New image processing and noise reduction technology allows reduction of radiation exposure in complex electrophysiologic interventions while maintaining optimal image quality: A randomized clinical trial

New image processing and noise reduction technology allows reduction of radiation exposure in complex electrophysiologic interventions while maintaining optimal image quality: A randomized clinical trial Lukas R.C. Dekker, MD,* Pepijn H. van der Voort, MD,* Timothy A. Simmers, MD,* Xander A.A.M. Verbeek, PhD,† Roland W.M. Bullens, PhD,† Marcel van’t Veer, PhD,‡ Peter J.M. Brands, MTD,‡ Albert Meijer, MD* From the *Department of Cardiology, Catharina Hospital Eindhoven, Eindhoven, The Netherlands, †Philips Healthcare, Best, The Netherlands, and ‡Department of Medical Physics, Catharina Hospital Eindhoven, Eindhoven, The Netherlands. BACKGROUND Despite their carcinogenic potential, X-rays remain indispensable for electrophysiologic (EP) procedures. OBJECTIVE The purpose of this study was to evaluate the dose reduction and image quality of a novel X-ray technology using advanced image processing and dose reduction technology in an EP laboratory. METHODS In this single-center, randomized, unblinded, parallel controlled trial, consecutive patients undergoing catheter ablation for complex arrhythmias were eligible. The Philips Allura FD20 system allows switching between the reference (Allura Xper) and the novel X-ray imaging technology (Allura Clarity). Primary end-point was overall procedural patient dose, expressed in dose area product (DAP) and air kerma (AK). Operator dose, procedural success, and necessity to switch to higher dose settings were secondary end-points. RESULTS A total of 136 patients were randomly assigned to the novel imaging group (n ¼ 68) or the reference group (n ¼ 68). Baseline characteristics were similar, except patients in the novel imaging group were younger (58 vs 65 years, P o .01). Median DAP and AK were 43% and 40% lower in the novel imaging group,

Introduction The number of ablations for complex arrhythmias such as atrial fibrillation (AF) and ventricular tachycardia (VT) has grown substantially over recent years due to better understanding of arrhythmia substrates and development of advanced electroanatomic mapping systems. Despite the growing use of these nonfluoroscopic mapping systems, fluoroscopy still constitutes an indispensable tool for various This study was supported by Philips Healthcare. Drs. Verbeek and Bullens are employees of Philips Healthcare. This trial is registered with ClinicalTrials.gov Number NCT01593852. Address reprint requests and correspondence: Dr. Lukas Dekker, Department of Cardiology, Catharina Hospital Eindhoven, PO Box 1350, 5602 ZA Eindhoven, Netherlands. E-mail address: lukas.dekker@catharina_ziekenhuis.nl.

1547-5271/$-see front matter B 2013 Heart Rhythm Society. All rights reserved.

respectively (P o .0001). A 50% operator dose reduction was achieved in the novel imaging group (P o .001). Fluoroscopy time, number of exposure frames, and procedure duration were equivalent between the two groups, indicating that the image quality was similarly adequate in both groups. Procedural success was achieved in 91% of patients in both groups; one pericardial tamponade occurred in the novel imaging group. CONCLUSION The novel imaging technology, Allura Clarity, significantly reduces patient and operator dose in complex EP procedures while maintaining image quality. KEYWORDS Ablation; Atrial fibrillation; Dose reduction; Imaging; Pulmonary vein isolation; Radiation dose ABBREVIATIONS AF ¼ atrial fibrillation; AK ¼ air kerma; BMI ¼ body mass index; DAP ¼ dose area product; EP ¼ electrophysiologic; EPD ¼ electronic pocket dosimeter; PVI ¼ pulmonary vein isolation; VT ¼ ventricular tachycardia (Heart Rhythm 2013;10:1678–1682) I 2013 Heart Rhythm Society. All rights reserved.

steps in these procedures, such as initial catheter placement, performance of transseptal punctures, and handling of sheaths.1,2 Moreover, for some techniques and in several institutions, imaging still completely depends on X-rays.3–5 Use of fluoroscopy is associated with risks on deterministic effects such as radiation injury to the skin caused by high-peak skin dose, stochastic effects such as increased radiation-induced cancer risk, and genetic effects. Previous studies have shown that exposure to radiation necessary for catheter treatment of arrhythmia patients varies widely, sometimes even exceeding the threshold dose required for the onset of radiation-induced skin injuries.6,7 Radiationassociated risks are of particular concern for young or obese patients, and for patients undergoing long and complex or repeated procedures.8 Operators, including technicians and http://dx.doi.org/10.1016/j.hrthm.2013.08.018

Dekker et al

New Image Processing Technology Reduces Radiation by 40%

nurses, and especially those performing large numbers of procedures, are also exposed to risks from radiation, such as malignancy.9 Operator dose primarily accumulates from radiation scatter from the patient. As stated in a 2007 consensus report jointly authored by several associations, electrophysiologists should make every attempt to minimize radiation exposure.2 Of particular relevance to dose reduction concerns are electrophysiologic (EP) procedures in which extended radiation time and contrast usage are common, such as pulmonary vein isolation (PVI) for AF treatment and catheter ablation for VT treatment. The image noise reduction system tested in this study (Allura Clarity, Philips Healthcare, Best, The Netherlands) uses new image processing technology that allows acquisition of quality X-ray images with reduced dose while maintaining similar image quality by application of improved image processing. The new image processing technology combines temporal and spatial noise reduction filters with automatic pixel shift functionality.10,11 Parameters that control the algorithms are tuned to achieve optimal results, depending on the specific demands for image quality by each clinical application (eg, neurology, cardiology, EP). In the current clinical research study, we tested if this novel advanced image processing and image noise reduction system resulted in overall procedural dose reduction while delivering optimal image quality for EP procedures.

Methods Study design and patients This single-center, randomized, unblinded, parallel controlled trial was undertaken at the Catharina Hospital Eindhoven, Eindhoven, The Netherlands. The trial was designed to compare the new advanced image processing and dose reduction technology (Allura Clarity, Philips Healthcare) with the reference technology (Allura Xper, Philips Healthcare). All procedures were performed by experienced operators (LRCD, PHV, TAS, and AM) at a single EP laboratory equipped with a Philips Allura FD20 system (Philips

1679

Healthcare), which could switch between Allura Xper and Allura Clarity system settings. When switching to the Clarity system setting, a real-time image processing chain with image noise reduction algorithms was activated and the X-ray dose intensity reduced. Image noise reduction algorithms have been the subject of several previous publications.12–15 Most of the image processing literature focuses on standard test sets of photographic images displaying, for example, human portraits (“Lena”, “Barbara”) and cannot be directly applied to cardiac X-ray images of distinctly different physical, spatial, and temporal characters.12–15 The new technology uses an image noise reduction algorithm that was specifically designed for X-ray images, which combines a spatial and a temporal filter. Both filters include an analysis operation revealing the predominant structures in the image and excluding them from the filter phase. This approach is deployed at different spatial scales by the use of multiresolution image decomposition.10,11 Prior to the start of this study, the set of parameters that control the image processing chain and noise reduction algorithm were tuned through an iterative process where X-ray dose intensity was stepwise reduced, while the operators confirmed that image quality remained optimal for further evaluation of the system. For this tuning process, 50 patients were included using the same inclusion criteria. Patient characteristics in terms of body mass index (BMI) and age were similar to those of the patients included in the present study. At the end of this process, X-ray intensity could be reduced by 50% compared with Allura Xper system settings while X-ray quality remained equal. Typical examples of fluoroscopy in both settings are shown in Figure 1. The programmed technique factors for Allura Clarity are 10mA tube current, 2-ms pulse, and 0.4-mmCu filtering for a typical patient of 20-cm equivalent water thickness. Based on these observations, a 40% reduction of system radiation dose was predicted. Based on historical dose observations, a sample size of 68 patients per study group (ie, 62 evaluable patients for 10% dropout rate) for a total of 136 patient randomized will allow for 80% power to detect approximately 40% reduction in dose area product (DAP).

Figure 1 Typical examples of anteroposterior views showing a circular diagnostic catheter in the left upper pulmonary vein, an ablation catheter in the left atrium, and a quadripolar diagnostic catheter in the coronary sinus with the new noise reduction technology switched ON (left) or OFF (right) with a 20-second time difference in the same patient.

1680 This sample size also will allow for detection of approximately 40% reduction in air kerma (AK). No adjustment for multiple end-points was performed because both end-points are assessing radiation dose. Consecutive patients, who were able to provide informed written consent, were eligible for the study if they were accepted for ablation of AF (paroxysmal, persistent), atypical atrial flutter, or ischemic or nonischemic VT. The study was performed in compliance with the Declaration of Helsinki and conducted in accordance with Good Clinical Practice guidelines.

Randomization To minimize the potential for selection bias, patient allocation (1:1) to either reference setting (reference) or the novel advanced X-ray imaging technology (novel X-imaging) was determined based on a predefined random pick-list just prior to the procedure and, therefore, was unknown at the moment of obtaining patient consent.

Procedures Procedure dose was the primary end-point and was determined by the cumulative DAP value and the cumulative AK value. As secondary end-points, we used clinical staff dose measured by electronic pocket dosimeters (EPD; DoseAware, Philips Healthcare), one worn by the operator over the lead apron (EPD operator) and the other mounted at a fixed location in the EP laboratory (EPD fixed). Additional secondary end-points were fluoroscopy and exposure times, procedure duration, operator-controlled fluoroscopy dose settings (low, medium, high), procedural success, and adverse events. In both the novel X-imaging and reference groups, default fluoroscopy dose settings were “low” but could be changed by the operator to a medium or high setting for better imaging. The exposure settings could not be changed by the operator. The necessity to increase fluoroscopy dose for better imaging (eg, during transseptal puncture) to medium or high was registered as a percentage of total number of fluoroscopy frames. Ablation procedures The novel image processing technique was tested in routine clinical practice, which includes different procedural techniques. Five procedure types were defined as follows. (1) A first PVI in paroxysmal AF patients treated for the first time, using either a single-tip, irrigated ablation catheter and electromagnetic mapping (CARTO, Biosense Webster, Diamond Bar, CA; and EnSite, St. Jude Medical, St. Paul, MN) or multicycle multielectrode ablation (Pulmonary Vein Ablation Catheter [PVAC], Medtronic Inc, Minneapolis, MN) and EP-navigator (Philips Healthcare).4,5 (2) Redo PVI for recurrence of paroxysmal AF using a single-tip, irrigated ablation catheter and fluoroscopy for imaging. (3) Left atrial ablations for persistent AF, atypical flutters, and atrial tachycardia, using electromagnetic mapping systems. (4) VT ablations in patients with idiopathic or substraterelated VT using an electroanatomic mapping system.

Heart Rhythm, Vol 10, No 11, November 2013 (5) “Other” procedures, such as postincisional and isthmusdependent (initially diagnosed as atypical) right atrial flutters, were grouped. For procedures involving the pulmonary veins, contrast venography was performed on each vein.

Statistical analysis Procedure dose data are expressed as median with interquartile range and compared with diagnostic reference levels.16,17 Other data are expressed as mean ⫾ SD. For dose data that showed a skewed distribution with large variability, the Mann-Whitney U test was used to compare differences in dose between the novel X-imaging and reference groups. For data with a normal distribution, the unpaired Student t test was used.

Results Of 136 patients enrolled in the randomized cohort, half (n = 68) were assigned to the novel X-imaging group and the other half to the reference group (n = 68). Baseline characteristics are summarized in Table 1. Patient characteristics were similar in both groups, except for age (novel X-imaging vs reference group: 58 vs 65 years, respectively, P o .01). Most notably, BMI and procedure type were not different across the groups. DAP was significantly lower (43%) in the novel X-imaging group compared with the reference group (8.8 vs 15.3 Gy*cm2, respectively, P o .0001; Table 2 and Figure 2A). Likewise, AK was reduced by 40% in the novel X-imaging group compared with the reference group (75 vs 126 mGy, respectively, P o .0001; Table 2 and Figure 2B). Finally, operator dose was reduced by 50% in the novel X-imaging group compared with the reference group (3 vs 6 mSv, respectively, P o .001; Table 2 and Figure 2C). Despite Table 1

Patient demographics and baseline characteristics

Age (years) Sex Male Female Body mass index (kg/m2) Index arrhythmia AF paroxysmal or persistent Atypical flutter/atrial tachycardia VT idiopathic or post infarction Other Procedure type First PVI Redo PVI Left atrial ablation VT ablation Other

Novel X-imaging (n ¼ 68)

Reference (n ¼ 68)

58 ⫾ 14

65 ⫾ 9

50 18 26 ⫾ 4

51 17 27 ⫾ 4

50

49

5

10

7

3

7

3

32 6 18 11 3

35 6 21 4 4

P value o.01 NS NS NS

NS

Values are given as mean ⫾ standard deviation or number. AF ¼ atrial fibrillation; NS ¼ not significant; PVI ¼ pulmonary vein isolation; VT ¼ ventricular tachycardia.

Dekker et al Table 2

New Image Processing Technology Reduces Radiation by 40%

Procedural dose and other characteristics

*

2

DAP (Gy cm ) AK (mGy) EPD operator (mSv) EPD fixed (mSv) Low Medium High Procedure duration (minutes) Procedural success (%) Fluoroscopy time (minutes) No. of exposure frames Serious adverse events

Novel X-imaging (n ¼ 68)

Reference (n ¼ 68)

P value

8.8 (8.2) 75 (80) 3 (5) 10 (12) 86 ⫾ 28 2⫾8 12 ⫾ 24 160 ⫾ 58

15.3 (16.4) 126 (141) 6 (7) 19 (30) 88 ⫾ 20 2⫾9 9 ⫾ 19 162 ⫾ 58

o.0001 o.0001 o.001 o.01 NS NS NS NS

91

91

NS

24 ⫾ 13

26 ⫾ 13

NS

83 ⫾ 89

61 ⫾ 66

NS

1

0

Values are given as median (interquartile range), mean ⫾ standard deviation, or number. AK ¼ air kerma; DAP ¼ dose area product; EPD fixed ¼ electronic pocket dosimeter mounted at a fixed location in the laboratory; EPD operator ¼ electronic pocket dosimeter worn by operator over lead apron; NS ¼ not significant.

the stated difference in age between groups, no relationship between age and dose was evident (data not shown). Fluoroscopy time (novel X-imaging vs reference group: 24 vs 26 minutes, respectively; Figure 2D), number of exposure frames (novel X-imaging vs reference group: 83 vs 61, respectively), and procedure duration (novel Ximaging vs reference group: 160 vs 162 minutes, respectively) were equivalent between the two groups, indicating that image quality was equally adequate in both groups (Table 2). This was emphasized by equal utilization of

operator-controlled fluoroscopy dose settings. Physicians did not perceive differences in image quality between groups. In each group, procedural success (91%) could not be achieved in six patients; one pericardial tamponade occurred in the novel X-imaging group.

Discussion In this study, we showed that this novel image processing and dose reduction technology significantly reduces both patient and operator radiation dose without compromising image quality. Although cancer risk associated with EP procedures is considered low, reducing radiation dose is essential.2,18 This is especially important given that the total number of ablations for complex arrhythmias, including repeat procedures, is rapidly increasing worldwide. In addition, obesity, which is an important risk factor for AF,19 will become increasingly prevalent and thereby will increase the overall cumulative effective dose required for catheter treatment of AF.8,18 Therefore, obesity will also increase operator dose due to enhanced scatter from the patient.8,18 The deleterious effects of radiation are differentiated in deterministic effects, which result from radiation-induced cell injury occurring above a threshold dose, and in stochastic effects, in which the probability and not severity is determined by radiation dose. Typical examples are skin injury and DNA mutations, respectively.20 Associated with deterministic impact of radiation is the patient’s entrance dose, expressed in terms of AK, whereas DAP reflects stochastic effects of radiation. All interventional X-ray systems display the cumulative DAP and AK values. Several other parameters have been developed to indicate the impact of radiation on the human body, such as effective dose. Because BMI and procedure type were not different between the two groups in the present study, we consider DAP and

43%, p < 0·0001

100

1000 100

AK (mGy)

DAP (Gy*cm2)

1000

10 1

10 1 40%, p < 0·0001

0·1

0·1 Novel X-imaging

1000

Novel X-imaging

Reference

50%, p < 0·0001

60 Fluoro time [min]

Operator dose (mSv)

1681

100 10 1 0·1

Reference

N.S.

40 20 0

Novel X-imaging

Reference

Novel X-imaging

Reference

Figure 2 Box and whisker plots with overlaid scatter plot data for procedural dose area product (DAP) (A), air kerma (AK) (B), and operator dose (C) on a logarithmic scale. D: Mean and SD for fluoroscopy times. Box illustrates median and interquartile range; whiskers illustrate maximum and minimum values.

1682 AK to be good estimates of the reduction in radiation exposure by the image noise reduction system. In the present study, several objective parameters related to image quality were assessed, such as procedure and fluoroscopy durations as well as necessity to increase dose. Because these parameters were not different between groups, we conclude that the lower radiation dose in the novel X-imaging group did not negatively affect image quality. Radiofrequency ablations for complex arrhythmias may result in long procedure durations and fluoroscopy times. However, demands with respect to image quality in EP are much lower compared with diagnostic applications, such as coronary angiography. Therefore, the new image processing and dose-reduction technology evaluated in this study results in DAP values well below the European diagnostic reference levels of 110 Gy*cm2 for interventional cardiology21 as well as below the 46 Gy*cm2 specific to radiofrequency ablations, as reported in a recent review.22 Additionally, the operator dose of 3 μSv per procedure dose exposure remains well below the occupational annual dose limits of 20 mSv.

Study limitations A possible limitation of the study was the fact that the operator performing the examination was not blinded to the treatment allocation of the study participants due to the legal requirement for X-ray systems to display dose and dose rates during interventions. However, individuals responsible for recruiting and scheduling patients were unaware of treatment allocation because this was determined just prior to the procedure. Also, there was a significant age difference between the two groups, which we cannot explain. However, we found no significant differences between groups in independent dose-determining factors, such as BMI, fluoroscopy time, and procedure duration. Therefore, we do not expect age difference to have affected our results. Additionally, there was no relation between age and dose. In the literature, reports on radiation for catheter ablations vary widely as a result of large differences in dose determining factors, such as X-ray equipment, operator experience, procedure type, and use of nonfluoroscopybased catheter guidance systems. Nonetheless, in the present randomized study we were able to demonstrate that the low dose in the reference group could be reduced even more by this new noise reduction technology.

Conclusion In this randomized trial with patients undergoing ablations for complex arrhythmias, we demonstrated that a novel image processing and image noise reduction technology results in significant reduction of both patient and physician dose by 43% and 50%, respectively. Moreover, image quality is maintained at a similar level. Use of this technology may further improve the safety of EP interventions.

Heart Rhythm, Vol 10, No 11, November 2013

Acknowledgment We thank Tam Vo, PhD, from Excerpta Medica for providing editorial support.

References 1. Cappato R, Calkins H, Chen SA, et al. Worldwide survey on the methods, efficacy, and safety of catheter ablation for human atrial fibrillation. Circulation 2005;111:1100–1105. 2. Calkins H, Brugada J, Packer DL, et al. HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for personnel, policy, procedures and follow-up. A report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation developed in partnership with the European Heart Rhythm Association (EHRA) and the European Cardiac Arrhythmia Society (ECAS); in collaboration with the American College of Cardiology (ACC), American Heart Association (AHA), and the Society of Thoracic Surgeons (STS). Endorsed and approved by the governing bodies of the American College of Cardiology, the American Heart Association, the European Cardiac Arrhythmia Society, the European Heart Rhythm Association, the Society of Thoracic Surgeons, and the Heart Rhythm Society. Europace 2007;9:335–379. 3. O’Neill MD, Wright M, Knecht S, et al. Long-term follow-up of persistent atrial fibrillation ablation using termination as a procedural endpoint. Eur Heart J 2009;30:1105–1112. 4. Stevenhagen J, Van Der Voort PH, Dekker LR, Bullens RW, Van Den Bosch H, Meijer A. Three-dimensional CT overlay in comparison to CartoMerge for pulmonary vein antrum isolation. J Cardiovasc Electrophysiol 2010;21:634–639. 5. Boersma LV, Wijffels MC, Oral H, Wever EF, Morady F. Pulmonary vein isolation by duty-cycled bipolar and unipolar radiofrequency energy with a multielectrode ablation catheter. Heart Rhythm 2008;5:1635–1642. 6. Lickfett L, Mahesh M, Vasamreddy C, et al. Radiation exposure during catheter ablation of atrial fibrillation. Circulation 2004;110:3003–3010. 7. Rosenthal LS, Beck TJ, Williams J, et al. Acute radiation dermatitis following radiofrequency catheter ablation of atrioventricular nodal reentrant tachycardia. Pacing Clin Electrophysiol 1997;20:1834–1839. 8. Ector J, Dragusin O, Adriaenssens B, et al. Obesity is a major determinant of radiation dose in patients undergoing pulmonary vein isolation for atrial fibrillation. J Am Coll Cardiol 2007;50:234–242. 9. Theocharopoulos N, Damilakis J, Perisinakis K, Manios E, Vardas P, Gourtsoyiannis N. Occupational exposure in the electrophysiology laboratory: quantifying and minimizing radiation burden. Br J Radiol 2006;79:644–651. 10. Jago J, Collet-Billon A, Chenal C, Jong JM, Makram-Ebeid S. XRESs: adaptive enhancement of ultrasound images. Medicamundi 2002;46:36–41. 11. Meuwly JY, Thiran JP, Gudinchet F. Application of adaptive image processing technique to real-time spatial compound ultrasound imaging improves image quality. Invest Radiol 2003;38:257–262. 12. Buades A, Coll B, Morel JM. A review of image denoising algorithms, with a new one. Multiscale Model Simul 2005;4:490–530. 13. Donoho DL. De-noising by soft thresholding. IEEE Trans Inf Theory 1995;41: 613–627. 14. Portilla J, Strela V, Wainwright MJ, Simoncelli EP. Image denoising using scale mixtures of Gaussians in the wavelet domain. IEEE Trans Image Process 2003;12:1338–1351. 15. Tomasi C, Manduchi R. Bilateral filtering for gray and color images. Sixth International Conference on Computer Vision (ICCV’98). doi: 10.1109/ICCV. 1998.710815. 16. Bar O, Maccia C, Pagès P, Blanchard D. A multicentre survey of patient exposure to ionising radiation during interventional cardiology procedures in France. EuroIntervention 2008;3:593–599. 17. Trueb PR, Aroua A, Stuessi A, et al. Diagnostic reference levels in cardiology and interventional radiology. IFMBE Proc 2009;25:136–139. 18. Kovoor P, Ricciardello M, Collins L, Uther JB, Ross DL. Risk to patients from radiation associated with radiofrequency ablation for supraventricular tachycardia. Circulation 1998;98:1534–1540. 19. Wang TJ, Parise H, Levy D, et al. Obesity and the risk of new-onset atrial fibrillation. JAMA 2004;292:2471–2477. 20. Einstein AJ. Effects of radiation exposure from cardiac imaging: how good are the data? J Am Coll Cardiol 2012;59:553–565. 21. Neofotistou V, Vano E, Padovani R, et al. Preliminary reference levels in interventional cardiology. Eur Radiol 2003;13:2259–2263. 22. Pantos I, Patatoukas G, Katritsis DG, Efstathopoulos E. Patient radiation doses in interventional cardiology procedures. Curr Cardiol Rev 2009;5:1–11.