Zero to minimal fluoroscopy for cardiac electronic device implantation: A systematic review and meta‐analysis

Abstract Background Fluoroscopy is conventionally performed for cardiac implantable electronic device (CIED) therapy and carries radiation drawback for both patients and medical workers. Recently, zero to minimal fluoroscopy (ZMF) approach is introduced to reduce radiation exposure of fluoroscopy. This study compares the feasibility and safety of ZMF approach to fluoroscopy for CIEDs therapy in adults. Method A systematic literature search was conducted on PubMed, ScienceDirect, and Web of Science in March 2023. All observational or experimental studies comparing ZMF approach to fluoroscopy for adult CIEDs therapy were included. Reviews, case report/series, animal studies, and non‐English articles were excluded. The success rate, procedural time, fluoroscopy time, radiation dose, and complications rate were compared for each approach. Results Seven articles for permanent and three articles for temporary CIEDs were included for analysis. The success rate of ZMF for permanent CIEDs was similar to fluoroscopy method (OR: 0.77, 95% CI: 0.33–4.15). The procedural time of ZMF was similar to fluoroscopy for both permanent and temporary CIEDs (standardized mean difference [SMD]: 0.10, 95% CI: −0.35 to 0.55 and SMD: −0.71, 95% CI: −1.87–0.44, respectively). However, ZMF approach markedly reduced the fluoroscopy time and radiation exposure for permanent CIEDs (SMD: −1.80, 95% CI: −2.49 to −1.12 and SMD: −1.26, 95% CI: −2.24 to −0.29). The complication rate was similar for permanent CIEDs (OR: 1.08, 95% CI: 0.41–2.84), yet lowered for temporary CIEDs (OR: 0.34, 95% CI: 0.20–0.59). Conclusion ZMF had similar success rate, procedural time, and sum complication rate for permanent CIEDs implantation with a significant reduction of fluoroscopy time and radiation exposure.


| INTRODUC TI ON
Implantation of electronic cardiac devices (CIEDs) has been one of the most ideal solutions in both monitoring and controlling patients with cardiac arrhythmias and heart failure, showing benefits in reducing morbidity and mortality. 1As the field of cardiac interventional electrophysiology has been rapidly progressing, there have been a diverse amount of implantable cardiac devices for a variety of indications, from permanent pacemaker (PPM), implantable cardioverter-defibrillator (ICD), to cardiac resynchronization therapy (CRT) devices. 2 However, such procedure requires a guidance, making fluoroscopy the most commonly used imaging modality for CIEDs implantation in the past few decades.
Fluoroscopy is a radiology-based modality used for both diagnostic and therapeutic purposes.This conventional method of imaging exposes both the patient and the operator during the CIEDs implantation procedure.The effective dose (ED) ranges around 4 millisievert (mSv) for PPM or ICD implant to 25 mSv for CRT implant, exposing 200-1100 times radiation than that of a single chest x-ray, making a CIEDs operator more vulnerable than a diagnostic radiologist.To minimalize radiation exposure, there are a few approaches that can be done.The first and second methods were to reduce the time spent near the radiation source and to keep as much distance as possible, which were not very feasible for both the medical staff and the patient when fluoroscopy is performed. 3The only available method was by shielding.Nevertheless, even with the use of radioprotective gears, radiation exposure could only be reduced up to a thousand-fold.A cumulative effective radiation dose of 100 mSv or higher was known to be correlated with a higher risk of cancer, which may be reached after a patient underwent four fluoroscopy procedures with two CT scans, equivalent to 30 years of work for an experienced cardiologist.
Moreover, these populations were more prone to radiation-associated injuries.In addition, not all patients in need of CIEDs implantation were allowed to undergo fluoroscopy, for example, pregnant women, patients with kidney diseases, and those with contrast allergies.Therefore, an alternative with comparable outcomes and minimal drawbacks to that of fluoroscopy is exigently in demand. 4ro-to-minimal fluoroscopy (ZMF) has been deemed as an alternative to fluoroscopy, as a meta-analysis demonstrated comparable success rates and complications but with less radiation exposure for catheter ablation procedures. 5However, to our knowledge, no meta-analysis has been conducted to compare the ZMF approach to fluoroscopy for the implantation of CIEDs.Therefore, this meta-analysis was aimed to evaluate the feasibility and safety of the two approaches in navigating CIEDs implantation in adults.

| Study design
This systematic review and meta-analysis were conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.This meta-analysis has also been registered to PROSPERO (CRD42023414051).

| Literature search
A literature search was conducted at three online databases (PubMed, ScienceDirect, and Web of Science) in March 2023.We used "zero fluoroscopy," "cardiac pacemaker," "cardiac pacing," "cardiac implantable electronic device," "cardiac resynchronization therapy," "implantable cardioverter defibrillator," and their synonyms as keywords during literature search, along with Boolean operators (AND, OR, and NOT).
The reference lists of the studies were also screened to identify any additional appropriate article.

| Eligibility criteria
All observational or experimental studies comparing the ZMF approach to conventional fluoroscopy for adult CIEDs implantation were included.Meanwhile, reviews, case reports/series, single-arm, or animal studies were excluded.Articles published in non-English languages were also excluded.The eligibility assessment was carried out by two independent authors (KL and CM).Disagreements between authors were resolved by the third author (RJ).Following articles with incomplete data, the author (KL or CM) contacted the corresponding author via email.If the corresponding author did not answer or decline the request within 14 days, the respective article was excluded.

| Data extraction and collection
Two independent authors (KL and CM) extracted the following data for each article: authors-publication year, location, patient(s) demographics, ZMF method, type of CIEDs, clinical indication, follow-up duration, complications reported, success rate, procedural time, fluoroscopy time, and sum complication rate.The data presented in median and IQR were converted to mean and standard deviation according to the previous study. 6The data were collected into a dedicated spreadsheet.

| Methodological quality assessment
Methodological quality assessment for the included articles was performed by two independent authors (KL and CM).Newcastle-Ottawa Scale (NOS) was utilized for non-randomized studies, otherwise modified Jadad scale was applied.The NOS is composed of three domains (Selection, Comparability, and Outcome), assessing the studies with a maximum score of 9. A score of 7-9 is considered good, 5-6 is fair, otherwise is poor studies.Meanwhile, the modified Jadad scale is composed of 8 yes/no questions.A score above 4 is considered a good-quality study.

| Outcome
The primary outcomes of this meta-analysis were the success rate for the ZMF approach compared to the conventional fluoroscopy.
Meanwhile, the secondary outcomes included procedural time, fluoroscopy time, radiation dose, and sum complications rate for the two.

| Statistical analysis
Dichotomous variables (success rate and complication rate) were presented as odds ratio (OR), while continuous variables (procedural time and fluoroscopy time) were presented as standardized mean difference (SMD).An SMD of 0.2 represents a small effect, 0.5 represents a medium effect, and 0.8 or larger represents large effect. 7The heterogeneity was evaluated (subased on I 2 result.High heterogeneity is defined as I 2 above 50%, indicating the application of a random Mantel-Haenszel effect.A sensitivity analysis was carried-out using the leave-one-out method to identify the etiology of heterogeneity.All statistical analysis was performed using RevMan 5.4.The result is considered significant if the p value scores less than .05,except for heterogeneity test (p < .10).

| Included studies and baseline characteristics
The initial search resulted a total of 481 articles.After removing duplicates, 386 articles were screened, resulting into 56 relevant studies which were further assessed for eligibility.Finally, 7 articles with permanent CIEDs and 3 articles with temporary CIEDs were included for analysis (Figure 1).
Most participants were male and aged above 70 years old.
Three-dimensional electroanatomic mapping approach (3D-EAM) and transthoracic echocardiography (TTE) were used in all permanent and temporary CIEDs implantation accordingly.Most studies included sinus node dysfunction (SND) and atrioventricular node block (AVB) as the clinical indications for CIEDs implantation (Table 1).Based on NOS criteria, all observational studies were considered good.However, the study by Ruiz-Granell et al. ( 2008) did not provide a clear comparability analysis of its confounding factors (Table 2).One study by Hua et al. (2021), on the other hand, was evaluated using the modified Jadad scale and was considered good (6 of 8 points).

| Success rate
Six studies reported the success rate of the ZMF approach for permanent CIEDs.The success rate of the ZMF approach was similar to the fluoroscopy method (OR: 0.77, 95% CI: 0.33-4.15,p = .54).
The success rate for temporary CIEDs implantation using TTE was also comparable to the conventional approach, which ranged around 98%-100% (Figure 2).

| Complication rate
The complication rates for both ZMF and fluoroscopy approaches were relatively low.The overall complication of permanent CIEDs implantation using ZMF was not different from the fluoroscopy approach (OR: 1.08, 95% CI: 0.41-2.84,p = .88).The TTE guidance for CIEDs implantation was also found to be safer compared to the traditional fluoroscopy method (OR: 0.34, 95% CI: 0.20-0.59,p = .0001)(Figure 5).

| DISCUSS ION
Fluoroscopy is one of the most commonly used imaging modalities for numerous cardiac intervention procedures, including catheter Many published articles reported the success of the ZMF approach for numerous cardiac procedures, such as catheter ablations and correction of congenital heart diseases.Arrhythmia termination using the ZMF approach (3D-EAMS) was not inferior compared to conventional fluoroscopy. 5,18,19Meanwhile, transcatheter correction under echocardiography guidance could also be done to treat atrial septal defect and patent ductus arteriosus. 20,21Interestingly, the ZMF approach had also been performed for CIEDs implantation.
To the best of our knowledge, this is the first meta-analysis comparing the ZMF approach to conventional fluoroscopy for CIEDs implantation.The 3D-EAMS was utilized for permanent CIEDs, while TTE was employed for temporary CIEDs implantation.Our results showed that not only the implantation under 3D-EAMS guidance was comparable to conventional fluoroscopy in terms of success rate, PT, and complication rate but it also significantly reduced FT and RD.Lower complication rate was also observed in temporary CIEDs implantation using TTE approach.
3D-EAMS reconstructs the geometry of cardiac chambers based on magnetic or impedance measurements.The 3D-EAMS also provides precise position and movement of catheters along with the gradient of electrical activity in cardiac tissue. 22Currently, there are two most-used 3D-EAMS in the market: CARTO and EnSite. 23RTO was the first 3D-EAMS introduced by Biosense Webster (Johnson and Johnson).CARTO uses a magnetic field to reconstruct 3D images.However, the CARTO system is limited to only a few types of catheters. 24Meanwhile, EnSite (NavX and Velocity) reconstructs 3D images based on tissue impedance and is suitable with more catheter choices. 25,26  Despite our findings, we identified two barriers the 3D-EAMS approach for CIEDs implantation.The first problem is the cost.The 3D-EAMS method is 6% more expensive due to the additional use of decapolar catheters with magnetic sensors. 13,28Currently, there was no comparison data regarding medical expenses of 3D-EAMS and traditional fluoroscopy for CIEDs implantation.Castrejón et al.
(2013) noted 3D-EAMS cost more than traditional fluoroscopy due to the single use of 3D-EAMS wear-out components. 29Economic analysis study on SVT catheter ablation suggested that 3D-EAMS potentially increases the cost by $207-3.454(2014-USD). 30,31The 2019 Asia Pacific Heart Rhythm Society (APHRS) consensus also agreed that the 3D-EAMS method is very beneficial for the patients, yet is limited to its availability and financial issues.Therefore, 3D-EAMS should be offered to selective population, respectively. 22other barrier includes operator experience since 3D-EAMS is a relatively new method, especially for CIEDs implantation.One study mentioned that 3D-EAMS procedures took longer than the conventional approach, even for experienced operators.However, as the operators experienced more cases, the overall procedure time was found to be reduced. 32Another study also showed that 26 cases were sufficient to reduce procedural time by 2.3 times (136-59 min). 12This outcome suggests that the ZMF approach has the potential to be the guiding option for CIED insertion that is as effective and efficient as the fluoroscopy approach with a potential operator-dependence barrier.

| Benefits for clinical practice
ZMF guiding for CIEDs implantation provides benefits for both patients and medical staffs.The magnitude of fluoroscopy radiation depends on the clinical indications, comorbidities, and device type. 33,34Patients with long, multiple, and complicated procedures had higher risks of radiation injury, especially skin injuries (20 min or more of high contrast fluoroscopy or 60 min of low fluoroscopy). 4As important as the patients, medical staffs, namely interventional cardiologists, electrophysiologists, and cardiac catheterization laboratory technicians also had an increased risk of radiation-associated injuries, such as skin lesions, orthopedic problems, cataracts, and hypercholesterolemia. 35,36 The ZMF approach also allows interventional cardiac procedures for susceptible populations, such as pregnant women, pediatrics, and those with chronic kidney disease or allergic reaction to contrast. 18

| Limitations of the study
This review has several limitations.First, this review did not include all identified studies exploring the ZMF approach for CIEDs implantation.Although three studies had fulfilled our eligibility criteria, the reported data were not complete enough to be analyzed.
We had contacted the corresponding author, but there was no response. 32,37,38However, the results of these studies were linear to our results.Second, this review only included 995 participants (620 and 375 participants for permanent and temporary CIEDs, respectively), which was relatively small to draw sufficient conclusions.
Seventy percent of the studies had a sample size of less than 70.
Third, fluoroscopic measurements, such as radiation dosage and contrast volume, were underreported in most studies.Lastly, it is important to recognize that the generalizability of these findings might be constrained due to the limited focus of the included studies, one of them being the lack of data regarding pregnancy status.

2
Success rate for (A) permanent and (B) temporary CIEDs.ablation and CIEDs implantation.Despite its crucial role, fluoroscopy holds the risk of radiation exposure.4Many approaches have been carried out to reduce radiation exposure, one of them using no or less fluoroscopy.

F I G U R E 3
Procedural time for (A) permanent and (B) temporary CIEDs.F I G U R E 4 (A) Fluoroscopy time and (B) radiation dose for permanent CIEDs.

F I G U R E 5
Sum complication rate for (A) permanent and (B) temporary CIEDs.
Baseline characteristics of included studies.
27DEX-EPD, on the other hand, is the currently most novel 3D-EAMS that utilizes dielectric characteristics to reconstruct 3D images.27