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Abstract
Introduction The reduction of fluoroscopic exposure during catheter ablation of supraventricular arrhythmias is widely adopted by experienced electrophysiology physicians with a relatively short learning curve and is becoming standard of care in many parts of the world. While observational studies in the USA and some parts of Western Europe have evaluated the minimal fluoroscopic approach, there are scarce real-world data for this technique and generalisability of outcome in other economic regions.
Methods and analysis The arrhythmias with as low as reasonably achievable X-ray exposure study is a prospective, observational, multicentre and multinational open-label registry study. Up to 700 patients undergoing catheter ablation for right-sided supraventricular arrhythmias (according to national guidelines) will be enrolled for the routine use of the EnSite Precision 3D mapping system. Participating sites are distributed in 13 countries from Central Eastern Europe, North and South Africa, the Middle East and the CIS (Commonwealth of Independent States), with different levels of expertise using minimal fluoroscopic exposure techniques. After electrophysiological procedure, patients will be followed up for 6 months either in-clinic or via telephone interview. Patients will be asked to complete a study questionnaire at enrolment and 6 months after the invasive procedure to assess quality of life changes secondary to the procedure. The study’s primary objective is to describe ionising radiation exposure during catheter ablation when the EnSite Precision 3D mapping system is used in supraventricular tachycardia ablation. The study’s secondary objective is to assess the safety and efficacy of this method. Furthermore, fluoroscopy timing, total procedure time, success rate and complications will be reported.
Ethics and dissemination The study was approved by the ethics committee at Mohammed Bin Khalifa Specialist Cardiac Centre (BDF/R&REC/2020-504) and the medical ethics committees of all participating sites. Participants will be required to provide informed consent before enrolment in the study. The study results will be published and presented at conferences.
Trial registration number NCT04716270
- Pacing & electrophysiology
- RADIOLOGY & IMAGING
- Adult cardiology
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STRENGTHS AND LIMITATIONS OF THIS STUDY
Multinational observational registry study in Central Eastern Europe, Africa, the Middle East and CIS to investigate real-world outcomes of low fluoroscopy ablation treatment in right-sided supraventricular tachycardia.
Six months follow-up.
Independent data entry in electronic case report form.
Unblinded non-comparative study.
Introduction
Catheter ablation is used extensively in the electrophysiological (EP) management of symptomatic and recurrent supraventricular tachycardia (SVT).1 In this procedure, thermal injury of arrhythmogenic substrates is delivered by EP catheter. Patient-reported outcome measures consistently demonstrate that patients experience significant improvements in their quality of life following ablation.2–5
Current guidelines from European Society Cardiology (ESC), American College of Cardiology (ACC), American Heart Association (AHA), and Heart Rhythm Society (HRS) support catheter ablation as a modality of choice for long-term treatment of different types of SVTs (recommendation class I).1 6 The success rates are greater than 90% for SVT such as atrioventricular nodal reentrant tachycardia and atrioventricular re-entrant tachycardia.6
Typically, radiofrequency catheter ablation of SVT is performed under fluoroscopic guidance to navigate catheters and to monitor their location, and pulsed fluoroscopy has so far been used in interventional cardiology to track in real time the position and advancement of catheters.7 The associated exposure of ionising radiation (X-rays) in both the patient and the operator, gives rise to concern.8–10 In fact, cardiac EP procedures in their therapeutic and imaging modalities are responsible for a large share of the annual medical ionising radiation exposure.11 12 Efforts to reduce radiation exposure during catheter ablation procedures have included various technological, physical and organisational measures.13–15 The American College of Cardiology recommends the adoption of the ‘ALARA’ (as low as reasonably achievable) principle in all interventional EP laboratories.16 The Near zero fluoroscopic exposure during catheter ablation of supraventricular arrhythmias multicentre, randomised trial compared patients receiving EP treatment of their SVTs using a minimal fluoroscopic exposure approach (EnSite) and the conventional approach of catheter ablation. The effective dose was significantly reduced in the former compared with the latter group, which translates to a reduction by 96% in age-dependent lifetime attributable risks of developing or dying of cancer for those receiving an advanced ALARA treatment modality.17
A parallel comparison in a multicentric registry study of outcomes from a zero-fluoroscopy approach and conventional fluoroscopy approach in the treatment of SVT showed similar ablation and procedure times and comparable success rates in excess of 98%.18 Catheter ablation in the treatment of SVT in adults using non-fluoroscopic mapping systems such as the EnSite system has been reproducibly found to be feasible, safe and effective.19–25
Study objectives
The arrhythmias with as low as reasonably achievable X-ray exposure (AALARA) study is an international, multicentre registry study, which recruits cases as per clinical routine, and evaluates the routine use of EnSite Precision mapping during transcatheter ablation of right-sided SVT. Real-world data are used to specifically address feasibility of reduced ionising radiation exposure of EnSite assisted EP procedures in centres experienced in using three-dimensional (3D)-mapping EP technologies in Central East Europe, North and South Africa, the Middle East and the Commonwealth Independent States. Potential procedurally related quality of life changes will be assessed with patient outcome questionnaires as secondary outcome. Quantification of the fluoroscopy timing, total procedure time, procedure success rate and procedural safety are secondary objectives.
Methods and analysis
Study design
The AALARA study is a prospective, observational, multicentre and multinational open-label study, with patients being recruited from 30 sites across 13 countries: Bahrain, Bulgaria, Czech Republic, Hungary, Kazakhstan, Morocco, Russia, Serbia, Slovakia, South Africa, Tunisia, United Arab Emirates and Ukraine. The Mohammed Bin Khalifa Specialist Cardiac Centre, Riffa, Kingdom of Bahrain, is the legal sponsor, and responsible for developing, implementing and managing the study in accordance with the protocol and all applicable laws and regulations. A clinical research organisation (CRO Dr. med Kottmann GmbH & Co. KG, Hamm, Germany) has been appointed for managing regulatory submissions, creation of study database, monitoring of the sites, project management, data management and statistical analysis. The study is compliant with the requirements of ‘Good Clinical Practice’ according to ISO 14155:2020.
Participants
Inclusion criteria
Consecutive patients with SVT (at least 18 years old) for whom EP catheterisation is indicated will be screened for study participation. After written informed consent is freely given, they will be enrolled in the study.
Exclusion criteria
Pregnancy, contraindications to ionising radiation exposure in a diagnostic context, life expectancy of less than 1 year, complex congenital heart disease, cardiac implantable electronic devices, known pathological venous access to the heart and known left-sided arrhythmia substrate are exclusion criteria for this study. Patients, who are diagnosed with a left-sided arrhythmia substrate during the EP study, will be excluded from the study.
Study procedures and follow-up
This is an observational study for which pseudonymised data from patients will be collected to evaluate the study objectives. Eligible subjects will undergo EP Study (EPS) and radiofrequency catheter ablation as per routine local practice while using the EnSite Precision 3D system (figure 1).
Patient flow chart (*denotes clinic visit or phone call).
The EnSite Precision Cardiac Mapping System is a catheter navigation and mapping system capable of displaying the 3D position of conventional and sensor enabled EP catheters, as well as displaying cardiac electrical activity as waveform traces and as dynamic 3D isopotential maps of the cardiac chamber. The contoured surfaces of these 3D maps are based on the anatomy of the patient’s own cardiac chamber. Skin patches and intracardiac catheters are used as positional reference points to aid in the digital reconstruction of vascular and cardiac anatomy.26
Through a hybrid combination of impedance and magnetic field technology, the EnSite Precision system allows non-fluoroscopic positioning of catheters.
Briefly, once the right atrium is reached, the catheter is advanced and pulled back to mark the inferior and superior vena cava. A provisional right atrial geometry is created in the attempt to reconstruct the interatrial septum and to localise the ostium of the coronary sinus, where a diagnostic catheter is positioned as an anatomical reference point for the remainder of the procedure, unless a skin patch is used. The other diagnostic and ablation catheters are advanced and positioned using the same technique. After performing impedance calibration and compensation for respiratory movements, one of the catheters will be used as a roving catheter and swept through the cardiac chambers, to define endocardial boundaries and to obtain a more accurate geometry of the right atrium. If necessary, a separate geometry will be acquired in a similar manner for the right ventricle and its outflow tract.27
From this point on, the EP study and subsequent catheter ablation are carried out according to the respective guidelines and as per local standard. The use of minimum-possible fluoroscopy will be allowed whenever the operator considers it necessary for the effective and/or safe continuation of the procedure.
Follow-up visits will occur at 1 and 6 months either as in-clinic visit or phone call (table 1). The following assessments will be completed as follows:
Any postprocedural serious adverse event (SAE) defined as an adverse event that resulted from cardiac involvement during the procedure and led to death or a serious deterioration in the health of a patient that resulted in a permanent impairment of a body structure or a body function. Examples include death, cardiac tamponade, myocardial infarction, stroke, need for emergency cardiac surgery or pacemaker implantation, vascular bleeding, local haematoma, AV fistulae, pseudoaneurysm, thromboembolism, air embolism, pneumothorax and haemothorax, etc.
Change in cardiac medication.
Patient Global Assessment questionnaire at a baseline and at a 6-month visit.
Study parameters at baseline and follow-up visits
Data collection
Subject and procedural data will be recorded in electronic case report forms (eCRFs) of a customised clinical database (secuTrial, InterActive Systems GmbH, Berlin, Germany) that is FDA compliant (electronic audit trail). Patient-reported outcome questionnaires are entered by study teams at the individual sites.
Cardiac-related SAEs and SAEs related to the EP procedure will be collected in the eCRF. A reablation procedure is not considered to be an SAE.
Outcomes
Primary objective
Use of ionising radiation exposure during transcatheter ablation of SVT using the EnSite precision mapping system in a real-world clinical setting.
Secondary (safety) objectives
Efficacy of the procedure defined by non-inducibility at the end of the procedure (or bidirectional block in case of cavotricuspid isthmus ablation), and the arrhythmia-free survival during the 6 months follow-up.
Safety of the procedure defined as the incidence of procedure-related SAEs.
Quantification of the fluoroscopy timing, total procedure time.
Quality of life changes.
Data management and monitoring
The study data management plan outlines the procedures for managing study data for the AALARA study, to ensure all data are collected, verified, validated and reconciled in a manner that preserves the scientific integrity of the research.
Visual and/or electronic data review will be performed in all sites to identify possible data discrepancies or implausibilities. Manual and/or automatic queries will be created in the data management system and are issued to the site for appropriate response. Site staff trained in the study are responsible for resolving all queries within the eCRF. Reporting of SAEs follows country-specific obligations. All SAEs will be captured.
Sample size calculation
This is an observational study. No formal power analysis and sample size calculations were performed. Approximately 700 subjects will be enrolled in this study. To ensure enrolment balance across study centres, it was initially decided that no single centre would enrol more than 15% of the maximum sample size (105 subjects). However, various constraints brought about by the COVID pandemic justified the pursuit by some sites for a protocol amendment that extended their enrolment numbers (up to 135).
Statistical analysis
No hypothesis tests will be performed. Statistical analysis will be performed by using SAS, or other analysis tools/software as necessary. The primary efficacy parameter will be the ionising radiation exposure during transcatheter ablation of SVT. The endpoints will be summarised descriptively based on available data or measurements in the analysis population. Continuous variables will be summarised with the numbers of observations, means with SDs, quartiles, minimums, maximums and 95% CIs for the means. Categorical variables will be summarised with subject counts and percentages/rates and exact 95% Clopper-Pearson CIs, where appropriate.
Bias
The multicentre participation of EP laboratories is designed to depict generalisable real-world data for the catheter radiofrequency ablation of SVT.
Patient and public involvement
None.
Ethics and dissemination
The study was approved by the ethics committee at Mohammed Bin Khalifa Cardiac Centre (BDF/R&REC/2020-504) and the medical ethics committees of all participating sites. The study is conducted in accordance with the ethical principles for medical research involving human subjects (Declaration of Helsinki). Eligible participants will be informed and consented before enrolment in the study. Their pseudonymised data will be collected in a study specific, password secure electronic database. All research documents (investigator site files) are stored in a safe location in each of the study sites.
The multicentre study is conducted at sites with staff trained in the outcomes of the study protocol. The study team at each site includes the local primary investigator, EP assistants, study nurses, research coordinator, etc. The results from the study will be published and presented at conferences.
Discussion
3D electroanatomic mapping systems have significantly enhanced the portfolio of interventional cardiology: the ability to visualise EP catheters without the use of fluoroscopy has led to catheter ablation of SVT with zero or minimal fluoroscopy.28–30 The technique can be used in routine clinical practice by experienced operators and applied to a wide range of patient presentations.31 32
Constraints in countries’ health economies are relevant in the introduction and application of new generation mapping systems in the treatment of tachycardias,33 leading to a worrisome disparity in specialist cardiological care.34
Two recent European registry studies have demonstrated that reduced use of fluoroscopy did not compromise safety or efficacy of indicated interventional EP procedures.35 36 With regard to Ensite Precision mapping system assisted catheter ablation of SVT, prospective and retrospective studies have shown a stark reduction in fluoroscopy time: no X-rays were used in 96/134 cases,17 in 70/70 cases25 and in 47/50 cases.24 These studies highlight that affordability of zero or minimal fluoroscopic EP ablation procedures need to be balanced against shortened procedural time, greater anatomic and EP information and long-term cost-effectiveness.
An observational study of ablations performed with Ensite conducted in high-income countries has recently been published but excluded patients with AV node dependent tachycardia.37 A recent meta-analysis of 24 studies comparing procedural parameters and outcomes of conventional, fluoroscopy-guided versus minimal fluoroscopic approaches in patients undergoing electrophysiology (EP) procedures for SVTs showed feasibility of this method in reducing radiation exposure and ablation time without compromising the acute and long-term success or complication rates.38
AALARA is the first international, prospective, observational study designed to provide real-world data on low fluoroscopy ablation in right-sided SVTs, collected from a large sample size across different geographies. It primarily aims to demonstrate in a real-world clinical setting that a clinically significant reduction of ionising radiation exposure during transcatheter ablation of SVT does not compromise efficacy and safety of invasive EP procedures. The limitations are the relatively short-term follow-up of 6 months, the non-world-wide enrolment and the unblinded, non-comparative nature. The results of the study could help re-educate EP-centres that the reduced use of X-ray during the ablation of supraventricular arrhythmias that minimises the radiation burdens for both patients and importantly EP physicians is an efficient and beneficial advance in medical technology.
Study status
The registry study started on 20 January 2022 and is currently recruiting patients. Results are expected in 2023.
Ethics statements
Patient consent for publication
References
Footnotes
Twitter @Аян Абдрахманов
Contributors Study design: NS, EK, AA, FL, VT, OS and MA. Drafting of the manuscript: MA. Critical revision of the manuscript: NS, MA, SS, VT, FL and AA. Approval of the final version (on behalf of all investigators): MA.
Funding The AALARA study is funded by Abbott Medical. The funder had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.