Basket catheter-guided ultra-high-density mapping of cardiac arrhythmias: a systematic review and meta-analysis
Abstract
Aim: Ultra-high-density mapping (HDM) is increasingly used for guidance of catheter ablation in cardiac arrhythmias. While initial results are promising, a systematic evaluation of long-term outcome has not been performed so far. Methods: A systematic review and meta-analysis was conducted on studies investigating long-term outcome after Rhythmia HDM-guided atrial fibrillation (AF) or atrial tachycardia catheter ablation. Results: Beyond multiple studies providing novel insights into arrhythmia mechanisms, follow-up data from 17 studies analyzing Rhythmia HDM-guided ablation (1768 patients, 49% with previous ablation) were investigated. Cumulative acute success was 100/90.2%, while 12 months long-term pooled success displayed at 71.6/71.2% (AF/atrial tachycardia). Prospective data are limited, showing similar outcome between HDM-guided and conventional AF ablation. Conclusion: Acute results of HDM-guided catheter ablation are promising, while long-term success is challenged by complex arrhythmogenic substrates. Prospective randomized trials investigating different HDM-guided ablation strategies are warranted and underway.
Ultra-high-density mapping (HDM) in conjunction with novel automated annotation algorithms is increasingly used in clinical routine as it provides novel insights into arrhythmia mechanisms. The Rhythmia HDM system (Boston Scientific, MA, USA) was introduced in 2012 and has since proven to be feasible and safe in various settings, while showing promising acute results in early studies [1–3]. The technical features consist of a 64-pole basket catheter of variable diameter minimizing far-field signals, as well as background noise of up to 0.01 mV [4,5] and automated point annotation during acquisition thousands of mapping points, resulting in higher resolution mapping of low-voltage zones and scar tissue with a more detailed display of myocardial wavefront propagation in cardiac arrhythmia. An increasing number of single-center and first multicenter studies have been published recently, while long-term outcome following HDM-guided catheter ablation in several patient populations remains unclear.
Objective
The aim of the present systematic review and meta-analysis was to analyze procedural characteristics as well as acute and long-term outcome of studies investigating Rhythmia HDM-guided catheter ablation with special emphasis on patients with atrial fibrillation (AF) and atrial tachycardia (AT). Furthermore, we analyzed studies investigating HDM-guided ablation of arrhythmia in patients with congenital heart disease and studies investigating a novel algorithm (LUMIPOINT) for postprocedural signal processing.
Methods
Literature search
Two investigators assessed potentially eligible studies independently (FA Alken and C Meyer). All studies referencing the Rhythmia HDM system and catheter ablation of AF or AT were identified. Furthermore, all studies investigating Rhythmia HDM-guided ablation in patients with congenital heart disease as well as studies analyzing a novel algorithm for postprocedural signal analysis (LUMIPOINT) were separately identified. The literature search was initiated on 20 January 2020 and was repeated periodically until 2 February 2020. We searched PubMed/MEDLINE (7 January 2020 until 2 February 2020), EMBASE (7 January 2020 until 2 February 2020), and the Cochrane Central Register of Controlled Trials (CENTRAL – until 2 February 2020) using the following search terms: ‘rhythmia;’ ‘high-density mapping;’ ‘high-density mapping;’ ‘ultra-high density mapping;’ ‘ultra high density mapping;’ ‘ablation;’ ‘ atrial fibrillation;’ ‘AF;’ ‘atrial tachycardia;’ ‘AT;’ ‘atrial flutter;’ ‘LUMIPOINT;’ ‘congenital heart disease;’ ‘arrhythmia.’ We excluded references not published in English unless an English version of the abstract was accessible. In an attempt to access the grey literature, we searched the OpenGrey Database [6] and the online trial registry [7]. The screening process was facilitated using the reference management software Endnote X9 and the selection process was documented using a PRISMA [8] flow diagram. A completed PRISMA checklist can be accessed in the Supplementary material.
Study selection & eligibility criteria
There were no restrictions regarding the study design. For the primary analysis, we only included studies investigating patient outcome (including a follow-up of >3 month) of HDM-guided catheter ablation of AF or AT using the Rhythmia system. Secondary, all studies investigating long-term outcome in HDM-guided ablation of arrhythmias in patients with congenital heart disease as well as outcome of studies analyzing the LUMIPOINT algorithm were analyzed.
The following exclusion criteria were applied: (1) Studies investigating Rhythmia HDM without guided ablation or including other HDM systems in the same study group additional to Rhythmia; (2) case reports and case series; (3) animal studies; (4) review articles; (5) studies published in abstract form only; (6) studies of which the abstract was not available in English; (7) studies not including a follow-up beyond the 3 months blanking period; (8) studies investigating arrhythmias other than AF/AT; (9) studies of the same authors investigating nearly identical cohorts in different publications on distinct topics. Furthermore, we qualitatively analyzed HDM long-term ablation outcome in adults with congenital heart disease and the application of a novel algorithm (LUMIPOINT) for postprocedural signal processing separately. We supplemented our database searches with manual searches of the reference lists of published studies and major review articles.
Assessment of risk of bias
The quality of included studies was assessed using the Risk of Bias Assessment Tool for Nonrandomized Studies (RoBANS) [9]. This assesses the following domains: selection bias (bias due to selection of participants/confounding variables); performance bias (bias in measurement of exposure); detection bias (blinding of outcome assessments); attrition bias (bias due to incomplete data) and reporting bias (bias due to selective outcome reporting). For randomized studies, the Cochrane risk-of-bias tool for randomized trials (RoB 2) was used [10]. Where impact studies were identified, quality assessment was extended using additional tools depending on the study design. For assessment of risk of publication bias across all included studies, funnel as well as Doi plot analysis were conducted [11].
End points & data analysis
The following outcomes of interest were extracted and analyzed from each publication: Acute success, freedom of arrhythmia during long-term follow-up, procedure duration, fluoroscopy time, radiofrequency energy application duration, mapping time and collected points per map. Data extraction was conducted using a predefined custom data extraction form (Microsoft Excel 2019). We attempted to contact authors to clarify any areas of uncertainty regarding study data. Statistical analysis was conducted using Graphpad Prism 8 (CA, USA) and OpenMetaAnalyst (version 10.12). A p-value < 0.05 was considered statistically significant. For random effects, the empirical bayes and for fixed effects the inverse variance model were calculated. For comparison of long-term outcome after AF ablation using HDM vs conventional point-by-point mapping-guided ablation, the pooled risk ratio was calculated using the Mantel-Haenszel random effects model with a 95% confidence interval. For assessment of heterogeneity between studies, measurement of inconsistency using the I2 index was conducted which describes the total variation percentage across all studies. Heterogeneity was classified into small, moderate, and large amounts (I2 values of 25, 50 and 75%, respectively). Forrest, funnel and Doi plots were generated using the Microsoft Excel add-in MetaXL (version 5.3, EpiGear International Pty. Ltd.).
Additionally, studies investigating long-term outcome of HDM-guided ablation in adults with congenital heart disease as well as studies investigating novel LUMIPOINT algorithm for guidance of reentrant tachycardia ablation were each narratively analyzed separately, as meta-analysis was not possible due to heterogenous patient cohorts and investigated arrhythmias.
Results
Study selection & characteristics
A detailed flowchart of the study selection process is shown in Figure 1. The initial literature search resulted in 349 titles and abstracts, with subsequent exclusion of 296 abstracts. In total, 53 full-length manuscripts were reviewed for final inclusion, of which 17 were eligible for systematic analysis (AF ablation n = 6; AT ablation n = 11) published between October 2016 and February 2020. The most common reasons for exclusion were no long-term follow-up included in studies (n = 10) or ablation of arrhythmias other than AF/AT (n = 12). Furthermore, four articles investigating Rhythmia HDM-guided ablation in patients with congenital heart disease, two articles describing a novel algorithm (LUMIPOINT) and one article investigating both HDM in congenital heart disease and LUMIPOINT were analyzed separately.
Flow diagram of included studies for primary outcome of arrhythmia recurrence during long-term follow-up after HDM-guided catheter ablation.
AF: Atrial fibrillation; AT: Atrial tachycardia; CHD: Congenital heart disease; HDM: Ultra-high-density mapping.
Study and baseline patient characteristics as well as procedural data and follow-up outcome rates are shown in Tables 1 and 2, respectively. The selected studies included 1768 patients (AF n = 1246; AT n = 522; range 8–602) from 21 centers in 7 countries, with 49% of patients having undergone previous catheter ablation. In total, seven studies were designed prospectively with one randomized single-center study, whereas 10 studies were conducted in multiple centers. All studies investigating AF/AT included a 3-month blanking period, with duration of follow-up differing between studies (range 6–24 months).
| Study, year | Study design | CNT | Groups | Arrhythmia type | Age (years) | SHD (%) | CHF (%) | HTN (%) | DM (%) | CAD (%) | CHA2DS2- VASc, n | LVEF (%) | Previous ablation (%) | Ref. |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| AF | ||||||||||||||
| Ballesteros, 2019 | Prospective, observational (index or redo ablation) | 1 | HDM | Paroxysmal/ persistent AF | 64 ± 9 | NA | 10 | 57 | 13 | 4 | NA | 62 ± 7 | 42 | [12] |
| Masuda, 2019 | Retrospective, comparative (redo ablation) | 1 | HDM | Paroxysmal/ persistent AF | 68 ± 10 | NA | 14 | 50 | 19 | NA | 2.2 ± 1.2 | 63 ± 9 | 100 | [13] |
| COM | Paroxysmal/ persistent AF | 67 ± 9 | NA | 11 | 59 | 12 | NA | 2.2 ± 1.4 | 65 ± 9 | 100 | ||||
| Siebermair, 2019 | Retrospective, comparative (index ablation) | 1 | HDM | Paroxysmal/ persistent AF | 65 ± 12 | NA | NA | 70 | 15 | 24 | 2.6 ± 1.8 | 60 ± 10 | 0 | [14] |
| 66 ± 10 | NA | NA | 80 | 13 | 17 | 2.3 ± 1.5 | 63 ± 12 | 0 | ||||||
| Segerson, 2018 | Retrospective, comparative (index or redo ablation) | 3 | HDM (index + redo) | Paroxysmal/ persistent AF | 66 ± 19 | NA | 6 | 62 | NA | NA | 1.1 ± 1.9 | NA | 26 | [15] |
| COM (index) | Paroxysmal/ persistent AF | 67 ± 20 | NA | 5 | 60 | NA | NA | 1.2 ± 1.8 | NA | 0§ | ||||
| Garcia-Bolao, 2017 | Retrospective, observational (redo ablation) | 1 | HDM | Paroxysmal/ persistent AF | 66‡ | NA | NA | NA | NA | NA | 1.1 ± 1.9 | 63‡ | 100 | [16] |
| COM | Paroxysmal/ persistent AF | 64‡ | NA | NA | NA | NA | NA | 1.2 ± 1.8 | 65‡ | 100 | ||||
| Rottner, 2017 | Prospective, comparative, randomized (index ablation) | 1 | HDM | Paroxysmal/ persistent AF | 64 ± 10 | NA | NA | 62 | 11 | NA | 2 (1–2) | 60 (59–65) | 0 | [17] |
| COM | Paroxysmal/ persistent AF | 66 ± 9 | NA | NA | 65 | 14 | NA | 2 (1–3) | 65 (50–65) | 0 | ||||
| AT | ||||||||||||||
| De Simone, 2020 | Retrospective, observational | 4 | HDM | Intra-atrial reentry | 54 ± 9 | NA | NA | NA | NA | NA | NA | NA | 79 | [18] |
| Barkagan, 2019 | Prospective, observational | 1 | HDM | Perimitral macro-reentry | 59 ± 7 | NA | NA | 39 | NA | NA | NA | 58 ± 7 | 75 | [19] |
| Maury (Heart Vessels), 2019 | Retrospective, comparative | 1 | HDM | Right/left AT | 63 ± 11 | 78 | 50 | 57 | 12 | NA | NA | 52 ± 13 | 78 | [20] |
| COM | Right/left AT | 64 ± 11 | 82 | 57 | 57 | 22 | NA | NA | 46 ± 16† | 58 | ||||
| Maury (JACC CE), 2019 | Retrospective, observational | 2 | HDM | Right/left AT | 61 ± 13 | 47 | 25 | NA | NA | NA | NA | 54 ± 12 | 90 | [21] |
| Yamashita, 2019 | Retrospective, observational | 6 | HDM | Pulmonary vein reentry | 63 ± 11 | NA | NA | NA | NA | NA | 0.7 ± 0.6 | 57 ± 11 | 100 | [22] |
| Kitamura, 2018 | Retrospective, observational | 2 | HDM | Biatrial AT | 60 (51–69) | NA | 13 | NA | NA | NA | 1.0 (1.0–3.0) | 60 (58–66) | 100 | [23] |
| Takigawa (Heart Rhythm), 2018 | Prospective, observational | 1 | HDM | Anatomic macro-reentry | 62 ± 9 | 23 | 8.8 | 42 | 4 | NA | 1.4 ± 1.2 | 54 ± 11 | 100 | [24] |
| Takigawa (Circulation AE), 2018 | Retrospective, observational | 4 | HDM | Post AF ablation AT | 66 ± 8 | 36 | 26 | 52 | 7 | NA | 2.0 ± 1.3 | 53 ± 11 | 100 | [25] |
| Xue, 2018 | Prospective, observational | 1 | HDM | Post-surgical AT | 53 ± 12 | 100 | 9 | 18 | 14 | 6 | NA | NA | 47 | [26] |
| Latcu, 2017 | Prospective, observational | 1 | HDM | Scar-related | 71 (64–75) | 42 | 53 | 55 | NA | 10 | 2 (1–3) | 62 (55–67) | 84 | [27] |
| Anter, 2016 | Prospective, observational | 3 | HDM | Previously failed AT- ablation | 62 ± 7 | NA | NA | NA | NA | NA | NA | 60 (50–60) | 100 | [28] |
| Study, year | Patients enrolled, n | Procedure duration (min) | Fluoroscopy time (min) | Radiofrequency application time (min) | Mapping points, n | Acute success (%) | Follow-up (months) | Freedom of arrhythmia (%) | Ref. |
|---|---|---|---|---|---|---|---|---|---|
| AF | |||||||||
| Ballesteros, 2019 | 98 | NA | NA | NA | 12,567 ± 5,486 | NA | 12‡ | 70 | [12] |
| Masuda, 2019 | HDM: 103 COM: 153 | NS‡ | NS‡ | HDM<COM‡ | NA NA | 100 100 | 12‡ | 59.2 56.2 | [13] |
| Siebermair, 2019 | HDM: 54 COM: 54 | 248 ± 60 263 ± 50 | 19 ± 11 30 ± 13† | NS‡ | NA NA | 100 100 | 24 (495 ± 26 days) | 53.5 57.8 | [14] |
| Segerson, 2018 | HDM:150 COM: 452 | NA NA | NA NA | NA NA | 4,000‡,¶ NA | 99 100 | 12 (320 ± 120 days) | 90.3 73.9† | [15] |
| Garcia-Bolao, 2017 | HDM: 54 COM: 54 | 142 ± 42 138 ± 44 | NA NA | 7.6 ± 3 9.3 ± 5† | 13,425 ± 5,422 NA | 100 100 | 6‡ | 85.2 70.4 | [16] |
| Rottner, 2017 | HDM: 37 COM: 37 | 110 ± 33 108 ± 20 | 22 ± 6 13 ± 7† | 46 (38–57) 40 (35–50) | 8,365 (6,183–12,625) 96† (72–112) | 100 100 | 6 (187 [152–203] days) | 85 88 | [17] |
| AT | |||||||||
| De Simone, 2020 | 24 | NA | NA | NA | 19,023 ± 11,197 | 96 | 18 ± 3 | 88 | [18] |
| Barkagan, 2019 | 56 | NA | NA | NA | NA | 96 | 15 ± 5 | 76.8 | [19] |
| Maury (Heart Vessels), 2019 | HDM: 60 COM: 60 | 216 ± 66 195 ± 61 | 29 ± 16 25 ± 12 | 27 ± 17 27 ± 22 | 10,543 ± 5,854 689 ± 1,827† | 77 77 | 12‡ | 63 49† | [20] |
| Maury (JACC CE), 2019 | 100 | 244 ± 79 | 55 ± 33 | NA | 13,550 ± 6,316 | NA | 12 ± 6 | 40 | [21] |
| Yamashita, 2019 | 26 | NA | NA | NA | 18,596 ± 7,434 | 100 | 12‡ | 77 | [22] |
| Kitamura, 2018 | 8 | 245 (240–375) | 20 (17–25) | NA | 11,083 ± 5,495 | 88 | 12 (9–20) | 88 | [23] |
| Takigawa (Heart Rhythm), 2018 | 57 | NA | NA | 6.4 ± 8.8 | 15,350 ± 7,638 | 75 | 6‡ | 84 | [24] |
| Takigawa (Circulation: AE), 2018 | 41 | 305 ± 93 | NA | 35.5 ± 15.0 | 16,270 ± 7,575 | 100 | 12‡ | 53.7 | [25] |
| Xue, 2018 | 51 | NA | NA | NA | 9059 (1,804–41,827) | 88 | 10‡ (median; range 1–22) | 82 | [26] |
| Latcu, 2017 | 19 | 257 ± 64 | 18 ± 10 | 18 ± 12 | 25,684 ± 14,276 | 97 | 12 (9–14) | 84§ | [27] |
| Anter, 2016 | 20 | NA | NA | 3.2 ± 2.6 | 12,480 ± 4,266 | 100 | 7.5 ± 3 | 75 | [28] |
Atrial fibrillation
A total of 1246 patients (HDM ablation only n = 496) were included in 6 studies [12–17] published during 2017–2019, with 4 studies being retrospective and 2 prospective by design. In 5 studies, a comparison of HDM to conventional mapping-guided ablation was conducted, with 1 study being prospective by design. Acute success of index or redo AF ablation was investigated in 2 studies each, while 2 studies investigated outcome in patients undergoing either index or redo AF ablation.
All patients presented with either paroxysmal or persistent AF, with persistent AF being present in approximately half of overall included patients (mean 51%). Baseline patient characteristics were similar between HDM and conventional mapping groups, with the pooled mean age being 66 years and 63% being male. Previous catheter ablation was conducted in 36% of patients.
Procedural characteristics showed no differences between groups regarding mean procedure time, while radiofrequency application time appeared to be significantly lower in the HDM group in 2 studies [14,16]. In contrast, 1 study including a learning curve reported higher mean fluoroscopy times in the HDM group [17]. Major cardio-/cerebrovascular complications were relatively low (range 0–8.1%), with no procedure-related deaths or significant differences in complication rates being reported between groups in all studies. Procedural characteristics showed acute procedural success rates of 100% in almost all studies with no significant differences between groups.
Antiarrhythmic drugs were systematically discontinued after a 90-days blanking period in 24.6% of patients and in 3 out of 6 studies. The follow-up range was 6–24 months, with freedom of all atrial arrhythmia after HDM-guided ablation ranging between 59.2–90.7% of patients.
When comparing HDM and conventional mapping-guided ablation, pooled single-procedure success rates (freedom from all atrial arrhythmias) at 6 months for HDM/conventional mapping-guided ablation were 80.3/73.8% in 4 studies with a risk ratio of 0.812 (0.601; 1.095) using the random effect model, showing a trend towards HDM-guided ablation without reaching significance level (Figure 2A). Similarly, pooled 12 months success rates described in 4 studies for HDM/ 3 studies for HDM and conventional mapping-guided ablation were 71.6 (59.0; 84.2)/65.7 (55.6; 75.9)% and showed no significant difference between both groups with a risk ratio of 0.720 (0.372; 1.395) (Figure 2B). When separating studies conducting first AF ablation versus redo ablation only (n = 2 each), no significant difference regarding outcome was observed between HDM and conventional mapping-guided ablation.
(A) Six months freedom of all atrial arrhythmia after first or redo atrial fibrillation (AF) ablation is being shown, comparing ultra-high-density mapping (HDM) vs conventional point-by-point mapping (COM).
(B) Twelve months success after first or redo AF ablation is demonstrated. Both groups show no significant difference regarding atrial arrhythmia freedom.
(C) Pooled 12 months success after HDM-guided atrial tachycardia (AT) ablation is presented. Using the random effect model, approximately 71.2% of patients showed freedom of arrhythmia during the first-year post-ablation.
AF: Atrial fibrillation; AT: Atrial tachycardia; CI: Confidence interval; COM: Conventional point-by-point mapping; HDM: Ultra-high-density mapping.
Atrial tachycardia
Eleven studies [18–28] enrolling a total of 522 patients (HDM only n = 462) were analyzed, with 6 studies being prospective by design. Four studies investigated post-interventional scar-related AT (AF/AT ablation, cardiac surgery; n = 131), while 2 studies each included patients with any AT (n = 220) or biatrial AT (n = 32 patients) and 1 study each examining anatomic macro-reentry AT (n = 57), perimitral AT (n = 56) and pulmonary vein reentry AT (n = 26).
Overall patient characteristics displayed as following: The pooled mean age was 63 years, with 55% being male and 64% having undergone previous catheter ablation. Patients presented with a mean of 1.15 ATs per patient, with the majority displaying a macroreentrant circuit (83%). Periprocedural complications were relatively low, ranging from 0–3.8% (cerebral hemorrhage, respectively).
Acute success was 90.2% across all studies. Nine studies reported a follow-up of 12 months after ablation, with 1 displaying outcome after multiple procedures [27]. Therefore, analysis of 8 studies showed a pooled mean 12 months success rate of HDM-guided AT ablation of 71.2 (58.7; 83.6)% using the random effect model (Figure 2C). One study prospectively investigated HDM-guided AT ablation in comparison to conventional mapping-guided procedures, showing similar procedural characteristics between groups and a significant benefit for HDM during 12 months follow-up of 63% arrhythmia freedom compared with 49% in the conventional mapping group [20].
HDM-guided ablation in adults with congenital heart disease
A detailed study overview is displayed in the Supplementary material. Five studies (four single-central and one multicentral, all retrospective by design) investigated acute and long-term outcome of HDM-guided ablation in a total of 120 adults with congenital heart disease, with 2 studies evaluating patients with AT only [29,30] and 3 studies analyzing ablation in heterogenous atrial/ventricular arrhythmias [31–33]. According to the current classification of anatomy and physiological stage in congenital heart disease [34], overall 15/57/28% presented with congenital heart disease of mild/moderate/severe complexity. Mean/median age ranged between 33 and 53 years, with approximately 40/70% of patients having undergone prior catheter ablation/cardiac correction surgery, respectively.
The range of acute complete ablation success was 66.7–96.7% across all studies. During a follow-up of 4–15 months, long-term success rate after HDM-guided ablation was reported to be 44–87%, while long-term success rates appeared to be higher in studies investigating AT ablation only [29,30].
Postprocedural signal processing: LUMIPOINT algorithm
A detailed study overview is displayed in the
Risk of bias
Detailed results are displayed in Figure 3. Overall, 7 studies (41%) indicated selection bias, as defined groups either differed in cohort [14]/case-control studies [15] or before-after studies being retrospectively designed [18,21–23]. Furthermore, there was poor reporting regarding analysis of confounding variables such as a learning effect during performance of HDM-guided ablation over time, with only 3 studies (18%) clearly indicating low bias. Performance bias caused by inadequate measurements of exposure was estimated to be low in 12 studies (71%). Moreover, reports regarding blinding of outcome assessment indicating detection bias was insufficient in 9 studies (53%). The majority of studies showed low attrition bias, as complete report of data was observed in 16 studies (94%). Selective outcome reporting bias was high/unclear in 4/1 studies (24/6%).
(A) Assessment of risk of bias using the Risk of Bias Assessment Tool for Nonrandomized Studies (RoBANS) [9]. A high degree of potential bias was detected in the selection of participants in included studies.
(B & C) Estimation of overall publication bias using the funnel as well as Doi plot in studies investigating atrial fibrillation (B) as well as atrial tachycardia ablation (C). Overall, a major asymmetry is visible, indicating a high probability of publication bias.
There was a high risk of publication bias across all studies, as a major asymmetry was indicated by funnel and Doi plot analysis, with a calculated LFK index of -4.33/-2.12 in AF/AT studies.
Discussion
This is the first systematic review and meta-analysis investigating outcome in patients undergoing Rhythmia HDM-guided catheter ablation of atrial cardiac arrhythmias. The following main findings can be summarized: (1) An increasing amount of studies accumulated within the last 5 years opened-up new avenues in the mechanistic understanding of complex arrhythmias including AF and AT. However, large randomized controlled studies are still lacking. (2) In patients with AF, mid-term 12 months success rates were comparable between HDM and conventional mapping-guided procedures during either first AF ablation or redo procedures. (3) Acute success rates of HDM-guided catheter ablation are high, but are challenged by mid-term outcome especially in patients with complex arrhythmia substrates with previous ablation procedures. (4) Reported single-center and one multi-center experiences of HDM-guided ablation in patients with congenital heart disease seems promising especially for ablation of complex scar-related AT. (5) Postprocedural signal analysis using novel algorithms may be beneficial for enhanced critical isthmus detection, but prospective data are needed for further validation.
The role of HDM in atrial fibrillation ablation
Pulmonary vein isolation has been established as an important catheter-based ablation strategy of choice in patients with symptomatic paroxysmal or persistent AF [37], as additional approaches (i.e., linear ablation or ablation of complex fractionated atrial electrograms) resulted in heterogenous outcomes without proving consistent benefit in multicenter randomized trials [38,39]. HDM has now deepened our understanding of cardiac electrophysiology and arrhythmogenesis due to rapid acquisition of thousands of activation points with high spatiotemporal resolution [40]. In reviewed studies, overall procedural characteristics as well as acute and long-term results were similar between HDM and conventional mapping-guided radiofrequency ablation.
No comparisons of HDM to ‘one-shot’ devices like the established cryo-balloon for index AF ablation have been conducted so far. The cryo-balloon seems to provide shorter left atrial as well as overall procedure times in comparison to radiofrequency energy with possibly better outcome and safety profile during first time pulmonary vein isolation [41–43]. However, antral excitability can be present after pulmonary vein isolation even when a reconnection is not observable using conventional methods, resulting in overestimation of set lesions [38,44,45]. Anter et al. described enhanced detection of persistent pulmonary vein potentials after incomplete ablation using HDM in comparison to a spiral catheter [46]. Segerson et al. demonstrated a possible benefit of HDM-guided additional targeting of persistent antral potentials in comparison to conventional pulmonary vein isolation alone [15]. In redo procedures, HDM based approaches might reduce radiofrequency application duration due to enhanced detection of pulmonary vein reconnection [13,16,47]. As AF activation mapping was not conducted in included studies, the value of HDM for AF rotor detection and consecutive long-term outcome remains unclear [48].
HDM might therefore be valuable for enhanced elimination of (recurrent) conduction between pulmonary veins and the left atrial appendage needed for sufficient AF termination as well as avoiding stiff atrial syndromes in some patients [49]. Nevertheless, prospective randomized multicenter studies are needed and underway for further evaluation.
Of interest, several studies showed a correlation between the extent of atrial low-voltage areas assessed by HDM and functional as well as structural parameters of atrial function, higher arrhythmia recurrence rates and cardioembolic incidences [50–52]. Therefore, HDM-guided AF ablation might be useful for further characterization and risk stratification of a possible ‘atrial cardiomyopathy’ beyond improvement of long-term ablation success rates only [53].
Analysis of atrial tachycardia circuits
Complex ATs have been encountered more frequently during the last decade especially due to rising numbers of catheter-based ablation procedures. While only 1 study has investigated HDM in comparison to conventional mapping-guided ablation [20], we found a recurrence rate of the index AT to be <2% in a patient series including >200 patients (unpublished). Overall, long-term success rates showed a relevant variance (range 40–91%), as challenging AT cohorts with distinct tachycardia mechanisms were investigated.
Previous data of conventional mapping-guided AT ablation reported acute success rates to be 80% in a Swedish registry of AT ablation and 18% repeat ablation rate during 3 years follow-up [54]. Another study investigating long-term conventional mapping-guided AT ablation success displayed 65.7% of patients with freedom of atrial tachyarrhythmias during a mean follow-up time of 90 months including patients with post-incisional AT. However, the majority of patients in this study presented with typical cavotricuspid dependent atrial flutter [55]. Therefore, a direct comparison of recurrence rates has to be conducted with care. A first randomized controlled study investigating different AT ablation strategies is underway (CONCLUDE study).
In our meta-analysis, approximately 83% of AT patients showed underlying macro-reentry circuits. Post AF ablation patients showed a significant amount of multiple-loop macroreentrant ATs often involving non-anatomic and anatomic circuits [24]. Moreover, HDM recently revealed the relevance of epicardial structures involved, which were difficult to diagnose in conventional mapping-guided procedures [56]. HDM can therefore be an important tool for precise diagnosis of wavefront propagation and detection of complex AT circuits [19,24,57].
HDM-guided ablation in congenital heart disease: the ‘ideal’ candidate?
Previous surgical interventions as well as anatomic anomalies often create complex arrhythmias in adults with congenital heart disease [58], with catheter ablation remaining the therapy of choice because of limited options for antiarrhythmic drug treatment [59]. In our meta-analysis, long-term freedom of arrhythmia was described to be between 44–87% across studies, showing a significant variance. This may be due to a relevant heterogeneity between cohorts: Higher success rates were observed in the studies of Mantziari [30] and Martin [29] having investigated congenital heart disease patients with AT only in comparison to our recently published data having investigated multiple arrhythmias [31]. Moreover, in line with previous studies success rates seemed to be overall lower compared with the general population investigated despite using the same HDM system, which may be explained by the overall more complex underlying arrhythmogenic substrate.
Rapid & automated signal processing for analysis of complex activation pattern
While HDM has been implemented over the last 5 years into clinical practice, novel standardized ablation strategies are still to be established. Over a decade ago, Knecht et al. proposed a practical algorithm involving electrophysiological mapping and entrainment for correct AT diagnosis [60]. Nevertheless, entrainment suffers from several limitations such as potentially leading to AT termination or overestimation of isthmus dimensions [27,61,62]. On the other hand, a relevant rate of multiple-loop macroreentry and localized-reentry ATs may not be classified correctly by HDM, as visual differentiation of active from passive or blind loops can be challenging [63,64]. With the addition of postprocedural signal processing algorithms (here: LUMIPOINT), detection of the potential critical isthmus may be enhanced as the algorithm highlights areas with simultaneous activation independent of activation time annotation with increased precision.
We therefore propose a modified step-wise approach for correct AT diagnosis and tailored catheter ablation (Figure 4): After initial activation mapping of the clinical AT, advanced automated signal analysis (here LUMIPOINT algorithm) can be conducted in case of suspected multiple-loop AT or microreentry mechanism as well as complex single-loop AT for potential critical isthmus site detection. Afterwards, targeted entrainment can be considered for differentiation of active and passive/blind loops [63]. Beyond correct analysis of atrial activation and isthmus localization alone, future innovations such as catheters incorporating local impedance data [65] may improve catheter energy application for more durable lesions, which is of great importance for long-term success.
A possible standardized approach for tailored ablation of complex AT is displayed, aiming for enhanced detection of critical isthmus sites using ultra-high-density mapping with postprocedural signal processing tools (here: LUMIPOINT) and targeted entrainment.
AT: Atrial tachycardia.
Limitations
There are several limitations to this study. First, information of several parameters were not obtainable in some studies. Second, in patients with AF studies included index as well as redo ablation procedures with a heterogenous cohort of patients. As a result, success rates are related to overall AF ablation. Third, AT ablation cohorts were heterogenous and investigated several distinct AT mechanisms, which has to be considered during interpretation of presented data. Fourth, follow-up duration and strategies differed between studies. Fifth, overall safety has not been investigated in detail. Nevertheless, acute safety and feasibility of the Rhythmia system have been already demonstrated in the recently published TRUE HD study with prospective multicentral inclusion [3]. Sixth, different ablation catheters were used throughout all studies and 5 studies implemented contact force analysis for ablation, which might be a confounder for presented results [66]. Seventh, this study only investigated the performance of the Rhythmia HDM system, as a comparison to other HDM systems was not the aim of this study. Lastly, current data availability is limited as prospective randomized trials are lacking and the risk of bias assessment showed a high risk of publication as well as selection bias, which has to be considered for the interpretation of presented results.
Conclusion
Catheter ablation based on basket catheter-guided HDM provides promising acute success rates in patients with AF or AT even having undergone multiple previous catheter ablation and/or surgical procedures. However, prospective long-term follow-up data so far are sparse and success rates are challenged by complex arrhythmogenic substrates. Beyond systematic investigation of novel HDM-guided ablation strategies, improved approaches for creation of durable transmural lesions appear to be key for successful long-term arrhythmia freedom. Prospective randomized trials investigating different HDM-guided ablation strategies are warranted and underway.
Future perspective
Novel algorithms may enhance automatized processing and interpretation of thousands of activation points, allowing to predict not only critical isthmus sites of present but also future arrhythmias. These algorithms, alongside with classical strategies including targeted entrainment can guide precise critical isthmus site detection while avoiding ‘hot’ or ‘ablation mapping.’ For improved therapy planning, future approaches are increasingly under development including various machine learning algorithms from body surface and intracardial electrical signatures of the heart. In conjunction with novel imaging modalities including periprocedural integration of scar areas, these tools might additionally help to avoid unnecessary radiofrequency application. These advanced mapping strategies combined with improved lesion formation and its monitoring might hopefully translate into improved patient outcome in the future.
Within the last 5 years, an increasing amount of studies provided new insights into arrhythmogenic substrate and myocardial wavefront propagation in different arrhythmias using ultra-high-density mapping (HDM).
Acute success rates of HDM-guided atrial fibrillation/atrial tachycardia ablation including patients with complex arrhythmia substrates are promising, showing overall acute success rates of 100/90.2% throughout various patient populations.
Procedural characteristics as well as long-term success rates of atrial fibrillation ablation were comparable between HDM and conventional mapping-guided ablation in patients undergoing either index or redo atrial fibrillation ablation.
HDM-guided atrial tachycardia ablation showed long-term success rates of 71%, being challenged by complex arrhythmogenic substrate and lack of unified ablation strategies.
Adults with congenital heart disease appear to be a suitable target group for primary use of HDM, as previous catheter ablation and surgical lesions can create complex anatomic as well functional arrhythmogenic substrate.
Simultaneous use of classical strategies including targeted entrainment as well as novel signal processing tools (here: LUMIPOINT algorithm) are useful for exact localization of the critical isthmus and tailored ablation in patients with reentry tachycardias.
Future randomized controlled trials are needed for investigation of the benefit of HDM in different arrhythmias as well as investigation of different ablation strategies.
Supplementary data
To download the supplementary material that accompanies this paper, please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/fca-2020-0032
Author contributions
Conception and design: FA Alken and C Meyer. Literature search: FA Alken and C Meyer. Collection and assembly of data: FA Alken and C Meyer. Data analysis and interpretation: All authors. Manuscript writing: All authors. Final approval of manuscript: All authors.
Financial & competing interests disclosure
C Meyer: Speaking honorarium and consulting for Abbott, Biosense Webster, Biotronik and Boston Scientific. P Jais: Speaking honorarium from Boston Scientific, Biosense Webster, Abbott, Medtronic and Microport. F Sacher: Consulting fees and speaking honoraria from Boston Scientific. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
Open access
This work is licensed under the Attribution-NonCommercial-NoDerivatives 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/
Papers of special note have been highlighted as: • of interest; •• of considerable interest
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