Paroxysmal atrial fibrillation ablation with a novel temperature‐controlled CF‐sensing catheter: Q‐FFICIENCY clinical and healthcare utilization benefits

The prospective, nonrandomized, multicenter Q‐FFICIENCY study demonstrated the safety and 12‐month efficacy of paroxysmal atrial fibrillation (AF) ablation with the novel QDOT MICRO temperature‐controlled, contact force‐sensing, radiofrequency (RF) catheter. Participants underwent pulmonary vein isolation with very high‐power short‐duration (vHPSD) mode (90 W, ≤4 s) alone or combined with conventional‐power temperature‐controlled (CPTC) mode (25–50 W). This study aimed to assess quality‐of‐life (QOL) and healthcare utilization (HCU) benefits experienced by Q‐FFICIENCY study participants.


| INTRODUCTION
Atrial fibrillation (AF) is a serious medical condition that disrupts patients' physical, mental, and social function, imposing a substantial burden on patients' quality of life (QOL). 1,2AF is responsible for >450,000 hospitalizations and nearly 5 million physician visits each year in the United States, with consequent burden on patients, their families, and healthcare systems. 3In patients with symptomatic AF, catheter ablation leads to clinically important and significant improvement of QOL after arrhythmia-related symptoms, 4 with electrical isolation of the pulmonary veins with radiofrequency (RF) energy considered a cornerstone of AF ablation. 1,5Continuous advances in RF technologies and techniques have supported improved procedural efficiency and long-term success rates. 6wever, with an estimated AF prevalence of 12.1 million in the United States by 2030, 7 advanced ablation technologies to further increase ablation success in conjunction with streamlined treatment pathways would be critical to increase the capacity to care for the burgeoning AF population.QDOT MICRO (QDM; Biosense Webster, Inc.) is a novel contact force-sensing catheter optimized for temperature-controlled RF ablation that can be used in two ablation modalities: very highpower short-duration (vHPSD, QMODE+) and conventional-power temperature-controlled (CPTC, QMODE) mode.In the vHPSD mode (90 W for ≤4 s), power is automatically modulated if the maximum target temperature is reached, while in CPTC (≤50 W) mode, irrigation flow and power are modulated automatically based on temperature feedback to maintain the target temperature. 8,9FFICIENCY was a prospective, multicenter, nonrandomized US Food and Drug Administration-regulated investigational device exemption study that evaluated the safety and efficacy of temperature-controlled RF ablation with the QDM catheter in participants with drug-refractory paroxysmal AF followed up for 12 months (3-month blanking and 9-month evaluation periods).The vHPSD mode was used as the primary setting for pulmonary vein isolation, with CPTC allowed for touch-up; non-pulmonary vein ablations were performed on either mode per investigator discretion.The primary adverse event rate was low (3.6% overall, 1.8% catheter-related).Based on stringent monitoring (i.e., transtelephonic monitoring [TTM], Holter monitoring, and electrocardiograms), 12-month freedom from atrial tachyarrhythmia recurrence regardless of antiarrhythmic drug (AAD) use and single procedure success at 12 months off Class I/III AADs were 82.1% and 64.3%, respectively.
Freedom from repeat ablation was 92.1%.Procedure and fluoroscopy times were substantially lower than with historical power-controlled point-by-point catheters. 6The purpose of this analysis was to assess QOL and healthcare utilization (HCU) benefits experienced by Q-FFICIENCY participants (Central Illustration 1).

| Study design and participants
The Q-FFICIENCY study design was previously reported. 6The study was conducted in accordance with Good Clinical Practice, 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.All patients enrolled in the study provided written informed consent.

| Clinical benefit assessment
Participants' QOL was assessed with the Atrial Fibrillation Effect on Quality-of-Life Tool (AFEQT), a 20-item, AF-specific questionnaire that measures four domains: symptoms, daily activities, treatment concerns, and treatment satisfaction.Overall score (composed of the first three domains) and individual subscales range from 0 (worst) to 100 (best). 10Scores of <70 correlate with severely symptomatic AF, scores of 70-89 correlate with moderately symptomatic AF, and scores of ≥90 correlate with minimally symptomatic or asymptomatic AF. 4 A change of ≥5 points, regardless of direction, has been identified as a clinically important difference in patients' QOL. 10 Change in overall AFEQT scores was calculated for all evaluable participants with available data, by those stratified by documented atrial arrhythmia recurrence status (defined as documented atrial tachyarrhythmia episodes of ≥30 s on Holter recordings/transtelephonic monitoring or continuously recorded on the standard 12-lead electrocardiogram during the evaluation period [Days 91-365]), as well as for participants with primary effectiveness success or failure (success defined as freedom from documented atrial arrhythmia during the evaluation period and freedom from acute procedural failure, repeat ablation failure, and AAD failure).Stringent arrhythmia monitoring was performed via 12-lead electrocardiogram (at 1-, 3-, 6-, and 12-month visits), TTM (weekly from 3-5 months, monthly from 6-12 months, or when symptomatic), and 24-h Holter monitoring (12-month visit).
Besides assessing procedural characteristics as previously reported, 6 additional HCU study endpoints included the proportion of participants with AAD use after the blanking period, cardioversion rates (direct-current or pharmacological cardioversion), and all-cause and cardiovascular hospitalization rates postablation.

| Statistical analyses
Outcomes were analyzed for participants in the effectiveness cohort (i.e., per-protocol population), which included participants who were enrolled, met all eligibility criteria, and underwent RF ablation with the study catheter for study-related arrhythmia without major Kaplan-Meier estimates of freedom from all-cause and cardiovascular hospitalizations over 12 months after the index procedure were also performed.
All statistical tests used 2-sided p-values and a significance level of 0.05.Statistical analyses were performed using SAS V.9.4 (SAS Institute).

| Study population
Between January and September 2019, 191 participants were enrolled in the study, 166 of whom received RF ablation with the study catheter and were included in the effectiveness cohort.Of the 25 participants excluded from the effectiveness cohort, 14 did not have the catheter inserted, one did not have RF energy delivered, and 10 were identified as eligibility criteria failures postprocedure.
The mean age was 63.2 years, and 60.8% were male.Table 1 lists baseline characteristics of participants.

| QOL assessment
Of the 166 evaluable participants, 149 (89.8%) completed AFEQT questionnaires at both baseline and the 12-month follow-up meeting.
AFEQT score increase was also observed for the symptoms, daily activities, treatment concerns, and treatment satisfaction domains (p < 0.0001; Figure 1A).Using the commonly accepted threshold of an increase of ≥5 points in overall AFEQT score as reflective of a meaningful clinically important difference in QOL, most study participants exceeded the threshold at 3 months; the benefit was sustained through 6 and 12 months of follow-up (Figure 1B).Table 2 compares characteristics and outcomes among participants with and without significant QOL gains (≥5 points) from baseline to 12 months; 131 (87.9%) participants exceeded this threshold while 18 (12.1%)did not.Sex and all-cause hospitalization were significantly different between the subgroups.While the distribution of males versus females among participants with QOL gains ≥5 points was relatively balanced (55.7% males vs. 44.3%females), of the participants with QOL gains <5 points, 88.9% were male and 11.1% were female (p = 0.009).Significantly more participants with QOL gains <5 points experienced all-cause hospitalization within 12 months postablation (38.9%) compared to participants with QOL gains ≥5 points (16.0%, p = 0.047).1C).No differences were observed in the proportion of participants achieving meaningful clinically important difference based on the status of primary effectiveness, freedom from documented recurrence, or freedom from symptomatic recurrence (Supporting Information: Table 1).

| Hospitalization
The Kaplan-Meier estimate of 12-month freedom from all-cause and cardiovascular hospitalization was 80.9% (95% confidence interval [CI], 74.8%-86.9%)and 88.8% (95% CI, 84.0%-93.7%),respectively (Figure 4A,B).The freedom from cardiovascular hospitalization rate was numerically higher in patients who were off Class I/III AAD postblanking (90.3%) than for those who remained on Class I/III AAD postblanking (84.3%; Figure 4C).A total of 25 cardiovascular hospitalizations were recorded in 18 participants.Of these, the most common reasons for cardiovascular hospitalizations were AF (eight events in seven participants), atrial flutter (four participants), and tachycardia (three events in two participants  With a 31-point gain in overall AFEQT score at 12 months, the QOL outcomes are consistent with improvements in the 17-33 point range reported in contemporary multicenter AF ablation studies with power-controlled RF catheters (Figure 5), 4,11,12 validating QDM's utility in providing the meaningful improvements in QOL that patients expect when choosing catheter ablation as a treatment option.Taken together, the catheter's unique design, enhanced procedural efficacy and efficiency, and favorable QOL and HCU outcomes, further enhance the clinical benefits observed with the predecessor RF catheters. 6 Q-FFICIENCY, participants with primary effectiveness failures and those with arrhythmia recurrence experienced similar QOL improvements as those with primary effectiveness successes or who were arrhythmia free at the end of the follow-up period, consistent with reports that QOL may improve despite AF recurrence, unless AF burden is high. 5Taken together, the results suggest that QOL improvements likely reflect a variety of factors that are important to individual patients, such as symptom relief, reduction in medication burden, and freedom from clinic visits and procedures.Although the number of participants who did not achieve the meaningful clinically important difference in QOL score was small, we observed a significant difference based on sex, with a higher proportion of treatment results and suggest an integrated holistic AF patient management approach to minimize the impact of important outcomes, including hospitalization. 1,5 places a substantial burden on individuals' daily lives and healthcare resources in terms of physician visits, procedures, drug costs and side effects, and hospitalizations.Cardioversion is a recommended treatment option for AF. 5 Electrical and pharmacological cardioversion are effective in restoring sinus rhythm; however, AF recurrence occurs frequently.With only 20%-30% of patients remaining in sinus rhythm after 1 year following cardioversion, 13 providers often must assess the need for further interventions.In our study cohort, 31% of participants underwent electrical cardioversion in the 12 months before enrollment, compared with <2% during Months 3-12 postablation.A similar pattern was seen in the reduction in AAD use; while almost all participants were using an AAD at study baseline, less than half were on an AAD by Months 6-12, suggesting a clinically meaningful AF burden reduction.The use of many AADs is limited by safety concerns, such as proarrhythmic effects and toxicity profiles, 14 and recent studies showed that early rhythm control with catheter ablation in paroxysmal AF patients is associated with a lower risk of adverse cardiovascular events and a slower rate of disease progression to persistent AF. 15,16 The primary cost driver in the management of AF is hospitalization; AF patients are more than twice as likely to be hospitalized each year compared with people without AF and three times as likely to experience multiple hospitalizations. 17Following a first hospitalization for AF, more than half of readmissions are for cardiovascular causes, most commonly recurrent AF. 18 In the current study, most patients were free from all-cause and cardiovascular hospitalizations for the duration of the 12-month study follow-up, with freedom from hospitalization particularly high in patients who remained off AAD treatment.Taken together, reductions in cardioversion, AAD use, and cardiovascular hospitalization resulting from catheter ablation may potentially reduce long-term treatment costs for individuals with AF.

| Study limitations
The limitations of the current study include its nonrandomized, single-arm design.In addition, QOL perceptions may be influenced by treatment expectations resulting from participation in a clinical trial, although given the magnitude of improvement in AFEQT scores, it is unlikely that the perceived improvement could be completely attributed to a placebo effect or recall bias.Although our results support the patient-focused benefits of ablation overall, comparative studies would be required to assess the benefits of ablation with the QDM catheter compared with other AF treatment strategies.Our study did not evaluate costeffectiveness associated with the QOL improvement and HCU reduction; further research and analyses would be needed to understand these health economic impacts.

| CONCLUSIONS
Paroxysmal AF ablation with the QDM temperature-controlled RF catheter in vHPSD mode, alone or combined with CPTC mode, led to clinically meaningful improvement in QOL and substantial reduction in AAD use, cardioversion, and cardiovascular hospitalization.
protocol deviations.Changes in AFEQT score from baseline to 12 months were summarized descriptively.Paired t-tests were used to compare continuous variables, and McNemar tests were used to compare nominal measures across time points, including the QOL score at baseline versus 12 months.The differences in baseline characteristics and outcomes between participants with and without significant QOL gains were summarized descriptively; Wilcoxon ranksum tests were used to compare continuous measures, and Fisher exact tests were used to compare nominal outcomes.Changes in the proportion of participants using AADs from baseline to during Months 3-6 and Months 6-12 were summarized descriptively.The change in the proportion of patients who underwent direct-current or pharmacological cardioversion during the 12 months before the ablation procedure compared with during the blanking period and during the evaluation period was summarized descriptively.McNemar tests were used to compare the counts of cardioversion at baseline versus the evaluation period and the counts of AAD utilization at baseline versus at 6-12 months.
C E N T R A L I L L U S T R A T I O N 1 Improved QOL and reduced HCU with temperature-controlled very high-power short-duration paroxysmal atrial fibrillation ablation.a Patients who completed AFEQT questionnaires.AAD, antiarrhythmic drug; AF, atrial fibrillation; AFEQT, Atrial Fibrillation Effect on Quality-of-Life Tool; CHA2DS2-VASc, congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism, vascular disease, age 64-74 years, sex category; CV, cardiovascular; HCU, healthcare utilization; LA, left atrium; LVEF, left ventricular ejection fraction; QOL, quality-of-life.
When participants were stratified by symptom severity based on the baseline overall AFEQT score, 89.6% (86/96) of those classified as severely symptomatic at baseline gained ≥20 points.Most participants classified as mildly to moderately symptomatic at baseline also showed gains in AFEQT scores, with 38.1% (16/42) improving by ≥20 points and 26.2% (11/42) improving by 15-19 points.Most participants who were classified as minimally symptomatic at baseline maintained their AFEQT scores during the study period (Figure One participant was contraindicated to AAD use due to bradycardia.The proportion of participants on all AADs decreased from 99.4% (165/166) at baseline to 50.0% (81/162) during Months 3-6 and 46.8% (74/158) during Months 6-12.Class I/III AAD use was reduced by 79.9% from baseline to 12 months following ablation (p < 0.0001; Figure2; Supporting Information: Table2).Only three (1.8%)participants in the effectiveness cohort initiated new Class I/III AADs after a failed ablation instead of using an alternative rhythm control (i.e., current/previous AAD dose adjustment, repeat ablation, or cardioversion).T A B L E 1 Demographics and baseline characteristics.

F
I G U R E 1 QOL assessment by AFEQT (effectiveness cohort, n = 166).(A) Mean AFEQT overall and domain subscores throughout the study period.Treatment satisfaction Q1: How well current treatment controls your AF.Treatment satisfaction Q2: The extent to which treatment has relieved your symptoms of AF. (B) AFEQT total score scatterplot (dotted lines showing ±5-point clinically meaningful difference).(C) AFEQT overall score change at 12-month follow-up based on baseline symptom severity classification.AF, atrial fibrillation; AFEQT, Atrial Fibrillation Effect on Quality-of-Life Tool; QOL, quality-of-life.

F I G U R E 2
AAD use (effectiveness cohort, n = 166).Diagram of percentage of participants with AAD use at baseline and throughout the 12-month follow-up period.AAD, antiarrhythmic drug.F I G U R E 3 Cardioversion use (effectiveness cohort, n = 166).Cardioversion use during the 12 months before enrollment and during the 12-month study follow-up period.F I G U R E 4 Kaplan-Meier analyses of HCU Outcomes (effectiveness cohort, n = 166).(A) Freedom from all-cause hospitalization.(B) Freedom from CV hospitalization.(C) Freedom from CV hospitalization in participants with versus without Class I/III AAD use during the evaluation period.The 95% CI of the survival probability is based on Greenwood's formula.AAD, antiarrhythmic drug; CI, confidence interval; CV, cardiovascular; HCU, healthcare utilization.discontinuing all AADs postablation.Compared with the 12-month preablation period, the cardioversion rate decreased by >90% during the evaluation period.Hospitalizations were low following ablation, with an estimated freedom of cardiovascular hospitalization approaching 90%.The primary indication for catheter ablation is to reduce AF symptoms and to improve patients' QOL; therefore, QOL assessments have played an increasingly important role in evaluating outcomes of new ablation technologies.1,5In the current study, QOL improvements assessed by the AFEQT instrument were noticeable as early as 3 months postablation and sustained through 12 months of follow-up.We observed a mean improvement of ~30-40 points, considerably greater than the 5-point meaningful clinically important difference that has previously been shown to correlate with an improvement in patients' functional status by one European Heart Rhythm Association class.10Approximately 90% and 40% of participants classified as severely symptomatic or mildly to moderately symptomatic at baseline, respectively, reported ≥20-point gain in overall AFEQT score at the 12-month follow-up visit.
men not reporting ≥5-point AFEQT score gain at the 12-month follow-up.Additionally, the participants who did not reach clinically meaningful QOL improvements were associated with experiencing hospitalization during the study period.These results are aligned with AF treatment guidelines, which identify sex as a factor influencing AF F I G U R E 5 QOL improvement in contemporary paroxysmal AF studies.Summary of QOL improvements across four contemporary paroxysmal AF studies: CABANA, CIRCA-DOSE, VISTAX, and Q-FFICIENCY.a Reporting enrollment in the relevant arm of the randomized controlled studies (i.e., catheter ablation for CABANA and RF ablation for CIRCA-DOSE).AF, atrial fibrillation; AFEQT, Atrial Fibrillation Effect on Quality-of-Life Tool; CF, contact force; QOL, quality-of-life; RF, radiofrequency.
Differences between patients with and without significant QOL gains (effectiveness cohort, n = 166).
).A case of cardiac tamponade and a case of pericardial effusion were reported during index ablations.One cardiac tamponade occurred during a repeat This Q-FFICIENCY study analysis demonstrated the positive QOL and HCU benefits of paroxysmal AF ablation with the novel QDM temperature-controlled RF catheter.Most participants experienced QOL improvements exceeding the clinically important difference threshold of the AFEQT assessment.In addition, an ~80% reduction in Class I/III AAD use was reported, with >50% of participants T A B L E 2Note: Values presented as n (%) or median (Q1-Q3), using Wilcoxon rank-sum test for medians and Fisher exact test for counts.Abbreviations: AAD, antiarrhythmic drug; AF, atrial fibrillation; AFEQT, Atrial Fibrillation Effect on Quality-of-Life Tool; BMI, body mass index; CHA 2 DS 2 -VASc, congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism, vascular disease, age 64-74 years, sex category; CV, cardiovascular; DC, direct-current; LA, left atrial; LVEF, left ventricular ejection fraction; QOL, quality-of-life.