higher extent than the transfemoral approach (97,98). As assessed by magnetic resonance imaging, 15% of patients suffered embolization toward the brain when the catheter passed from the right arm to the aorta in those examined with transradial access compared with none in the transfemoral group (p=0.567)(98). Transcranial Doppler showed that significantly more microemboli passed the right middle cerebral artery with right radial access than with the femoral (for radial median number of microemboli was 10 (1-120) and 6 (1-19) for femoral) (97).

Nevertheless, these two small studies have to be interpreted with caution for many reasons. The limited number of patients, the not so well reported operators experience for transradial approach but also the restricted use of the right radial artery may have negatively influenced the results. The clinical implications of these observations and the risk of cognitive impairment have not been explored further.

after PCI (odds ratio = 0.52 [95% CI 0.31 to 0.89]) (94). Subsequently, the PRESTO ACS vascular substudy, including patients with non-ST-elevation acute coronary syndromes, also showed significant reduction in bleedings with the radial approach (0.7% versus 2.4% for femoral, p=0.05) and for the combined endpoint of 1-year mortality or re-infarction (4.9% versus 8.3%, p=0.05)(95). In patients suffering ST-segment elevation myocardial infarction (STEMI), the meta-analysis conducted by Vorobcsuk demonstrated a significant mortality reduction with transradial PCI (2.04% versus 3.06% for femoral, odds ratio= 0.54 [95% CI 0.33-0.86], p=0.01) (96). In the meta-analysis conducted by Jolly et al., despite the confirmation of a dramatic reduction of major access site bleedings with the transradial approach (0.05% versus 2.3% for femoral, odds ratio= 0.27 [95% CI 0.16, 0.45], p < 0.001), no significant association between this approach and a reduced 1-year mortality was found (24). In the same way, in the RIVAL study including patients with acute coronary syndromes, radial access did not reduce the primary outcome of death, myocardial infarction, stroke or non-CABG-related major bleeding compared with femoral approach even if radial access significantly reduced vascular access complications and insured similar procedural success rates (but patients presented with cardiogenic shock, known severe peripheral vascular disease precluding a femoral approach or previous coronary bypass surgery using the two internal mammary artery were ineligible for this trial). Nevertheless when the results of the RIVAL study ,restricted to centers with the highest radial tertile in this study, are included in an updated meta-analysis of all randomized trials conducted by known radial experts, the composite of death, myocardial infarction, or stroke was lower in the radial group than in the femoral group (2.3% versus 3.5%, p=0.005) (2). These observations suggest that the effectiveness of radial access might be linked to operator's or

**5.2 Does transradial approach influence the occurrence of silent cerebral injuries or** 

Stroke is also a subject that people are worried about with the radial approach but previous studies have never demonstrated higher rates of TIAs or strokes with this technique even if

Lund et al. and more recently Jurga et al. raised concern about the possibility that transradial access may induce subclinical solid cerebral microemboli at a higher extent than the transfemoral approach (97,98). As assessed by magnetic resonance imaging, 15% of patients suffered embolization toward the brain when the catheter passed from the right arm to the aorta in those examined with transradial access compared with none in the transfemoral group (p=0.567)(98). Transcranial Doppler showed that significantly more microemboli passed the right middle cerebral artery with right radial access than with the femoral (for

Nevertheless, these two small studies have to be interpreted with caution for many reasons. The limited number of patients, the not so well reported operators experience for transradial approach but also the restricted use of the right radial artery may have negatively influenced the results. The clinical implications of these observations and the risk of

used in higher risk subgroups of patients, such as the octogenarians (2,24,27).

radial median number of microemboli was 10 (1-120) and 6 (1-19) for femoral) (97).

cognitive impairment have not been explored further.

center's expertise in transradial PCI.

**post-procedural strokes?** 

#### **5.3 What about operator and patient radiation exposure during a transradial approach?**

Interventional cardiology is known to be one of the professions with the greatest exposure to radiation. This is currently a growing problem for the cardiologist's health. Therefore, data regarding transradial technique are of great interest.

When interventional cardiologists, or fellows during their training, are dealing with a new technique they are often confronted with a higher level of radiation. When skills improve, catheter manipulations are more efficient and procedures are shortened which finally helps minimize radiation exposure.

For the transradial approach the problem is the same but, being technically more demanding, this technique is associated with a longer learning curve. However, in current literature, radial access is consistently associated, when compared to femoral, with longer procedural and fluoroscopic times which slightly but significantly increase occupational radiation exposure for operators but also irradiation for patients (1,2,11,24,99). In the RIVAL study, median fluoroscopy time was higher in the radial group than in the femoral group (9.8 min versus 8.0 min, p<0.0001) and these results were similar to those reported by Agostoni et al. (8.9 min versus 7.8 min, p< 0.001) or Rao et al. (13.5 versus 11.3 min, p<0.01).Jolly et al. have reported a mean difference of 0.4 minutes of fluoroscopy between the two techniques ([95% CI 0.3-0.5], p<0.001). The main limitation of previous observations is the significant variability among operators' performances. Some other confounding factors have to be discussed.

First of all, fluoroscopy time does not always correlate well with radiation dose received by operators (100). Secondly, many centers used classic catheter curves (Judkins, Amplatz, etc) for either diagnosis or intervention but the use of a dedicated radial catheter (Optitorque TIG™ catheter, Terumo corp.) may have influenced total fluoroscopic time. Indeed, radial operators have to take advantage of the possibility to complete a full coronary and left ventricular study with only one catheter to reduce radiation exposure (which is a significant difference compared to the femoral technique). Third, the exact puncture site is not always clearly reported in these trials. As mentioned before, a recent randomized trial, designed to evaluate safety and efficacy of left radial approach compared with right radial approach for coronary diagnostic and interventional procedures, showed that the left side was associated with slight but significantly lower fluoroscopy time and radiation dose adsorbed by patients. The left radial access advantages were particularly seen in older patients and for operators in training (66). These results are encouraging and future trials may further explore the potential advantages of a systematic left radial approach with the use of dedicated radial catheters to reduce the amount of fluoroscopy and finally the gap with femoral approach in terms of radiation exposure.

In addition, impact of operator ability in catheters or X-Ray tube manipulations (beam collimation, adequate tube angulations and operator position), as well as the use of radiation protection devices (low leaded flaps, upper mobile leaded glass, lead shields, lead aprons) are not often evaluated. The procedural setting (coronary angiography versus angioplasty, ad-hoc versus staged or urgent coronary interventions) may also influence measurements. Moreover many of these studies have been performed in centers (or by operators) with

Transradial Approach

an unrestricted post-catheterization ambulation (109).

**6.2 Reductions of hospitalizations stays and costs** 

60.2 and femoral with closure device 553.4 \$ ± 81.0; p < 0.001) (118).

for Coronary Interventions: The New Gold Standard for Vascular Access? 19

have demonstrated a higher incidence of local vascular complications either with or without the use of a vascular closure device and despite an optimal post-PCI recumbency depending on the vascular access management strategy chosen by the operator. Moreover, patients undergoing a transfemoral access, even if receiving closure devices, more frequently need to be reassured regarding early ambulation compared to those with a transradial approach and

Several dedicated costs analyses have shown a significant reduction in hospital costs with transradial access compared to other arterial access sites .The economic benefits of the transradial approach are mainly derived from its known advantages: a reduced incidence of vascular access site complications and immediate ambulation after the procedure (45).

A lower rate of access site complications also means decreased length of stay and costs compared with those observed in case of an adverse event (1,113,114). A vascular complication inevitably drives additional charges related to its careful medical evaluation using different diagnostic vascular imaging techniques and because of treatments required. Red blood cell or platelet transfusions (preceded by numerous laboratory tests), thrombin injections or operating room charges for surgical repair rapidly increase hospitalization costs. These adverse outcomes inevitably prolong hospitalization but indirect costs linked with an increased nursing and staff workload must also be considered even if they are more difficult to appreciate. Several authors have evaluated the negative economic impact of vascular access complications and the incremental costs ranged from \$ 4000 for minor complications up to \$ 14 000 for major events (114-116). Cooper et al. have showed, in a single center randomized study, that transradial access for diagnostic cardiac catheterization led to significant reductions in hospital costs when compared to femoral access (\$ 2010 versus \$2299 respectively, p< 0.001). Lower bed costs, mainly, taking into account nursing workload, but also pharmacy explain the median cost reduction of 289 \$ per procedure (117). In the same way, Roussanov et al. have shown that a femoral access with or without the use of a closure device also failed to reduce total hospitalization costs as compare to radial access even in case of similar recovery times (radial =369.5 \$ ± 74.6, femoral= 446.9 \$ ±

Immediate ambulation, in addition to showing radial approach safety, provides additional cost reductions through different mechanisms. First, transradial approach provides shorter length of stay .A systematic review and meta-analysis of randomized trials showed that radial access reduced hospital stay by a mean of 0.4 days [95% CI 0.2-0.5], p=0.0001) which also means an expedited room turn-over (24).Secondly, as reported by Amoroso et al, nursing workload can be significantly reduced inside (86 min versus 174 min for femoral access) as well as outside the catheterization laboratory (386 min versus 720 min for femoral access) when the radial way is systematically used for a catheterization procedure (119).An increased catheterization laboratory throughput can also be expected with radial access because less time is spent for sheath removal. Third, it has been shown that same day home discharge after an uncomplicated transradial percutaneous intervention results in a 50% relative reduction in post-PCI medical costs. In the EASY trial, at 30-day follow-up, the mean cumulative medical cost per outpatient was \$1,117 ± \$1,554 versus \$2,258 ± \$1,328 for overnight-stay patients (Canadian dollars). The mean difference of \$1,141[95% CI: \$962 to \$1,320] was mainly due to the extra night for overnight hospital stay (120). Finally, with

limited experience in transradial approach and results have not been corrected for probable improvements with greater expertise.

Finally, even if differences in terms of radiation dose beneath the lead apron are minimal between these approaches, their clinical impact in the long term is not known and operators should always apply all efforts to reduce the radiation dose in their daily practice.

#### **5.4 Conclusions**

Concerning many points, the debate is not closed and future randomized trials, if correctly powered to demonstrated differences in primary outcomes between the two vascular approaches and designed to avoid confounding factors, will be useful to confirm these findings. However, all the previous authors agree with the fact that clinicians may choose radial access for percutaneous coronary interventions because of its similar performances and above all, its reduced vascular complications.
