Radiation Exposure During Distal and Traditional Radial Coronary Angiography and Percutaneous Coronary Intervention: A Meta-analysis of Randomized Controlled Trials

Objectives. Previous studies show that the distal transradial approach (dTRA) is safe and effective for coronary angiography and percutaneous coronary intervention. However, the effect of dTRA on radiation exposure in the catheterization laboratory has not been characterized. The authors analyzed the available literature to compare the radiation exposure associated with dTRA vs the traditional radial approach (TRA). Methods. A systematic review and meta-analysis of the scientific literature was conducted by using relevant terms to search the PubMed, Embase, and Cochrane Library databases from their inception until October 13, 2022, to identify randomized controlled trials (RCTs) comparing dTRA with TRA. The primary outcome was radiation exposure reported as fluoroscopy time, air kerma, or kerma-dose product. The standard mean difference (SMD) and its 95% confidence interval were used to summarize continuous variables. Random effect and meta-regression also were used for analyses. Results. Among 484 studies identified, 7 were RCTs, with a total of 3427 patients (1712 dTRA, 1715 TRA). No difference was found between dTRA and TRA in radiation exposure quantified as fluoroscopy time (SMD −0.10 [−0.36, 0.15], P=.43) or air kerma (SMD −0.31 [−0.74, 0.13], P=.17). The overall estimate favored lower kerma-area product in the TRA (SMD 0.19 [0.08, 0.30], P=.0006). Meta-regression showed no correlation between fluoroscopy time and year of publication. Conclusions. Compared with TRA, dTRA was associated with significantly greater radiation exposure per the kerma-area product during interventional cardiology procedures, with no differences in fluoroscopy time and air kerma.

The transradial approach (TRA) is the most common approach for diagnostic coronary angiography or percutaneous coronary intervention.¹ Compared with transfemoral access, TRA significantly reduces access-related bleeding,² vascular complications,³ and patient discomfort.^4,5 However, initial TRA studies showed that this technique exposes patients and healthcare workers to higher levels of ionizing radiation than the transfemoral approach. Subsequently, several trials^6-8 exploring radiation exposure and TRA linked higher radiation dose to operators’ expertise, volume of cases, and learning curve when starting a new technique.⁹

Recently, a new approach using the distal radial artery at the snuffbox level has been adopted in clinical practice during interventional procedures.^10,11 The distal transradial approach (dTRA) might be of more benefit to patients than the traditional TRA because it is associated with a lower rate of radial artery occlusion after the procedure and a shorter hemostasis time.^12-14 Similar to TRA when it was first introduced, dTRA will probably face comparable obstacles until operators overcome the learning curve and achieve proficiency. In particular, new dTRA adopters might initially be exposed to a higher radiation dose during their learning curve,^14,15 although this speculation has not been the subject of clinical research.

 Accordingly, a systematic review and meta-analysis was performed to gather data from all available randomized controlled trials (RCTs) to compare the radiation exposure associated with dTRA and traditional TRA during invasive cardiology procedures.

The systematic review and meta-analysis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement.¹⁵  Because published data were used and no human study participants or private information were accessed, the study did not require institutional review board approval.

Research question. Using the Population, Interventions, Comparison, Outcome, and Time (PICOT)¹⁶ strategy, studies were included if the following criteria were fulfilled:

1. Population: patients who underwent coronary angiography and/or percutaneous coronary intervention;

2. Intervention: distal radial approach;

3. Control: traditional radial approach;

4. Outcomes: reported radiation exposure during coronary angiography and/or percutaneous coronary intervention; and

5. Time: long-term follow-up was not required because radiation exposure was restricted to the procedure.

Search strategy. The scientific literature comparing studies of coronary angiography or percutaneous coronary intervention performed through dTRA and TRA was pooled. Radiation exposure was the primary endpoint. PubMed, Embase, and the Cochrane Library were searched systematically by using specific keywords and Boolean connectors. The search strategy used was (“coronary angiography” OR “percutaneous coronary intervention” OR “cardiac catheterization”) AND (“transradial” OR “radial”) AND (“distal radial” OR “distal transradial” OR “snuffbox” OR “snuff box”). Date restrictions were not applied, and all studies published from database inception until October 13, 2022, were collected. The systematic search included the contents of major reviews focusing on distal and transradial access for diagnostic and interventional procedures; cross-references (“snowballing”) and cited papers were checked to identify other relevant studies and reduce missed publications. This meta-analysis was registered in PROSPERO,  an international prospective register of systematic reviews (PROSPERO 2022 CRD42022379383).

Inclusion and exclusion criteria. Studies were included in the meta-analysis if they met 3 criteria: (1) randomized trials comparing distal and traditional radial approach/access, (2) published data as a full article, and (3) reported radiation exposure data. Radiation exposure reported as fluoroscopy time, air kerma, or kerma-area product was examined. Only studies written in English, Spanish, or Portuguese were included. Editorials, letters, review articles, and abstracts presented at scientific meetings were excluded.

Data extraction and quality assessment. Two investigators (CC, KL) evaluated the potentially relevant studies; those whose title and abstract suggested that the studies fit the study criteria were then judged by full-text review. The investigators collected information about the study design, sample size, procedural characteristics, access site, and radiation exposure according to the predefined outcomes and PICOT question. The information was extracted and then transferred to an Excel spreadsheet (Microsoft). All analyses were conducted using Cochrane's Review Manager, version 5.4.1. To ensure accuracy, each data transfer underwent a thorough double-check by both investigators responsible for data extraction and quality assessment.

The bias risk of the included studies was assessed with the RoB-2 tool for evaluating the risk of bias in randomized trials¹⁷ as recommended by the latest version of the Cochrane manual, version 6.3. To identify possible study biases, RoB2 uses signaling questions to assess 5 domains: randomization process (D1), deviations from intended interventions (D2), missing outcome data (D3), measurement of the outcome (D4), and selection of the reported results (D5). Each domain is rated as low risk, high risk, or having some concerns of bias, and an algorithm determined each study’s overall risk of bias. All discrepancies raised during data extraction and quality assessment were resolved by consensus between the 2 study investigators.

Endpoints. The 3 primary outcomes for this analysis were fluoroscopy time, air kerma, and kerma-area product.

Statistical analysis. Cochrane's Review Manager, version 5.4.1, was used to meta-analyze the data. Standard mean difference (SMD) and its 95% confidence interval (95% CI) were used to analyze continuous variables. Statistical tests τ2, χ2, and I2 were used to assess heterogeneity. A random effect analysis was applied for all comparisons. Two-sided P <0.05 was considered statistically significant. If the authors of the included studies did not provide mean or standard deviation data, these data were estimated according to the method described by Wan et al.¹⁸ A meta-regression for substantial unaccounted heterogeneity in the outcome of interest was performed across studies. Meta-regression was calculated with Comprehensive Meta-Analysis software, Version 4 (CMA – Biostat Inc.).

Search results. The literature search yielded 484 articles, of which 155 were excluded because they were duplicates and 179 because the title or abstract indicated that they were not eligible. The remaining 150 articles were deemed relevant to the topic and were screened by full-text reading; of these, 7 articles met the predetermined inclusion criteria and were included in the meta-analysis. Figure 1 details the PRISMA flow of study screening and selection.

Radiation exposure. Radiation exposure was reported in all 7 studies, but studies differed concerning predefined outcomes. Fluoroscopy time was reported in 5 studies, air kerma in three, and kerma-area product in two (Table 1).^14,19-24 The overall cohort comprised 1712 dTRA patients and 1715 TRA patients. The number of patients in the 2 groups was similar for studies that reported fluoroscopy time (1108 vs 1127), air kerma (852 vs 846), and kerma-area product (618 vs 724). Five of the 7 studies were single-center trials with small sample sizes; only 2 were large trials (Tables 1, 2).

Possible confounding factors were appraised that were related to clinical and procedure characteristics previously associated with higher radiation doses during interventional procedures (Table 3). Most studies included patients with such characteristics, such as age greater than 60 years, being overweight, and male gender, but excluded patients with previous coronary artery bypass grafting (CABG). Operator experience was heterogeneous. None of the articles reviewed included information about equipment setup for radiation exposure or any details about imaging acquisition, the number of runs, or projection angulation.

A bias risk assessment with the Rob2 tool was performed for all studies. None of them was classified as having an overall high risk for bias (Table 4).

The 5 studies that reported fluoroscopy time had considerably different results, which led to significant heterogeneity (I2=85%) among them. Although there was a trend favoring the dTRA, a random effect analysis found no significant difference between groups (Figure 2A).

Similarly, the heterogeneity was high (I2=91%) for the analysis of air kerma. The overall effect estimate favored the distal radial approach, but not significantly (Figure 2B).

In contrast, the 2 studies that included the kerma-area product had consistent results, leading to low heterogeneity (I2=0%). The overall effect estimate significantly favored a lower dose in the TRA patients (P=0.0006) than in the dTRA patients (Figure 2C).

Meta-regression. Because the learning curve plays an essential role in procedural outcomes, a meta-regression was performed with fluoroscopy time and the study year as covariates to determine whether radiation exposure differed between the most recent studies (ie, studies conducted further along the technique’s adoption timeline) and the older studies (ie, studies conducted at the technique’s onset). As shown in Figure 3, in the meta-regression of the 5 studies that examined fluoroscopy time, fluoroscopy times did not differ by study year. The studies that examined kerma-area product and air kerma were too few for meta-regression.

This work aimed to determine whether the distal radial approach promotes greater radiation exposure during diagnostic and interventional cardiology procedures than the traditional method. The current meta-analysis of 7 randomized trials indicated that dTRA and traditional TRA were not significantly different in terms of fluoroscopy time and air kerma. However, the kerma-area product was significantly lower with TRA than with dTRA.

Radiation exposure is probably the most significant problem for physicians, healthcare professionals, and patients in interventional cardiology. For staff working closely with ionizing radiation, the exposure is related to the development of premature cataracts²⁵ and lifetime risks of several cancers.²⁶ Because a lead apron and other equipment for personal protection are usually heavy, orthopedic injuries are among the secondary risks.^27,28 Thus, caution with ionizing radiation is of paramount importance for personal safety, and new techniques must benefit patients and keep cath lab personnel from possible harm at the same time.

Several factors can affect radiation exposure in the cath lab. When the transradial approach was first introduced and was compared to the femoral approach, patient age, body mass index, female gender, previous CABG, equipment setup, and technical details of the procedure (eg, number of runs, angulation shielding) were correlated with the procedure dose.^29,30 Operator expertise proved to be crucial to executing TRA procedures and was related to better results when operators became more experienced with the technique.^6,31

Although all of these factors might be possible confounders, it is difficult to control all of them in a randomized trial. Therefore, the current authors decided to review some potential confounding factors in the randomized trials and appraise them in their meta-analysis. This appraisal showed that most of the randomized trials were performed by operators experienced in TRA. However, the included patients had a low probability for procedure complexity, as shown by the disproportionate representation of men (around 75% in all studies), low patient age, and low prevalence of previous CABG. For an operator using a new technique, performing it in favorable patients can make it easier, which is essential at the beginning of the learning curve.³² In the present study, we observed that patients with less complex disease were selected for dTRA in the original publications, which may have enhanced operator performance. Other concerns were the lack of information regarding fluoroscopy and cine mode for image acquisition and details of equipment operation (eg, number of runs, angulation, proper use of filters and collimator). These technical features significantly affect procedure dose. Even with no access to that information, it is expected that operators followed radiation protection principles (“as low as reasonably achievable" – ALARA principle), regardless of the vascular access site used.

In interventional cardiology, fluoroscopy time is generally reported as a measure of radiation exposure. However, fluoroscopy time does not correlate perfectly with radiation dose.³³ The current generation of equipment allows several setups for pulsed fluoroscopy and image acquisition. Thus, 10 minutes of fluoroscopy can expose patients to different doses if the frame rate is decreased from the traditional 15 fps to 10 or 7.5 fps, for example. Longer fluoroscopy times are probably related to greater procedure complexity but not necessarily to a higher dose. Thus, we can consider fluoroscopy time as a surrogate marker of procedure complexity that does not correlate linearly with radiation exposure dose. In the current meta-analysis, there was significant heterogeneity among studies reporting fluoroscopy time (I2=85%, P<.0001). Some studies favor dTRA, and others the traditional technique. The current authors speculated that the learning curve and proficiency with dTRA influenced procedure execution. After TRA was first introduced, several trials^34,35 comparing the femoral and radial approach associated the radial approach with a higher radiation dose. However, later studies^7,31 proved that the higher dose associated with the radial approach was related to less operator expertise, lower procedure volume, and the learning curve.

One of the most common complications of radial catheterization is radial artery spasm due to the extensive innervation of alpha-1 terminals of vascular smooth muscle. Its incidence varies widely in population studies, but young age, female gender, vessel diameter, and more than three catheter changes during the procedure are associated with this complication.⁷ In the DISCO RADIAL trial,¹⁹ radial artery spasm (2.7% vs 5.4%; P=.015) and crossover rates (3.5% vs 7.4%; P=.002) were higher with dTRA. Thus, vasospasm and the crossover may have contributed to increased radiation exposure. Although most trials included in the current meta-analysis involved experienced operators, the possibility that operator expertise also affected the results cannot be excluded. However, the current meta-regression did not associate earlier year of publication with longer fluoroscopy time.

Cumulative air kerma measures the radiation energy deposited in air at the interventional reference point and is closely linked to deterministic skin effects, making it an important parameter for patient safety. The International Commission on Radiological Protection (ICRP publication 120)³⁶ advises that dose data should be recorded in the patient’s medical record after the procedure. When the patient’s radiation dose from an interventional procedure exceeds the institution’s trigger level, clinical follow-up should be performed for early detection and management of skin injuries. The threshold varies among countries, and there are no standard parameters between the US and the rest of the world. Although current equipment generally displays air kerma time on screen, only 3 trials reported related data. The current authors noted higher values with traditional TRA than with dTRA. As with fluoroscopy time, there was significant study heterogeneity (I2 = 91%, P<.0001) regarding air kerma; no statistical difference was noted between groups. It is unclear why previous studies did not report air kerma routinely in their publications. Although these trials did not use radiation exposure as an outcome, trials of new techniques should include safety as an outcome. In this context, radiation exposure should have received more attention from authors in the field.

Dose-kerma area is the cumulative sum of the instantaneous air kerma and the X-ray field area. Thus, this parameter also incorporates the area of tissue irradiated. It monitors patient dose and is a good indicator of stochastic effects. The greater the quantity of tissue that receives a given dose, the greater the risk. With this outcome, the authors had the most consistent results and heterogeneity (I2 = 0%, P=.57) between the 2 randomized trials that reported this outcome. The overall effect estimate associated TRA with lower radiation exposure than dTRA during interventional cardiology procedures (P=.0006). Thus, the currently available randomized studies suggest that dTRA results in greater radiological exposure in interventional procedures. Similar results were found at the beginning of the adoption of the radial technique. Higher radiation doses also were associated with the traditional radial vascular access approach in a substudy of the RIVAL trial³¹ (median air kerma with radial vs femoral access 1046 × 930 mGy; P=.051) and in the results of a meta-analysis.⁹ However, differences were mainly related to study center and operator volume.

Thus, the results of the current study should not discourage operators from adopting dTRA as an alternative to vascular access. As occurred with early use of TRA, extensive training at the beginning of the learning curve can overcome its possible drawbacks. It is essential to remember that radiation exposure depends on numerous factors, and protective actions such as shielding, additional disposable radiation-blocking drapes,^37,38 a low fluoroscopy rate,³⁹ and apron-free solutions can minimize radiological exposure in the catheterization laboratory. In the future, robotic percutaneous coronary intervention⁴⁰ may promote a safe environment for operators, regardless of the vascular access technique used.

Limitations

This meta-analysis has limitations. Few randomized trials reporting radiation exposure data were available in the literature. In addition, none of the reports included the operator dose, the number of cine/fluoroscopy runs, angiographic projections, or details about shielding. Also, analyzed articles were limited to only 3 languages. However, the greatest limitation was the lack of a standardized method of reporting radiation exposure in clinical trials. The authors believe researchers should offer an appropriate measurement to describe it, similar to the standard radiation exposure report used in pediatric interventional cardiology.⁴¹ A specific trial with radiation exposure as the primary outcome should be devised to provide a definitive answer. Until a dedicated trial has been published, this meta-analysis may serve as a reference for radiation exposure and distal radial approach.

Compared with the traditional radial approach, the dTRA was associated with significantly greater radiation exposure (kerma-area product) during interventional cardiology procedures. As the distal radial approach gains popularity, it will be crucial for operators to prioritize honing their technique and optimizing radiation protection. Because of the effects of heterogenous data used in the study analyses, a specific trial with radiation exposure as the primary outcome is warranted.

From the ¹Center for Preclinical Surgical & Interventional Research, The Texas Heart Institute, Houston, Texas, USA; ²Clinica Confamiliar, Pereira, Colombia; ³SOS Cardio Hospital, Florianópolis, Santa Catarina, Brazil; ⁴Willis Knighton Heart Institute, Bossier City, Louisiana, USA;⁵Division of Cardiology, Department of Medicine, University of Washington, Seattle, Washington, USA; and the ⁶Center for Clinical Research, The Texas Heart Institute, Houston, Texas, USA.

Acknowledgments: Stephen N. Palmer, PhD, ELS, of the Department of Scientific Publications at The Texas Heart Institute, contributed to the editing of the manuscript.

Disclosures: Dr. Azzalini received consulting fees from Teleflex, Abiomed, GE Healthcare, Asahi Intecc, Philips, Abbott Vascular, and Cardiovascular Systems, Inc. Dr. Franklin Hanna received consulting fees from Boston Scientific, LEVBETH Medical, and Bolt Medical. The other authors declare no conflict of interest related to this work.

Funding: No financial support was provided for this work.

Address for correspondence: Cristiano Cardoso, MD, PhD, FSCAI, The Texas Heart Institute, 6770 Bertner Avenue, MC 1-268, Houston, TX 77030, USA. Office: 832-355-4527; fax: 832-355-4205; Email: ccardoso@texasheart.org.