Very High-Power Short-Duration, Temperature-Controlled Radiofrequency Ablation in Paroxysmal Atrial Fibrillation: The Prospective Multicenter Q-FFICIENCY Trial
Catheter Ablation
Central Illustration
Abstract
Background
QDOT MICRO (QDM) is a novel contact force–sensing catheter optimized for temperature-controlled radiofrequency (RF) ablation. The very high-power short-duration (vHPSD) algorithm modulates power, maintaining target temperature during 90 W ablations for ≤4 seconds.
Objectives
This study aims to evaluate safety and 12-month effectiveness of the QDM catheter in paroxysmal atrial fibrillation (AF) ablation using the vHPSD mode combined with conventional-power temperature-controlled (CPTC) mode.
Methods
In this prospective, multicenter, nonrandomized study, patients with drug-refractory, symptomatic paroxysmal AF underwent pulmonary vein (PV) isolation with QDM catheter with vHPSD as primary ablation mode, with optional use of the CPTC mode (25 to 50 W) for PV touch-up or non-PV ablation. The primary safety endpoint was incidence of primary adverse events within ≤7 days of ablation. The primary effectiveness endpoint was freedom from documented atrial tachyarrhythmia recurrence and acute procedural, repeat ablation, and antiarrhythmic drug failure.
Results
Of 191 enrolled participants, 166 had the catheter inserted, received RF ablation, and met eligibility criteria. Median procedural, RF application for ablating PVs, and fluoroscopy times were 132.0, 8.0, and 9.1 minutes, respectively. The primary adverse event rate was 3.6%. Imaging conducted in a subset of participants (n = 40) at 3 months did not show moderate or severe PV stenosis. The Kaplan-Meier estimated 12-month rate for primary effectiveness success was 76.7%; freedom from atrial tachyarrhythmia recurrence was 82.1%; clinical success (freedom from symptomatic recurrence) was 86.0%; and freedom from repeat ablation was 92.1%.
Conclusions
Temperature-controlled paroxysmal AF ablation with the novel QDM catheter in vHPSD mode (90 W, ≤4 seconds), alone or with CPTC mode (25 to 50 W), is highly efficient and effective without compromising safety. (Evaluation of QDOT MICRO Catheter for Pulmonary Vein Isolation in Subjects With Paroxysmal Atrial Fibrillation [Q-FFICIENCY]; NCT03775512)
Introduction
Atrial fibrillation (AF) is the most common sustained cardiac arrythmia worldwide and is associated with considerable morbidity, mortality, and burden to patients and health care systems.1 Electrical isolation of the pulmonary veins (PVs) with catheter ablation is the cornerstone of treatment for paroxysmal AF, with radiofrequency (RF) energy as the most frequently used energy source.1,2 Incremental advances in contact force (CF)–sensing RF technology have resulted in improved procedural safety and efficiency, as well as long-term effectiveness.3-7 A 12-month success rate of ∼80% with stringent monitoring has shown reproducibly from multiple studies.6,8 Real-time CF-sensing enables operators to avoid excessive force, which may help with minimizing complications, such as cardiac tamponade.3 While use of open-irrigation in CF-sensing catheters decreases the risk of thrombus and char formation on the catheter tip, this can also prevent accurate temperature feedback because the catheter tip will be at a lower temperature than the actual temperature reached at the catheter tip-tissue interface. Therefore, RF catheter ablation with open-irrigated catheters has been generally operated in a power-control mode.9 Until recently, focal RF ablations were performed with moderate power (20 to 40 W) for a relatively long duration (20 to 40 seconds) per application; the time taken to deliver each application for optimal lesion formation is highly dependent on catheter stability, which impacts long-term outcomes.4 The long procedure times and considerable PV reconnections drove interest in exploring high-power short-duration ablation, with power ranges of 40 to 90 W and an RF application time of <15 seconds per lesion.10
The novel QDOT MICRO (QDM) catheter (Biosense Webster, Inc) is based on the spring-loaded CF catheter platform. It is the first and only temperature-controlled CF-sensing catheter with 2 ablation modes for procedural flexibility and full 3-dimensional (3D) electroanatomical mapping system integration. The very high-power short-duration (vHPSD) mode (90 W for ≤4 seconds) modulates power automatically if maximum temperature cutoff is reached, whereas the conventional-power temperature-controlled (CPTC) mode (≤50 W) adjusts irrigation flow and power based on temperature feedback to maintain the target temperature.11,12 Real-time temperature monitoring is achieved via 6 thermocouples embedded into the tip to provide tip-tissue interface temperature feedback in parallel or perpendicular catheter orientation, while 3 microelectrodes provide high-resolution electrograms for finer endocardial electrical mapping to better assess possible conduction gaps.13,14 The integrated 3D electroanatomical mapping system supports minimal fluoroscopy workflow incorporation as needed.15
The first-in-human study with vHPSD showed initial clinical feasibility and safety, with substantially lower procedure and fluoroscopy times than historical power-controlled RF focal catheters.11 In this study, we sought to evaluate the safety and 12-month effectiveness of the QDM catheter in the ablation of drug-refractory paroxysmal AF using primarily the vHPSD ablation mode in combination with CPTC ablation (Central Illustration).
Temperature-Controlled Very High-Power Short-Duration Paroxysmal Atrial Fibrillation Is Efficient, Safe, and Effective
AF = atrial fibrillation; LA = left atrial; LVEF = left ventricular ejection fraction; PV = pulmonary vein; PVI = pulmonary vein isolation; RF = radiofrequency.
Methods
Study design and oversight
The study was conducted in accordance with Good Clinical Practices, the Declaration of Helsinki, and applicable regulations. The Institutional Review Board or Ethics Committee at each of the 22 participating centers approved the study protocol (see Supplemental Table 1 for a list of the clinical sites and participating investigators). All enrolled participants provided written informed consent.
The Q-FFICIENCY (Evaluation of QDOT MICRO Catheter for Pulmonary Vein Isolation in Subjects With Paroxysmal Atrial Fibrillation) trial was a prospective, multicenter, nonrandomized, U.S. Food and Drug Administration–regulated investigational device exemption study that aimed to evaluate the safety and effectiveness of the QDM catheter in treating drug-refractory, symptomatic paroxysmal AF compared to predefined performance goals. The study design is summarized in Figure 1. After the ablation procedure, participants entered a 3-month blanking period followed by a 9-month effectiveness evaluation period, for a total of 12 months of follow-up. A telephone follow-up was scheduled at 7 days after ablation and clinic visits at 1, 3, 6, and 12 months after ablation. In response to the public health emergency related to the COVID-19 pandemic, adjustments to follow-up visits were implemented to improve study compliance (see COVID-19 Considerations in Supplemental Material). Stringent arrhythmia monitoring was performed via 12-lead electrocardiogram (at 1-, 3-, 6-, and 12-month visits), transtelephonic monitoring (weekly from 3 to 5 months, monthly from 6 to 12 months, or when symptomatic), and 24-hour Holter monitoring (12-month visit). An independent central core laboratory was used for objective adjudication of all recordings. Primary adverse events (PAEs) were similarly adjudicated by an independent Clinical Events Committee.
Follow-Up and Monitoring Schedule Showing the Definition of Primary Effectiveness Failure Modes
aParticipants also had a telephone follow-up visit at 7 days. During the coronavirus disease of 2019 pandemic, remote (telemedicine) visits were allowed in situations where a clinic visit was stipulated. Assessments at these visits that could not be administered via telemedicine were not conducted (eg, electrocardiograms [ECGs] and physical examinations). Holter monitors were shipped to participants by the study sites with instructions on application, recording, and transmission of Holter monitoring. bPulmonary vein (PV) imaging (computed tomography [CT]/magnetic resonance angiography [MRA]) for participants in the CT/MRA PV analysis population (participants with symptoms suggestive of PV stenosis could undergo CT/MRA at any clinic visit). AAD = antiarrhythmic drug; AF = atrial fibrillation; AFL = atrial flutter; AT = atrial tachycardia; TTM = transtelephonic monitoring.
Study population
Eligible participants were 18 years of age or older, were diagnosed with symptomatic paroxysmal AF with an electrocardiographically documented episode within 6 months before enrollment and a physician’s note indicating recurrent self-terminating AF within 7 days, had nonresponse or intolerance to at least 1 Class I or III antiarrhythmic drug (AAD), and were able to comply with follow-up clinic visits. Exclusion criteria included previous surgical or catheter ablation for AF; previous diagnosis of persistent, long-standing persistent AF, or continuous AF lasting >7 days; coronary artery bypass graft, carotid stenting, or endarterectomy within the past 6 months; documented left atrial thrombus at preprocedure imaging; left ventricle ejection fraction <40%; left atrial diameter >50 mm; thromboembolic event within the past 12 months; and uncontrolled New York Heart Association functional Class III or IV heart failure.
Ablation procedure
After transseptal puncture, electroanatomic mapping was performed with the CARTO 3 system using either a LASSO or PENTARAY catheter (Biosense Webster, Inc). The primary ablation mode for pulmonary vein isolation (PVI) was vHPSD ablation (90 W for ≤4 seconds, target temperature 60ºC, 8 mL/min flow rate; ablation stopped automatically if temperature increased above the 65ºC cutoff). An interlesion distance of ∼4 mm was recommended. Additional PV ablation in CPTC mode (25 to 50 W, target temperature 50ºC, CF range 5 to 30 g) may be used for PV touch-up if needed. For ablation outside the PV ostia, vHPSD or CPTC mode could be used at the investigator’s discretion. Linear ablations were required to treat documented macro–re-entry atrial tachycardias and were limited to the left atrial roof line, mitral valve isthmus line, left atrial floor line, and cavotricuspid isthmus. A right atrial cavotricuspid isthmus linear ablation was required in cases with documented typical atrial flutter either before or during the procedure. Ablation of complex fractionated atrial electrograms was not recommended. All linear lesions required confirmation of bidirectional conduction block by pacing and/or mapping maneuvers. Postablation, a 20-minute waiting period was required before pacing procedures and/or infusion of cardiac medications to induce AF or reconnection (eg, adenosine, isoproterenol 2 to 20 μg/min). Ablation of spontaneous or adenosine/isoproterenol-induced non-PV triggers was performed if necessary. Confirmation of entrance block by LASSO or PENTARAY in all targeted PVs was required.
Esophageal monitoring
An appropriate strategy to minimize the risk of esophageal injury was required using ≥1 of the following methods: esophageal temperature monitoring with an esophageal temperature probe, esophageal visualization with CARTOSOUND (Biosense Webster, Inc) and/or intracardiac echocardiography, or esophageal visualization using barium swallow.
Safety outcomes
The primary safety endpoint was the incidence of predefined PAEs occurring within 7 days after the ablation procedure (including initial and repeat procedures), including death, atrioesophageal fistula, myocardial infarction, stroke/cerebrovascular accident, thromboembolism, transient ischemic attack, phrenic nerve injury/diaphragmatic paralysis, heart block, PV stenosis, pulmonary edema (respiratory insufficiency), vagal nerve injury, pericarditis, and major vascular access complication/bleeding. Atrioesophageal fistula and PV stenosis that occurred between 7 and 90 days after the ablation procedure, as well as cardiac tamponade/perforation occurring within 30 days of ablation, were also considered PAEs.
At a subset of sites, 40 participants underwent computed tomography (CT)/magnetic resonance angiography (MRA) at 3 months, in addition to the baseline CT/MRA performed on all participants, to assess the incidence of postablation severe PV stenosis regardless of symptoms. Additionally, any participants with signs or symptoms of PV stenosis at any clinic visit underwent postablation CT/MRA. PV stenosis was categorized as mild (<50%), moderate (50% to 70%), or severe (>70%) per the measured reduction in PV or PV branch diameter.
Effectiveness outcomes
The primary effectiveness endpoint was freedom from documented recurrence of atrial tachyarrhythmias (AF, atrial flutter, and atrial tachycardia) ≥30 seconds and freedom from 3 additional failure modes (acute procedural failure, repeat ablation failure, and AAD failure) as detailed in Figure 1.
Acute procedural success was defined as confirmation of entrance block in all PVs at the end of the procedure. The incidence of repeat ablation procedures during the evaluation period was calculated. Clinical success was defined as freedom from documented symptomatic AF/atrial tachycardia/atrial flutter recurrence. The 12-month single procedure success was defined as freedom from documented AF/atrial flutter/atrial tachycardia recurrence (episodes ≥30 seconds) during the evaluation period after a single ablation procedure; any repeat ablation procedure was deemed an effectiveness failure for this analysis. Procedural data including total procedure time, fluoroscopy time, RF application time, CF, and maximum temperature were recorded.
Statistical methods
Standard descriptive statistics for continuous variables included mean ± SD and median (25th and 75th percentile, minimum and maximum) values. For categorical variables, counts (percentages) were calculated, with percentages based on the number of participants without missing data.
Trial simulations were performed to estimate the power for the success of the safety and effectiveness endpoints. Based on a performance goal of 14% for the primary safety endpoint and a performance goal of 50% for the primary effectiveness endpoint, 185 participants would provide >80% power to declare success for both endpoints controlling the overall type-I error rate at 1-sided 2.5% level, assuming the true PAE rate is 7% and the true effectiveness failure-free rate is 65%. It was also assumed that there would be 5% and 12% attrition rates for the safety and effectiveness endpoints, respectively.
The final analyses for primary safety and effectiveness endpoints were evaluated by Bayesian methods using beta-binomial models. Noninformative uniform priors were used for the primary safety and effectiveness rates. The study was considered to have shown the safety and effectiveness of the device if the posterior probability of the safety rate being less than the predetermined performance goal of 14% was greater than 0.975, and the posterior probability of the effectiveness rate being greater than 50% performance goal was higher than 0.9775.
The estimate for the raw PAE rate was based on participants with ≥3 months of primary safety follow-up. The Fisher exact test was used to examine differences in the primary safety endpoint by sex; P < 0.15 was considered statistically significant.
Kaplan-Meier estimates and plots were used to characterize effectiveness endpoints. The estimated probabilities of freedom from effectiveness failure, along with 2-sided 95% confidence bounds intervals, were presented.
To identify risk factors associated with primary effectiveness failure, univariable and multivariable logistic regression models were fit to the data. Univariate logistic regression models were first used to evaluate the association between demographics, baseline medical history, and procedural data with the primary effectiveness endpoint. Continuous variables were divided into categories. If any statistically significant associations were observed at P < 0.10 in the univariable analysis, the variables were considered for the multivariable model. In case of severe multicollinearity, only 1 variable was selected for the multivariable model.
All statistical analyses were performed using SAS 9.4 or SAS Studio 3.8 (SAS Institute Inc) and R version 3.6.3.
Results
Study population
Participants were enrolled at 22 U.S. sites from January to September 2019. Of 191 enrolled participants, 177 had the study catheter inserted; 167 had the study catheter inserted, met all eligibility criteria, and were included in the modified intent-to-treat population used to assess primary safety; and 166 received RF ablation and were included in the per-protocol population for effectiveness evaluation. Figure 2 describes study populations and details participant disposition and accountability. Participant characteristics at study baseline are described in Table 1. Visit compliance was high at >93% for all visits.
Participant Disposition and Accountability
The safety analysis population included enrolled participants who had the investigational device inserted, regardless of radiofrequency (RF) energy delivery. The modified intent-to-treat (mITT) population included enrolled participants who met eligibility criteria and had the investigational device inserted (participants who were discontinued for reasons related to the study catheter were considered acute effectiveness failures). The per-protocol population included enrolled participants who met eligibility criteria, underwent RF ablation, were treated with study catheters, and had been treated for the study-related arrhythmia without major protocol deviations that affected the study’s scientific integrity. The CT/MRA population included the first 40 consecutively enrolled participants who underwent a 3-month CT/MRA for PV stenosis assessment and had readable outcomes at baseline and 3 months. Primary safety outcomes were evaluated in the mITT population. Procedural efficiency and primary effectiveness were evaluated in the per-protocol population. Abbreviations as in Figure 1.
| Primary Safety Cohort (mITT Population, n = 167) | Effectiveness Cohort (Per-Protocol Population, n = 166) | |
|---|---|---|
| Men | 101 (60.5) | 101 (60.8) |
| Age, y | 63.1 ± 11.0 | 63.2 ± 11.0 |
| Race | ||
| White | 149 (89.2) | 148 (89.2) |
| Black or African American | 6 (3.6) | 6 (3.6) |
| Asian | 1 (0.6) | 1 (0.6) |
| Not reported | 11 (6.6) | 11 (6.6) |
| Ethnicity | ||
| Not Hispanic or Latino | 146 (87.4) | 145 (87.3) |
| Hispanic or Latino | 6 (3.6) | 6 (3.6) |
| Not reported | 15 (9.0) | 15 (9.0) |
| Medical history | ||
| Congestive heart failure | 9 (5.4) | 9 (5.4) |
| NYHA functional class | ||
| I | 1 (0.6) | 1 (0.6) |
| II | 7 (4.2) | 7 (4.2) |
| Unknown | 1 (0.6) | 1 (0.6) |
| Coronary disease | 33 (19.8) | 33 (19.9) |
| Vascular disease | 22 (13.2) | 22 (13.3) |
| Myocardial infarction | 10 (6.0) | 10 (6.0) |
| Hypertension | 116 (69.5) | 115 (69.3) |
| Stroke | 5 (3.0) | 5 (3.0) |
| Transient ischemic attack | 3 (1.8) | 3 (1.8) |
| Type II diabetes | 33 (19.8) | 33 (19.9) |
| Obstructive sleep apnea | 44 (26.3) | 44 (26.5) |
| Atrial flutter | 40 (24.0) | 40 (24.1) |
| AAD history | ||
| Class I | 82 (49.1) | 82 (49.4) |
| Class II | 91 (54.5) | 90 (54.2) |
| Class III | 89 (53.3) | 88 (53.0) |
| Class IV | 33 (19.8) | 33 (19.9) |
| Class V | 4 (2.4) | 4 (2.4) |
| Number of AADs failed | 1.6 ± 0.8 | 1.6 ± 0.8 |
| CHA2DS2-VASc score | 2.4 ± 1.5 | 2.4 ± 1.5 |
| LVEF, % | 59.7 ± 7.0 | 59.7 ± 7.0 |
| LA diameter, mm | 38.1 ± 6.0 | 38.2 ± 5.9 |
| Duration of symptomatic paroxysmal AF, mo | 51.7 ± 76.9 | 51.9 ± 77.1 |
Procedural data
Confirmation of entrance block was achieved in all PVs in participants undergoing ablation with the study catheter (n = 164). PVI was performed with vHPSD mode-only in 89 of 164 (54.3%) participants, with reconnection after first encirclement observed in 29 participants. The posterior segment (including carina) and the superior segment of the right pulmonary vein had the highest and lowest acute reconnection rate, respectively (Supplemental Table 3). Non-PV targets were ablated beyond PVI in 39.8% (66 of 166) of participants; cavotricuspid isthmus lines, the most common non-PV targets, were placed in the right atrium during 27.7% (46 of 166) of index procedures. Median total procedure (including a protocol-mandated 20-minute waiting period) and fluoroscopy times were 132 and 9.1 minutes, respectively. Median total RF application time for ablating PVs was 8.0 minutes. Median fluid delivery via study catheter was 500 mL, and most participants (59.6%) did not require insertion of a Foley catheter. Procedural details are reported in Table 2. The mean number of RF applications per procedure was 121.2, with a median of 93.3% of the applications delivered in vHPSD mode. The mean average power was higher in the vHPSD ablation mode (84.1 ± 2.2 W) compared to CPTC mode (37.9 ± 6.9 W). The mean maximum temperature, impedance drop, and CF were similar between the 2 ablation modes (Supplemental Figure 1).
| Total procedure time, min | 132.0 (108.0, 171.0) |
| Total ablation time, min | 65.0 (43.0, 94.0) |
| Total mapping time, min | 8.0 (4.0, 13.0) |
| Total fluoroscopy time, min | 9.1 (0.7, 16.2) |
| RF application time, mina | 9.8 (6.8, 15.7) |
| Total RF application time for ablating PVs, min | 8.0 (6.0, 13.0) |
| Method of esophageal monitoring/localization | |
| Esophageal temperature probe | 122 (73.5) |
| Esophageal visualization with CARTOSOUND and/or ICE | 63 (38.0) |
| Esophageal visualization using barium swallow | 6 (3.6) |
| Other | 15 (9.0) |
| Fluid delivered via the study catheter, mL | 500.0 (400.0, 650.0) |
| Foley catheter placed | 67 (40.4) |
| Ablation targets | |
| PVI only | 100 (60.2) |
| Non-PVb | 66 (39.8) |
| Cavotricuspid isthmus | 46 (27.7) |
| Roof line | 16 (9.6) |
| Other linear lesion | 15 (9.0) |
| Other AF foci | 16 (9.6) |
| Other | 3 (1.8) |
Safety
The PAE rate was 3.6% (7 PAEs in 6 participants) (Table 3). The posterior mean of the PAE rate was 4.2%, with a 95% Bayesian credible interval of 1.7% to 7.7%, well below the 14% performance criterion. The safety performance goal was met. There were no reports of device- or procedure-related death, atrioesophageal fistula, stroke, transient ischemic attack, or PV stenosis. All PAEs resolved with appropriate management, except for 1 event of phrenic nerve injury/diaphragmatic paralysis that was deemed nonassessable by the Clinical Events Committee due to poor image quality. Subgroup analysis showed no statistically significant differences in the PAE rates between men and women (2.8% vs 4.3%, respectively; P = 0.68; n = 177). No procedure-related esophageal injuries were reported during the study.
| Primary Adverse Event | No. of Events | Relationship With Deviceb |
|---|---|---|
| Major vascular access complication/bleeding | 3 | Not related |
| Cardiac tamponade/perforation | 2 | Possibly related |
| Phrenic nerve injury/diaphragmatic paralysisc | 2 | Definitely related |
| Atrioesophageal fistula | 0 | — |
| Death (device or procedure related) | 0 | — |
| Heart block | 0 | — |
| Myocardial infarction | 0 | — |
| Pericarditis | 0 | — |
| Pulmonary edema (respiratory insufficiency) | 0 | — |
| Pulmonary vein stenosis | 0 | — |
| Stroke/cardiovascular accident | 0 | — |
| Thromboembolism | 0 | — |
| Transient ischemic attack | 0 | — |
| Vagal nerve injury | 0 | — |
Of the 40 participants who underwent CT/MRA imaging of the PVs preprocedure and 3 months postprocedure, none showed evidence of moderate or severe PV stenosis.
Effectiveness
Acute procedural success, PVI with confirmation of entrance block in all PVs, was achieved in all participants in the effectiveness cohort who were treated with the study catheter (164 of 164; 2 participants were treated with a nonstudy catheter and excluded from this analysis).
The Kaplan-Meier estimate for freedom from primary effectiveness failure at 12 months was 76.7% (Figure 3A). The posterior mean of the event-free rate at month 12 was 75.9%, with a 95% Bayesian credible interval of 69.0% to 82.3%. The posterior probability that the event-free rate at month 12 was greater than the performance goal of 50% was close to 1.0000 (ie, 0.99995), which exceeded the prespecified threshold of 0.9775. The primary effectiveness endpoint was therefore met.
Kaplan-Meier Analyses of Effectiveness Outcomes (Effectiveness Cohort, n = 166)
(A) Freedom from primary effectiveness failure. (B) Freedom from documented AF/AT/AFL recurrence and clinical success (freedom from documented symptomatic recurrence). (C) Single procedure success. (D) Freedom from repeat ablation. The 95% confidence interval of the survival probability is based on Greenwood’s formula. Abbreviations as in Figure 1.
Subgroup analysis by sex showed overlapping Kaplan-Meier curves through 42 weeks postprocedure. A few late failures after 44 weeks were observed in women, resulting in higher primary effectiveness in men (79.5%) vs women (72.3%) at 12 months, consistent with published literature.16
The Kaplan-Meier estimate of freedom from arrhythmia recurrence and clinical success at 12 months was 82.1% and 86.0%, respectively (Figure 3B). Single procedure success at 12 months was estimated at 64.3% and 76.3% off Class I/III AADs and regardless of Class I/III AADs use postblanking (ie, patients may be on or off AAD per discretion of investigators), respectively (Figure 3C). The Kaplan-Meier estimate of freedom from repeat ablation was 92.1% (Figure 3D).
Risk factors associated with primary effectiveness outcomes
Logistic regression modeling was performed to identify potential risk factors associated with the primary effectiveness endpoint (Supplemental Table 4). Based on a 0.10 alpha level, in the final multivariable model the odds of primary effectiveness failure for subjects with pharmacologic cardioversion in the past 12 months was 2.82 (95% CI: 1.14 to 6.97; P = 0.025), with previous atrial flutter ablation was 3.12 (95% CI: 0.86 to 11.35; P = 0.085), and with known cardiovascular medical history was 3.51 (95% CI: 0.97 to 12.67; P = 0.055) compared to those without.
Discussion
The prospective, multicenter Q-FFICIENCY study showed the safety and 12-month effectiveness of the novel QDM catheter for PVI performed primarily in vHPSD mode (90 W, for ≤4 seconds), in combination with CPTC mode, in paroxysmal AF patients. The PAE rate was low (3.6%), with no occurrences of device- or procedure-related death, atrioesophageal fistula, or PV stenosis. Twelve-month primary effectiveness and clinical success rates were 76.7% and 86.0% (both Kaplan-Meier estimates), respectively. Freedom from repeat ablation was >90% at 12-month follow-up.
These results build on those from previous studies, charting the evolution of power-controlled RF ablation catheters that have used similarly stringent arrhythmia monitoring (Figure 4A). Although superiority of catheter ablation over AAD was shown more than a decade ago, 12-month outcomes were suboptimal with only ∼60% of patients experiencing freedom from documented recurrence.17 The incorporation of CF improved the long-term success rate to 70%, with a higher success rate of ∼80% seen with more stable catheter-tissue contact.3,4 The recognition of the importance of catheter stability led to the development of VISITAG SURPOINT and the CLOSE protocol, which simplified PVI via focal RF catheter and led to reproducible 12-month success.6,18,19 Q-FFICIENCY showed that the novel temperature-controlled QDM catheter further improves 12-month success rates (>80%), while supporting improved temperature monitoring and visualization to enhance safety. This represents up to 30% and 23% improvements in 12-month freedom from all documented recurrence and documented symptomatic recurrence, respectively, with the novel temperature-controlled QDM catheter compared to predecessor power-controlled RF ablations.
Evolving RF Ablation Technology in Studies With Stringent Arrhythmia Monitoring
(A) 12-month effectiveness. (B) Procedural parameters. Clinical success was defined as freedom from documented symptomatic recurrence. aData derived from CARTO file for accuracy. Mean values reported for historical studies; median values reported for Q-FFICIENCY for accuracy. IDE = investigational device exemption; NR = not reported; other abbreviation as in Figure 1.
Along with these improvements in effectiveness, corresponding trends in improved procedural efficiency were also observed across these studies, as shown by shorter procedural, ablation, fluoroscopy, and RF application times, as well as reduced fluid delivery via the ablation catheter (Figure 4B).3,6,17 Consistent with the first-in-human study, the median total RF application time for vHPSD ablation was approximately 8 to 9 minutes, which is substantially shorter than historical data with power-controlled ablation (Figure 4B).11 The data reported in this study represent initial results when investigators had no prior experience with the new QDM catheter. As observed with past devices, learning curves usually improve rapidly over time, and outcomes such as procedural efficiencies and effectiveness may further improve when the catheter is more widely used in routine clinical practice. As reported in a recent real-world QDM catheter study in Europe where the catheter is available, operators are already reporting 89% first-pass isolation with no steam pops or periprocedural complications when vHPSD ablation mode is used.20
Various benefits of vHPSD ablation have been previously proposed. Catheter-tissue contact stability is an important factor in successful lesion creation, with a balance required between sufficient CF for good and stable catheter-tissue contact for transmural lesion creation, and avoiding collateral tissue injury from excessive CF.4,11 The use of vHPSD ablation mode may aid in achieving this balance, as lesions are created after a short RF application, such that the CF stability issue may be mitigated.21,22 The observation of similar average maximum temperature, impedance drop, and CF per RF application between vHPSD and CPTC ablation provides further evidence that vHPSD ablation mode is as safe and effective as CPTC ablation mode. Preclinical studies also showed that vHPSD ablation creates well-defined, predictable lesions that have improved lesion-to-lesion uniformity, transmurality, and linear continuity, with a shorter ablation time and a comparable safety profile relative to power-controlled ablation, while decreasing the transient hemorrhage ring at the periphery of the lesion core that can lead to reconnection and clinical recurrence.13,23,24 Recently published preclinical work has confirmed the vHPSD lesion anatomy to have a higher ratio of diameter/depth, which may be favorable for linear ablation at sites with thin atrial walls to minimize collateral injury.21 Taken together, vHPSD ablation mode may be more suitable on the thin atrial tissue and for the posterior wall; ablation at thicker tissues such as the carina, ridge, and septum may require CPTC mode with lesion tag index. The versatility of the QDM catheter, which can be used in vHPSD and CPTC modes, alone or in combination, gives physicians the flexibility to adjust the RF application at various cardiac anatomies to improve outcomes while optimizing their preferred workflows.22,25-26
The low adverse event rate observed in this study is aligned with ranges observed in power-controlled RF ablation studies and clinical practice.2 Specifically, no esophageal injury or severe PV stenosis were reported in the study despite stringent complication monitoring. The data corroborate the initial findings from the first-in-human QDOT FAST (Clinical Study for Safety and Acute Performance Evaluation of the THERMOCOOL SMARTTOUCH SF-5D System Used With Fast Ablation Mode in Treatment of Patients With Paroxysmal Atrial Fibrillation) study.11 Although it was initially thought that the safety of vHPSD ablation may be the result of less conductive heating to adjacent tissues, new data showed that conductive heating remains an important contributor to lesion formation due to thermal latency.13,21 As such, it is important to avoid overlapping vHPSD lesions when ablating around areas of thin tissues or near the esophagus.
CF-sensing and index-based ablation revolutionized catheter ablation, allowing electrophysiologists to become better and more efficient at performing ablation procedures while improving patients’ clinical outcomes and quality of life. Conventional power-controlled CF-sensing ablations enabled operators to verify appropriate catheter-tissue contact before initiating lesion delivery, balance the catheter-tissue contact stability during RF delivery for effective lesion creation, and avoid excessive CF that could result in serious complications such as cardiac tamponade.3 The novel QDM catheter builds on previous CF-sensing platforms and brings back temperature-controlled ablation, potentially further enhancing the overall simplicity, efficiency, efficacy, and safety of RF ablation procedures with 3D electroanatomical mapping visualization, integrated lesion tag index (power, time, and CF), and minimal fluoroscopy exposure.6,27
Study limitations
This was a single-arm, nonrandomized study; larger studies are needed to evaluate the generalizability of the study results to a broader population of patients with AF. In addition, a randomized controlled study would be required to draw direct comparisons of clinical outcomes with other AF ablation technologies.
Conclusions
The Q-FFICIENCY study has shown the clinical safety and effectiveness of the novel temperature-controlled CF-sensing QDM catheter for paroxysmal AF ablation with primarily vHPSD mode (90 W, ≤4 seconds) in combination with CPTC mode (25 to 50 W). Compared to similarly designed studies with predecessor power-controlled non-CF or CF-based catheters temperature-controlled ablation with the QDM catheter improved procedural efficiency and enhanced 12-month effectiveness without compromising safety.
Perspectives
COMPETENCY IN MEDICAL KNOWLEDGE: The results of this study establish the novel QDM catheter, used with vHPSD mode alone or in combination with CPTC mode, as a safe and effective option for paroxysmal AF ablation.
TRANSLATIONAL OUTLOOK: This analysis has shown procedural efficiency and 12-month effectiveness with the QDM catheter in a stringently monitored clinical study, representing an advancement in temperature-controlled, CF-sensing RF ablation. Future studies are required to determine the generalizability of these results in a broader population of patients with AF and to directly compare clinical outcomes with other AF ablation technologies.
Funding Support and Author Disclosures
This study was supported by Biosense Webster, Inc. Dr Osorio has received grants from Biosense Webster, Inc, and Abbott; has received consulting fees from Biosense Webster, Inc, Boston Scientific, and Medtronic; and has received payments or honoraria for lectures/presentations/Speakers Bureau from Biosense Webster, Inc, and Boston Scientific. Dr Hussein has received steering committee funding from Biosense Webster, Inc. Dr Delaughter has received consulting fees and advisory board payments from Biosense Webster, Inc. Dr Natale has received consulting fees from Abbott, Baylis, Biosense Webster, Inc, Boston Scientific, Biotronik, and Medtronic. Dr Dukkipati has received grants from Biosense Webster, Inc. Dr Oza has received consulting fees from Biosense Webster, Inc and Atricure. Dr Daoud has received consulting fees from Biosense Webster, Inc, Medtronic, and S4 Medical; has received payments or honoraria for lectures/presentations/Speakers Bureau from ABIM, Western AF, and JACC: Clinical Electrophysiology; has patents planned, issued, or pending; has a leadership role in S4 Medical; and has stock/stock options from S4 Medical. Dr Di Biase has received consulting fees from Biosense Webster, Inc, Stereoataxis, and Rhythm Management; and has received speaker honoraria/travel from Biosense Webster, Inc, St Jude Medical (now Abbott), Boston Scientific, Medtronic, Biotronik, Atricure, Baylis, and Zoll. Dr Mansour has received grants from Biosense Webster, Inc, and Boston Scientific; has received consulting fees from Biosense Webster, Inc, Boston Scientific, Philips, and Medtronic; has received support for attending meetings/travel from Biosense Webster, Inc, and Boston Scientific; and has stock/stock options from New Pace Limited and EPD Solutions. Dr Valderrabano has received consulting fees from Baylis and Circa; and has received payments or honoraria for lectures/presentations/speakers’ bureaus from Biosense Webster, Inc. Dr Ellenbogen has received grants, consulting fees, and payment for lectures and advisory board from Biosense Webster, Inc, and has leadership positions at the American College of Cardiology and Heart Rhythm Society. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Abbreviations and Acronyms
| 3D | 3-dimensional |
| AAD | antiarrhythmic drug |
| AF | atrial fibrillation |
| CF | contact force |
| CPTC | conventional-power temperature-controlled |
| CT/MRA | computed tomography/magnetic resonance angiography |
| PAE | primary adverse event |
| PV | pulmonary vein |
| PVI | pulmonary vein isolation |
| RF | radiofrequency |
| QDM | QDOT MICRO |
| vHPSD | very high-power short-duration |
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Footnotes
David Haines, MD, served as Guest Associate Editor for this paper. William Stevenson, MD, served as Guest Editor-in-Chief for this paper.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.
