Aim

Cryothermal energy has the ability reversibly to demonstrate loss of function with cooling, ice mapping, at less deep temperatures. The purpose of this study was to investigate the time course of the temperature during ice mapping of accessory pathways.

Methods and results

Thirteen patients with the Wolff–Parkinson–White (WPW) syndrome underwent cryoablation. After identification of a prospective ablation site, ice mapping was performed by cooling the tip to a minimum of −30 °C. Successful ice mapping was defined by loss of accessory pathway (AP) conduction. A total of 104 ice maps were analyzed. Successful ice mapping was demonstrated in 17 attempts. There was no significant difference in mapping temperature between successful and unsuccessful ice mapping (−29.4±3.2 °C vs −30.4±1.7 °C). The temperature time constant τ during successful ice mapping was significantly shorter compared with unsuccessful ice mapping (7.0±1.1 s vs 10.1±1.3 s; P<0.0001). The response time (RT) to mapping temperature of −30 °C was significantly prolonged in unsuccessful ice mapping attempts (35.8±4.5 s vs 53.5±11.0 s; P<0.0001). Significant correlations were found between successful ice mapping and the temperature time constant, and between RT and the temperature time constant (P<0.001).

Conclusion

The ability to identify prospective ablation sites by ice mapping was demonstrated. Successful ice mapping attempts were characterized by a short temperature time constant and a short response time to mapping temperature with a sudden disappearance of pathway conduction.

## Introduction

Radiofrequency (RF) catheter ablation is a very effective and well-recognized treatment for abnormal pathway conduction [1,,2]. However, RF energy has several limitations [3–,5]. Success of RF application at a specific site cannot be predicted prior to energy delivery. Lesions created by RF energy, inevitably involve some tissue disruption which is irreversible. In contrast to RF energy, cryothermal energy has the ability to demonstrate reversible loss of function of tissue during progressive lowering of the temperature (ice mapping) [6–,8]. Therefore, this property of cryothermy has the potential to predict a successful ablation site, without causing irreversible damage.

The aim of the present study was to investigate whether the time course of temperature during ice mapping of the AP in patients with Wolff–Parkinson–White (WPW) syndrome would predict a successful outcome.

## Methods

### Study population

The study population consisted of 13 patients who were treated with cryothermal ablation of accessory pathways in the WPW syndrome, confirmed by 12-lead ECG and electrophysiological study. Antiarrhythmic drug therapy was discontinued for a duration of 5 half-lives prior to the study. All patients underwent a standard electrophysiological study in the sedated, postabsorptive state.

### Electrophysiological study

Two quadripolar diagnostic catheters and one bipolar diagnostic catheter were inserted via the right femoral vein and advanced to the high right atrium, His bundle position, and the right ventricular apex under fluoroscopic control. A decapolar diagnostic catheter was positioned into the coronary sinus via the left subclavian vein. The earliest retrograde atrial activation during ventricular extrastimulus testing and tachycardia was registered to assess the location of the accessory pathway. The location of the accessory pathways was described using the new nomenclature [9]. In case of tachycardia, single ventricular premature stimuli were applied at the time the His bundle was refractory to reset retrograde atrial activation and tachycardia. This confirmed the involvement of an accessory pathway. After the diagnostic study, the high right atrial catheter was replaced with a 7F Freezor cryothermal ablation catheter (Cryocath Technologies Inc, Kirkland, Quebec, Canada). Right-sided accessory pathways were mapped and ablated using the cryothermal ablation catheter positioned from the inferior vena cava. In case of left-sided accessory pathways, mapping and ablation were performed using either the retrograde aortic approach or a transseptal approach as previously described [10].

### Cryoablation system

The cryothermal ablation catheter is a 7F steerable catheter with a 4-mm-tip electrode at its distal end and 3 proximal ring electrodes. Temperature is recorded at the distal tip by using an integrated thermocouple. A refrigerant fluid (nitrous oxide) is delivered under pressure through an inner lumen from the console into the hollow tip of the catheter. Within the tip, a liquid-to-gas phase change occurs which causes cooling of the tip to temperatures as low as −70 °C. The resultant gas is removed from the tip under vacuum and is collected in the console.

### Ice mapping procedure

One of the potential advantages of cryothermal technology is the ability to demonstrate reversible loss of function of tissue with cooling which is called “ice mapping”. Further, the progressive ice formation at the catheter tip during cooling causes adherence to the adjacent tissue (cryoadherence) which can prevent dislodgment of the catheter.

In patients with manifest ventricular preexcitation during simus rhythm, the site of earliest ventricular activation was identified, characterized by a short local AV interval with local ventricular activation preceding the onset of the delta wave on the surface ECG. The earliest retrograde atrial activation was identified during orthodromic circus movement tachycardia and/or ventricular pacing. After identification of a prospective ablation site, ice mapping was performed by cooling to a minimum of −30 °C, for a maximum time of 80 s. Successful ice mapping was defined if loss of accessory pathway conduction properties was demonstrated (Fig. 1). In case of successful ice mapping, cryoablation was immediately carried out by cooling to −70 °C for a duration of 4 min, creating a permanent lesion. If ineffective results were obtained after 80 s, ice mapping was discontinued to allow rewarming of the catheter tip. The catheter was relocated to an adjacent site and ice mapping was repeated.

Figure 1

Loss of ventricular preexcitation during ice mapping of a right inferoparaseptal accessory pathway. Shown from top to bottom are recordings from the proximal coronary sinus (CS 9-10), distal bipolar ablation (AblBiD), and distal unfiltered ablation (Abl Unf); and ECG leads, I, aVF, and V6. Left panel (A) shows the recordings at the onset of ice mapping. In the right panel (B), a transient lesion is produced by cryothermy. At this site of successful ice mapping a permanent block will be created.

Figure 1

Loss of ventricular preexcitation during ice mapping of a right inferoparaseptal accessory pathway. Shown from top to bottom are recordings from the proximal coronary sinus (CS 9-10), distal bipolar ablation (AblBiD), and distal unfiltered ablation (Abl Unf); and ECG leads, I, aVF, and V6. Left panel (A) shows the recordings at the onset of ice mapping. In the right panel (B), a transient lesion is produced by cryothermy. At this site of successful ice mapping a permanent block will be created.

During ablation, ventricular pacing was performed to confirm loss of accessory pathway conduction. Ablation was defined as successful by atrial and ventricular incremental pacing and extrastimulus testing, if both antegrade and retrograde accessory pathway conductions were completely abolished.

### Data analysis

The entire dataset was reviewed from digitally stored files using time-logged parameters. Ice mapping sections were selected and submitted to detailed analysis of the time course of the temperature during ice mapping.

To facilitate comparisons, the time course of the temperature was described in terms of an exponential function that was fitted to the data by using a non-linear-regression technique. The computation of best fit parameters was chosen to minimize the sum of the squared differences between the fitted function and the observed response.

### Temperature

The mathematical model for the temperature response during ice mapping consisted of an exponential term (Fig. 2). The exponential term began after a time delay

$T(t)=T(b)−A(1−e−(t−TD)/τ)$

where T(b) is the temperature baseline value, A is the asymptotic value for the exponential term, τ is the time constant, and TD is the time delay. The relevant amplitude of the exponential term was set to the value of the steady level of mapping temperature.

Figure 2

Features of the exponential model used to describe the temperature response during ice mapping. A, asymptotic value; RT, response time; τ, time constant; TD, time delay.

Figure 2

Features of the exponential model used to describe the temperature response during ice mapping. A, asymptotic value; RT, response time; τ, time constant; TD, time delay.

The response time (RT) of temperature was calculated as the interval between the onset of ice mapping and onset of steady-state of mapping temperature.

### Flow and pressure

The flow and pressure response had a similar but not identical appearance to temperature. The monoexponential models were described as

$Fl(t)=Fl(b)+A(1−e−t/τ)$

$P(t)=P(b)+A(1−e−t/τ)$

where Fl(b) and P(b) are the baseline values of flow and pressure.

### Statistical analysis

Continuous variables are summarized as mean ± standard deviation. The level of significance was set at P<0.05. Non-parametric data were compared using Wilcoxon signed-rank test. Correlations between continuous variables were assessed using the Pearson correlation test. Binary logistic regression analysis was used to test the correlation between successful ice mapping, the different time constants and RT. Statistical analysis was made with SPSS (Statistical Package for Social Sciences, version 9.0) for Windows.

## Results

Thirteen patients (mean age 33±14 years, 7 men) were treated with cryothermal ablation for accessory pathway conduction (Table 1). At baseline, ventricular preexcitation with antegrade accessory pathway conduction was seen in all patients. Five patients had a left-sided AP and 8 patients had a right-sided AP. For the 5 left-sided APs, a transseptal approach was used in 4 patients and a retrograde approach in 1 patient.

Table 1

Characteristics of the patients and ice mapping attempts at −30 °C

Patient no. Gender Age (years) Site of AP No. of maps at −30 °C Average τT unsuccessful Average τT successful
1 16 RSPS 11.33 6.49
2 44 LP NA 6.84
3 18 RS 12.51 6.91
4 22 LIPS 30 9.54 7.26
5 42 LP 11 8.78 6.87
6 32 LP 9.30 8.55
7 17 RIPS 9.69 6.59
8 50 RIPS 10.99 NA
9 15 RIPS 10.66 6.73
10 26 RA 20 10.42 NA
11 53 RIPS 10.50 4.38
12 45 RSPS 11.02 7.85
13 43 LP 10.24 7.33
Patient no. Gender Age (years) Site of AP No. of maps at −30 °C Average τT unsuccessful Average τT successful
1 16 RSPS 11.33 6.49
2 44 LP NA 6.84
3 18 RS 12.51 6.91
4 22 LIPS 30 9.54 7.26
5 42 LP 11 8.78 6.87
6 32 LP 9.30 8.55
7 17 RIPS 9.69 6.59
8 50 RIPS 10.99 NA
9 15 RIPS 10.66 6.73
10 26 RA 20 10.42 NA
11 53 RIPS 10.50 4.38
12 45 RSPS 11.02 7.85
13 43 LP 10.24 7.33

M = male; F = female; LIPS = left inferoparaseptal; LP = left posterior; RA = right anterior; RIPS = right inferoparaseptal; RS = right septal; RSPS = right superoparaseptal; τT = temperature time constant; NA = not available.

### Ice mapping of accessory pathway

A total of 104 ice maps were analyzed. An average of 8 ice maps (range 2–19) per patient with a mean duration of 72±14 s were attempted. Successful ice mapping of the accessory pathway was demonstrated in 17 maps at a tip temperature of −30 °C. There was no significant difference in mapping temperatures between successful ice mapping and unsuccessful ice mapping (−29.4±3.2 °C vs −30.4±1.7 °C). In 11 ice maps, a sudden loss of accessory pathway conduction was demonstrated. In the remaining 6 maps, a gradual disappearance of accessory pathway conduction was registered. No differences in electrogram characteristics were demonstrated in maps with sudden or gradual loss of accessory pathway conduction.

The temperature time constant τ during all successful ice maps was significantly shorter compared with unsuccessful ice maps (7.0±1.1 s vs 10.1±1.3 s; P<0.0001). The RT to mapping temperature of −30 °C was significantly prolonged in unsuccessful ice mapping attempts compared with successful attempts (35.8±4.5 s vs 53.5±11.0 s; P<0.0001). Subanalysis of the temperature time constant and RT between ice maps with sudden or gradual disappearance of accessory pathway conduction demonstrated a significantly shorter time constant and RT in ice maps with sudden loss of pathway conduction (P<0.01). In Fig. 3, examples with a prolonged and a short temperature time constant are displayed.

Figure 3

The time course of tip temperature during ice mapping. The upper panel shows an ice mapping attempt with a long time constant, and the lower panel shows an ice mapping attempt with a short time constant. The bipolar electrograms recorded by the cryoablation catheter at the onset of ice mapping are displayed for both attempts.

Figure 3

The time course of tip temperature during ice mapping. The upper panel shows an ice mapping attempt with a long time constant, and the lower panel shows an ice mapping attempt with a short time constant. The bipolar electrograms recorded by the cryoablation catheter at the onset of ice mapping are displayed for both attempts.

Successful ice mapping was not significantly different between left-sided and right-sided accessory pathways. The temperature time constant τ during successful ice mapping was not significantly different between left-sided and right-sided accessory pathways (7.4±0.7 s vs 6.5±1.1 s).

The correlation between the temperature measurements is shown in Table 2. There were significant correlations between successful ice mapping and the temperature time constant as well as RT (P<0.001). The correlation between RT and the temperature time constant was significant (r=0.98; P<0.001).

Table 2

Correlation between temperature variables during ice mapping

τ Temp RT Success τ Flow
RT r=0.98
P<0.001
Success r=0.69 r=0.72
P<0.001 P<0.001
τ Flow r=0.30 r=0.20 r=0.01
P<0.01 P<0.05 NS
τ Pressure r=0.31 r=0.24 r=0.03 r=0.87
P<0.01 P<0.05 NS P<0.001
τ Temp RT Success τ Flow
RT r=0.98
P<0.001
Success r=0.69 r=0.72
P<0.001 P<0.001
τ Flow r=0.30 r=0.20 r=0.01
P<0.01 P<0.05 NS
τ Pressure r=0.31 r=0.24 r=0.03 r=0.87
P<0.01 P<0.05 NS P<0.001

RT = response time; τ = time constant; Temp = temperature.

There were no significant correlations between successful ice mapping and the flow time constant as well as the pressure time constant. The correlation between the flow time constant and the pressure time constant was significant (P<0.001). The correlations between the temperature time constant and the pressure time constant as well as the flow time constant were significant (P<0.01).

### Cryothermal ablation

Success at the end of the procedure was achieved in 9 patients (69%). The not successfully ablated pathways were located right anterior (n=1), right inferoparaseptal (n=1), left inferoparaseptal (n=1) and left posterior (n=1). Patients with a successful cryoablation demonstrated during ice mapping a sudden disappearance of pathway conduction compared with patients with an unsuccessful ablation. The time interval between the onset of ice mapping and the disappearance of accessory pathway conduction was significantly shorter in successfully ablated pathways compared with unsuccessfully ablated pathways (21.8±9.7 s vs 44.5±0.7 s; P<0.05). In 6 ice mapping attempts, the disappearance of accessory pathway conduction was gradual. In none of these sites could a successful cryoablation be performed.

### Complications

Two patients developed right bundle branch block. This block remained present after 1 day, but disappeared at the first follow-up after 6 weeks. One patient had temporary, inadvertent, complete heart block, 30 s after ice mapping. It resolved spontaneously and was probably a mechanically induced block.

## Discussion

This report describes the first results of cryomapping during percutaneous catheter cryothermal ablation of accessory pathways in WPW. The use of cryothermal energy for accessory pathway ablation was initially described in cryosurgical reports [11–,13]. Cryothermal energy has several advantages over radiofrequency energy. In contrast to radiofrequency energy, cryothermy causes tissue destruction with preservation of the underlying tissue architecture which decreases the risk of thromboembolism and tissue perforation [4]. The potential benefit of cryothermal energy is the ability reversibly to demonstrate loss of electrophysiological properties of tissue before the creation of a permanent lesion [6,,8]. Furthermore, the formation of ice during cooling causes adherence of the catheter to the adjacent tissue (cryoadherence) allowing atrial and ventricular pacing without catheter dislodgment.

The results of this study confirm the concept of ice mapping. The use of cryothermal energy to demonstrate reversible loss of function has been described in the surgical literature [11]. Differences in mapping temperature with reversible effect between surgical mapping and our mapping are explained by differences in the warming effect of the blood pool circulating around the catheter tip. In this study, a minimum temperature of −29.4 °C±3.2 °C was reached during ice mapping. This mapping temperature is in agreement with experimental animal data on ice mapping of the atrioventricular node which demonstrated only irreversible lesions created by cooling to temperatures lower than −30 °C [6,,14].

The course of the temperature during ice mapping can be described by the temperature time constant. The time constant is reflected in the time interval between the onset of ice mapping and the steady-state mapping temperature of −30 °C. In this study, sudden disappearance of accessory pathway conduction was demonstrated during ice mapping attempts with a short temperature time constant. The response time to steady-state mapping temperature of −30 °C in those attempts was less than 40 s. The temperature time constant is dependent on several factors.

First, the efficiency of cooling during cryothermal energy delivery can be affected by poor electrode contact with the endocardium. A significant “thermal sink” can be created when a major part of the electrode is in contact with the bloodstream. This warming effect will result in a prolonged response time to reach the mapping temperature. A loss of freezing power was not reflected in the flow time constant and the pressure time constant, although significant correlations between the temperature time constant and the pressure time constant as well as the flow time constant were found. This means that a higher pressure to maintain delivery of the refrigerant fluid is necessary to reach the mapping temperature when electrode contact with endocardium is poor. Secondly, the warming effects of the blood pool in regions with a high blood flow can have effects on the outcome [4]. However, our results did not demonstrate a difference in temperature time constant between left- and right-sided located accessory pathways. The temperature time constant is an indication of the electrode contact with the endocardium. This time constant is reflected in the response time to steady-state mapping temperature of −30 °C. During this time interval, the electrophysiological properties of accessory pathway conduction can be modified.

In our study, there was a significant difference in time intervals with respect to the disappearance of accessory pathway conduction. In successfully ablated patients, the disappearance of pathway conduction during ice mapping was sudden. This observation is in agreement with the sudden loss of preexcitation as seen during radiofrequency ablation. In the unsuccessfully ablated pathways, there was a gradual loss of preexcitation during mapping. This observation was not related to mapping temperature. Possible explanations for this observation are a suboptimal (remote) ablation site or intramurally/epicardially located pathways. Some data suggest that the volume of the lesion is smaller with cryothermy compared with radiofrequency energy [15]. Other data suggested a comparable size for both energy forms [6], but the lesion size will be clearly dependent on the catheter tip.

From results in previous studies and the data in our study, the following characteristics of the temperature curve during ice mapping can be described. First, the temperature time constant is an indication for the electrode contact with the endocardium. The temperature time constant is reflected in the response time to steady-state mapping temperature of −30 °C. Good electrode contact with the endocardium is indicated by a short response time to steady-state mapping temperature. Arbitrarily, a cut-off value of 40 s as maximum for the response time was chosen, which was based on observations during our study. The second point is that during this interval of 40 s, the electrophysiological properties of the accessory pathway conduction have to be modified. A sudden modification of the electrophysiological properties within this interval is an indication of being at the right prospective ablation site.

Therefore, successful cryoablation could be predicted by both a short temperature time constant and a short response time to mapping temperature combined with a sudden loss of accessory pathway conduction.

## Study limitations

The number of mapping attempts per patient varied considerably and also reflected our learning curve. The results are likely to improve as the experience with this novel technique increases. Repeated ice mapping, with different time constants at the same spot should be performed to prove our point. However, fluoroscopic visualization of the catheter tip has several limitations. With better imaging techniques, a series of ice mapping attempts at the same spot could be performed to determine the temperature time constant during these attempts and to analyze the concept of ice mapping in a different way.

## Conclusion

Ice mapping allows accurate localization of accessory pathways before creating a permanent lesion. This technique provides a potential benefit in the ablation of “delicate” accessory pathways in close proximity of the AV node. The time course of the temperature during ice mapping can be used clinically to predict a successful ablation site. Therefore, successful ablation of an accessory pathway with cryothermal energy is characterized by reaching the mapping temperature of −30 °C within 40 s combined with sudden disappearance of pathway conduction.

## References

[1]
Jackman
W.M.
Wang
X.Z.
Friday
K.J.
Roman
C.A.
Moulton
K.P.
Beckman
K.J.
et al.
Catheter ablation of accessory atrioventricular pathways (Wolff–Parkinson–White syndrome) by radiofrequency current
N Engl J Med

1991
324
1605
1611
[2]
Calkins
H.
Sousa
J.
el-Atassi
R.
Rosenheck
S.
de Buitleir
M.
Kou
W.H.
et al.
Diagnosis and cure of the Wolff–Parkinson–White syndrome or paroxysmal supraventricular tachycardias during a single electrophysiologic test
N Engl J Med

1991
324
1612
1618
[3]
Hindricks
G.
The Multicentre European Radiofrequency Survey (MERFS): complications of radiofrequency catheter ablation of arrhythmias. The Multicentre European Radiofrequency Survey (MERFS) investigators of the Working Group on Arrhythmias of the European Society of Cardiology
Eur Heart J

1993
14
1644
1653
[4]
Lustgarten
D.L.
Keane
D.
Ruskin
J.
Cryothermal ablation: mechanism of tissue injury and current experience in the treatment of tachyarrhythmias
Prog Cardiovasc Dis

1999
41
481
498
[5]
Scheinman
M.M.
Huang
S.
The 1998 NASPE prospective catheter ablation registry
Pacing Clin Electrophysiol

2000
23
1020
1028
[6]
Dubuc
M.
Roy
D.
Thibault
B.
Ducharme
A.
Tardif
J.C.
Villemaire
C.
et al.
Transvenous catheter ice mapping and cryoablation of the atrioventricular node in dogs
Pacing Clin Electrophysiol

1999
22
1488
1498
[7]
Skanes
A.C.
Dubuc
M.
Klein
G.J.
Thibault
B.
Krahn
A.D.
Yee
R.
et al.
Cryothermal ablation of the slow pathway for the elimination of atrioventricular nodal reentrant tachycardia
Circulation

2000
102
2856
2860
[8]
Kimman
G.J.
Szili-Torok
T.
Theuns
D.A.
Jordaens
L.J.
Transvenous cryothermal catheter ablation of a right anteroseptal accessory pathway
J Cardiovasc Electrophysiol

2001
12
1415
1417
[9]
Cosio
F.G.
Anderson
R.H.
Kuck
K.H.
Becker
A.
Borggrefe
M.
Campbell
R.W.
et al.
Living anatomy of the atrioventricular junctions. A guide to electrophysiologic mapping. A Consensus Statement from the Cardiac Nomenclature Study Group, Working Group of Arrhythmias, European Society of Cardiology, and the Task Force on Cardiac Nomenclature from NASPE
Circulation

1999
100
e31
e37
[10]
Szili-Torok
T.
Kimman
G.
Theuns
D.
Res
J.
Roelandt
J.R.
Jordaens
L.J.
Transseptal left heart catheterisation guided by intracardiac echocardiography
Heart

2001
86
E11
[11]
Gallagher
J.J.
Sealy
W.C.
Anderson
R.W.
Kasell
J.
Millar
R.
Campbell
R.W.
et al.
Cryosurgical ablation of accessory atrioventricular connections: a method for correction of the pre-excitation syndrome
Circulation

1977
55
471
479
[12]
Rowland
E.
Robinson
K.
Edmondson
S.
Krikler
D.M.
Bentall
H.H.
Cryoablation of the accessory pathway in Wolff–Parkinson–White syndrome: initial results and long term follow up
Br Heart J

1988
59
453
457
[13]
Watanabe
S.
Koyanagi
H.
Endo
M.
Yagi
Y.
Shiikawa
A.
Kasanuki
H.
Cryosurgical ablation of accessory atrioventricular pathways without cardiopulmonary bypass: an epicardial approach for Wolff–Parkinson–White syndrome
Ann Thorac Surg

1989
47
257
264
[14]
Dubuc
M.
Talajic
M.
Roy
D.
Thibault
B.
Leung
T.K.
Friedman
P.L.
Feasibility of cardiac cryoablation using a transvenous steerable electrode catheter
J Interv Card Electrophysiol

1998
2
285
292
[15]
Mahvi
D.M.
Lee
F.T.
Radiofrequency ablation of hepatic malignancies: is heat better than cold?
Ann Thorac Surg

1999
230
9
11