- Email: [email protected]
or after radiofrequency or cryothermal ablations
Optimal contact forces to minimize cardiac perforations before, during, and/or after radiofrequency or cryothermal ablations Stephen G. Quallich, BS,*† Michael Van Heel, BS,‡ Paul A. Iaizzo, PhD*† From the Departments of *Biomedical Engineering, †Surgery, and ‡Mechanical Engineering, University of Minnesota, Minneapolis, Minnesota. BACKGROUND Catheter perforations remain a major clinical concern during ablation procedures for treatment of atrial arrhythmias and may lead to life-threatening cardiac tamponade. Radiofrequency (RF) ablation alters the biomechanical properties of cardiac tissue, ultimately allowing for perforation to occur more readily. Studies on the effects of cryoablation on perforation force as well as studies defining the perforation force of human tissue are limited. OBJECTIVE The purpose of this study was to investigate the required force to elicit perforation of cardiac atrial tissue after or during ablation procedures. METHODS Effects of RF or cryothermal ablations on catheter perforation forces for both swine (n ¼ 83 animals, 530 treatments) and human (n ¼ 8 specimens, 136 treatments) cardiac tissue were investigated. RESULTS Overall average forces resulting in perforation of healthy unablated tissue were 406g ⫾ 170g for swine and 591g ⫾ 240g for humans. Post-RF ablation applications considerably reduced these forces to 246g ⫾ 118g for swine and 362 ⫾ 185g for humans
Introduction Today, atrial fibrillation (AF) affects more than 5.1 million people in the United States, and, as the population continues to age, the incidence is expected to increase at least 2.5-fold by 2050.1,2 Recently, a complication rate of 4% to 6% was reported for catheter ablation procedures performed for treatment of AF.3,4 These complications can be prompted by a number of factors, ranging from induced septal defects after transseptal punctures to perforation of the atria. More specifically, cardiac tamponade has been reported to occur in 1.3% of ablation procedures.3 It is considered that complications may arise throughout these procedures due to a number of factors, such as transseptal punctures, adverse catheter maneuvers, or excessive contact forces during energy applications.
Conflict of interest: Research contract with Medtronic Inc. This study was funded, in part, by Medtronic Inc. Address reprint requests and correspondence: Dr. Paul A. Iaizzo, 420 Delaware St SE, B172 Mayo, MMC195, Minneapolis, MN 55455. E-mail address: [email protected].
1547-5271/$-see front matter B 2015 Heart Rhythm Society. All rights reserved.
(P o.001). Treatments with cryoablation did not significantly alter forces required to induce perforations. Decreasing catheter sizes resulted in a reduction in forces required to perforate the atrial wall (P o.001). Catheter perforations occurred over an array of contact forces with a minimum of 38g being observed. CONCLUSION The swine model likely underestimates the required perforation forces relative to those of human tissues. We provide novel insights related to the comparative effects of RF and cryothermal ablations on the potential for inducing undesired punctures, with RF ablation reducing perforation force significantly. These data are insightful for physicians performing ablation procedures as well as for medical device designers. KEYWORDS Catheter ablation; Cardiac tamponade; Arrhythmia; Cardiac perforation; Radiofrequency ablation; Cryoablation ABBREVIATIONS AF ¼ atrial fibrillation; RF ¼ radiofrequency (Heart Rhythm 2015;12:291–296) I 2015 Heart Rhythm Society. All rights reserved.
Perforation of the atrial wall during ablation procedures, which may lead to pericardial effusions and/or lifethreatening cardiac tamponade, has only recently gained attention. Cardiac perforation is most common during AF procedures and occurs less frequently during other cardiac procedures.5 It is suggested that perforation may result from use of high power and/or high contact forces to ensure the creation of transmural lesions by radiofrequency (RF) energies. Unfortunately, no comprehensive studies investigating the causes of cardiac tamponade during ablation procedures have been reported in the literature. However, it is important to note that procedures such as transseptal puncture are associated with a complication rate as high as 0.79% and cardiac perforation with tamponade in 0.11% of cases.6 It also is known that mechanical perforations with diagnostic catheters also are associated with cardiac tamponade. Interestingly, the presentation of pericardial effusion in RF and cryoablation procedures is not significantly different.7 Furthermore, patients with AF have been reported to have thinner atrial walls; this likely elicits http://dx.doi.org/10.1016/j.hrthm.2014.11.028
292 Table 1
Heart Rhythm, Vol 12, No 2, February 2015 Human heart demographics
Heart no,
Age (years)
Weight (kg)
Heart weight (g)
Gender
Cause of death
Cardiac history
1 2 3 4 5 6 7 8
45 34 62 52 81 67 69 67
96 86 73 74 75 82 77 59
537 422 456 401 504 330 456 496
M M F F F M M F
Cerebral vascular accident Cerebral vascular accident Cerebral vascular accident Cerebral vascular accident N/A Bladder cancer Chronic obstructive pulmonary disease Chronic obstructive pulmonary disease
Hypertension, alcoholism None Hypothyroidism, hyperlipidemia None Atrial fibrillation, mitral regurgitation None None None
circumstances that allow for perforations to occur even more readily.8 Other important factors to consider during these clinical procedures include movements of the heart throughout the cardiac cycle as well as those due to respiration, because these can alter the applications of desired contact forces and provide added challenges for clinicians.9 Additionally, it is regarded that the biomechanical properties are altered during the heating and cooling of tissues. For example, loss of pulmonary vein compliance and denaturation of collagen occurs at temperatures of 60–651C, yet elastin remains unchanged until temperatures of 801C are reached.10 During cryoablation, structural proteins remain intact, although realignments occur as a result of ice crystal formations.11 Therefore, better understanding of the contact forces required for proper lesion formation, while minimizing ruptures, may lead to reduced occurrences of cardiac tamponade. This study provides novel insights into the biomechanical effects of RF and cryoablations relative to the potential to induce punctures of cardiac atrial tissues. The study could be considered translational because we compared results for both isolated viable swine and human atrial samples.
Methods Sample preparation Human heart specimens (n ¼ 8) were obtained from nonviable organ transplant donors through our local organ procurement organization LifeSource (St. Paul, MN; Table 1). These tissues were considered viable because they
typically were acquired and tested within 6 to 12 hours after explantation. All non-AF hearts had a nondilated atrial pathology. Healthy 7- to 9-month-old Yorkshire Cross swine cardiac specimens (n ¼ 83, animal weight 75–110 kg, heart weight 400–650 g) were acquired from the University of Minnesota Meat Sciences Laboratory and the Visible Heart Lab (waste tissue from unrelated experiments) and stored in saline before testing. Fresh atrial samples from the free wall (atrial appendage and atrial roof) were carefully dissected out. Atrial samples (n ¼ 666) were randomized to the following study groups: (1) no treatment; (2) RF ablation with a nonirrigated RF Marinr catheter (Medtronic, Minneapolis, MN) for 1 minute at 30 W with a temperature limit of 651C; (3) RF ablation using the same parameters as (2), with induced perforation during the last 5 seconds of applied ablation; or (4) focal cryoablation with a Freezer MAX catheter (Medtronic) for 2 minutes (Figure 1). Cryoablated samples were permitted a sufficient amount of time for ice to thaw before the induced perforations. All samples were carefully anchored and submerged in saline before each ablative modality was applied. Each catheter was subsequently advanced at a rate of 500 mm/min with a mechanical force tester (Chatillon, Largo, FL) until perforation occurred. An array of catheter sizes (5, 7, and 8Fr) was also investigated in these experiments.
Statistical analysis The maximum force readings corresponding to the perforation forces were analyzed with Minitab (State College, PA). All
Figure 1 Graphic depiction of the treatment groups in relation to the application of ablation and the induction of catheter perforation. Cryo ¼ cryoablation treatment; RF ¼ radiofrequency treatment.
Quallich et al
Ablation Contact Forces to Minimize Perforations
force values are reported as mean ⫾ SD. The Student’s T-test for 1:1 comparisons or analysis of variance for the various study groups was used to compare normally distributed data. P r.05 was considered significant.
Results Catheter perforation forces for the right and left atria were significantly different for the prepared human and swine tissue samples for all ablation groups investigated (P o.001). Importantly, the required perforation forces for the RF-ablated samples were almost 2-fold less than those required for the cryoablated or untreated samples (P o.001; Figure 2). In other words, the cryoablation procedures appeared to have little or no effect on perforation forces compared to the control (no treatment) group (P ¼ .43). The effects of perforation during RF ablations were minimal and not statistically significant compared to the other RF ablation group (P ¼ .27). A noteworthy observation was that catheter size was highly correlated with the likelihood to perforate the myocardium after or during an ablation. Smaller catheters required lower forces to induce ruptures than larger catheters for all ablation modalities and tissue types (Po.05; Table 2). Ablation modality effects with RF reducing perforation forces were also confirmed within each catheter size. Additionally, human atrial perforation forces were significantly different than those for the swine tissues (Table 3). Here we
293 observed that the minimum forces to perforate ablated and healthy human atrium were 38g and 57g, respectively (Table 4). Similar minimum perforation forces of 63g and 96g for ablated and healthy swine atrium were also observed. It should be noted that the human atrial samples used in this experiment were from individuals without known histories of AF for all but 1 individual.
Discussion Here we describe novel results from in situ experiments designed to investigate the force required to elicit perforation of cardiac atrial tissue after or during ablation procedures. We used a translational approach in which we studied both viable swine and human specimens. Perforation forces after or during RF ablation and in the control/no treatment group were similar to those reported in the literature, with RF ablation reducing the forces required to elicit perforation significantly.12,13 In these previous studies, an individual user manually advanced the catheter until perforation occurred, whereas in the present study we used a uniaxial testing machine to automate advancement of the catheter at a constant speed. In other words, in our testing methodology, the goal was to remove variations due to the operator. Interestingly, we observed that the minimum perforation force was 63g for RF atrial ablated swine tissue vs 96g for healthy nonablated tissue, whereas Shah et al12 reported values of 40g and 131g, respectively, for swine atrial tissue.
Figure 2 Perforation force for swine right and left atria compared across different ablation modalities (*Po.001). Perforation of the right atrium required substantially less force compared to the left atrium. Also, perforation after either radiofrequency (RF) ablation group entailed significantly less force than the cryoablated (Cryo) or the untreated (Normal) samples. Error bars represent standard deviation.
294 Table 2
Heart Rhythm, Vol 12, No 2, February 2015 Comparison of perforation force sorted by catheter size, tissue type, and ablation modality Perforation force (g)
Tissue type RA LA
Ablation modality
5Fr
N Cryo RF N Cryo RF
293 ⫾ 318 ⫾ 214 ⫾ 345 ⫾ 451 ⫾ 246 ⫾
7Fr 337 ⫾ 333 ⫾ 209 ⫾ 421 ⫾ 394 ⫾ 237 ⫾
91 124 76 115 109 76
P value
8Fr 120 106 79 120 106 78
425 412 294 691 699 426
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
115 141 134 148 155 172
o.001 .033 o.001 o.001 o.001 o.001
Cryo ¼ cryoablation treatment; LA ¼ left atrium; N ¼ no treatment; RA ¼ right atrium; RF ¼ radiofrequency ablation treatment.
To our knowledge, comparison studies relative to perforation forces following RF or cryoablations have not yet been reported in the literature. Cryothermal ablations did not alter perforation forces compared to untreated fresh tissue for both the swine and human tissue samples. It is important to note that we used fresh, viable tissue samples in these investigations. It was previously reported that frozen tissue samples typically are altered in the low stress state, with possible differences in other portions of the stress–strain curve.14 Thus, any changes observed exist at the onset of force application and dissipate substantially as the applied force increases. It has been reported that freezing (application of cryoablation) does not change the ultimate tensile strength or, if so, does so minimally.15,16 This suggests that the forces required to perforate are similar to those of native unablated tissue, which holds true for the results presented here. RF ablation is considered to cause denaturation of collagen as well as cell membrane disruption. Specifically, at high temperatures (60–651C) collagen breakdown occurs.17 It is also suspected that while physicians attempt to create transmural atrial lesions, heat builds up in the myocardium. Typically, an ablation console will only provide data on catheter tip temperatures, which are not representative of tissue temperatures. One can consider that thermal energy builds up transmurally within the myocardium because the endocardial surface and catheter tip will be convectively cooled by the flow of blood through the heart. Whereas while ablating tissue to a minimum of 501C will ensure the creation of a myocardial scar for a successful isolation procedure, reaching temperatures of 601C, (the transition zone for
collagen breakdown) is not unforeseeable. A breakdown of collagen in the ablated myocardium will weaken it, thus explaining the reduction in perforation force after RF ablation. Catheter size is not often considered during ablation procedures, yet it is an important factor influencing the incidence of cardiac perforation. We found that using a larger-size catheter significantly reduces the risk of perforation. Even enlarging the catheter size by a single French often increases the required force for perforation. It is important to note that, given the aggressive ablation parameters used, transmural lesions were observed for all catheter sizes. Thus, lesion size likely had a minimal effect on the observed perforation forces because it encompassed a much greater volume than the catheters. Therefore, with similar tissue damage, a smaller catheter will perforate more easily. This finding is intuitive when considered from a mechanic’s perspective of the relationship between applied force, surface area, and resultant pressure. Implementing this knowledge regarding catheter size and punctures relative to clinical procedures may reduce the occurrence of cardiac tamponade. Further research investigating the effects of catheter size on perforation force is needed to determine whether these results can be extrapolated to catheters larger than 8Fr. Physicians quite often apply contact forces that exceed the lower limit perforation forces we report here, which increases the likelihood of complications. For example, Kuck et al18 observed that during AF procedures, contact forces 4100g were recorded in 79% of patients with a high degree of interoperator and intraoperator variability. Importantly, high contact forces are detected not only during ablations but also
Table 3 Comparison of perforation forces between swine and human tissue sorted by ablation modality and tissue type
Table 4 Minimum perforation forces of swine and human tissue sorted by ablation modality and tissue type Perforation force (g)
Perforation force (g)
Tissue type RA LA
Ablation modality
Swine
Human
P value
N Cryo RF N Cryo RF
337 ⫾ 120 333 ⫾ 106 192 ⫾ 78 421 ⫾ 137 394 ⫾ 136 237 ⫾ 79
545 ⫾ 238 595 ⫾ 183 386 ⫾ 186 692 ⫾ 218 668 ⫾ 278 445 ⫾ 235
o.001 o.001 o.001 o.001 o.001 o.001
Cryo ¼ cryoablation treatment; LA ¼ left atrium; N ¼ no treatment; RA ¼ right atrium; RF ¼ radiofrequency ablation treatment.
Tissue type RA LA
Ablation modality
Swine
Human
N Cryo RF N Cryo RF
96 104 63 187 131 67
57 98 38 149 258 62
Cryo ¼ cryoablation treatment; LA ¼ left atrium; N ¼ no treatment; RA ¼ right atrium; RF ¼ radiofrequency ablation treatment.
Quallich et al
Ablation Contact Forces to Minimize Perforations
throughout cardiac procedures, such as with catheter manipulations and the relative movement of the heart associated with contractions and/or respiration. It should be noted that extensive catheter manipulation on the left side of the heart (via a transseptal puncture) also increases the risk for formation of iatrogenic atrial septal defects.19 Additionally, transseptal punctures account for some portion of cardiac tamponade cases, so diagnostic and ablation catheters are not the sole cause. High contact forces also increase the risk for either elicitation of steam pops and/or thrombus formation.20,21 This underlies the need for force sensing catheter technologies, along with greater physician awareness of acceptable contact forces. It is important to note that average contact forces o10g have been reported to result in higher incidences of AF recurrence, whereas contact forces 420g lower the likelihood of such incidences.22 This suggests that a lower bound for contact force of 20g exists, thus facilitating successful ablation procedures. Defining the upper boundaries of applied ablative contact forces will be a step forward in reducing related complications such as cardiac tamponade. Note again the minimum forces for perforation of human tissue (37g and 57g for ablated and healthy atrium, respectively) and the average forces to perforate (386g and 545g for ablated and healthy atrium). Therefore, we suggest that contact forces o50g should greatly reduce the occurrence of cardiac perforations and/or tamponade. Perhaps a “sweet spot” of 20–50g would be the ideal contact force range that physicians should aim to apply in order to achieve successful procedures that do not result in recurrences while ensuring minimal risk of cardiac perforations.
Study limitations Minimal human heart availability, the in vitro nature of experiment, and the inability to measure tissue temperatures were the major study limitations. Measurement of tissue temperatures in this experimental paradigm would have compromised the biomechanical properties of the cardiac tissue. However, transmural tissue temperatures would allow for more accurate analysis of the interplay between ablations, temperatures, and biomechanical properties of the cardiac specimens. In addition, conducting an in vivo assessment of perforation forces would aid in clinical applicability but would add in cofounding factors we desired to remove, such as variations due to the operator. The use of nonirrigated ablation catheters and the inability to measure compressive force during tissue anchoring are other important limitations to note. Furthermore, several of the human specimens were stored in saline for up to 24 hours because immediate testing was not feasible. It is important to consider that these punctures were performed in nonbeating tissue and not in intact hearts. Also, limited human heart availability for research was anticipated, so swine hearts were used instead to approximate the biomechanical properties of cardiac tissue. The available human tissue included only 1 individual with a history of AF, which restricts the ability to elucidate significant findings for AF patients. Unfortunately, the swine
295 hearts lack thinner atrial walls like the typical AF patient, so a direct translational comparison to the patient population of interest is restricted in nature. This highlights the need for further studies on human tissue from patients with a history of AF.
Conclusion Cryoablation did not result in statistically significant reductions in the contact forces required to perforate atrial tissues. In contrast, applied RF ablations elicited reductions in the forces required to perforate these tissues. This is the first study to investigate perforation forces during RF ablations and after RF or cryothermal ablations, as well as the impact of catheter size. We consider that these data should be of substantial interest to clinicians because the findings may help define an ideal contact force range for minimizing the occurrence of cardiac tamponade while still promoting transmural lesion generation.
Acknowledgments We express our gratitude to LifeSource as well as the organ donors and their families for the hearts used in this research. We thank Monica Mahre for preparation of the manuscript.
References 1. Go AS, Hylek EM, Phillips KA, Chang Y, Henault LE, Selby JV, Singer DE. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA 2001;285:2370–2375. 2. Miyasaka Y, Barnes ME, Gersh BJ, Cha SS, Bailey KR, Abhayaratna WP, Seward JB, Tsang TSM. Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence. Circulation 2006;114:119–125. 3. Cappato R, Calkins H, Chen S-A, et al. Updated worldwide survey on the methods, efficacy, and safety of catheter ablation for human atrial fibrillation. Circ Arrhythm Electrophysiol 2010;3:32–38. 4. Natale A, Raviele A, eds. Atrial Fibrillation Ablation, 2011 Update: The State of the Art Based on the Venicechart International Consensus Document. Hoboken, NJ: Wiley-Blackwell; 2011. 5. Bohnen M, Stevenson WG, Tedrow UB, Michaud GF, John RM, Epstein LM, Albert CM, Koplan BA. Incidence and predictors of major complications from contemporary catheter ablation to treat cardiac arrhythmias. Heart Rhythm 2011;8:1661–1666. 6. De Ponti R, Cappato R, Curnis A, Della Bella P, Padeletti L, Raviele A, Santini M. Salerno-Uriarte JA/ Trans-septal catheterization in the electrophysiology laboratory: data from a multicenter survey spanning 12 years. J Am Coll Cardiol 2006;47:1037–1042. 7. Chierchia GB, Capulzini L, Droogmans S, Sorgente A, Sarkozy A, Müller-Burri A, Paparella G, de Asmundis C, Yazaki Y, Kerkhove D, Van Camp G, Brugada P. Pericardial effusion in atrial fibrillation ablation: a comparison between cryoballoon and radiofrequency pulmonary vein isolation. Europace 2010;12: 337–341. 8. Platonov PG, Ivanov V, Ho SY, Mitrofanova L. Left atrial posterior wall thickness in patients with and without atrial fibrillation: data from 298 consecutive autopsies. J Cardiovasc Electrophysiol 2008;19:689–692. 9. Friedman PA. Hitting a moving target: catheter ablation and respiration. Heart Rhythm 2012;9:1048–1049. 10. Kok LC, Everett TH, Akar JG, Haines DE. Effect of heating on pulmonary veins: how to avoid pulmonary vein stenosis. J Cardiovasc Electrophysiol 2003;14: 250–254. 11. Venkatasubramanian RT, Wolkers WF, Shenoi MM, Barocas VH, Lafontaine D, Soule CL, Iaizzo PA, Bischof JC. Freeze-thaw induced biomechanical changes in arteries: role of collagen matrix and smooth muscle cells. Ann Biomed Eng 2010;38:694–706.
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12. Shah D, Lambert H, Langenkamp A, Vanenkov Y, Leo G, Gentil-Baron P, Walpoth B. Catheter tip force required for mechanical perforation of porcine cardiac chambers. Europace 2011;13:277–283. 13. Perna F, Heist EK, Danik SB, Barrett CD, Ruskin JN, Mansour M. Assessment of catheter tip contact force resulting in cardiac perforation in swine atria using force sensing technology. Circ Arrhythm Electrophysiol 2011;4:218–224. 14. Venkatasubramanian RT, Grassl ED, Barocas VH, Lafontaine D, Bischof JC. Effects of freezing and cryopreservation on the mechanical properties of arteries. Ann Biomed Eng 2006;34:823–832. 15. Litwin S, Cohen J, Fine S. Effects of sterilization and tensile strength preservation of canine aortic tissue. J Surg Res 1973;15:198–206. 16. Krag S, Andreassen T. Effect of freezing on lens capsule mechanical behavior. Ophthalmic Res 1998;30:280–285. 17. Haines DE. The biophysics of radiofrequency catheter ablation in the heart: the importance of temperature monitoring. Pacing Clin Electrophysiol 1993;16: 586–591.
18. Kuck KH, Reddy VY, Schmidt B, et al. A novel radiofrequency ablation catheter using contact force sensing: Toccata study. Heart Rhythm 2012;9:18–23. 19. Howard SA, Quallich SG, Benscoter MA, Holmgren BC, Rolfes CD, Iaizzo PA. Tissue properties of the fossa ovalis as they related to transseptal punctures: a translational approach. J Interv Cardiol (in press, 2015). 20. Yokoyama K, Nakagawa H, Shah DC, Lambert H, Leo G, Aeby N, Ikeda A, Pitha JV, Sharma T, Lazzara R, Jackman WM. Novel contact force sensor incorporated in irrigated radiofrequency ablation catheter predicts lesion size and incidence of steam pop and thrombus. Circulation 2008;1:354–362. 21. Thiagalingam A, D’Avila A, Foley L, Guerrero JL, Lambert H, Leo G, Ruskin JN, Reddy VY. Importance of catheter contact force during irrigated radiofrequency ablation: evaluation in a porcine ex vivo model using a force-sensing catheter. J Cardiovasc Electrophysiol 2010;21:806–811. 22. Reddy VY, Shah D, Kautzner J, et al. The relationship between contact force and clinical outcome during radiofrequency catheter ablation of atrial fibrillation in the TOCCATA study. Heart Rhythm 2012;9:1789–1795.
CLINICAL PERSPECTIVES The aim of this study was to define the contact forces required to elicit perforation of cardiac atrial walls during and after RF and cryoablations. Subsequently, we propose that contact force ranging between 20g and 50g be applied during ablations to minimize AF recurrence and limit the incidence of cardiac perforation. Furthermore, after RF ablation, perforations were induced at lower contact forces compared to nonablated tissues. In contrast, the application of cryoablation did not reduce the required perforation forces. The selection of catheter size was also identified as a principal factor altering required contact forces to elicit perforation after transmural lesions were induced. Interestingly, smaller catheters increased the risk for perforation. Translational investigations of contact forces to induce perforation after RF or cryoablation and the effect of catheter size are currently absent in the literature. Nevertheless, during clinical procedures, physicians often exceed the minimum thresholds of contact force to cause perforations. It is considered here that increased awareness of these contact force boundaries and their implementation into clinical settings should greatly reduce the occurrence of cardiac perforation or tamponade associated with ablation procedures. This knowledge, along with the potential use of force sensing catheter technologies, has the potential to improve clinical outcomes during cardiac ablative procedures.
Introduction Today, atrial fibrillation (AF) affects more than 5.1 million people in the United States, and, as the population continues to age, the incidence is expected to increase at least 2.5-fold by 2050.1,2 Recently, a complication rate of 4% to 6% was reported for catheter ablation procedures performed for treatment of AF.3,4 These complications can be prompted by a number of factors, ranging from induced septal defects after transseptal punctures to perforation of the atria. More specifically, cardiac tamponade has been reported to occur in 1.3% of ablation procedures.3 It is considered that complications may arise throughout these procedures due to a number of factors, such as transseptal punctures, adverse catheter maneuvers, or excessive contact forces during energy applications.
Conflict of interest: Research contract with Medtronic Inc. This study was funded, in part, by Medtronic Inc. Address reprint requests and correspondence: Dr. Paul A. Iaizzo, 420 Delaware St SE, B172 Mayo, MMC195, Minneapolis, MN 55455. E-mail address: [email protected].
1547-5271/$-see front matter B 2015 Heart Rhythm Society. All rights reserved.
(P o.001). Treatments with cryoablation did not significantly alter forces required to induce perforations. Decreasing catheter sizes resulted in a reduction in forces required to perforate the atrial wall (P o.001). Catheter perforations occurred over an array of contact forces with a minimum of 38g being observed. CONCLUSION The swine model likely underestimates the required perforation forces relative to those of human tissues. We provide novel insights related to the comparative effects of RF and cryothermal ablations on the potential for inducing undesired punctures, with RF ablation reducing perforation force significantly. These data are insightful for physicians performing ablation procedures as well as for medical device designers. KEYWORDS Catheter ablation; Cardiac tamponade; Arrhythmia; Cardiac perforation; Radiofrequency ablation; Cryoablation ABBREVIATIONS AF ¼ atrial fibrillation; RF ¼ radiofrequency (Heart Rhythm 2015;12:291–296) I 2015 Heart Rhythm Society. All rights reserved.
Perforation of the atrial wall during ablation procedures, which may lead to pericardial effusions and/or lifethreatening cardiac tamponade, has only recently gained attention. Cardiac perforation is most common during AF procedures and occurs less frequently during other cardiac procedures.5 It is suggested that perforation may result from use of high power and/or high contact forces to ensure the creation of transmural lesions by radiofrequency (RF) energies. Unfortunately, no comprehensive studies investigating the causes of cardiac tamponade during ablation procedures have been reported in the literature. However, it is important to note that procedures such as transseptal puncture are associated with a complication rate as high as 0.79% and cardiac perforation with tamponade in 0.11% of cases.6 It also is known that mechanical perforations with diagnostic catheters also are associated with cardiac tamponade. Interestingly, the presentation of pericardial effusion in RF and cryoablation procedures is not significantly different.7 Furthermore, patients with AF have been reported to have thinner atrial walls; this likely elicits http://dx.doi.org/10.1016/j.hrthm.2014.11.028
292 Table 1
Heart Rhythm, Vol 12, No 2, February 2015 Human heart demographics
Heart no,
Age (years)
Weight (kg)
Heart weight (g)
Gender
Cause of death
Cardiac history
1 2 3 4 5 6 7 8
45 34 62 52 81 67 69 67
96 86 73 74 75 82 77 59
537 422 456 401 504 330 456 496
M M F F F M M F
Cerebral vascular accident Cerebral vascular accident Cerebral vascular accident Cerebral vascular accident N/A Bladder cancer Chronic obstructive pulmonary disease Chronic obstructive pulmonary disease
Hypertension, alcoholism None Hypothyroidism, hyperlipidemia None Atrial fibrillation, mitral regurgitation None None None
circumstances that allow for perforations to occur even more readily.8 Other important factors to consider during these clinical procedures include movements of the heart throughout the cardiac cycle as well as those due to respiration, because these can alter the applications of desired contact forces and provide added challenges for clinicians.9 Additionally, it is regarded that the biomechanical properties are altered during the heating and cooling of tissues. For example, loss of pulmonary vein compliance and denaturation of collagen occurs at temperatures of 60–651C, yet elastin remains unchanged until temperatures of 801C are reached.10 During cryoablation, structural proteins remain intact, although realignments occur as a result of ice crystal formations.11 Therefore, better understanding of the contact forces required for proper lesion formation, while minimizing ruptures, may lead to reduced occurrences of cardiac tamponade. This study provides novel insights into the biomechanical effects of RF and cryoablations relative to the potential to induce punctures of cardiac atrial tissues. The study could be considered translational because we compared results for both isolated viable swine and human atrial samples.
Methods Sample preparation Human heart specimens (n ¼ 8) were obtained from nonviable organ transplant donors through our local organ procurement organization LifeSource (St. Paul, MN; Table 1). These tissues were considered viable because they
typically were acquired and tested within 6 to 12 hours after explantation. All non-AF hearts had a nondilated atrial pathology. Healthy 7- to 9-month-old Yorkshire Cross swine cardiac specimens (n ¼ 83, animal weight 75–110 kg, heart weight 400–650 g) were acquired from the University of Minnesota Meat Sciences Laboratory and the Visible Heart Lab (waste tissue from unrelated experiments) and stored in saline before testing. Fresh atrial samples from the free wall (atrial appendage and atrial roof) were carefully dissected out. Atrial samples (n ¼ 666) were randomized to the following study groups: (1) no treatment; (2) RF ablation with a nonirrigated RF Marinr catheter (Medtronic, Minneapolis, MN) for 1 minute at 30 W with a temperature limit of 651C; (3) RF ablation using the same parameters as (2), with induced perforation during the last 5 seconds of applied ablation; or (4) focal cryoablation with a Freezer MAX catheter (Medtronic) for 2 minutes (Figure 1). Cryoablated samples were permitted a sufficient amount of time for ice to thaw before the induced perforations. All samples were carefully anchored and submerged in saline before each ablative modality was applied. Each catheter was subsequently advanced at a rate of 500 mm/min with a mechanical force tester (Chatillon, Largo, FL) until perforation occurred. An array of catheter sizes (5, 7, and 8Fr) was also investigated in these experiments.
Statistical analysis The maximum force readings corresponding to the perforation forces were analyzed with Minitab (State College, PA). All
Figure 1 Graphic depiction of the treatment groups in relation to the application of ablation and the induction of catheter perforation. Cryo ¼ cryoablation treatment; RF ¼ radiofrequency treatment.
Quallich et al
Ablation Contact Forces to Minimize Perforations
force values are reported as mean ⫾ SD. The Student’s T-test for 1:1 comparisons or analysis of variance for the various study groups was used to compare normally distributed data. P r.05 was considered significant.
Results Catheter perforation forces for the right and left atria were significantly different for the prepared human and swine tissue samples for all ablation groups investigated (P o.001). Importantly, the required perforation forces for the RF-ablated samples were almost 2-fold less than those required for the cryoablated or untreated samples (P o.001; Figure 2). In other words, the cryoablation procedures appeared to have little or no effect on perforation forces compared to the control (no treatment) group (P ¼ .43). The effects of perforation during RF ablations were minimal and not statistically significant compared to the other RF ablation group (P ¼ .27). A noteworthy observation was that catheter size was highly correlated with the likelihood to perforate the myocardium after or during an ablation. Smaller catheters required lower forces to induce ruptures than larger catheters for all ablation modalities and tissue types (Po.05; Table 2). Ablation modality effects with RF reducing perforation forces were also confirmed within each catheter size. Additionally, human atrial perforation forces were significantly different than those for the swine tissues (Table 3). Here we
293 observed that the minimum forces to perforate ablated and healthy human atrium were 38g and 57g, respectively (Table 4). Similar minimum perforation forces of 63g and 96g for ablated and healthy swine atrium were also observed. It should be noted that the human atrial samples used in this experiment were from individuals without known histories of AF for all but 1 individual.
Discussion Here we describe novel results from in situ experiments designed to investigate the force required to elicit perforation of cardiac atrial tissue after or during ablation procedures. We used a translational approach in which we studied both viable swine and human specimens. Perforation forces after or during RF ablation and in the control/no treatment group were similar to those reported in the literature, with RF ablation reducing the forces required to elicit perforation significantly.12,13 In these previous studies, an individual user manually advanced the catheter until perforation occurred, whereas in the present study we used a uniaxial testing machine to automate advancement of the catheter at a constant speed. In other words, in our testing methodology, the goal was to remove variations due to the operator. Interestingly, we observed that the minimum perforation force was 63g for RF atrial ablated swine tissue vs 96g for healthy nonablated tissue, whereas Shah et al12 reported values of 40g and 131g, respectively, for swine atrial tissue.
Figure 2 Perforation force for swine right and left atria compared across different ablation modalities (*Po.001). Perforation of the right atrium required substantially less force compared to the left atrium. Also, perforation after either radiofrequency (RF) ablation group entailed significantly less force than the cryoablated (Cryo) or the untreated (Normal) samples. Error bars represent standard deviation.
294 Table 2
Heart Rhythm, Vol 12, No 2, February 2015 Comparison of perforation force sorted by catheter size, tissue type, and ablation modality Perforation force (g)
Tissue type RA LA
Ablation modality
5Fr
N Cryo RF N Cryo RF
293 ⫾ 318 ⫾ 214 ⫾ 345 ⫾ 451 ⫾ 246 ⫾
7Fr 337 ⫾ 333 ⫾ 209 ⫾ 421 ⫾ 394 ⫾ 237 ⫾
91 124 76 115 109 76
P value
8Fr 120 106 79 120 106 78
425 412 294 691 699 426
⫾ ⫾ ⫾ ⫾ ⫾ ⫾
115 141 134 148 155 172
o.001 .033 o.001 o.001 o.001 o.001
Cryo ¼ cryoablation treatment; LA ¼ left atrium; N ¼ no treatment; RA ¼ right atrium; RF ¼ radiofrequency ablation treatment.
To our knowledge, comparison studies relative to perforation forces following RF or cryoablations have not yet been reported in the literature. Cryothermal ablations did not alter perforation forces compared to untreated fresh tissue for both the swine and human tissue samples. It is important to note that we used fresh, viable tissue samples in these investigations. It was previously reported that frozen tissue samples typically are altered in the low stress state, with possible differences in other portions of the stress–strain curve.14 Thus, any changes observed exist at the onset of force application and dissipate substantially as the applied force increases. It has been reported that freezing (application of cryoablation) does not change the ultimate tensile strength or, if so, does so minimally.15,16 This suggests that the forces required to perforate are similar to those of native unablated tissue, which holds true for the results presented here. RF ablation is considered to cause denaturation of collagen as well as cell membrane disruption. Specifically, at high temperatures (60–651C) collagen breakdown occurs.17 It is also suspected that while physicians attempt to create transmural atrial lesions, heat builds up in the myocardium. Typically, an ablation console will only provide data on catheter tip temperatures, which are not representative of tissue temperatures. One can consider that thermal energy builds up transmurally within the myocardium because the endocardial surface and catheter tip will be convectively cooled by the flow of blood through the heart. Whereas while ablating tissue to a minimum of 501C will ensure the creation of a myocardial scar for a successful isolation procedure, reaching temperatures of 601C, (the transition zone for
collagen breakdown) is not unforeseeable. A breakdown of collagen in the ablated myocardium will weaken it, thus explaining the reduction in perforation force after RF ablation. Catheter size is not often considered during ablation procedures, yet it is an important factor influencing the incidence of cardiac perforation. We found that using a larger-size catheter significantly reduces the risk of perforation. Even enlarging the catheter size by a single French often increases the required force for perforation. It is important to note that, given the aggressive ablation parameters used, transmural lesions were observed for all catheter sizes. Thus, lesion size likely had a minimal effect on the observed perforation forces because it encompassed a much greater volume than the catheters. Therefore, with similar tissue damage, a smaller catheter will perforate more easily. This finding is intuitive when considered from a mechanic’s perspective of the relationship between applied force, surface area, and resultant pressure. Implementing this knowledge regarding catheter size and punctures relative to clinical procedures may reduce the occurrence of cardiac tamponade. Further research investigating the effects of catheter size on perforation force is needed to determine whether these results can be extrapolated to catheters larger than 8Fr. Physicians quite often apply contact forces that exceed the lower limit perforation forces we report here, which increases the likelihood of complications. For example, Kuck et al18 observed that during AF procedures, contact forces 4100g were recorded in 79% of patients with a high degree of interoperator and intraoperator variability. Importantly, high contact forces are detected not only during ablations but also
Table 3 Comparison of perforation forces between swine and human tissue sorted by ablation modality and tissue type
Table 4 Minimum perforation forces of swine and human tissue sorted by ablation modality and tissue type Perforation force (g)
Perforation force (g)
Tissue type RA LA
Ablation modality
Swine
Human
P value
N Cryo RF N Cryo RF
337 ⫾ 120 333 ⫾ 106 192 ⫾ 78 421 ⫾ 137 394 ⫾ 136 237 ⫾ 79
545 ⫾ 238 595 ⫾ 183 386 ⫾ 186 692 ⫾ 218 668 ⫾ 278 445 ⫾ 235
o.001 o.001 o.001 o.001 o.001 o.001
Cryo ¼ cryoablation treatment; LA ¼ left atrium; N ¼ no treatment; RA ¼ right atrium; RF ¼ radiofrequency ablation treatment.
Tissue type RA LA
Ablation modality
Swine
Human
N Cryo RF N Cryo RF
96 104 63 187 131 67
57 98 38 149 258 62
Cryo ¼ cryoablation treatment; LA ¼ left atrium; N ¼ no treatment; RA ¼ right atrium; RF ¼ radiofrequency ablation treatment.
Quallich et al
Ablation Contact Forces to Minimize Perforations
throughout cardiac procedures, such as with catheter manipulations and the relative movement of the heart associated with contractions and/or respiration. It should be noted that extensive catheter manipulation on the left side of the heart (via a transseptal puncture) also increases the risk for formation of iatrogenic atrial septal defects.19 Additionally, transseptal punctures account for some portion of cardiac tamponade cases, so diagnostic and ablation catheters are not the sole cause. High contact forces also increase the risk for either elicitation of steam pops and/or thrombus formation.20,21 This underlies the need for force sensing catheter technologies, along with greater physician awareness of acceptable contact forces. It is important to note that average contact forces o10g have been reported to result in higher incidences of AF recurrence, whereas contact forces 420g lower the likelihood of such incidences.22 This suggests that a lower bound for contact force of 20g exists, thus facilitating successful ablation procedures. Defining the upper boundaries of applied ablative contact forces will be a step forward in reducing related complications such as cardiac tamponade. Note again the minimum forces for perforation of human tissue (37g and 57g for ablated and healthy atrium, respectively) and the average forces to perforate (386g and 545g for ablated and healthy atrium). Therefore, we suggest that contact forces o50g should greatly reduce the occurrence of cardiac perforations and/or tamponade. Perhaps a “sweet spot” of 20–50g would be the ideal contact force range that physicians should aim to apply in order to achieve successful procedures that do not result in recurrences while ensuring minimal risk of cardiac perforations.
Study limitations Minimal human heart availability, the in vitro nature of experiment, and the inability to measure tissue temperatures were the major study limitations. Measurement of tissue temperatures in this experimental paradigm would have compromised the biomechanical properties of the cardiac tissue. However, transmural tissue temperatures would allow for more accurate analysis of the interplay between ablations, temperatures, and biomechanical properties of the cardiac specimens. In addition, conducting an in vivo assessment of perforation forces would aid in clinical applicability but would add in cofounding factors we desired to remove, such as variations due to the operator. The use of nonirrigated ablation catheters and the inability to measure compressive force during tissue anchoring are other important limitations to note. Furthermore, several of the human specimens were stored in saline for up to 24 hours because immediate testing was not feasible. It is important to consider that these punctures were performed in nonbeating tissue and not in intact hearts. Also, limited human heart availability for research was anticipated, so swine hearts were used instead to approximate the biomechanical properties of cardiac tissue. The available human tissue included only 1 individual with a history of AF, which restricts the ability to elucidate significant findings for AF patients. Unfortunately, the swine
295 hearts lack thinner atrial walls like the typical AF patient, so a direct translational comparison to the patient population of interest is restricted in nature. This highlights the need for further studies on human tissue from patients with a history of AF.
Conclusion Cryoablation did not result in statistically significant reductions in the contact forces required to perforate atrial tissues. In contrast, applied RF ablations elicited reductions in the forces required to perforate these tissues. This is the first study to investigate perforation forces during RF ablations and after RF or cryothermal ablations, as well as the impact of catheter size. We consider that these data should be of substantial interest to clinicians because the findings may help define an ideal contact force range for minimizing the occurrence of cardiac tamponade while still promoting transmural lesion generation.
Acknowledgments We express our gratitude to LifeSource as well as the organ donors and their families for the hearts used in this research. We thank Monica Mahre for preparation of the manuscript.
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CLINICAL PERSPECTIVES The aim of this study was to define the contact forces required to elicit perforation of cardiac atrial walls during and after RF and cryoablations. Subsequently, we propose that contact force ranging between 20g and 50g be applied during ablations to minimize AF recurrence and limit the incidence of cardiac perforation. Furthermore, after RF ablation, perforations were induced at lower contact forces compared to nonablated tissues. In contrast, the application of cryoablation did not reduce the required perforation forces. The selection of catheter size was also identified as a principal factor altering required contact forces to elicit perforation after transmural lesions were induced. Interestingly, smaller catheters increased the risk for perforation. Translational investigations of contact forces to induce perforation after RF or cryoablation and the effect of catheter size are currently absent in the literature. Nevertheless, during clinical procedures, physicians often exceed the minimum thresholds of contact force to cause perforations. It is considered here that increased awareness of these contact force boundaries and their implementation into clinical settings should greatly reduce the occurrence of cardiac perforation or tamponade associated with ablation procedures. This knowledge, along with the potential use of force sensing catheter technologies, has the potential to improve clinical outcomes during cardiac ablative procedures.