- Email: [email protected]
Evaluation of post-radiofrequency myocardial injury by measuring cardiac troponin I levels
International Journal of Cardiology 117 (2007) 173 – 177 www.elsevier.com/locate/ijcard
Evaluation of post-radiofrequency myocardial injury by measuring cardiac troponin I levels Zahra Emkanjoo ⁎, Morteza Mottadayen, Nozar Givtaj, Mohammad Alasti, Arash Arya, Majid Haghjoo, Amir F. Fazelifar, Abollfath Alizadeh, Mohammad A. Sadr-Ameli Department of Pacemaker and Electrophysiology, Rajaie Cardiovascular Medical Center, Tehran 1996911151, Iran Received 1 December 2005; received in revised form 16 March 2006; accepted 28 April 2006 Available online 12 July 2006
Abstract Background: The aim of this study was to investigate the extent of myocardial injury created by radiofrequency (RF) ablation. We assessed the changes in levels of cardiac biochemical markers in patients who underwent RF ablation and we sought to evaluate the utility of cardiac troponin I (cTnI) in detecting minor myocardial injury following RF ablation and determine its procedural correlates. Methods: We analyzed the data of 115 consecutive patients who underwent RF ablation. The target sites of RF ablation were slow pathway in 56, left atrioventricular (AV) annulus in 31, right AV annulus in 14, atrial wall in 3, ventricular wall in 6 and AV node in 3 patients. The levels of creatine kinase (CK), CK-MB, cTnI and myoglobin were compared with procedural data and targeted arrhythmia. Results: Post-RF ablation the concentration of cTnI, CM-MB, CK and myoglobin were significantly different than those of the initial sample. The mean and peak cTnI levels were raised above normal in 63 patients (54.8%). Mean levels of cTnI correlated with the site of RF ablation, being significant for slow pathway ablation, ventricular tachycardia and left AV annulus. We also found a significant association of mean CKMB, CK levels and left AV annulus. Conclusion: Our results indicate that radiofrequency ablation results in only minor injury. This marker is effective for detection of RF current induced myocardial injury. Lesions applied to the mitral annulus at the ventricular endocardium are associated with significantly greater myocardial damage. © 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Cardiac biochemical markers; Cardiac troponin I; Radiofrequency ablation
1. Introduction Radiofrequency (RF) catheter ablation has become the treatment of choice for many types of cardiac arrhythmias [1]. RF ablation produces a small area of myocardial necrosis. It is hypothesized that the mechanism of cell injury and death in response to hyperthermic exposure is primarily mediated by injury to the sarcolemmal membrane. The cellular electrophysiological changes observed during hyperthermic myocyte injury are temperature dependent. When temperature exceed 50 °C, the cell become more depolarized, the transmembrane pump activities become impaired, the calcium buffering capacity of the cell is ⁎ Corresponding author. Tel.: +98 2123922931; fax: +98 212055594. E-mail address: [email protected] (Z. Emkanjoo). 0167-5273/$ - see front matter © 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2006.04.066
overwhelmed and cell death occurs. Several biochemical parameters have been validated in the diagnosis of the myocardial damage induced by RF ablation. After RF ablation, there may be a minimal increase in creatine kinase (CK) which depends on the number of RF lesions and the substrate of catheter ablation [2]. Creatine kinase inactivation by RF ablation has been proposed as a cause of underestimation of the total myocardial injury incurred [3]. Troponin is a regulatory protein complex in striated muscle. It consists of three components: troponin C (the calcium binding element), troponin I (the tropomyosin ATPase inhibitory element) and troponin T (the tropomyosin binding element). Troponin I exists in three distinct molecular forms found in fast-twitch skeletal muscle, slowtwitch skeletal muscle and heart. The cardiac isotype is specific for heart muscle injury. However, it has rarely been
174
Z. Emkanjoo et al. / International Journal of Cardiology 117 (2007) 173–177
used previously to monitor myocardial injury during RF ablation. Recently, the sensitivity and specificity of cardiac troponin I and T for the detection of minor myocardial injury during RF ablation has been confirmed by several authors for RF ablation [3–9]. Cardiac troponin I (cTnI) has been shown to be more sensitive and specific than CK-MB and more specific than cardiac troponin T for the diagnosis of minor myocardial injury [10–12]. The aim of this study was to assess the changes in levels of cardiac biochemical markers in patients who underwent RF ablation and to establish the utility of cTnI for detection of minor myocardial injury post-RF ablation. In addition, we conducted this study to disclose any correlation between the site of ablation and levels of cardiac serum markers.
using transaortic technique for RF ablation of left-sided accessory pathways as well as left septal ventricular tachycardia. We included all applications of RF energies either successful or failed. During RF ablation of a left-sided arrhythmia focus, anticoagulation was performed by a bolus administration of heparin 5000 IU, followed by continuous intravenous heparin infusion at a rate of 1000 IU/h. After the procedure, serial ECGs were obtained to evaluate for recurring arrhythmia and an echocardiogram was performed to evaluate for cardiac complications. We excluded the patients requiring cardioversion during procedure.
2. Methods
We collected four venous peripheral blood samples from each patient. First sample was taken just before the procedure. The second sample was obtained 6 h after the completion of the procedure. The other blood samples were taken as follows: at 12 and 24 h afterward. The samples were centrifuged for 10 min at 3000 rpm and serum removed. A part of serum (0.5 ml) used for measurement of CK, CK-MB, myoglobin and another part of serum (0.5 ml) was kept at − 20 °C until the troponin I assay was performed. CK, CKMB and myoglobin levels were determined by routine laboratory assays (by Pars Azmon company kits by use of COBBAS Mira autoanalyser). Troponin I levels were measured by enzyme immunosorbent assay (ELISA) method by use of Dima company (Ges. F. diagnostika mbh Gottinyen, Germany) kits. The reference range of the substances analyzed in our laboratory were as follows: for cTnI 0–0.8 ng/ml, for CK 24–195 IU/l, for CK-MB 0–24 IU/l and for myoglobin 0– 70 μg/l. It is noted that the CK was not measured in two patients and CK-MB in one patient.
We analyzed the data of 115 consecutive patients who underwent RF ablation in this prospective study. All patients had structurally normal hearts with normal echocardiography. The patients with recent ischemic events (< 1 month) were excluded. None of the patients had renal insufficiency. An inform consent was obtained from all patients. There were 44 (38.3%) men and 71 (61.7%) women, aged 45.5 ± 15.8 (range 9–79 years) who underwent RF ablation. We included 31 left accessory pathways, 14 right accessory pathways, 2 atrial flutter, 1 focal atrial tachycardia, 6 idiopathic ventricular tachycardia (5 RVOT VT, and 1 left septal VT), 54 typical AVNRT, 2 atypical AVNRT, 3 AV nodal ablation and 2 multiple sites of tachycardia. 3. Electrophysiological study and ablation Following discontinuation of all antiarrhythmic medications for at least 48 h before the study, each patient underwent a standard diagnostic electrophysiological study before RF ablation. Depending on the substrate for RF ablation, three 6 Fr quadripolar electrode catheters were introduced percutaneously into the femoral veins and positioned at the high right atrium, His-bundle region, right ventricular apex and a 7 Fr steerable decapolar catheter was placed in the coronary sinus from the right femoral vein or subclavian vein for recording and stimulation. Positioning of the diagnostic catheters was performed under fluoroscopy with standard projections. Mapping and RF ablation were performed using a steerable 7 Fr quadripolar catheter with a 4-mm tip and 2-mm interelectrode spacing (Ablatr or Mariner, Medtronic, Minneapolis, Minn). RF current was delivered by a 500 kHz generator (Attakr II, Medtronic Inc., MN, USA) at a constant preset electrical power (30–50 W) between the distal electrode and a large patch electrode on the posterior thorax as the indifferent electrode. A preset target temperature of 40–70 °C was programmed. Once the target site was identified, 30–50 W of RF energy was delivered. The time of energy application varied between 15 and 60 s every time. Access to the left heart was obtained
4. Blood sample collection
5. Statistical analysis All variables are expressed as mean ± S.D. Correlation between procedural variables and serum cardiac markers levels were performed using linear regression (Pearson). Also we used paired sample t test to compare the means of pre- and post-procedural serum cardiac markers. A p value of < 0.05 was considered significant. 6. Results 6.1. Procedural data Clinical and procedural characteristics are listed in Table 1. One hundred and fifteen patients undergoing RF ablation were included in this study. All procedures were successfully completed without clinically significant complications relevant to ablation. No patient had clinical signs of coronary ischemic events after the procedure.
Z. Emkanjoo et al. / International Journal of Cardiology 117 (2007) 173–177 Table 1 Clinical and procedural characteristics of patients Age Men/women Ablation target Slow pathway Right AV annulus Left AV annulus Atrial wall Ventricular wall AV node Ventricular foci and slow pathway Accessory pathway and slow pathway Mean duration of RF delivery (s) Number of RF lesions Maximum power (W)
9–79 years (mean:45.5 ± 15.8) 71/44 n = 56 n = 14 n = 31 n=3 n=6 n=3 n=1 n=1 328 ± 335 11.17 ± 11.05 46.87 ± 9.66
At the end of the RF ablation, cTnI levels rose to 1.306 ± 1.61 ng/ml ( p < 0.001), CK levels rose to 181.92 ± 209 IU/l ( p < 0.001), CK-MB levels rose to 21.32 ± 17.33 IU/l ( p = 0.004) and myoglobin levels rose to 52.20 ± 54.15 μg/l ( p = 0.003), representing a significant increase in comparison with baseline. Troponin I concentration was raised above normal in 63 patients (54.8%). An abnormal value of CK-MB was found in 31 (27%) of 114 patients of this group. The levels of CK were abnormal in 24 (20.9%) of 113 patients of this group. Myoglobin showed abnormal values in only 17 (14.8%) of 113 patients. 8. Correlation between substances analyzed and clinical markers
AV = atrioventricular.
The mean duration of the RF delivery was 328 ± 335 s. The mean number of RF lesions was 11.17 ± 11.05, 74 patients (67%) had ≤ 10 lesions and 38 patients (33%) had > 10 lesions. The target sites of RF lesions were atrial wall in 3 (2.6%) patients, ventricular wall in 6 (6.1%) patients, slow pathways in 56 (79.6%), left AV annulus in 31 (28.7%), right AV annulus in 14 (13.9%), AV node in 3 (2.6%), both ventricular foci and slow pathway in 1 and both slow pathway and accessory pathway in 1 patient (0.9%). Cardiac function was compared in each patient before and after RF ablation procedure, using transthoracic echocardiography, and there was no anatomic demonstration of injury to the myocardium in addition to the biochemical markers. 7. Cardiac troponin I, CK, CK-MB and myoglobin levels The percentage of patients with abnormal values is shown in Table 2. Before RF ablation, the mean cTnI level was 0.243 ± 0.29 ng/ml, CK level was 93.12 ± 116 IU/l, CK-MB level was 17.58 ± 8.8 IU/l and myoglobin level was 38.14 ± 26.07 μg/l. During baseline measurements, before RF ablation, cTnI was found elevated (> 0.8 ng/ml) in 8 patients, CK was abnormal (> 195 IU/l) in 11 patients and CK-MB (> 24 IU/l) in 2 patients. There was no significant increase in the levels of cTnI ( p = NS), post-RF ablation, in those with elevated levels at baseline measurements.
Table 2 Number of patients with pathologic serum values after radiofrequency ablation
We analyzed the correlation between the mean and peak levels of biochemical markers and the data obtained from RF generator: number of applications, mean temperature, total applied energy and duration of RF ablation. The best correlation was found between the peak and mean levels of myoglobin and the number of RF applications, duration of RF ablation and total energy. We also found a statistically significant correlation between the peak levels of cTnI and duration of RF delivery and total energy ( p = 0.037); there was no significant correlation between the peak levels of cTnI and number of RF applications (Table 3). Despite a statistically significant correlation between peak levels of cTnI and CK, peak levels of CK-MB and cTnI ( p = 0.002 and p = 0.044, respectively) and also between peak levels of CK and myoglobin ( p < 0.001), no significant correlation was observed between CK-MB and CK and the parameters of total energy, numbers of RF applications and duration of RF ablation. To determine whether the size of myocardial lesion and the release of biochemical markers were different for each ablation site, we separated different groups. The correlation was different for each arrhythmia targeted. Mean levels of cTnI correlated with the site of RF ablation, being significant for slow pathway ablation, ventricular tachycardia and left atrioventricular annulus ( p = 0.002, p < 0.001, p = 0.03, respectively). There was also a statistically significant correlation of mean CK-MB, CK levels and left AV annulus ( p = 0.03, p = 0.03, respectively). Table 3 Correlation between cardiac biochemical markers and clinical markers Total energy Burn numbers Duration of RF delivery
Cutoff points cTnI (ng/ml) CK-MB (IU/l) CK (IU/l) Myoglobin (μg/l)
63 (54.8%) 31 (27%) 24 (20.9%) 17 (14.8%)
175
>0.8 ng/ml >24 IU/l >195 IU/l >70 μg/l
cTnI (ng/ml) CK-MB (IU/l) CK (IU/l) Myoglobin (μg/l)
p value
p value
p value
0.045 0.935 0.763 0.002
0.090 0.920 0.392 <0.001
0.037 0.505 0.619 <0.001
176
Z. Emkanjoo et al. / International Journal of Cardiology 117 (2007) 173–177
9. Kinetics The peak value of cTnI (1.8 ± 2.18) was documented 6 h after procedure ( p < 0.001). Similarly, the peak levels of CKMB and myoglobin (21.80 ± 16 and 53.88 ± 56) were measured at 6 h sampling ( p = 0.002, p < 0.001, respectively). The peak level of CK was 214.85 ± 35, measured at 24 h sampling ( p < 0.001). 10. Discussion This study confirms previous studies that cTnI is the more accurate marker for the assessment of myocardial injury post-RF ablation. Manolis et al. [8] reported 68% elevated cTnI values in the largest group of patients undergoing RF ablation and monitoring of cardiac serum markers. The reported percentage of pathological values for cTnI varies between 58.3% found by Jiang et al. [13], 84% published by Macaluso et al. [14], 92% found by Madrid et al. [7] and 92% found by Del Rey et al. [15,16]. In all of these studies, the sensitivity of cTnI is far greater than that of the other cardiac serum markers. In our study, the peak level of cTnI was 1.8 ± 2.18 ng/ml and found 6 h after RF ablation. It is noted that the peak level of cTnI in our series was small, lower than those found in other published studies [4,7,8,15]. Our study also demonstrated that RF ablation creates a small lesion with low release of several serum cardiac markers. In our series, 63 (54.8%) out of 115 demonstrated elevation of cTnI. Manolis et al. [8] reported 27% elevated CKMB values. This was in accordance with the present study. Myoglobin after RF ablation has been studied only by Madrid et al. [7]. They found that the sensitivity for myoglobin was 67%, which is significantly higher compared to our findings. Manolis at al. [8] investigated procedural correlates and found a correlation between cTnI levels and the number of RF applications and the site of RF ablation (ventricular myocardium > atrial myocardium > AV annuli). A correlation between cTnI levels and the number of RF applications and the total time of RF applications also reported by Madrid et al. [7]. In our study, the best correlation was found between the peak and mean levels of myoglobin and the number of RF applications, duration of RF ablation and total energy. We also found a good correlation between the peak and mean levels of cTnI and duration of RF ablation and total energy but there was no correlation between the peak and mean levels of cTnI and number of RF applications. The lack of correlation may be explained by the fact that some of the RF applications resulted in ineffective lesion formation either due to instability of the catheter or interruption of RF energy prematurely (< 15 s) when it was unsuccessful. Madrid et al. [8] showed a correlation between the degree of myocardial injury incurred during RF ablation as reflected
by cTnI levels and the site of ablation. Lesions created in the ventricular myocardium, albeit numerically fewer, entailed more extensive myocardial injury compared with RF application in the atrial myocardium or in the annuli. In our study, there was a significant correlation between the levels of cTnI, CK and CK-MB and the site of RF applications. The concentration of cTnI was higher for RF ablation of slow pathway and ventricular tachycardia. This is in contrast with the findings of Del Rey et al. [16] that showed the lowest release of cTnI in the AV node reentrant tachycardia. Mean levels of cTnI also correlated with RF application in the left AV annulus. Another significant correlation detected between the mean levels of CK-MB and left AV annulus. There was also a significant correlation of CK levels and RF application in the left AV annulus. In our practice, the ablation site of for the left accessory pathways was usually in the ventricular endocardium, but in the cases of right-sided accessory pathways, the atrial aspect of the endocardium above the tricuspide annulus was targeted. The lesions applied to mitral annulus at the ventricular site produced more increase in cTnI levels. It is important to note that we used transaortic approach in all of our patients; thus, this result could also be dependent on the approach to the annulus. 11. Study limitations A control group who underwent electrophysiological study without RF ablation was not included in our study. Thus, we could not isolate the mechanical effect of the manipulating catheter. 12. Conclusion Our results indicate that radiofrequency ablation results in only minor injury. cTnI exhibited a small but distinct increase and demonstrated more sensitivity for detection of RF current induced myocardial injury compared to CKMB, CK and myoglobin. RF current seems to be safe and this has been attributed to the small and homogenous lesions. Lesions applied to the mitral annulus at the ventricular endocardium, using transaortic approach, are associated with significantly greater myocardial damage. References [1] Morady F. Radiofrequency ablation as treatment for cardiac arrhythmia. N Engl J Med 1999;340:534–44. [2] Ravkilde J, Nissen H, Horder M, Thygesen K. Independent prognostic value of serum creatine kinase isoenzyme MB mass, cardiac troponin T and myosin light chain levels in suspected acute MI. J Am Coll Cardiol 1995;25:574–81. [3] Haines DE, Whayne JG, Waker J, Nath S, Bruns D. The effect of radiofrequency catheter ablation on myocardial creatine kinase activity. J Cardiovasc Electrophysiol 1995;6:79–88. [4] Shyu KG, Lin JL, Chen JJ, Chang H. Use of cardiac troponin T, creatine kinase and its isoforms to monitor myocardial injury during
Z. Emkanjoo et al. / International Journal of Cardiology 117 (2007) 173–177
[5]
[6]
[7]
[8]
[9]
radiofrequency ablation for supraventricular tachycardia. Cardiology 1996;87(5):392–5. Katritsis DG, Hossein-Nia M, Anastasakis A, et al. Use of troponin T concentrations and kinase isoforms for quantification of myocardial injury induced by radiofrequency catheter ablation. Eur Heart J 1997;18:1007–13. Katritsis DG, Hossein-Nia M, Anastasakis A, et al. Myocardial injury induced by radiofrequency and low energy ablation: a quantitative study of CK isoforms, CKMB and troponin-T concentration. PACE 1998;21(7):1410–6. Madrid AH, Del Rey JM, Rubi J, et al. Biochemical markers and cardiac troponin I release after radiofrequency catheter ablation; approach to size of necrosis. Am Heart J 1998;136:948–55. Manolis AS, Vassilikos V, Maounis T, et al. Detection of myocardial injury during radiofrequency catheter ablation by measuring serum cardiac troponin I levels: procedural correlates. J Am Coll Cardiol 1999;34:1099–105. Rao SP, Miller S, Rosenbaume R, Lakier JB. Cardiac troponin I and cardiac enzymes after electrophysiologic studies, ablation and defibrillator implantations. Am J Cardiol 1999;84:470.
177
[10] Hamm CW, Goldmann BU, Heeschen C, Kreymann G, Berger J, Meinertz T. Emergency room triage of patients with acute chest pain by means of rapid testing for cardiac troponin T or troponin I. N Engl J Med 1997;337:1648–53. [11] Adams III JE, Bodor GS, Davila-Roman VG, et al. Cardiac troponin I: a marker with high specificity for cardiac injury. Circulation 1993;88:101–6. [12] Brown CS, Bertolet BD. Cardiac troponin: see ya later CK! Chest 1997;111:2–4. [13] Jiang J, Wang JA, Chen XY, Lu D. Radiofrequency catheter ablation autonomic nerve injury. Zhejiang Da Xue Xue Bao Yi Xue Ban jun 2002;31(3):195–8 [Abstract]. [14] Macaluso G, Comet B, Bouvier JL, et al. Biochemical markers of myocardial damage after high-energy radiofrequency ablation of atrial flutter. Arch Mal Coeur Vaiss feb 2002;95(2):102–8. [15] Del Rey JM, Madrid AH, Novo L, Sanchez A, Martin J, Rubi J. Evaluation of biochemical markers of myocardial lesion after radiofrequncy ablation. Value of troponin I. Rev Esp Cardiol aug 1997;50(8):552–60. [16] Del Rey JM, Madrid AH, Valino JM, et al. Cardiac troponin I and minor cardiac damage: biochemical markers in a clinical model of myocardial lesions. Clin Chem 1998;44(11):2270–6.
Evaluation of post-radiofrequency myocardial injury by measuring cardiac troponin I levels Zahra Emkanjoo ⁎, Morteza Mottadayen, Nozar Givtaj, Mohammad Alasti, Arash Arya, Majid Haghjoo, Amir F. Fazelifar, Abollfath Alizadeh, Mohammad A. Sadr-Ameli Department of Pacemaker and Electrophysiology, Rajaie Cardiovascular Medical Center, Tehran 1996911151, Iran Received 1 December 2005; received in revised form 16 March 2006; accepted 28 April 2006 Available online 12 July 2006
Abstract Background: The aim of this study was to investigate the extent of myocardial injury created by radiofrequency (RF) ablation. We assessed the changes in levels of cardiac biochemical markers in patients who underwent RF ablation and we sought to evaluate the utility of cardiac troponin I (cTnI) in detecting minor myocardial injury following RF ablation and determine its procedural correlates. Methods: We analyzed the data of 115 consecutive patients who underwent RF ablation. The target sites of RF ablation were slow pathway in 56, left atrioventricular (AV) annulus in 31, right AV annulus in 14, atrial wall in 3, ventricular wall in 6 and AV node in 3 patients. The levels of creatine kinase (CK), CK-MB, cTnI and myoglobin were compared with procedural data and targeted arrhythmia. Results: Post-RF ablation the concentration of cTnI, CM-MB, CK and myoglobin were significantly different than those of the initial sample. The mean and peak cTnI levels were raised above normal in 63 patients (54.8%). Mean levels of cTnI correlated with the site of RF ablation, being significant for slow pathway ablation, ventricular tachycardia and left AV annulus. We also found a significant association of mean CKMB, CK levels and left AV annulus. Conclusion: Our results indicate that radiofrequency ablation results in only minor injury. This marker is effective for detection of RF current induced myocardial injury. Lesions applied to the mitral annulus at the ventricular endocardium are associated with significantly greater myocardial damage. © 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Cardiac biochemical markers; Cardiac troponin I; Radiofrequency ablation
1. Introduction Radiofrequency (RF) catheter ablation has become the treatment of choice for many types of cardiac arrhythmias [1]. RF ablation produces a small area of myocardial necrosis. It is hypothesized that the mechanism of cell injury and death in response to hyperthermic exposure is primarily mediated by injury to the sarcolemmal membrane. The cellular electrophysiological changes observed during hyperthermic myocyte injury are temperature dependent. When temperature exceed 50 °C, the cell become more depolarized, the transmembrane pump activities become impaired, the calcium buffering capacity of the cell is ⁎ Corresponding author. Tel.: +98 2123922931; fax: +98 212055594. E-mail address: [email protected] (Z. Emkanjoo). 0167-5273/$ - see front matter © 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2006.04.066
overwhelmed and cell death occurs. Several biochemical parameters have been validated in the diagnosis of the myocardial damage induced by RF ablation. After RF ablation, there may be a minimal increase in creatine kinase (CK) which depends on the number of RF lesions and the substrate of catheter ablation [2]. Creatine kinase inactivation by RF ablation has been proposed as a cause of underestimation of the total myocardial injury incurred [3]. Troponin is a regulatory protein complex in striated muscle. It consists of three components: troponin C (the calcium binding element), troponin I (the tropomyosin ATPase inhibitory element) and troponin T (the tropomyosin binding element). Troponin I exists in three distinct molecular forms found in fast-twitch skeletal muscle, slowtwitch skeletal muscle and heart. The cardiac isotype is specific for heart muscle injury. However, it has rarely been
174
Z. Emkanjoo et al. / International Journal of Cardiology 117 (2007) 173–177
used previously to monitor myocardial injury during RF ablation. Recently, the sensitivity and specificity of cardiac troponin I and T for the detection of minor myocardial injury during RF ablation has been confirmed by several authors for RF ablation [3–9]. Cardiac troponin I (cTnI) has been shown to be more sensitive and specific than CK-MB and more specific than cardiac troponin T for the diagnosis of minor myocardial injury [10–12]. The aim of this study was to assess the changes in levels of cardiac biochemical markers in patients who underwent RF ablation and to establish the utility of cTnI for detection of minor myocardial injury post-RF ablation. In addition, we conducted this study to disclose any correlation between the site of ablation and levels of cardiac serum markers.
using transaortic technique for RF ablation of left-sided accessory pathways as well as left septal ventricular tachycardia. We included all applications of RF energies either successful or failed. During RF ablation of a left-sided arrhythmia focus, anticoagulation was performed by a bolus administration of heparin 5000 IU, followed by continuous intravenous heparin infusion at a rate of 1000 IU/h. After the procedure, serial ECGs were obtained to evaluate for recurring arrhythmia and an echocardiogram was performed to evaluate for cardiac complications. We excluded the patients requiring cardioversion during procedure.
2. Methods
We collected four venous peripheral blood samples from each patient. First sample was taken just before the procedure. The second sample was obtained 6 h after the completion of the procedure. The other blood samples were taken as follows: at 12 and 24 h afterward. The samples were centrifuged for 10 min at 3000 rpm and serum removed. A part of serum (0.5 ml) used for measurement of CK, CK-MB, myoglobin and another part of serum (0.5 ml) was kept at − 20 °C until the troponin I assay was performed. CK, CKMB and myoglobin levels were determined by routine laboratory assays (by Pars Azmon company kits by use of COBBAS Mira autoanalyser). Troponin I levels were measured by enzyme immunosorbent assay (ELISA) method by use of Dima company (Ges. F. diagnostika mbh Gottinyen, Germany) kits. The reference range of the substances analyzed in our laboratory were as follows: for cTnI 0–0.8 ng/ml, for CK 24–195 IU/l, for CK-MB 0–24 IU/l and for myoglobin 0– 70 μg/l. It is noted that the CK was not measured in two patients and CK-MB in one patient.
We analyzed the data of 115 consecutive patients who underwent RF ablation in this prospective study. All patients had structurally normal hearts with normal echocardiography. The patients with recent ischemic events (< 1 month) were excluded. None of the patients had renal insufficiency. An inform consent was obtained from all patients. There were 44 (38.3%) men and 71 (61.7%) women, aged 45.5 ± 15.8 (range 9–79 years) who underwent RF ablation. We included 31 left accessory pathways, 14 right accessory pathways, 2 atrial flutter, 1 focal atrial tachycardia, 6 idiopathic ventricular tachycardia (5 RVOT VT, and 1 left septal VT), 54 typical AVNRT, 2 atypical AVNRT, 3 AV nodal ablation and 2 multiple sites of tachycardia. 3. Electrophysiological study and ablation Following discontinuation of all antiarrhythmic medications for at least 48 h before the study, each patient underwent a standard diagnostic electrophysiological study before RF ablation. Depending on the substrate for RF ablation, three 6 Fr quadripolar electrode catheters were introduced percutaneously into the femoral veins and positioned at the high right atrium, His-bundle region, right ventricular apex and a 7 Fr steerable decapolar catheter was placed in the coronary sinus from the right femoral vein or subclavian vein for recording and stimulation. Positioning of the diagnostic catheters was performed under fluoroscopy with standard projections. Mapping and RF ablation were performed using a steerable 7 Fr quadripolar catheter with a 4-mm tip and 2-mm interelectrode spacing (Ablatr or Mariner, Medtronic, Minneapolis, Minn). RF current was delivered by a 500 kHz generator (Attakr II, Medtronic Inc., MN, USA) at a constant preset electrical power (30–50 W) between the distal electrode and a large patch electrode on the posterior thorax as the indifferent electrode. A preset target temperature of 40–70 °C was programmed. Once the target site was identified, 30–50 W of RF energy was delivered. The time of energy application varied between 15 and 60 s every time. Access to the left heart was obtained
4. Blood sample collection
5. Statistical analysis All variables are expressed as mean ± S.D. Correlation between procedural variables and serum cardiac markers levels were performed using linear regression (Pearson). Also we used paired sample t test to compare the means of pre- and post-procedural serum cardiac markers. A p value of < 0.05 was considered significant. 6. Results 6.1. Procedural data Clinical and procedural characteristics are listed in Table 1. One hundred and fifteen patients undergoing RF ablation were included in this study. All procedures were successfully completed without clinically significant complications relevant to ablation. No patient had clinical signs of coronary ischemic events after the procedure.
Z. Emkanjoo et al. / International Journal of Cardiology 117 (2007) 173–177 Table 1 Clinical and procedural characteristics of patients Age Men/women Ablation target Slow pathway Right AV annulus Left AV annulus Atrial wall Ventricular wall AV node Ventricular foci and slow pathway Accessory pathway and slow pathway Mean duration of RF delivery (s) Number of RF lesions Maximum power (W)
9–79 years (mean:45.5 ± 15.8) 71/44 n = 56 n = 14 n = 31 n=3 n=6 n=3 n=1 n=1 328 ± 335 11.17 ± 11.05 46.87 ± 9.66
At the end of the RF ablation, cTnI levels rose to 1.306 ± 1.61 ng/ml ( p < 0.001), CK levels rose to 181.92 ± 209 IU/l ( p < 0.001), CK-MB levels rose to 21.32 ± 17.33 IU/l ( p = 0.004) and myoglobin levels rose to 52.20 ± 54.15 μg/l ( p = 0.003), representing a significant increase in comparison with baseline. Troponin I concentration was raised above normal in 63 patients (54.8%). An abnormal value of CK-MB was found in 31 (27%) of 114 patients of this group. The levels of CK were abnormal in 24 (20.9%) of 113 patients of this group. Myoglobin showed abnormal values in only 17 (14.8%) of 113 patients. 8. Correlation between substances analyzed and clinical markers
AV = atrioventricular.
The mean duration of the RF delivery was 328 ± 335 s. The mean number of RF lesions was 11.17 ± 11.05, 74 patients (67%) had ≤ 10 lesions and 38 patients (33%) had > 10 lesions. The target sites of RF lesions were atrial wall in 3 (2.6%) patients, ventricular wall in 6 (6.1%) patients, slow pathways in 56 (79.6%), left AV annulus in 31 (28.7%), right AV annulus in 14 (13.9%), AV node in 3 (2.6%), both ventricular foci and slow pathway in 1 and both slow pathway and accessory pathway in 1 patient (0.9%). Cardiac function was compared in each patient before and after RF ablation procedure, using transthoracic echocardiography, and there was no anatomic demonstration of injury to the myocardium in addition to the biochemical markers. 7. Cardiac troponin I, CK, CK-MB and myoglobin levels The percentage of patients with abnormal values is shown in Table 2. Before RF ablation, the mean cTnI level was 0.243 ± 0.29 ng/ml, CK level was 93.12 ± 116 IU/l, CK-MB level was 17.58 ± 8.8 IU/l and myoglobin level was 38.14 ± 26.07 μg/l. During baseline measurements, before RF ablation, cTnI was found elevated (> 0.8 ng/ml) in 8 patients, CK was abnormal (> 195 IU/l) in 11 patients and CK-MB (> 24 IU/l) in 2 patients. There was no significant increase in the levels of cTnI ( p = NS), post-RF ablation, in those with elevated levels at baseline measurements.
Table 2 Number of patients with pathologic serum values after radiofrequency ablation
We analyzed the correlation between the mean and peak levels of biochemical markers and the data obtained from RF generator: number of applications, mean temperature, total applied energy and duration of RF ablation. The best correlation was found between the peak and mean levels of myoglobin and the number of RF applications, duration of RF ablation and total energy. We also found a statistically significant correlation between the peak levels of cTnI and duration of RF delivery and total energy ( p = 0.037); there was no significant correlation between the peak levels of cTnI and number of RF applications (Table 3). Despite a statistically significant correlation between peak levels of cTnI and CK, peak levels of CK-MB and cTnI ( p = 0.002 and p = 0.044, respectively) and also between peak levels of CK and myoglobin ( p < 0.001), no significant correlation was observed between CK-MB and CK and the parameters of total energy, numbers of RF applications and duration of RF ablation. To determine whether the size of myocardial lesion and the release of biochemical markers were different for each ablation site, we separated different groups. The correlation was different for each arrhythmia targeted. Mean levels of cTnI correlated with the site of RF ablation, being significant for slow pathway ablation, ventricular tachycardia and left atrioventricular annulus ( p = 0.002, p < 0.001, p = 0.03, respectively). There was also a statistically significant correlation of mean CK-MB, CK levels and left AV annulus ( p = 0.03, p = 0.03, respectively). Table 3 Correlation between cardiac biochemical markers and clinical markers Total energy Burn numbers Duration of RF delivery
Cutoff points cTnI (ng/ml) CK-MB (IU/l) CK (IU/l) Myoglobin (μg/l)
63 (54.8%) 31 (27%) 24 (20.9%) 17 (14.8%)
175
>0.8 ng/ml >24 IU/l >195 IU/l >70 μg/l
cTnI (ng/ml) CK-MB (IU/l) CK (IU/l) Myoglobin (μg/l)
p value
p value
p value
0.045 0.935 0.763 0.002
0.090 0.920 0.392 <0.001
0.037 0.505 0.619 <0.001
176
Z. Emkanjoo et al. / International Journal of Cardiology 117 (2007) 173–177
9. Kinetics The peak value of cTnI (1.8 ± 2.18) was documented 6 h after procedure ( p < 0.001). Similarly, the peak levels of CKMB and myoglobin (21.80 ± 16 and 53.88 ± 56) were measured at 6 h sampling ( p = 0.002, p < 0.001, respectively). The peak level of CK was 214.85 ± 35, measured at 24 h sampling ( p < 0.001). 10. Discussion This study confirms previous studies that cTnI is the more accurate marker for the assessment of myocardial injury post-RF ablation. Manolis et al. [8] reported 68% elevated cTnI values in the largest group of patients undergoing RF ablation and monitoring of cardiac serum markers. The reported percentage of pathological values for cTnI varies between 58.3% found by Jiang et al. [13], 84% published by Macaluso et al. [14], 92% found by Madrid et al. [7] and 92% found by Del Rey et al. [15,16]. In all of these studies, the sensitivity of cTnI is far greater than that of the other cardiac serum markers. In our study, the peak level of cTnI was 1.8 ± 2.18 ng/ml and found 6 h after RF ablation. It is noted that the peak level of cTnI in our series was small, lower than those found in other published studies [4,7,8,15]. Our study also demonstrated that RF ablation creates a small lesion with low release of several serum cardiac markers. In our series, 63 (54.8%) out of 115 demonstrated elevation of cTnI. Manolis et al. [8] reported 27% elevated CKMB values. This was in accordance with the present study. Myoglobin after RF ablation has been studied only by Madrid et al. [7]. They found that the sensitivity for myoglobin was 67%, which is significantly higher compared to our findings. Manolis at al. [8] investigated procedural correlates and found a correlation between cTnI levels and the number of RF applications and the site of RF ablation (ventricular myocardium > atrial myocardium > AV annuli). A correlation between cTnI levels and the number of RF applications and the total time of RF applications also reported by Madrid et al. [7]. In our study, the best correlation was found between the peak and mean levels of myoglobin and the number of RF applications, duration of RF ablation and total energy. We also found a good correlation between the peak and mean levels of cTnI and duration of RF ablation and total energy but there was no correlation between the peak and mean levels of cTnI and number of RF applications. The lack of correlation may be explained by the fact that some of the RF applications resulted in ineffective lesion formation either due to instability of the catheter or interruption of RF energy prematurely (< 15 s) when it was unsuccessful. Madrid et al. [8] showed a correlation between the degree of myocardial injury incurred during RF ablation as reflected
by cTnI levels and the site of ablation. Lesions created in the ventricular myocardium, albeit numerically fewer, entailed more extensive myocardial injury compared with RF application in the atrial myocardium or in the annuli. In our study, there was a significant correlation between the levels of cTnI, CK and CK-MB and the site of RF applications. The concentration of cTnI was higher for RF ablation of slow pathway and ventricular tachycardia. This is in contrast with the findings of Del Rey et al. [16] that showed the lowest release of cTnI in the AV node reentrant tachycardia. Mean levels of cTnI also correlated with RF application in the left AV annulus. Another significant correlation detected between the mean levels of CK-MB and left AV annulus. There was also a significant correlation of CK levels and RF application in the left AV annulus. In our practice, the ablation site of for the left accessory pathways was usually in the ventricular endocardium, but in the cases of right-sided accessory pathways, the atrial aspect of the endocardium above the tricuspide annulus was targeted. The lesions applied to mitral annulus at the ventricular site produced more increase in cTnI levels. It is important to note that we used transaortic approach in all of our patients; thus, this result could also be dependent on the approach to the annulus. 11. Study limitations A control group who underwent electrophysiological study without RF ablation was not included in our study. Thus, we could not isolate the mechanical effect of the manipulating catheter. 12. Conclusion Our results indicate that radiofrequency ablation results in only minor injury. cTnI exhibited a small but distinct increase and demonstrated more sensitivity for detection of RF current induced myocardial injury compared to CKMB, CK and myoglobin. RF current seems to be safe and this has been attributed to the small and homogenous lesions. Lesions applied to the mitral annulus at the ventricular endocardium, using transaortic approach, are associated with significantly greater myocardial damage. References [1] Morady F. Radiofrequency ablation as treatment for cardiac arrhythmia. N Engl J Med 1999;340:534–44. [2] Ravkilde J, Nissen H, Horder M, Thygesen K. Independent prognostic value of serum creatine kinase isoenzyme MB mass, cardiac troponin T and myosin light chain levels in suspected acute MI. J Am Coll Cardiol 1995;25:574–81. [3] Haines DE, Whayne JG, Waker J, Nath S, Bruns D. The effect of radiofrequency catheter ablation on myocardial creatine kinase activity. J Cardiovasc Electrophysiol 1995;6:79–88. [4] Shyu KG, Lin JL, Chen JJ, Chang H. Use of cardiac troponin T, creatine kinase and its isoforms to monitor myocardial injury during
Z. Emkanjoo et al. / International Journal of Cardiology 117 (2007) 173–177
[5]
[6]
[7]
[8]
[9]
radiofrequency ablation for supraventricular tachycardia. Cardiology 1996;87(5):392–5. Katritsis DG, Hossein-Nia M, Anastasakis A, et al. Use of troponin T concentrations and kinase isoforms for quantification of myocardial injury induced by radiofrequency catheter ablation. Eur Heart J 1997;18:1007–13. Katritsis DG, Hossein-Nia M, Anastasakis A, et al. Myocardial injury induced by radiofrequency and low energy ablation: a quantitative study of CK isoforms, CKMB and troponin-T concentration. PACE 1998;21(7):1410–6. Madrid AH, Del Rey JM, Rubi J, et al. Biochemical markers and cardiac troponin I release after radiofrequency catheter ablation; approach to size of necrosis. Am Heart J 1998;136:948–55. Manolis AS, Vassilikos V, Maounis T, et al. Detection of myocardial injury during radiofrequency catheter ablation by measuring serum cardiac troponin I levels: procedural correlates. J Am Coll Cardiol 1999;34:1099–105. Rao SP, Miller S, Rosenbaume R, Lakier JB. Cardiac troponin I and cardiac enzymes after electrophysiologic studies, ablation and defibrillator implantations. Am J Cardiol 1999;84:470.
177
[10] Hamm CW, Goldmann BU, Heeschen C, Kreymann G, Berger J, Meinertz T. Emergency room triage of patients with acute chest pain by means of rapid testing for cardiac troponin T or troponin I. N Engl J Med 1997;337:1648–53. [11] Adams III JE, Bodor GS, Davila-Roman VG, et al. Cardiac troponin I: a marker with high specificity for cardiac injury. Circulation 1993;88:101–6. [12] Brown CS, Bertolet BD. Cardiac troponin: see ya later CK! Chest 1997;111:2–4. [13] Jiang J, Wang JA, Chen XY, Lu D. Radiofrequency catheter ablation autonomic nerve injury. Zhejiang Da Xue Xue Bao Yi Xue Ban jun 2002;31(3):195–8 [Abstract]. [14] Macaluso G, Comet B, Bouvier JL, et al. Biochemical markers of myocardial damage after high-energy radiofrequency ablation of atrial flutter. Arch Mal Coeur Vaiss feb 2002;95(2):102–8. [15] Del Rey JM, Madrid AH, Novo L, Sanchez A, Martin J, Rubi J. Evaluation of biochemical markers of myocardial lesion after radiofrequncy ablation. Value of troponin I. Rev Esp Cardiol aug 1997;50(8):552–60. [16] Del Rey JM, Madrid AH, Valino JM, et al. Cardiac troponin I and minor cardiac damage: biochemical markers in a clinical model of myocardial lesions. Clin Chem 1998;44(11):2270–6.