Advice

Evidence review

Evidence review

Clinical and technical evidence

Regulatory bodies

The Medicines and Healthcare products Regulatory Agency has published 3 Field Safety Notices for ThermoCool SmartTouch, 1 of which was for ThermoCool SmartTouch SF, and all of which were monitored to a satisfactory conclusion. No adverse incidents were received relating to the issues in the safety notices.

A US Food and Drug Administration (FDA) major product recall was posted in October 2014 and terminated in October 2015. The recall resulted in Biosense Webster providing additional labelling for the safe and effective use of ThermoCool SmartTouch.

A search of the FDA database: Manufacturer and User Device Facility Experience (MAUDE) for 'SmartTouch' identified 939 records all describing the use of ThermoCool SmartTouch in cardiac ablation procedures. These reported events occurred after January 2012, with the most recent occurring in October 2015. The records were categorised by the following indications:

  • atrial fibrillation (464 records)

  • ventricular tachycardia, premature ventricular contractions (199 records)

  • atrial flutter (29 records)

  • atrial tachycardia (12 records)

  • Wolff–Parkinson–White syndrome (3 records)

  • multiple indications (5 records)

  • indication undefined (227 records).

Reported event types for the 464 atrial fibrillation records included the following common issues:

  • Injury/known risks associated with the procedure (283 records), including pericardial effusion, cardiac tamponade, atrioesophageal fistula, perforation, cerebrovascular accident and steam pop.

  • Malfunction (172 records), including catheter damage, internal components exposed, noise on all signals, char on catheter tip, deflection issue, loss of contact force, temperature issue and clot formation.

  • Death (9 records), including atrioesophageal fistula, cardiac tamponade, pericarditis, effusion and cerebrovascular accident.

Analysis by the manufacturer is ongoing in 132 cases and corrective actions have been started in 22 cases.

The FDA's major product recall for ThermoCool SmartTouch was ended on 31 October 2014. Of the 464 atrial fibrillation records, 190 were reported before this date and 273 were reported after (the event date of 1 record was not reported).

The MAUDE database houses reports on medical devices that were submitted because of suspected device‑associated deaths, serious injuries and malfunctions. Reports are submitted by mandatory reporters such as manufacturers, importers and facilities where the devices are used and voluntary reporters such as health care professionals, patients and consumers.

It should be noted that the MAUDE database is a passive surveillance system and potentially includes incomplete, inaccurate, untimely, unverified or biased data. The incidence of an event cannot be determined from this reporting system alone due to potential under‑reporting of events and lack of information about frequency of device used.

Clinical evidence

A systematic literature search identified 20 primary studies that reported on ThermoCool SmartTouch ablation catheter for radiofrequency ablation in patients with atrial fibrillation. The highest quality evidence was selected for inclusion in this briefing, including 2 randomised controlled trials (Nakamura et al. 2015, Kimura et al. 2014). Two retrospective cohort studies (Lee et al. 2015, Jarman et al. 2015) were included because they recruited a large number of patients, were UK‑based and used routine data. Ten additional non‑randomised comparative studies were identified, but only 6 were prospective in design (Andrade et al. 2014, Itoh et al. 2015, Makimoto et al. 2015, Marijon et al. 2014, Martinek et al. 2012, Sciarra et al. 2014) and have therefore been summarised. The other studies were excluded from this briefing as they were judged to provide lower quality evidence.

The study by Nakamura et al. (2015) prospectively enrolled 120 consecutive patients who were randomly assigned to have contact force‑guided circumferential pulmonary vein isolation (CPVI; contact force [CF] group, n=60) or CPVI with the operators blinded to the CF information (blind group, n=60). ThermoCool SmartTouch and the CARTO 3 navigation system was used in both groups. The CF group had fewer pulmonary vein reconnections (0.67±0.91 per patient compared with 1.16±1.16 per patient; p=0.007) and a shorter procedural time (50 minutes compared with 56 minutes; p=0.019) than the blind group. The mean contact force applied was higher in the CF group than the blind group (18.0 g compared with 16.1 g, p<0.001), with the most significant difference observed along the posterior right‑sided pulmonary veins and anterior left‑sided pulmonary veins. The arrhythmia‑free survival rate at 12 months was not significantly different between the 2 groups (89.9% compared with 88.2%; p=0.624). The authors stated that the similar clinical outcomes may have been a result of the learning effect from using the CF‑guided technique and repeated stimulation of inactive pulmonary vein conduction. The authors concluded that contact force‑guided CPVI could reduce pulmonary vein reconnections and the procedural time. An overview and summary of results can be found in table 1 and table 2 of the appendix.

The randomised controlled trial by Kimura et al. (2014) aimed to compare procedural parameters and outcomes between contact force‑guided (n=19) and non‑contact force‑guided (n=19) CPVI in consecutive patients with atrial fibrillation (28 people with paroxysmal and 10 with non‑paroxysmal). ThermoCool SmartTouch was used in both arms but operators were blinded to contact force information in the non‑CF group. The CARTO 3 navigation system was used in both groups. In the CF group, the contact force was kept between 10 g and 20 g during the procedure. The mean contact forces observed in the CF and non‑CF groups were 11.1±4.3 g and 5.9±4.5 g for left side CPVI (p<0.001) and 12.1±4.8 grams and 9.8±6.6 g for right side CPVI (p<0.001) respectively. The procedure time for CPVI in the CF group was 59±16 minutes and in the non‑CF group was 96±39 minutes (p<0.001). The total number of residual connection gaps needing touch‑up ablation was 2.8±1.9 in the CF group and 6.3±3.0 in the non‑CF group (p<0.001). At 6‑month follow‑up, 94.7% of patients in the CF group and 84.2% in the non‑CF group were free from any atrial tachyarrhythmias (p=0.34). The authors concluded that contact force‑guided CPVI was effective in reducing residual conduction gaps that need touch‑up ablation, and therefore reducing procedure time. They also stated that it may improve long‑term outcomes, although further evidence is needed. A summary of the study can be found in table 3 and table 4 of the appendix.

The retrospective observational cohort study by Lee et al. (2015) aimed to determine the 'real‑world' impact of ThermoCool SmartTouch for the treatment of AF when used with Carto 3.1 software on the CARTO 3 navigation system (n=510). This was compared with non‑contact force‑sensing catheters used alongside standard 3D‑mapping CARTO‑XP and EnSite NavX software (n=1,005). Patients having ThermoCool SmartTouch had a significantly lower fluoroscopy time (9.5 minutes compared with 41 minutes, p<0.001), radiation doses (1,044 mGy cm2 compared with 3571 mGy cm2, p<0.001) and shorter procedural time (195 minutes compared with 240 minutes, p<0.001) compared with the control group. However, no difference in the rate of cardiac complications following the procedure was found. An overview and summary of results can be found in table 5 and table 6 of the appendix.

The retrospective study by Jarman et al. (2015) matched procedures using contact force‑sensing catheters (n=200) to procedures without contact force‑sensing (n=400), taking into account the type of atrial fibrillation (paroxysmal, persistent or long‑lasting persistent). The authors did not describe the mapping systems used. They found that the use of contact force‑sensing catheters independently predicted clinical success in ablation in paroxysmal atrial fibrillation (hazard ratio [HR] 2.24, 95% confidence interval [CI] 1.29 to 3.90, p=0.04), but not in non‑paroxysmal atrial fibrillation (HR 0.73, 95% CI 0.41 to 1.30, p=0.289) in multivariate analysis. This study also reported a reduction in fluoroscopy time in the contact force‑sensing group of 7.7 minutes (p<0.001) compared with the control group. An overview and summary of results can be found in table 7 and table 8 of the appendix.

Six prospective non‑randomised controlled trials compared ThermoCool SmartTouch with non‑contact force‑sensing ablation (Andrade et al. 2014, Itoh et al. 2015, Makimoto et al. 2015, Marijon et al. 2014, Martinek et al. 2012, Sciarra et al. 2014). The non‑contact force‑sensing catheters included conventional catheters such as the standard ThermoCool, EZ steer ThermoCool or Navistar ThermoCool, and ThermoCool SmartTouch but with the operator blinded to contact force information. The studies included 418 patients, 186 having ThermoCool SmartTouch and 232 having non‑contact force‑sensing ablation for AF. Three studies showed a statistically significant reduction in atrial fibrillation recurrence in patients having ThermoCool SmartTouch at 12 months' follow‑up (Andrade et al. 2014, Itoh et al. 2015, Marijon et al. 2014). Five of the 6 studies reported a statistically significant reduction in overall procedure time with contact force guidance, with 1 study reporting a significant increase in overall procedure time (Andrade et al. 2014). Three of the 5 studies that measured ablation times reported a statistically significant reduction in this outcome in patients having ThermoCool SmartTouch (Marijon et al. 2014, Martinek et al. 2012, Sciarra et al. 2014). Similarly, 3 of the 6 studies that measured fluoroscopy times reported a statistically significant reduction in patients having ThermoCool SmartTouch (Andrade et al. 2014, Itoh et al. 2015, Marijon et al. 2014). Only 1 study reported a significant increase in fluoroscopy time (Andrade et al. 2014). Procedural complications were reported in the ThermoCool SmartTouch group in 3 studies: 1 atrioventricular fistula and 1 pericardial tamponade (Martinek et al. 2012), 1 mild groin haematoma (Sciarra et al. 2014), 1 local haematoma and 2 pericardial effusions (Marijon et al. 2014). Only 1 study (Andrade et al. 2014) reported adverse events at 1‑year follow‑up, but the authors did not report in which group the complications occurred. A summary of results can be found in table 9 of the appendix.

Recent and ongoing studies

Ten ongoing or in‑development trials on ThermoCool SmartTouch for atrial fibrillation were identified in the preparation of this briefing.

Completed trials

  • NCT01677052: ThermoCool SmartTouch Registry – Designed to measure 'real‑world' clinical use of contact force measurements during ablation procedures.

Active studies recruiting patients

  • NCT02217657: SmartTouch catheter for left anterior line, smart line study – This prospective, randomised study will investigate whether information about the catheter force applied during ablation of a left anterior line reduces total radiofrequency application time by preventing ineffective lesions.

  • NCT02485925: SMART China, a multicentre clinical registry study – This is a prospective effectiveness and safety assessment of the study device during radiofrequency ablation treatment of patients with drug‑refractory symptomatic atrial fibrillation.

  • NCT01730924: Comparison of pulmonary vein isolation using the SmartTouch catheter with or without real‑time contact force data – The purpose of this study is to evaluate whether contact force information affects the time to perform the procedure, or the outcomes as a result of it.

  • NCT02364401: Impedance versus contact force‑guided atrial fibrillation ablation using an automated annotation system – The purpose of this study is to compare the efficacy of catheter ablation for atrial fibrillation between contact force‑guided and impedance‑guided annotation using an automated annotation system (Visitag).

  • NCT01587404: Catheter contact force and electrograms – The purpose of the study is to examine how contact force affects the electrical behaviour of heart muscle tissue in atrial fibrillation.

  • NCT01570361: Atrial fibrillation progression trial (ATTEST) – The objective of this study is to determine whether early radiofrequency ablation treatment in patients with paroxysmal atrial fibrillation delays progression of atrial fibrillation compared with drug therapy (either rate or rhythm control) using current atrial fibrillation management guidelines.

Active studies not recruiting patients

  • NCT02359890: SMART‑SF radiofrequency ablation safety study – This is a prospective safety assessment of the study device during radiofrequency ablation treatment of drug‑refractory symptomatic atrial fibrillation.

Studies of unknown status

  • NCT01630330: Contact force‑sensing use in atrial fibrillation ablation – The purpose of the study is to determine whether the contact between the catheter tip and the inside of the heart wall improves the effectiveness of catheter ablation for atrial fibrillation patients.

  • NCT01693107: Atrial fibrillation force contact ablation study (CAFCAS) – The purpose of the study is to assess the current force being used for ablation of symptomatic paroxysmal atrial fibrillation in a wide range of operators in different Canadian centres, with the operators being blinded to the contact force data, and to assess the efficiency of using ThermoCool SmartTouch.

Costs and resource consequences

ThermoCool SmartTouch would replace conventional catheters without contact force‑sensing technology used in radiofrequency ablation for atrial fibrillation. Conventional radiofrequency ablation catheters without contact force‑sensing technology are available from Biosense Webster and have a list price of about £1,250 (ThermoCool Nav). Separate circular mapping catheters (to confirm electrical PVI) are also available from Biosense Webster. The list prices range from £1,000 to £1,200, excluding VAT.

When compared with standard ablation catheters, using ThermoCool SmartTouch and the additional components needed (the CARTO 3 navigation system and additional software either integrated or non‑integrated into a dedicated workstation) would pose an additional expense to the NHS. However, this could be offset if the device is associated with a long‑term reduction in atrial fibrillation recurrence (fewer healthcare visits, reduced medications), reduction in procedure and fluoroscopy time, and reduced complications.

No published evidence on resource consequences was identified.

Strengths and limitations of the evidence

There are several published studies on the use of ThermoCool SmartTouch for atrial fibrillation. A systematic literature search identified 20 relevant articles, 4 of which were selected for full review and 6 that were summarised in the briefing. The 2 randomised controlled trials were both small single‑centre studies and not done in the UK. However, the 2 retrospective studies recruited substantially more patients and were both done in UK hospitals. Although the 2 randomised controlled trials have an important contribution, they both suffer from the same flaw. The contact force measurements suggested reconnection early, during the index ablation procedure. However, they did not report on late reconnection, for example at 6‑month follow‑up.

The randomised controlled trial by Nakamura et al. (2015) was a slightly larger study with 120 consecutive patients randomised into either a contact force‑guided CPVI group or non‑contact force‑guided CPVI group, where the operators were blinded to the contact force measurements. Four operators did the CPVI procedures for each group, reducing operator variability. The authors noted that a learning effect may have improved the operators' manipulation of the catheter, which may have negatively impacted the earlier reported outcomes in the intervention group. However, because all 4 operators performed both procedures, this could also have affected the non‑CF‑guided group. The authors highlighted that although the target contact force application was 20 g, the mean contact force applied was less than 20 g in certain segments, which was caused by technical difficulty in manipulating the catheter, particularly around the ridge between the left pulmonary veins and the left atrial appendage.

The randomised controlled trial by Kimura et al. (2014) was a relatively small study with only 38 consecutive patients included across the 2 groups. However, after completion of the trial, the authors attempted to validate the effectiveness of contact force between 10 g and 20 g in accomplishing CPVI in a separate cohort of 20 patients. Although consecutive patients were enrolled, limiting selection bias, no exclusion criteria were described within the report. The authors noted that despite a run‑in period to improve operator familiarity with the device there was evidence of a learning effect, so it might be expected that performance with ThermoCool SmartTouch would improve with time. Overall, the methodology of this randomised controlled trial was poor, as the authors did not calculate power, there were no prespecified primary outcomes and they only reported technical and surrogate outcomes.

The retrospective comparator study by Lee et al. (2015) reported data on the most patients of any included trial (n=510 using ThermoCool SmartTouch and n=1,005 in the control arm). Major limitations of this study include the use of multiple models of catheters and different mapping systems across the 2 arms, making it difficult to attribute outcomes to ThermoCool SmartTouch alone. Furthermore, the absolute numbers of cardiac complications were tabulated but no statistical comparisons were described (the odds ratios calculated by the authors of this briefing confirmed no statistical difference in individual or combined cardiac complication rates between groups). Because this was a UK study using routine data, the results are generalisable to current practice. However, the weakness lies in its internal validity which is intrinsic to the study design.

The retrospective observational study by Jarman et al. (2015) matched cases using ThermoCool SmartTouch in a 1:2 ratio to cases not having a contact force‑sensing catheter, taking the type of atrial fibrillation into account during matching. The authors correctly accounted for differences in baseline characteristics between cases and controls by conducting multivariate analysis. As a result of the use of retrospective data in the chosen study design, the authors acknowledge that the results of this study are limited by selection bias and confounding from other variables is not recorded.