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(Circulation. 1996;94:253-257.)
© 1996 American Heart Association, Inc.

Articles

Low-Temperature Mapping Predicts Site of Successful Ablation While Minimizing Myocardial Damage

Jean-Marc Cote, MD; Michael R. Epstein, MD; John K. Triedman, MD; Edward P. Walsh, MD; J. Philip Saul, MD

Children's Hospital, Department of Cardiology, Department of Pediatrics, Harvard Medical School, Boston, Mass.

Correspondence to J. Philip Saul, MD, Children's Hospital, Department of Cardiology, 300 Longwood Ave, Boston, MA 02115. E-mail psaul@cardio.tch.harvard.edu.

	Abstract

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Background Temperatures near 50°C can cause reversible loss of excitability in myocardial cells.

Methods and Results Low-temperature, short-duration applications of radiofrequency energy were used to determine the adequacy of electrophysiological mapping of accessory pathway (AP) locations in 15 patients at 27 target sites using a closed-loop, temperature-controlled generator set to 50°C. Energy was delivered until evidence of conduction block, or for a maximum of 10 seconds. If AP block occurred, a full 70°C set point radiofrequency application was delivered to the same site. In the absence of AP block, tests with higher temperature settings (60°C and 70°C) were delivered to determine if inadequate temperature or catheter position led to failure of the initial 50°C test. At 15 successful target sites where permanent AP block was achieved, the 50°C test resulted in AP block in 14 (93%). Conduction returned in 13 of 14 APs after radiofrequency power was turned off. The time to block for the 70°C applications was significantly shorter than for the 50°C tests, and the peak temperature achieved was significantly higher. At unsuccessful sites where permanent AP block was not achieved, no block was induced with 11 of 12 tests at 50°C, 6 of 6 tests at 60°C, and 1 of 2 tests at 70°C, suggesting that failure was due to incorrect catheter position. The sensitivity and positive predictive values of a 50°C test identifying a successful site were >90%.

Conclusions Low-temperature radiofrequency applications that cause transient AP block predict permanent success when a higher-temperature application is delivered at the same site. The time to achieve conduction block is a function of the temperature set point, and low-temperature tests produce reversible conduction block, suggesting minimal permanent injury.

Key Words: ablation • mapping • electrophysiology

	Introduction

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Both in vitro and in vivo studies have demonstrated that temperatures near 50°C can result in reversible loss of excitability in myocardial tissue. Catheter tip temperatures close to 50°C have been associated with acutely reversible accessory pathway (AP) block during clinical ablation procedures in humans,¹ and reversible conduction block has been observed at temperatures close to 50°C in tissue bath studies,² with permanent block at temperatures of 52°C to 54°C. The purpose of this study was to test the hypothesis that low-temperature radiofrequency test applications titrated to achieve transient AP conduction block can be a useful mapping tool to identify AP location while simultaneously minimizing myocardial damage.

	Methods

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Fifteen symptomatic patients (age, 13.5±6.7 years; range, 5 to 34 years; median, 11.9 years) with single manifest (n=10) or unidirectional retrograde (n=5) APs were studied. AP locations were left free wall for 8 patients, right freewall for 1, and posteroseptal for 6. Informed written consent was obtained from each patient/parent.

An atrial approach to the atrioventricular groove was used for all APs (transseptal for left-sided).³ APs were mapped in either sinus rhythm, atrial pacing, orthodromic tachycardia, or ventricular pacing. Target sites were selected on the basis of local atrial or ventricular activation times, the presence of both atrial and ventricular electrograms, and occasionally the presence of an AP potential. All ablations were performed with a steerable 7F quadripolar electrode catheter (Marinr, Medtronic CardioRhythm) with a 4-mm distal platinum electrode and a thermocouple embedded in its center for temperature monitoring (See Fig 1 in Reference 4). All applications were performed with the radiofrequency generator (Atakr, Medtronic CardioRhythm) in its temperature control mode, where the generator automatically modulates the power delivered from 0.5 to 50 W to attempt to achieve a selected target temperature of between 45°C and 95°C.

View larger version (44K): [in this window] [in a new window]   Figure 1. Result of 50°C test at 27 target sites. A, Sites of eventual permanent accessory pathway (AP) block. B, Sites where permanent AP block was not achieved.

Ablation and Temperature Mapping Protocol
At identified target sites, a low-temperature test application was performed with the radiofrequency generator set initially to 50°C. The test application was continued for a maximum of 10 seconds or until evidence of AP conduction block was noted. If either AP conduction returned or 15 minutes passed, a second radiofrequency application was made with a 70°C set point at the same site for a maximum of 60 seconds. If the initial low-temperature 50°C test application was unsuccessful, a similar 60°C test application was given to determine if absence of AP block was due to incorrect catheter position or inadequate heating. Any test application that resulted in AP block was followed by a 70°C application that was continued for a maximum of 60 seconds. Target sites of eventual permanent success, defined as no return of AP conduction prior to the end of the procedure, are referred to as "successful" sites. Target sites at which either AP conduction never blocked or conduction returned after a 70°C application of 10 seconds or longer are termed "unsuccessful" sites.

Statistical Analysis
Data are presented as mean±SD. Comparisons between the ablation parameters obtained at the same sites were performed with the paired Student's t test, while comparisons between different sites were performed with the unpaired Student's t test. A value of P<.05 was considered significant.

	Results

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Radiofrequency catheter ablation was successful in all 15 patients. Radiofrequency energy was delivered to a total of 27 target sites, 15 successful and 12 unsuccessful. Seven patients had AP conduction block and successful ablation at the first target site, whereas the other 8 had AP conduction block and successful ablation after failure at 1 to 4 other target sites. Although 50°C test applications were delivered at all successful and unsuccessful sites, due to protocol deviations, higher temperature test applications were delivered at only 7 of the 12 unsuccessful sites (n=6 at 60°C; n=2 at 70°C) (Fig 1, Table). No differences were found for the characteristics of test applications by pathway location; however, there were only 2 right freewall applications.

View this table: [in this window] [in a new window]   Table 1. Characteristics of Radiofrequency Applications

Successful Sites
The 50°C low-temperature application resulted in AP block at 14 of the 15 ultimately successful target sites (93%) (see Fig 1A and Table). Block occured at 2.4±1.6 seconds (t_block) into the test application (range, 1 to 7 seconds), with a peak temperature (T_peak) of 46±1.9°C (range, 44°C to 49°C; Fig 2A). AP block occurred at <5 seconds for 13 of the 14 applications (93%). Radiofrequency power was turned off (t_off) 1.9±0.9 seconds (range, 1.1 to 3.8 seconds) after evidence of AP block. AP conduction returned for 13 of the 14 pathways (93%) at 3.1±1.9 seconds (range, 0.7 to 7 seconds) after the power was turned off (t_return, Fig 2A).

View larger version (27K): [in this window] [in a new window]   Figure 2. A, Test application with radiofrequency generator set to 50°C. Maximal temperature achieved is 45°C. Rate was 25 mm/s. Accessory pathway (AP) block occurs after 1.8 seconds, and power is turned off after 3.1 seconds. AP conduction returns 3.6 seconds after power is turned off. B, After return of AP conduction, a full application is delivered with the radiofrequency generator set to 70°C. Peak temperature (Tpeak) achieved is 56°C, and AP conduction block occurs at 1.5 seconds. AVF indicates augmented VF (surface ECG lead); MAP, mapping electrical signal. Bar indicates 1000 ms.

The only successful target site that did not block with the 50°C low-temperature test did block after 8.4 seconds of a 10-second 60°C test with a T_peak of 58°C (Table, application 6). Conduction returned 1.8 seconds after the power was turned off. The only low-temperature test that resulted in AP block that was still persistent after 15 minutes was associated with a long delay between AP block and power termination (t_off-t_block=3.5 seconds) (Table, application 5).

After either return of conduction (n=14) or 15 minutes (n=1), a radiofrequency application with a set point of 70°C was delivered for 40 to 60 seconds at all 15 successful sites (Fig 2B). Permanent conduction block occurred at a t_block of 1.3±0.4 seconds (range, 0.7 to 2.1 seconds) and at a T_peak of 61±6°C (range, 52°C to 72°C). The t_block for the 70°C applications was significantly lower than that for the 50°C test applications (P<.05), and the T_peak was significantly higher (P<.001). All patients remain free of evidence of AP function at 6 to 11 months of follow-up (median=7 months).

Unsuccessful Sites
At 12 unsuccessful target sites, the 10-second 50°C test application achieved a T_peak of 47±1.9°C (range, 44°C to 50°C; P=NS versus successful sites), resulting in no block for 11 and transient block for 1 (see the Table and Fig 1B). A 60°C test application delivered to 6 of the 11 sites where a 50°C test failed also failed to achieve block with a T_peak of 54±4.5°C (range, 49°C to 62°C; P<.002 versus T_peak of 50°C test at the same site). At the 1 site with transient block, t_block occurred at 6.4 seconds with a T_peak of 46°C. A 60-second 70°C application at the same site yielded a lower t_block of 3.3 seconds with a peak temperature of 53°C, but conduction returned after an additional 12 seconds.

Summary
In summary, of the 15 tests at 50°C that caused AP conduction block, 14 of 15 were predictive of successful permanent ablation at that site (positive predictive value, 93%). Furthermore, at 15 ultimately successful target sites, the initial 50°C test resulted in conduction block in 14 (sensitivity, 93%). Because a 60-second 70°C application was not delivered at the site of unsuccessful test applications, an accurate negative predictive value and specificity cannot be computed; however, 93% (11 of 12) of the 50°C tests that did not cause conduction block were delivered at ultimately unsuccessful sites. Finally, the AP conduction block achieved with a short 50°C test was transient in 14 of 15 instances.

	Discussion

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Experimental studies of radiofrequency energy application to myocardium have shown that catheter electrode-tissue interface temperature is linearly related to lesion dimension^{5 6} and that tissue temperatures in the range of 48°C to 51°C can result in reversible electrophysiological effects.² On the basis of these observations, this study was designed to test the utility of using a temperature-controlled radiofrequency catheter ablation system to minimize myocardial damage and assess the accuracy of electrophysiological mapping of AP locations in humans. The results indicate, first, that a brief low-temperature test radiofrequency application that causes AP conduction block predicts permanent success when a higher-temperature application is delivered to the same site, while a 10-second low-temperature radiofrequency application that does not cause AP conduction block usually predicts failure when a higher-temperature application is delivered to the same site (six of seven cases in this study, Table). Second, with a closed-loop temperature-controlled system, the time to achieve conduction block appears to be a function of the temperature set point, either because the temperature required to achieve block is reached earlier or a stronger radiofrequency field leads to block at a lower temperature.⁷ Finally, brief low-temperature applications produce reversible conduction block, suggesting that the cellular injury is transient. Together, these findings indicate that low-temperature test applications may be useful for mapping AP locations while minimizing myocardial damage.

Interpretation of Low-Temperature Tests
This study demonstrates that tip temperatures of 44°C to 49°C measured with a thermocouple embedded centrally in the tip can cause reversible AP block. Blouin et al⁸ used an in vitro preparation to compare temperature monitoring done with a thermistor positioned at the tip of an electrode catheter with temperature monitoring done with a thermistor embedded in the distal electrode. They found that electrode-tissue interface temperatures were 2°C to 8°C higher than embedded-tip temperatures, with the difference linearly related to the tip temperature (45°C to 75°C). Extrapolation of their data to the test lesions in this study would predict a difference of 2°C to 2.5°C between the embedded thermocouple and the electrode-tissue interface temperatures. In the only in vivo comparison of multiple simultaneous temperature measurements, McRury et al⁹ compared temperatures at four thermistors embedded radially around the catheter tip with the temperature of a thermistor embedded at the tip and concluded that tip temperature was a reasonable measure of electrode-tissue interface temperature, regardless of catheter position or orientation. Although a recent report by Mackey et al¹⁰ using thermocouples embedded in the tissue has suggested that tissue temperatures may be as much as 44°C higher than the temperatures at the electrode-tissue interface, others using either fluoroptic temperature probes¹¹ or thermistors¹² have found that electrode-tissue interface temperatures are generally higher than those at 1 mm into the tissue. Finally, both theoretical finite-element temperature distributions and experimental distributions measured with optical thermometry in "tissue-equivalent media" have demonstrated that peak temperatures occur within 0.25 mm of the electrode-tissue interface.¹³

On the basis of the above findings, a conservative estimate of a difference of 2°C to 8°C between the tip and tissue temperatures in this study would yield tissue temperatures of 46°C to 57°C during the 50°C test, including the entire zone of reversible injury (49°C to 52°C)² and the zone of irreversible injury (52°C to 54°C). Since temperature falls off inversely with distance from these low maximal temperatures, one can also speculate that AP block during a low-temperature test application indicates close proximity between the tip and the AP. It is also noteworthy that the higher temperatures induced by the 60°C test applications did not usually cause AP block when a low-temperature 50°C test had failed, suggesting that inaccurate catheter positioning rather than inadequate heating was responsible for the absence of AP block.

Myocardial Damage
On the basis of previous studies demonstrating that the time to reach half the ultimate lesion dimensions (t_1/2) is between 6 and 12 seconds,^{6 14 15} it is likely that the typical 70°C test application applied for 10 seconds creates a significant lesion with a depth of 1 to 3 mm and a width of 2 to 5 mm.¹⁵ In contrast, the short 50°C test applications in this study should have caused much less, if any, permanent damage, consistent with their transient effect on AP conduction. Thus, the use of a 50°C test application should minimize any late effects of radiofrequency scar formation.

Time to AP Block
In the present study, at successful sites, t_block was significantly longer for the 50°C test applications than for the 70°C applications at the same site, suggesting that the time required to achieve AP block is a function of tissue temperature (Table). Lesion size is determined, among other factors, by the duration of the application. At the successful sites, t_block occurred in <5 seconds for 93% of the 50°C tests. For the 12 unsuccessful sites, there was only a single false-positive 50°C test, and it caused AP block at a t_block of 6.4 seconds. Finally, the only 50°C test that resulted in prolonged AP block (>15 minutes) was continued for a total of 6.2 seconds. These observations lead one to speculate that a shorter test application of 5 seconds would generally be sufficient to achieve AP block, while minimizing false-positive results and also further minimizing tissue damage.

Limitations
When an atrial approach is used for ablation of APs, the generator set temperature is rarely achieved even with closed-loop feedback control of power output. However, with the lower set point in this study, a temperature within 6°C of the 50°C target was achieved for all successful and unsuccessful test applications. A second issue relates to the effects of the 50°C test application. Since there was no independent measurement of tissue damage in this study, we cannot conclusively demonstrate the proposed minimal damage induced by the brief low-temperature applications. In fact, as noted above, tissue temperatures were probably higher than the T_peak measured at the catheter tip. However, when previous experimental data are combined with our observation of rapid reversible electrophysiological effects after the test applications, it seems likely that tissue damage was less than that resulting from standard techniques. Finally, conclusions regarding the adequacy of unsuccessful 50°C test applications for predicting failure with a higher temperature application at a particular site are limited by the study design and protocol deviations; however, the data do demonstrate that success is unlikely at sites where a 50°C test does not cause conduction block.

	Acknowledgments

 
This work was supported by the Sean Roy Johnson Memorial Fund. Dr Triedman is supported by a Career Development Award from the National Institutes of Health. Dr Saul was supported by a Clinical Investigator Award from the National Institutes of Health. The authors would like to thank Robyn Doody for her expert assistance in preparing the manuscript and Emily Flynn-McIntosh for her expertise in preparing the figures.

Received February 26, 1996; revision received May 31, 1996; accepted June 6, 1996.

	References

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