Efficacy of Low-Dose Compared With Standard-Dose Radiation for Cardiac Catheterization and Intervention (KAR RAD Study)

Abstract: Objectives. We evaluated the efficacy of low-dose (LD) radiation (≤7.5 frames/second [f/s]) compared with standard-dose (SD) radiation (≥10 f/s) in cardiac catheterization (CC) and percutaneous coronary intervention (PCI). Patients undergoing CC with LD vs SD radiation have not been previously studied. Methods. We performed an observational study of 452 consecutive patients (61 ± 12 years) who had coronary angiography or PCI from September 2016 to September 2017. Patients were divided into an LD radiation group (n = 136) consisting of 0.5 f/s and 1 f/s (n = 73), 4 f/s (n = 40), or 7.5 f/s fluoroscopy (n = 23) with 7.5 f/s cine angiography vs an SD group (n = 316) consisting of 10 f/s (n = 250), 15 f/s (n = 64), or 30 f/s fluoroscopy (n = 2) and 10-30 f/s cine angiography. Primary endpoints included air kerma, dose area product (DAP), fluoroscopy time, and contrast use. Results. Compared with SD radiation, LD radiation was associated with a significant reduction in air kerma (100.70 mGy [IQR, 46.42-233.35 mGy] vs 660.96 mGy [IQR, 362.78-1373.65 mGy]; P<.001), DAP (723.60 µGy•m² [IQR, 313.09-2328.22 µGy•m²] vs 5203.40 µGy•m² [IQR, 2743.55-10064.71 µGy•m²]; P<.001), and contrast use (100 mL [IQR, 60-150 mL] vs 115 mL [IQR, 80-180 mL]; P<.03). No difference in fluoroscopy time was noted (13.33 min [IQR, 6.93-25.55 min] vs 12.75 min [IQR, 7.75-22.55 min]; P=.95). Conclusions. LD radiation in CC was efficacious, with significant radiation reduction and without an increase in fluoroscopy time or contrast utilization. All patients underwent successful LD radiation catheterization without conversion to SD.

J INVASIVE CARDIOL 2019;31(6):187-194. Epub 2019 March 15.

Key words: acute coronary syndrome, percutaneous coronary intervention, radiation

Radiation in the cardiac catheterization (CC) laboratory is associated with an increased risk of malignancy, cataract formation, brain tumors, and various forms of radiation injury.^1-6 CC increases the lifetime risk of interventional cardiologists developing adverse health events.¹ Skin lesions, orthopedic injuries, hypertension, and hypercholesterolemia were also significantly increased from radiation exposure.^1,7 In high-volume operators who acquire yearly radiation exposure of 5 mSv, an extra lifetime risk of fatal or nonfatal cancer occurs in 1:100.⁸ Another study found that every 10 mSv of low-dose ionizing radiation was associated with a 3% increased risk of age- and sex-adjusted cancer over a 5-year follow-up period.⁹ This study of 82,861 patients found 12,020 incident cancers and concluded that ionizing radiation from cardiac imaging or therapeutic procedures was associated with an increased cancer risk. Therefore, reducing radiation in the CC laboratory is of vital importance. Our study sought to evaluate the efficacy of low-dose (LD) radiation in reducing radiation exposure in adult CC during coronary angiography and percutaneous coronary intervention (PCI).

Methods

Study population. We performed an observational study of 452 consecutive patients at an academic medical center who underwent coronary angiography or PCI from September 2016 to September 2017. Patients were divided into an LD radiation group (n = 136) consisting of 0.5 and 1 frames/second (f/s) fluoroscopy (n = 73), 4 f/s fluoroscopy (n = 40), or 7.5 f/s fluoroscopy (n = 23) with 7.5 f/s cine angiography vs a standard-dose (SD) group (n = 316) consisting of 10 f/s fluoroscopy (n = 250), 15 f/s fluoroscopy (n = 64), or 30 f/s fluoroscopy (n = 2) and 10-30 f/s cine angiography. Figure 1 displays the study cohort and the various categories of radiation utilized via fluoroscopy. Patients underwent CC via radial, ulnar, or femoral access. Primary endpoints included air kerma, dose area product (DAP), fluoroscopy time, and contrast use. The study was approved by the Texas Tech University Health Sciences Center El Paso institutional review board. All study participants provided informed written consent. The authors had full access to all study data and they take responsibility for its integrity and data analysis.

All procedures were performed using Siemens Artis CC x-ray equipment (Siemens Medical Solutions). The image quality was reviewed internally by all operators for all procedures. Five experienced operators performed CC and/or intervention using SD radiation. Only one operator performed CC and intervention using LD radiation. The sole operator initially started with fluoroscopy of 7.5 f/s, then converted to 4 f/s followed by 0.5 or 1 f/s for the remainder of his procedures. A learning curve was required in order to adapt to the technical challenges of the lower frame rates for fluoroscopy. After the specific fluoroscopy dose was chosen, the sole operator did not switch to a different dose of radiation during the procedure.

Statistical analyses. Quantitative data were expressed as mean ± standard deviation while categorical data were expressed using frequency (percentage). All cofactors and endpoints were compared according to the range of radiation doses using either one-way analysis of variance or Kruskal-Wallis test followed by post hoc multiple comparison using Bonferroni correction. Similarly, the variables were compared according to LD and SD radiation using Wilcoxon rank-sum test or unpaired t-test depending on the distribution of the data. The categorical variables were compared using Chi-square test or Fisher’s exact test. Furthermore, the effects of SD vs LD radiation on the primary endpoints were examined separately for procedures using unpaired t-test or Wilcoxon rank-sum test.

We utilized robust linear regression using mm-estimator for multivariable analysis since the outcomes did not follow a normal distribution. Initially, unadjusted association between each covariate and outcome using robust regression analysis was examined for each outcome separately. Then, a multivariable robust linear regression analysis with mm-estimator was carried out for each outcome separately. The significant variables at 15% level of significance in the unadjusted (univariable) regression analysis were included for multivariable analysis of each outcome. The significant factors at 5% level of significance were only retained in the multivariable analysis. The results of multivariable analysis were summarized using regression coefficient (RC), 95% confidence interval (CI), and P-values. A P-value of <.05 was considered statistically significant. Since DAP, air kerma, contrast amount, and fluoroscopy time did not follow normal distributions, these data were summarized using median and interquartile range (IQR) only. Univariable analysis was conducted using non-parametric tests (Wilcoxon rank-sum test). For multivariable analysis, we did not use log transformed values; instead, we used advanced linear regression analysis, which is robust for non-normal data, to avoid interpretation issues. All statistical analyses were carried out using SAS version 9.4 (SAS Institute, Inc) and STATA version 13 software (StataCorp, LLC).

Results

Baseline patient characteristics and CC indications. All patients (n = 452; age, 61 ± 12 years; body mass index, 30.7 ± 6.8 kg/m2) who presented to our CC laboratory were included in the study. The majority of patients were Hispanic (n = 354; 78.5%) and 61.3% were men (n = 277). The most common indication for CC was non-ST elevation myocardial infarction (n = 189; 41.8%). Other indications included ST-elevation myocardial infarction (n = 49; 10.8%), unstable angina (n = 70; 15.5%), abnormal stress test (n = 93; 20.6%), congestive heart failure/cardiomyopathy (n = 36; 8.0%) or preoperative evaluation for valvular heart disease/organ donation (n = 15; 3.3%).

Patient comorbidities included diabetes mellitus (52.3%), hypertension (82.7%), hyperlipidemia (67%), coronary artery disease (39.8%), congestive heart failure (36.1%), previous coronary artery bypass graft (6.4%), and former or current smoker (26.6%). Of the study population, 28.5% (n = 129) underwent PCI. Patients underwent radial (n = 228; 50.44%), ulnar (n = 24; 5.31%), and femoral arterial access (n = 200; 44.25%). The utilization of ulnar catheterization was considerably less compared with the other access sites because not all patients were ulnar candidates. The techniques, methodology, and algorithm for ulnar catheterization have been previously described.10 Table 1 lists the baseline patient characteristics and indications for CC.

Primary endpoints. The differences in the primary endpoints of air kerma, DAP, and contrast use were statistically significant (Table 1 and Figure 2). Compared with SD radiation (n = 316; 69.9%), LD radiation (n = 136; 30.1%)  was associated with a significant reduction in air kerma (100.70 mGy [IQR, 46.42-233.35 mGy] vs 660.96 mGy [IQR, 362.78-1373.65 mGy]; P<.001), DAP (723.60 µGy•m² [IQR, 313.09-2328.22 µGy•m²] vs 5203.40 µGy•m² [IQR, 2743.55-10064.71 µGy•m²]; P<.001], and contrast use (100 mL [IQR, 60-150 mL] vs 115 mL [IQR, 80-180 mL]; P<.03). No difference in fluoroscopy time was noted (13.33 min [IQR, 6.93-25.55 min] vs 12.75 min (IQR, 7.75-22.55 min]; P=.95). In multivariable robust linear regression analyses, PCI (RC, 6.68; 95% CI, 4.12-9.24; P<.001) and diabetes (RC, 1.66; 95% CI, 0.01-3.32; P<.049) were associated with increased fluoroscopy time for SD radiation. Likewise, in the pooled group analyses (LD and SD), PCI (RC, 6.65; 95% CI, 4.07-9.23; P<.001) and diabetes (RC, 9.98; 95% CI, 8.57-11.38; P<.049) were similarly associated with increased fluoroscopy time (Tables 2A-2D). Furthermore, contrast use was significantly higher using SD radiation (10 f/s: RC,17.04 95% CI, 1.83-32.25; P=.03; ≥15 f/s: RC, 32.66; 95% CI, 13.35-51.96; P<.01) compared with LD radiation.

Comparison of radiation from diagnostic CC vs PCI. As expected, patients who underwent diagnostic CC compared with PCI had significantly lower fluoroscopy time (P<.001), DAP (P<.01), contrast use (P<.001), and air kerma (P<.001) (Tables 2A-2D). Interestingly, patients who underwent PCI with LD (n = 44) compared with SD (n = 85) had lower fluoroscopy time (15.94 min [IQR, 9.31-33.64 min] vs 22.91 min [IQR, 14.98-34.81 min]; P=.04). Moreover, DAP (1278.42 µGy•m² [IQR, 271.92-4574.37 µGy•m²] vs 7848.08 µGy•m² [IQR, 3873.42-14194.51 µGy•m²]; P<.001), air kerma (170.4 mGy [IQR, 54.46-529.2 mGy] vs 1235.95 mGy [IQR, 529.08-2182.1 mGy]; P<.001) and contrast use (140 mL [IQR, 90-210 mL] vs 180 mL [IQR, 140-253 mL]; P<.001) was also lower (Figure 3).

Even patients who underwent diagnostic CC using LD compared with SD showed a significant reduction in DAP (623.24 µGy•m² [IQR, 326.31-1462.19 µGy•m²] vs 4530.5 µGy•m² [IQR, 2434.6-8313.1 µGy•m²]; P<.001) and air kerma (91.31 mGy [IQR, 43.98-146.8 mGy] vs 585.3 mGy [IQR, 321.58-1039.17 mGy]; P<.001). However, no significant difference was noted in fluoroscopy time (12.14 min [IQR, 6.19-21.26 min] vs 10.42 min [IQR, 6.33-17.38 min]; P=.40) or contrast use (90 mL [IQR, 60-140 mL] vs 90 mL [IQR, 70-130 mL]; P=.14).

Discussion

The pernicious effects of radiation are concerning and frequently overlooked in clinical practice. Roguin et al¹¹ reported 9 cases of brain tumors in interventional cardiologists. Cancer is a major risk from cardiac procedures, with a higher incidence of left-sided tumors.¹² The postulated mechanism is that chronic low doses of ionizing radiation induce somatic deoxyribonucleic acid damage.^11,13 Among the various physicians using fluoroscopy, interventional cardiologists receive the highest dose of radiation.^8,14 Therefore, methods and techniques to reduce radiation are critical to mitigate its harmful effects.¹⁵

Clinical studies. Low-frame invasive coronary angiography was evaluated in 39 patients (2:1 ratio of 7.5 f/s vs 15 f/s), with a reduction in radiation exposure and without a compromise in image quality.¹⁶ The effectiveness of using 7.5 f/s fluoroscopy vs 15 f/s fluoroscopy for radial catheterization (both groups used 15 f/s cine angiography) was studied with a decrease in radiation.¹⁷ Similarly, a retrospective study of 18,115 patients (18,115 procedures) showed a 40% reduction in radiation over 3 years by implementing a philosophy of radiation safety, decreasing fluoroscopy from 15 f/s to 7.5 f/s, and using copper x-ray beam spectral filters for acquisition imaging.¹⁸ Another study evaluated the benefits of simple radiation reduction protocols using limited ventriculographies and aortographies with a marked decrease in radiation (15 f/s fluoroscopy and cine angiography).¹⁹ A low frame rate protocol was analyzed in chronic total occlusion intervention to assess its safety and feasibility.²⁰ The protocol consisted of 15 f/s fluoroscopy and 7.5 f/s cine angiography along with the addition of copper and aluminum filters. The retrospective study of 192 patients revealed the safety and feasibility of the protocol with a reduction in radiation. An observational study of 307 patients (155 SD and 152 LD) evaluated the effects of LD radiation using 7.5 f/s fluoroscopy and 10 f/s cine angiography. The study found a significant reduction in DAP and air kerma.²¹ Pyne et al assessed the effect of fluoroscopy and cine acquisition on total x-ray dose and image quality during invasive cardiovascular procedures in a retrospective study.²² They reported that reducing default pulse rates (10 f/s fluoroscopy and cine) from the standard rate (15 f/s fluoroscopy and cine) yielded large and significant reductions in total x-ray energy with no decline in angiographic image quality.²² However, fluoroscopy frame rates of <7.5 f/s have not been previously studied for adult CC and intervention, and this was therefore one of the focuses of the present study.

Effects of LD radiation. In our study, we found that using LD fluoroscopy (≤7.5 f/s) significantly reduced radiation without increasing fluoroscopy time or contrast utilization. Also, LD radiation does not require any additional equipment or tools in the CC laboratory. Surprisingly, we found that LD radiation in PCI was associated with a significant reduction in contrast use and fluoroscopy time compared with SD. A possible explanation for this is that the single operator who performed LD-PCI used fluoroscopy only when necessary for imaging. Also, the LD operator did not routinely perform ventriculography on all patients.

Applications of LD radiation. LD radiation was feasible in an academic medical center with cardiovascular trainees. All patients underwent successful CC and PCI including those with ST-elevation myocardial infarction. Once LD radiation was chosen, the procedure was successfully performed in all patients (including those with ST-elevation myocardial infarction) without conversion to SD radiation. The sole LD operator initially started at 7.5 f/s of fluoroscopy (n = 23) and then transitioned to 4 f/s. After acquiring the necessary skills at 4 f/s (n = 40), he eventually performed procedures at the technically very difficult 0.5 and 1 f/s fluoroscopy rate (n = 73).

Experienced interventional cardiologists evaluated the diagnostic quality of the images for both interpretability and accuracy. Cine angiography at LD (7.5 f/s) vs SD (≥10 f/s) was not appreciably different and did not compromise image quality or anatomical visualization. The LD operator also collimated his images routinely to optimize image quality. Furthermore, no concession in determining lesions was found with increased body mass index, calcified lesions, or bifurcation lesions compared with SD. Fluoroscopy images were not utilized for lesion assessment, so the lower fluoroscopy frame rates were not a relevant factor for lesion evaluation. In addition, Ebrahimi et al¹⁶ performed a study using 7.5 f/s vs 15 f/s cine angiography for coronary angiography and found no significant difference in image quality. In borderline or intermediate lesions, fractional flow reserve was utilized for hemodynamic/physiological lesion assessment. Moreover, intravascular ultrasound was utilized in left main disease, ostial/proximal left anterior descending artery stenosis, stent restenosis/stent thrombosis, and/or bifurcation lesions for optimal vessel sizing, stent apposition, evaluation for the etiology of stent thrombosis/stent restenosis, and final evaluation after stent implantation.

Performing PCI with fluoroscopy at LD was technically extremely challenging because of the slow movement of the images. However, safety was not compromised and images were adequately visible for the sole operator. A few cases were performed by one operator at a higher rate (30 f/s) because of an inability to visualize the anatomy at 10 f/s or 15 f/s. The other five operators routinely performed procedures at 10 f/s or 15 f/s fluoroscopy and cine angiography, with the dose chosen at the discretion of the operator.

In PCI cases, LD radiation provided a substantial reduction in the primary radiation endpoints. The air kerma with SD-PCI was 725.3% higher compared with LD-PCI. In addition, the DAP was 613.9% higher in the SD-PCI group. Furthermore, the LD-PCI group had significantly lower fluoroscopy times (30.4% lower). Even in diagnostic CC, in which fluoroscopy times are routinely shorter than in PCI, a significant difference in radiation was still noted. Diagnostic CC using SD radiation increased DAP by 727.0% and air kerma by 641.0% compared with LD. Therefore, such radiation reduction techniques can have a dramatic impact on the lifetime radiation exposure to both patients and operators (less scatter radiation), especially patients who may undergo repeat CC and/or PCI along with operators who are exposed to lifelong radiation. Overall, the benefits of radiation reduction were clearly observed using LD radiation for PCI.

Study limitations. The study was performed in a single academic medical center with cardiovascular trainees. The LD radiation protocol was implemented by one operator, while five experienced operators used SD radiation; thus, randomization was not possible. The sole LD operator routinely wore his radiation badge during his procedures. However, the other operators did not, so an accurate assessment of individual radiation exposure and comparisons between LD and SD operators were not possible. Nevertheless, this is a valuable study that can be generalized to the overall population since all patients who presented for CC were studied without any exclusions, so it provides practical real-world data. Furthermore, this is the first study with the use of fluoroscopy in CC and PCI using <7.5 f/s, which significantly reduced the primary radiation endpoints.

Conclusion

Use of LD radiation in cases of adult CC and PCI was technically efficacious for all patients without any exclusions. Once LD catheterization with PCI was started, it was successfully completed without conversion to SD radiation. LD radiation is a technique to significantly reduce radiation (air kerma and DAP) without an increase in fluoroscopy time or contrast utilization. Such radiation protocols can have a meaningful clinical impact for patient care and the personnel in the catheterization laboratory.

Acknowledgments. We thank Alok Dwivedi, PhD, and Luis A. Alvarado, MS, for their statistical analyses.

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From the Division of Cardiovascular Medicine, Texas Tech University Health Sciences Center El Paso, Paul L. Foster School of Medicine, El Paso, Texas.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.

Manuscript submitted December 12, 2018, provisional acceptance given December 21, 2018, final version accepted December 26, 2018.

Address for correspondence: Subrata Kar, DO, FACC, FSCAI, Structural Heart Disease Interventional Cardiologist, Assistant Professor of Medicine, Division of Cardiovascular Medicine, Texas Tech University Health Sciences Center El Paso, Paul L. Foster School of Medicine, 4800 Alberta Avenue, El Paso, TX 79905. Email: skar762@aim.com