Abstract
Background: Radiofrequency hotballoon (RHB) is an ablation device used for atrial fibrillation (AF) treatment. The efficacy and safety of RHB-based pulmonary vein isolation (PVI) in real-world practice are unknown.
Methods and Results: A multicenter, prospective registry study (UMIN000029567) enrolled AF patients who underwent RHB-PVI. The primary endpoint was the AF recurrence-free survival rate at 12 months after PVI. Of the 679 patients enrolled, 613 (90.3%; paroxysmal AF, n=370; persistent AF, n=136; long-standing AF, n=107) underwent initial RHB-PVI. Acute isolation using only the RHB was successful for 55.6% of patients and 83.5% of pulmonary veins (PVs). The acute isolation rate was higher for patients with paroxysmal AF and more experienced centers. Antiarrhythmic drugs were prescribed after 3 months for 47.5% of patients. The AF recurrence-free survival rate at 12 months was 83.7%. Procedure-related complications including atrio-esophageal fistula (n=1) and phrenic nerve injury (persistent; n=4, permanent; n=2) were observed in 19 (3.1%) patients. Five (1.7%) of the 302 patients who underwent pre-procedural and post-procedural multidetector computed tomography had severe PV stenosis.
Conclusions: The size-adjustable RHB has been used for the treatment of various AF types. The arrhythmia recurrence-free rate at 12 months, with the use of antiarrhythmic drugs in approximately half of the patients, was acceptable, but the acute isolation rate using the RHB requires further improvement.
A radiofrequency hotballoon (RHB) catheter (SATAKE. HotBalloon; Toray Industries, Inc., Tokyo, Japan) comprises a highly compliant and size-adjustable balloon (diameter, 25–33 mm). The effectiveness of RHB ablation for atrial fibrillation (AF) treatment was evaluated during a single-center study performed in 2003.1–3 A multicenter randomized study was conducted in Japan between July 2012 and October 2014 to test the feasibility of pulmonary vein isolation (PVI) using the RHB catheter for the treatment of paroxysmal AF.4 During the clinical trial, energy applications were performed at the antrum, ostium, and carina of the pulmonary vein (PV).5 RHB-PVI demonstrated a high acute PVI rate of 98%; however, the high incidence (8.9%) of phrenic nerve injury (PNI) and severe PV stenosis (>70% narrowing) remained concerning. For these cases, the balloon was inflated with ≤8 mL of balloon injection volume. The RHB was approved in April 2016, with the recommendation that the balloon injection volume should be ≥10 mL to avoid complications. A larger balloon injection volume indicated a more proximal balloon position and lower balloon surface temperature, making it difficult to create a transmural lesion. However, a single-center study demonstrated that a larger balloon injection volume with longer energy application time could achieve antral PVI and reduce the complication rate.6 No multicenter study has evaluated the efficacy and safety of the RHB in clinical practice. The Japan Society of HotBalloon Catheter conducted the RHB-PVI registry study (HARVEST study) as the first nationwide observational study to investigate the real-world efficacy and safety of RHB use in Japan.
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Methods
Patient Enrollment
The HARVEST multicenter, prospective, observational study was conducted at 33 centers in Japan. The HARVEST study included consecutive AF patients aged ≥20 years who underwent RHB ablation. The RHB was approved for the treatment of paroxysmal AF, but it has also been used for the treatment of persistent and long-standing persistent AF according to the discretion of the physician. To collect real-world data regarding RHB ablation, patients with various AF types were enrolled between September 2017 and May 2018. The exclusion criteria of the study were patients with a survival prognosis of <1 year and those considered unsuitable for inclusion. There were no anatomical exclusion criteria. Only patients who underwent initial AF ablation were included for analysis. The study protocol was approved by the Tsukuba Clinical Research & Development Organization (H29-167) and each institution’s ethics committee and registered in the UMIN Clinical Trial Registry (UMIN000029567). An opt-out system was used to obtain patient consent for the use of their clinical data for research purposes.
Ablation Method
A randomized, controlled study using a pre-specified ablation protocol targeting the PV antrum and the ostium demonstrated a high success rate, but a high severe complication rate. Therefore, each participating center sought optimal energy application times and durations after the approval of the device. In this registry, no fixed ablation protocol was used, and balloon injection volume, balloon center temperature (maximum 73℃ for the left superior pulmonary vein [LSPV] and maximum 70℃ for other PVs), and total energy application time were decided by each physician. Touch-up ablation was performed if necessary. The endpoint of ablation was PV isolation confirmed by a circular catheter. The use of a three-dimensional mapping system was not mandatory. Esophageal temperature monitoring was performed for all cases, and cold saline was injected when the esophageal temperature exceeded 39℃.7 Additional ablations in the left atrium, superior vena cava (SVC) isolation, and isthmus ablation for typical flutter using a radiofrequency catheter were collected. Continuous heparin was administered to achieve the target activated clotting time of >300 s.
Follow-up
Follow-up visits comprised a clinical interview and electrocardiography at 3, 6, and 12 months. The patients received standard care provided by participating centers during follow up. The timing of the 24-h Holter electrocardiograms was not strictly defined in the protocol, and the results were collected when performed during routine visits. The use of antiarrhythmic drugs (AADs) after the procedure was administered according to the discretion of the physician. Although routine post-procedural multidetector computed tomography (MDCT) was not mandatory, PV narrowing was evaluated in patients who underwent pre-procedural and post-procedural MDCT.
Repeat ablation for atrial arrhythmia recurrence was performed if necessary. The association between PVs requiring repeat ablation and the acute isolation results of the initial procedure was assessed.
Definitions and Endpoints
The primary endpoint was the AF recurrence-free survival rate at 12 months after PVI. AF recurrence was defined as documentation of AF lasting ≥30 s that occurred 3 months after the procedure. The secondary endpoints included the acute isolation success rate, AF recurrence-free survival rate at 6 months, and adverse events (AEs) up to 12 months after PVI. Vaughan Williams Class I, Amiodarone, and Bepridil were considered as AADs. Acute isolation success was defined as PVI achieved using only RHB; it was calculated for each patient and each PV. Similar to the post-marketing surveillance,8 undesirable experiences that occurred during the follow-up period were defined as AEs and data about them were collected. AF recurrence was also considered an AE. Procedure-related AEs were defined as AEs that occurred within 30 days after the procedure and had an obvious causal relationship with the ablation procedure. Persistent PNI was defined as the persistence of an elevated hemidiaphragm noted by chest X-ray if PNI recovered within 12 months. Otherwise, the PNI was defined as permanent. Severe PV stenosis was defined as >70% narrowing compared to the pre-procedural PV diameter.
Statistical Analysis
Continuous data are expressed as the mean±standard deviation for normally distributed variables. The acute isolation success rate after single energy application with various ablation protocols was compared using the chi-squared test. Fisher’s exact test was used to compare categorical variables (e.g., sex and CHA2DS2-VASc scores). A one-way analysis of variance for numerical variables (e.g., age, body mass index, etc.) was performed to compare the 3 AF types and participating centers with different levels of experience. A Kaplan-Meier curve was plotted for the time to AF recurrence after ablation. A log-rank test was performed to compare AF recurrence-free rates at 6 months and 12 months. The impact of the number of procedures performed by each participating center on acute isolation success was analyzed in blocks of 25 patients and compared by using Fisher’s exact test. Statistical significance was set at P<0.05.
Results
Patient Characteristics
During the enrollment period, 679 patients from 33 centers were enrolled. All patients who underwent RHB-PVI at participating centers during the study period were enrolled. Of these 679 patients, 613 (90.3%) underwent initial RHB-PVI and were included in the analysis. Sixty-six patients who underwent RHB during repeated procedures were excluded from the analysis.
Among the patients with AF, paroxysmal AF was observed in 370 (60.4%), persistent AF was observed in 136 (22.2%), and long-standing persistent AF was observed in 107 (17.4%). Patient and procedural characteristics are shown in Table 1. The mean left atrial dimension and volume index were 40.2±6.5 mm and 39.9±15.0 mL/m2, respectively; they were significantly higher in patients with long-standing persistent AF. Left common PVs and right middle PVs were observed in 37 (6.0%) and 20 (3.3%) patients, respectively.
Table 1. Patient and Procedure Characteristics According to the Types of AF
| |
All |
Type of AF |
P value |
| Paroxysmal |
Persistent |
Long-standing
persistent |
| Patients, n (%) |
613 |
370 (60.4) |
136 (22.2) |
107 (17.5) |
|
| Male, n (%) |
439 (71.6) |
244 (65.9) |
108 (79.4)# |
87 (81.3)‡ |
0.0005 |
| Age, years |
65.4±10.4 |
65.7±10.6 |
64.2±10.2 |
65.6±9.9 |
0.32 |
| BMI, kg/m2 |
24.1±3.9 |
23.7±3.6 |
24.3±3.9 |
25.5±4.7‡,* |
0.0001 |
| Left atrial dimension, mm |
40.2±6.5 |
38.6±5.9 |
42.3±6.9# |
43.0±5.9‡ |
<0.0001 |
| Left atrial volume index, mL/m2 |
39.9±15.0 |
37.8±14.8 |
39.4±12.3 |
46.5±16.5‡,* |
<0.0001 |
| Ejection fraction, % |
63.6±9.3 |
64.8±8.4 |
61.2±10.5# |
62.4±10.0‡ |
0.0001 |
| CHA2DS2-VASc score, n (%) |
| 0–1 |
208 (33.9) |
111 (30) |
57 (41.9)# |
40 (37.4) |
0.03 |
| ≥2 |
405 (66.1) |
259 (70) |
79 (58.1) |
67 (26.2) |
| Total energy applications, n |
5.9±1.9 |
5.6±2.0 |
6.2±1.8# |
6.7±1.7‡ |
<0.0001 |
| Total ablation time, min |
16.8±5.2 |
15.8±5.4 |
18.1±4.5# |
18.7±4.4‡ |
<0.0001 |
| Procedure time, min |
158.0±53.5 |
161.9±57.4 |
151.5±48.9 |
152.8±43.2 |
0.09 |
| LA dwell time, min |
99.5±38.5 |
99.7±41.2 |
98.1±37.5 |
100.9±29.9 |
0.85 |
| Fluoroscopy time, min |
48.6±27.4 |
47.7±27.9 |
52.3±30.4 |
48.2±21.1 |
0.34 |
| PV diameter, mm |
| LSPV |
19.4±3.8 |
18.9±3.5 |
21.2±3.8# |
19.6±4.6 |
0.0003 |
| LIPV |
16.7±3.3 |
16.5±3.2 |
17.1±2.8 |
17.6±4.0 |
0.09 |
| RSPV |
19.4±3.6 |
19.1±3.3 |
20.2±3.8 |
20.0±4.6 |
0.06 |
| RIPV |
17.4±3.2 |
17.5±3.2 |
17.3±3.1 |
17.4±3.5 |
0.93 |
| Injection volume per PV, mL |
| LSPV |
12.5±1.8 |
12.1±1.7 |
13.2±1.8# |
12.8±1.6‡ |
<0.0001 |
| LIPV |
11.1±1.3 |
10.9±1.3 |
11.3±1.4# |
11.4±1.3‡ |
0.0009 |
| RSPV |
12.9±2.4 |
12.3±2.0 |
13.6±2.5# |
13.9±2.6‡ |
<0.0001 |
| RIPV |
10.9±1.6 |
10.6±1.6 |
11.2±1.6# |
11.3±1.5‡ |
<0.0001 |
| Total ablation time per PV, min |
| LSPV |
5.1±2.2 |
5.1±2.4 |
5.1±1.6 |
4.9±1.9 |
0.61 |
| LIPV |
2.9±1.1 |
2.9±1.2 |
3.0±1.1 |
2.8±0.9 |
0.44 |
| RSPV |
4.2±1.6 |
4.0±1.7 |
4.3±1.4 |
4.4±1.5 |
0.02 |
| RIPV |
3.1±1.1 |
3.1±1.2 |
3.1±0.9 |
3.0±1.1 |
0.99 |
| Acute PV isolation, per patient, n/N (%) |
341/613 (55.6) |
226/369 (61.2) |
66/136 (48.5)# |
49/107 (45.8)‡ |
0.003 |
| Acute PV isolation, per PV, n/N (%) |
2,016/2,414 (83.5) |
1,252/1,459 (85.8) |
430/529 (81.3)# |
334/426 (78.4)‡ |
0.0004 |
| LSPV |
386/577 (66.9) |
242/345 (70.1) |
80/130 (61.5) |
64/102 (62.7) |
0.13 |
| LIPV |
509/569 (89.5) |
308/343 (89.8) |
114/125 (91.2) |
87/101 (86.1) |
0.46 |
| RSPV |
531/607 (87.5) |
334/367 (91.0) |
112/134 (83.6)# |
85/106 (80.2)‡ |
0.003 |
| RIPV |
544/603 (90.2) |
333/364 (91.5) |
121/132 (91.7) |
90/107 (84.1) |
0.08 |
| Touch-up ablation per patient, n/N (%) |
261/613 (42.6) |
137/370 (36.9) |
69/136 (50.7)# |
55/107 (51.4)‡ |
0.002 |
| Touch-up ablation per PV, n/N (%) |
384/2,414 (15.9) |
197/1,459 (13.5) |
98/529 (18.5)# |
89/426 (20.9)‡ |
0.0002 |
| Additional ablation, n (%) |
| Superior vena cava isolation |
52 (8.5) |
26 (7.0) |
15 (11.0) |
11 (10.3) |
0.24 |
| RA isthmus ablation |
213 (34.7) |
109 (29.5) |
56 (41.2)# |
48 (44.9)‡ |
0.003 |
| Other |
15 (2.4) |
12 (3.2) |
2 (1.5) |
1 (0.9) |
0.37 |
| Anti-arrhythmic drug, n (%) |
| 3 months |
291 (47.5) |
123 (33.2) |
86 (63.2)# |
82 (76.6)‡,* |
<0.0001 |
| 6 months |
261 (42.6) |
108 (29.2) |
78 (57.4)# |
75 (70.1)‡,* |
<0.0001 |
| 12 months |
236 (38.5) |
96 (25.9) |
73 (53.7)# |
67 (62.6)‡ |
<0.0001 |
| Anti-arrhythmic drugs at 12 months, n (%) |
| Class I |
117 (19.1) |
74 (20.0) |
21 (15.4) |
22 (20.6) |
0.48 |
| Amiodarone/Bepridil |
147 (24.0) |
34 (9.2) |
58 (42.6)# |
55 (51.4)‡ |
<0.0001 |
#P<0.05, paroxysmal vs. persistent; ‡P<0.05, paroxysmal vs. long-standing persistent; *P<0.05, persistent vs. long-standing. AF, atrial fibrillation; BMI, body mass index; LA, left atrial; LIPV, left inferior pulmonary vein; LSPV, left superior pulmonary vein; PV, pulmonary vein; RA, right atrium; RIPV, right inferior pulmonary vein; RSPV, right superior pulmonary vein.
As shown in Table 1, the number of energy applications and ablation time for each procedure were 5.9±1.9 applications and 16.8±5.2 min, respectively. The balloon injection volume was significantly greater for all PVs with persistent and long-standing persistent AF than for paroxysmal AF. The rates of acute isolation using only the RHB were 55.6% for patients and 83.5% for PVs. Acute isolation rates for PVs with paroxysmal AF, persistent AF, and long-standing persistent AF were 85.8%, 81.3%, and 78.4%, respectively. Touch-up ablation was performed for 383 PVs, and PVI was achieved for 374 PVs (97.7%). In addition to PVI, SVC isolation was performed for 8.5%, isthmus ablation for typical atrial flutter was performed for 34.7%, and other ablations were performed for 2.4% of patients using a radiofrequency catheter.
Details of the representative ablation protocol and successful acute isolation after a single energy application are shown in Figure 1. Energy application to the LSPV using a higher balloon central temperature resulted in a significantly higher acute isolation success rate (P=0.002). A longer energy application time was associated with significantly higher rates of acute isolation success for the right superior pulmonary vein (RSPV) and right inferior pulmonary vein (RIPV), whereas those for the left inferior pulmonary vein (LIPV) with different energy application times were similar. The success rate of acute isolation using the RHB only was 90.2% for the RIPV; however, it remained 66.8% for the LSPV. The balloon injection volume was highest for the RSPV (12.9±2.4 mL) and lowest for the RIPV (10.9±1.6 mL). Thirty-seven left common PVs (6.0%) were treated with the RHB, and 74.2% of those were isolated using only the RHB. At the end of the procedure, a figure-8 suture was used to secure hemostasis in 407 (66.4%) patients.
After the procedure, antiarrhythmic drugs were prescribed after 3 months for 47.5% of patients with AF (paroxysmal AF, 33.2%; persistent AF, 63.2%; long-standing persistent AF, 77.6%); these patients were followed up for 326±73 days. The Kaplan-Meier plot of AF recurrence-free survival is presented in Figure 2. At 12 months, the AF recurrence-free rate for patients with paroxysmal AF, persistent AF, and long-standing persistent AF were 86.0%, 81.7%, and 78.1%, respectively (P=0.23).
Repeated procedures were performed for 58 patients (9.5%) and 224 PVs (including 7 left common PVs) at 234.7±97.3 days after the initial procedure. Reconnection of the PVs was observed in 38 patients and 62 PVs (28%). Lesion durability was 76% when PVs were isolated using only the RHB; however, it was 56% when touch-up ablation was required.
Adverse Events
Details of AEs during the follow-up period and procedure-related AEs are listed in Table 2. During the follow-up period, there were 132 (21.5%) AEs in 105 patients, including 47 (7.7%) atrial arrhythmia recurrences. Twenty-two procedure-related AEs were documented in 19 patients (3.1%). Four patients (0.7%) developed cardiac tamponade. One cerebral infarction (0.2%) occurred 1 day after the procedure in a patient with persistent AF and a history of cerebral infarction. Persistent (n=4) and permanent (n=2) PNI were detected in 6 (1.0%) patients (Supplementary Table 1). The balloon injection volume for patients with PNI was 11.0±1.1 mL. Aspiration pneumonitis related to the esophageal cold saline injection was observed in 3 (0.5%) patients. Complications related to groin puncture were observed in 2 (0.3%) patients; both of those patients received a figure-8 suture at the end of the procedure.
Table 2. Details of the AEs
| |
N=613 |
| All AEs |
132 (21.5) |
| Atrial arrhythmia recurrence |
47 (7.7) |
| Procedure-related AEs |
19 (3.1)‡ |
| Cardiac tamponade |
4 (0.7) |
| Groin hematoma |
2 (0.3) |
| Pseudo aneurysm |
2 (0.3) |
| Aspiration pneumonia |
3 (0.5) |
| Heart failure |
1 (0.2) |
| Phrenic nerve palsy |
6 (1.0) |
| Persistent |
4 (0.7) |
| Permanent |
2 (0.3) |
| Stroke/transient ischemic attack |
1 (0.2) |
| Left atrio-esophageal fistula |
1 (0.2) |
| Peri-esophageal nerve injury |
1 (0.2) |
| Postoperative endocarditis |
1 (0.2) |
| Death |
0 (0) |
| |
n=302 (49.3)# |
| Severe pulmonary vein stenosis (>70%) |
5 (1.7) |
Data are presented as n (%). ‡Three patients experienced 2 events. #Only patients who underwent repeat and post-procedural multidetector computed tomography were included. AE, adverse event.
An atrio-esophageal fistula developed in a 72-year-old woman with a large left common PV (diameter, 31 mm). Individual isolation of the left superior and left inferior pulmonary branches was attempted with balloon injection volumes of 18 mL and 15 mL, respectively. Energy application was delivered for 3 min at a target temperature of 70℃. During energy application, the esophageal temperature was elevated to >39℃ (maximum temperature, 41℃), and a total of 170 mL of cold saline was repeatedly injected. On day 20, she lost consciousness; computed tomography revealed multiple air emboli in the brain, left atrium, and space between the left common PV and esophagus, resulting in the diagnosis of an atrio-esophageal fistula. She underwent emergency surgical closure of the atrio-esophageal fistula (15×5 mm) that developed at the ostium of the left common PV. Although she survived, she remained in a vegetative state.
Among the 613 patients, 302 (49.3%) underwent pre-procedural and post-procedural MDCT. Severe PV stenosis, defined as a reduction of >70% of the PV diameter, was observed in 5 (1.7%) patients (LSPV; n=2, LIPV; n=1, RIPV; n=2, Supplementary Table 2). The balloon injection volume of these veins was 9.8±0.4 mL. All patients were asymptomatic, and no further intervention was required.
Learning Curve
The numbers of procedures performed per center before patient enrollment in the registry are shown in Figure 3A; 3 centers performed >100 procedures and enrolled 183 (29.9%) patients. Another 3 centers performed 51–75 procedures and enrolled 133 patients (21.7%). Four centers performed 26–50 procedures and enrolled 72 patients (11.7%). Twenty-three centers performed 0–25 procedures and enrolled 225 patients (36.7%). Patient characteristics and acute procedural outcomes of the participating centers were evaluated by comparing the number of procedures performed using the RHB for a group of 25 patients (Supplementary Table 3). Centers that performed >100 procedures had a significantly higher acute PV isolation success rate (P<0.001) (Figure 3B). Notably, the energy application time was significantly shorter at the most experienced centers despite a higher acute isolation success rate. The balloon injection volume was significantly greater at participating centers with >50 cases before study enrollment. At 12 months, the AF recurrence-free rates at 12 months were 83.6%, 94.4%, 84.2%, and 83.1% for centers that performed 0–25, 26–50, 51–75, and >100 procedures, respectively (P=0.23).
Discussion
The large, multicenter, prospective HARVEST study investigated the real-world efficacy and safety of the RHB in Japan. The results presented indicate several new findings. First, a size-adjustable, highly compliant RHB was used to treat patients with non-paroxysmal AF; these patients comprised approximately 40% of all enrolled patients. Second, acute PVI using only the RHB was achieved for 55.6% of patients and 83.5% of the PVs. The acute PV isolation rate was higher for patients with paroxysmal AF and for more experienced centers. Third, the rates of acute PVI of the LIPVs and RIPVs reached approximately 90% regardless of the AF type; however, the LSPV isolation rate was approximately 65%. The acute isolation success rate for the LSPV significantly increased with a higher balloon central temperature. Fourth, the arrhythmia recurrence-free rate at 12 months with the use of AADs in approximately half of the patients was acceptable. Finally, the combined rate of PNI and severe PV stenosis complications was 1.8%, which was lower than that observed during the clinical trial; however, an atrio-esophageal fistula developed in 1 patient.
Acute Procedure Results
In 2016, the RHB was approved as a “single-shot” device for the treatment of paroxysmal AF after limited experience with it. Nevertheless, 39.6% of the enrolled patients in the HARVEST study had non-paroxysmal AF with a larger left atrium than those with paroxysmal AF. During this study, a greater injection volume was used when treating patients with persistent or long-standing persistent AF compared to those with paroxysmal AF. Theoretically, there is a negative correlation between the balloon diameter and balloon surface temperature; therefore, the surface temperature of the balloon may decrease with a larger balloon injection volume if the central temperature of the balloon is fixed. During this study, the acute isolation rate using only the RHB was lower for persistent AF and long-standing persistent AF than for paroxysmal AF; this is partly explained by the lower balloon surface temperature attributable to the larger balloon injection volume.
In this registry, the balloon injection volume and energy application time were greater and shorter, respectively, than those in the clinical trial. As expected, the severe complication rate decreased; however, the acute isolation success rate per PV with paroxysmal AF was 85.8%, which was lower than that of clinical trials, including only paroxysmal AF patients.
Chronic Outcomes
The HARVEST study demonstrated clinical outcomes for various AF types. In this registry that enrolled patients from centers with various levels of experience, 38 patients underwent repeated procedures and 72% of PVs were still isolated at the time of the repeated procedure. A single-center study reported lesion durability in 26 patients who underwent repeat ablation at a median 378 days after the initial RHB-PVI.9 A durable PVI was observed in 83.5% of PVs; this rate was similar to, or better than that of the cryoballoon.10 Lesion characteristics evaluated using late gadolinium enhancement magnetic resonance imaging demonstrated that lesions after RHB ablation were more continuous and proximal irrespective of PV size than those after cryoballoon ablation.11 Although further studies are required to establish the optimal energy setting to improve the acute isolation success rate, the unique feature of the size-adjustable RHB enables its use as a single-shot device for patients with an enlarged PV antrum.
Adverse Events After RHB-PVI
In this registry, the average balloon injection volume was increased, and ablation times were shortened compared to the clinical trial to avoid complications. PNI and severe PV stenosis rates were reduced to 1.0% and 1.7%, respectively; however, the average balloon injection volume applied to PVs with severe complications was 10.8±1.1 mL, which is smaller than that of the second-generation cryoballoon. A balloon injection volume of 10 mL is the recommended minimum balloon injection volume, and the balloon size should be appropriately adjusted to the PV ostium diameter. Among the 6 patients with PNI, the diameter of the targeted PV was reported for only 1 patient, and the balloon injection volume may have been smaller than the targeted PV diameter. When determining the appropriate balloon injection volume, measurement of the PV diameter using pre-procedural MDCT or intra-procedural PV angiography is recommended to avoid a smaller balloon injection volume relative to the target PV antrum.
Esophageal injury occurs regardless of energy sources, including the cryoballoon.12,13 In this registry, 1 patient developed an atrio-esophageal fistula despite cold saline injection. For that patient, the cold saline injection volume was 170 mL, which was considerably greater than that reported by a previous study (median, 35 mL).6 Because the esophageal temperature remained high despite esophageal cooling, it was speculated that the extrinsic compression of the esophagus by the inflated balloon or anatomy of the esophagus itself limited effective cooling.14 A previous study demonstrated that asymptomatic esophageal erythema and gastric hypomotility were observed in 12.2% of patients after RHB-PVI, which was lower than that observed after cryoballoon ablation.6,15 In principle, overheating of the esophagus with any energy source must be avoided. A cold saline injection helps to reduce esophageal injury only when esophageal cooling is efficient. Counterclockwise manipulation of the guiding sheath and lowering the balloon central temperature prevented severe esophageal injury when a rapid decrease in esophageal temperature was not observed immediately after the cold saline injection.3,4,6,7 If a rapid decrease in esophageal temperature does not occur, then operators must abruptly stop the energy application and adjust the position and size of the balloon to avoid overheating the esophagus.
Learning Curve of the Radiofrequency HotBalloon Catheter
A post-marketing study of the RHB that enrolled the first 20 patients at 46 participating centers demonstrated that the acute isolation success rate for PVs was 77.3%.8 In the HARVEST study, 63.3% of the procedures were performed at centers with experience performing >25 procedures. The most experienced center (>100 procedures before the study period) had achieved an acute PVI rate of 88.3%, which was significantly higher than those of centers with less experience. A previous study demonstrated a learning curve for RHB-PVI and improvements in the acute isolation success rate even after 25 cases.6 These findings suggested that optimizing the balloon injection volume to achieve PV occlusion and maintaining the balloon position require some experience.
Comparison With Other Balloon Ablation Procedures
The RHB has a size-adjustable, highly compliant balloon and was developed as a single-shot device. During a single-center study, 9.5% of the total energy applications and 26% of the energy applications to the RSPV were performed with balloon volumes of >15 mL (estimated balloon diameter of 30 mm); these volumes were larger than those of the 28-mm cryoballoon.6 A wider isolation area with a larger balloon may improve the outcome and avoid PNI.
The acute procedure results of the HARVEST registry demonstrated the different characteristics of the RHB compared to the cryoballoon. With the RHB, the acute isolation success rate for the LSPV was the lowest at 66.3%. Although the current study did not examine the details of the touch-up ablation sites, several previous studies reported that the ridge of the LSPV and its thicker myocardium often require touch-up ablation.9,16,17 An animal study demonstrated that a longer energy application time or higher balloon temperature created deeper lesions.18 A higher balloon central temperature was expected to increase the acute isolation success rate for the LSPV; therefore, a balloon central temperature of 73℃ was adopted by some centers to improve the acute isolation success rate for the LSPV. The results of this study showed that a higher balloon central temperature nor longer energy application time significantly improved the acute isolation success rate, except for the LIPV. Another difference was that the highest acute isolation success rate with the RHB was achieved for the RIPV (90.2%), contrary to that of the cryoballoon.19 Achieving complete occlusion of the RIPV using the cryoballoon is difficult because of the shorter distance from the trans-septal puncture site to the ostium of the RIPV. As a result, touch-up ablation or PV reconnection was most frequently required in the RIPV.10 The balloon profile of the RHB is highly compliant; therefore, RIPV occlusion is relatively easy to achieve, resulting in a high success rate.9
A fundamental difference between the cryoballoon and the RHB was that the RHB system automatically maintains the target balloon central temperature, but not the balloon surface temperature, which directly affects lesion formation. The balloon injection volume and balloon surface temperature were negatively correlated; therefore, a larger balloon injection volume may lower the balloon surface temperature. Consequently, PVI becomes difficult even when complete PV occlusion is achieved with a larger balloon injection volume at the level of the PV antrum. To overcome this limitation, a new RHB that can monitor the balloon surface temperature is now available in Japan. A recent study demonstrated that the cut-off value for the balloon surface temperature to achieve PVI with a single shot was >58.7℃.20 In terms of safety, energy application with a smaller balloon injection volume may result in a higher balloon surface temperature and increased risks of severe PV stenosis and PNI. When balloon surface temperature-controlled ablation is available, the effectiveness and safety profile of the RHB are expected to improve.
Study Limitations
The results presented are important findings; however, this study had several limitations. First, there was no pre-defined ablation protocol. The ablation protocol and balloon injection volume were determined by the operators. Previous studies demonstrated that there is an apparent learning curve; therefore, physicians with less experience may have difficulty adjusting the balloon size and maintaining the optimal balloon position during energy application. Second, in the present study, the prevalence of AAD use beyond 3 months was higher than in previous studies, especially for patients with persistent and long-standing AF. Post-procedural AADs are an option to improve sinus rhythm maintenance; the rate of post-procedural AAD use was higher in the HARVEST study than in the AF Ablation Frontier Registry (23.5%) and KPAF study (18.9%).21,22 Higher use of post-procedural AADs in the HARVEST study presumably lead to similar arrhythmia-free rates for all types of AF. Third, the follow-up duration was limited. Recurrence monitoring was performed according to the standard of care of each center. More rigorous monitoring may have detected additional arrhythmia recurrences; therefore, asymptomatic arrhythmia recurrence, especially in persistent and long-standing AF, may have been underestimated. Finally, the results of the chronic outcomes in the HARVEST study cannot be generalized due to the high rate of post-procedural AAD use, and the lack of a strict follow-up protocol. Therefore, the impact of the RHB on chronic outcomes in various AF types needs further investigation by a prospective study with a strict follow-up protocol.
Conclusions
In real-world practice, a size-adjustable RHB has been used for the treatment of various AF types. The arrhythmia recurrence-free rate at 12 months with the use of AADs in approximately half of the patients was acceptable, but the acute isolation rate using the RHB requires further improvement.
Acknowledgment
We thank Editage (https://www.editage.jp) for English-language editing of this manuscript.
Sources of Funding
This work was supported by Toray Industries, Inc.
Disclosures
K.A. is a member of Circulation Journal’s Editorial Team. H.Y. received speaker honoraria and consulting fees from Toray Industries, Inc. and speaker honoraria from Century Medical, Inc. S.N. received speaker honoraria/consulting fees from Toray Industries, Inc. H.S. received speaker honoraria/consulting fees from Toray Industries, Inc., speaker honoraria from Japan Lifeline Co., Ltd., Johnson & Johnson, and K.K. Medical. Y.Y. received speaker honoraria/consulting fees from Toray Industries, Inc. and Medtronic Japan Co., Ltd. T.K. received speaker honoraria from Century Medical, Inc., Medtronic Japan Co., Ltd., Nihon Kohden Corporation, Japan Lifeline Co., Ltd., and Johnson & Johnson. K.K. received speaker honoraria from Medtronic Japan Co., Ltd. and Boston Scientific Japan and research grants from Medtronic Japan Co., Ltd. T.Y. received speaker honoraria from Abbott Japan, Medtronic Japan Co., Ltd., and Japan Lifeline Co., Ltd. K.A. belongs to the endowed department of Boston Scientific Japan, Japan Lifeline Co., Ltd., Nihon Kohden Corporation, Biotronik Japan, Inc., Toray Industries, Inc., Century Medical, Inc., and Boehringer Ingelheim GmbH. The other authors declare no conflicts of interest.
IRB Information
The Tsukuba Clinical Research & Development Organization (H29-167) approved this study.
Data Availability
The deidentified participant data will not be shared.
Supplementary Files
Please find supplementary file(s);
https://doi.org/10.1253/circj.CJ-21-0994
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