- Email: [email protected]
Effect of radiofrequency catheter ablation on the biochemical marker ischemia modified albumin
Effect of Radiofrequency Catheter Ablation on the Biochemical Marker Ischemia Modified Albumin Debashis Roy, MRCP, Juan Quiles, MD, Manas Sinha, MRCP, Dimitrios Floros, MD, David Gaze, BSc, Paul Collinson, Gary F. Baxter, PhD, and Juan Carlos Kaski, MD, DSc Ischemia-modified albumin (IMA) levels were measured after radiofrequency (RF) catheter ablation to evaluate the effect of direct myocardial necrosis on IMA formation. IMA levels have been shown to increase in patients after RF catheter ablation compared with those who undergo diagnostic electrophysiologic studies. The results of this study suggest that IMA may be a marker of myocardial injury. 䊚2004 by Excerpta Medica, Inc. (Am J Cardiol 2004;94:234–236)
albumin (IMA) is a new marker of transient myocardial ischemia. We and othIersschemia-modified have recently shown that IMA levels are elevated 1,2
3–5
6
after percutaneous coronary intervention (PCI) as a result of ischemia-reperfusion injury. IMA levels have been also shown to correlate with the magnitude and duration of PCI-induced myocardial ischemia.3 In the clinical setting, IMA has been shown to be a sensitive marker of cardiac ischemia in patients presenting with suspected acute coronary syndrome.1,7–9 The biochemical mechanism by which serum albumin is modified by ischemia, resulting in the formation of IMA, is unclear. It is speculated that oxidative processes associated with ischemia-reperfusion and organ injury may lead to N-terminus modification that results in a reduced binding capacity for cobalt cations.10 Radiofrequency (RF) catheter ablation is a widely used treatment for cardiac arrhythmias but results in a detectable injury to the myocardium, which is unrelated to ischemia-reperfusion injury per se.11 The present study sought to evaluate the effects of RF catheter ablation on serum levels of IMA. •••
We assessed 24 consecutive patients (16 men; mean age 54 years, range 30 to 74) who underwent RF catheter ablation for arrhythmias and 8 control patients (4 men; mean age 55 years, range 44 to 74) who underwent diagnostic electrophysiologic studies but no ablation procedures from April to November 2003. The study was approved by the local research ethics committee, and all patients gave written informed consent. Patients were excluded if they had experienced myocardial infarctions or unstable angina or if they had undergone coronary artery bypass surgery or coronary angioplasty in the 6 months before the study and if they had symptomatic peripheral vascular disFrom Cardiological Sciences and Chemical Pathology, St. George’s Hospital Medical School; and the Department of Basic Sciences, The Royal Veterinary College, London, United Kingdom. Dr. Kaski’s address is: Cardiological Sciences, St. George’s Hospital Medical School, Cranmer Terrace, London SW17 0RE, United Kingdom. Email: [email protected]. Manuscript received February 2, 2004; revised manuscript received and accepted March 25, 2004.
234
©2004 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 94 July 15, 2004
ease, renal failure, or a history of cerebrovascular disease. In the 2 groups of patients, the electrophysiologic study was performed with the patients in a nonsedated fasting state, using conventional techniques of intracardiac recording and pacing. Three sheaths (6Fr, 7Fr, and 8Fr) were inserted into the right femoral vein. Depending on the substrate for ablation, 2 to 4 multipolar catheters were introduced from the femoral vein. A femoral artery catheter was introduced for left accessory pathways. RF catheter ablation was performed in a unipolar, temperature-guided mode using either a 4-or 8-mm tip ablation electrode. Peripheral venous blood samples were obtained, and serum was used for the measurement of cardiac troponin T, creatine kinase, and IMA at baseline, 30 minutes, and 8 to 10 hours after ablation and the electrophysiologic study. IMA samples were frozen at ⫺70°C ⱕ2 hours after the procedure and stored until measurement. Serum IMA was measured by the albumin cobalt binding test on a Roche Cobas MIRA PLUS instrument (ABX Ltd., London, United Kingdom). The albumin cobalt binding test method has been validated and described in previous studies.8 The total interassay coefficient of variation was 4.9% to 7.5% at 72.54 to 140.16 U/ml for quality control material. For human serum pools, the total coefficient of variation was 5.3% to 8.8% at 95.07 to 97.35 U/ml, respectively. Cardiac troponin T was measured by electrochemiluminescence with an Elecsys 1010 analyzer (Roche Diagnostics, Lewes, West Sussex, United Kingdom, and levels ⬎0.05 g/L were considered to represent a positive result. Creatine kinase was measured on the Synchron LX 20 system (Beckman-Coulter, High Wycombe, United Kingdom) using the N-acetyl-Lcysteine method. The reference range was 30 to 210 U/L for creatine kinase. A 12-lead electrocardiogram was recorded before and after the procedure in every patient. Electrocardiographic changes were also recorded when new persistent ST-segment depression or elevation ⱖ0.2 mV or new T-wave inversion developed in ⱖ2 contiguous leads during RF ablation or the electrophysiologic study, as assessed by continuous electrocardiographic monitoring. The results for normally distributed continuous variables are expressed as the mean values ⫾ SD, and continuous variables with non-normal distribution are presented as the median values (interquartile interval). Continuous variables were tested for normal distribution with the Kolmogorov-Smirnov goodness-of-fit 0002-9149/04/$–see front matter doi:10.1016/j.amjcard.2004.03.073
FIGURE 1. Comparison of IMA, creatine kinase (CPK), and troponin T (TnT) levels in patients after ablation and the electrophysiologic study. *p <0.05 compared with baseline.
test for normality. IMA values were normally distributed. We used Pearson’s or Spearman’s test as appropriate to explore correlations between study variables and the duration of the ablation procedure. We used a repeated-measures analysis of variance test to assess IMA, creatine kinase, and cardiac troponin T values at every different time point and to adjust for the duration of the procedures. Statistical analyses were conducted with a commercially available software package (SPSS version 11, SPSS, Inc., Chicago, Illinois), and p values ⬍0.05 were considered statistically significant. In the control group, the electrophysiologic study was carried out to induce atrial flutter in 5 patients, ventricular tachycardia in 2 patients, and supraventricular tachycardia in 1 patient. Arrhythmias were induced in all patients during the procedure, except 1 patient with a diagnosis of supraventricular tachycardia. With respect to the ablation target, 9 patients had atrial fibrillation (37.5%), 7 had atrial flutter (29.2%), 5 had supraventricular tachycardia (20.8%; nodal reentry), 2 had ventricular tachycardia (8.3%), and 1 had an accessory pathway (4.2%). The mean procedure duration was 463 ⫾ 124 minutes, and mean screening time was 25 ⫾ 14 minutes. No patients had ischemic ST-T electrocardiographic changes during or after the procedure. Mean IMA levels were higher 30 minutes after ablation (96 ⫾ 18 U/ml compared with 81 ⫾ 13 U/ml at baseline, p ⫽ 0.01) and returned to preablation levels at 8 hours (81⫾ 15, p ⫽ 0.5, compared with baseline; Figure 1). There were no significant differences in IMA levels among patients with the different arrhythmias being studied (Figure 2). IMA levels were related to total screening time (r ⫽ 0.55, p ⫽ 0.005; Figure 3). Levels of creatine kinase and cardiac troponin T were elevated 30 minutes after ablation and remained significantly elevated at 8 hours (Table 1 and Figure 1). In the control group, there was no significant difference between mean IMA values (77
FIGURE 2. Comparison of IMA levels in patients who underwent ablation for different arrhythmias. Data are adjusted for the duration of the procedures. *p <0.05 compared with baseline; atrial flutter p ⴝ 0.1 and nodal reentry tachycardia p ⴝ 0.07.
FIGURE 3. The relation between IMA levels and screening time.
⫾ 16 U/ml before the electrophysiologic study compared with 77 ⫾ 16 U/ml 30 minutes afterward). Levels of creatine kinase and cardiac troponin T also remained unchanged from baseline values in control patients. •••
This study showed for the first time that IMA levels increase in patients after RF catheter ablation. It may be suggested that IMA was increased after ablation as a consequence of cardiac muscle damage as IMA elevation followed those of creatine kinase and troponin T. It has been suggested that increases in IMA could be attributed to oxidative processes related to organ injury,10 and our study using RF ablation appears to substantiate this. Levels of cardiac troponin T were elevated 30 minutes after the ablation procedure, which agrees with previous studies.11–13 Thus, ablation causes rapid focal myocardial necrosis, which is different from the gradual development of myocardial necrosis that occurs in ischemia-reperfusion injury.11 Thermal injury of myocardial cells occurs during RF catheter ablation and leads to a rapid release of BRIEF REPORTS
235
TABLE 1 Comparison of Biochemical Markers Depending on the Performance of an Ablation Procedure Electrophysiologic Testing (n ⫽ 8) Age (yrs) Men Study time (min) Screening time (mins) IMA (U/ml) Baseline 30 min 8 hours Cardiac troponin T (g/L) Baseline 30 min 8h Creatine kinase (U/L) Baseline 30 min 8h
Ablation Procedure (n ⫽ 24)
55 ⫾ 9 4 (50%) 36 ⫾ 10 0
54 16 97 25
⫾ 14 (67%) ⫾ 31 ⫾ 14
77 ⫾ 16 77 ⫾ 16 78 ⫾ 14
81 ⫾ 96 ⫾ 81 ⫾
0.009 ⫾ 0.003 0.01 ⫾ 0.000 0.01 ⫾ 0.000
0.01 ⫾ 0.27 ⫾ 0.49 ⫾
69 ⫾ 24 67 ⫾ 21 71 ⫾ 26
84 ⫾ 92 ⫾ 117 ⫾
Data are expressed as means ⫾ SDs.
electrolytes and free radicals from intracellular sites.14 Elevated levels of IMA in the absence of myocardial necrosis have also been observed after direct-current cardioversion, and it has been speculated that this may be a consequence of cardiac or skeletal muscle ischemia.15 It is believed that the underlying biochemical mechanism of IMA formation is damage to the Nterminus of albumin by reactive oxygen species, acidosis, membrane energy-dependent sodium, and calcium pump disruptions, resulting in a reduced metalbinding capacity of albumin.1 The results of our study are intriguing because despite the lack of evidence of ischemia in our patients, the transient elevation of IMA was observed, suggesting reduced cobalt binding secondary to direct myocardial injury. It can be speculated that the underlying mechanism is damage to the N-terminus by reactive oxygen species or disruption at the cellular level. IMA levels were also correlated with the total screening time. It is possible that patients with longer screening times underwent more complex procedures requiring greater numbers of RF applications and resulting in more oxidative stress and therefore higher IMA levels. Interestingly, the kinetics of IMA showed a similar pattern to that previously observed in the PCI model. IMA is a consistent marker of ischemia in patients who develop myocardial ischemia during PCI.4 PCI offers a clinical model of ischemia-reperfusion characterized by an increase in oxidative stress.16 Although as a model system, PCI is different from RF catheter ablation, the present findings suggest that the
236 THE AMERICAN JOURNAL OF CARDIOLOGY姞
p Value 0.8 0.4 ⬍0.0001 ⬍0.0001
underlying mechanism resulting in IMA production may be similar and involve albumin modification by reactive oxygen species.
1. Bar-Or D, Lau E, Winkler JV. A novel assay for cobalt-albumin binding and its potential as a marker for myocardial ischemia—a preliminary report. J Emerg Med 2000;19:311–315. 2. Bhagavan NV, Lai EM, Rios PA, Yang J, Ortega13 0.5 Lopez AM, Shinoda H, Honda SA, Rios CN, Sugiyama 18 0.01 CE, Ha CE. Evaluation of human serum albumin cobalt 15 0.5 binding assay for the assessment of myocardial ischemia and myocardial infarction. Clin Chem 2003;49: 581–585. 0.0 0.6 3. Quiles J, Roy D, Gaze D, Garrido IP, Avanzas P, 0.2 ⬍0.0001 Sinha M, Kaski JC. Relation of ischemia-modified al0.3 ⬍0.0001 bumin (IMA) levels following elective angioplasty for stable angina pectoris to duration of balloon-induced 32 0.2 myocardial ischemia. Am J Cardiol 2003;92:322–324. 25 0.02 4. Sinha MK, Gaze DC, Tippins JR, Collinson PO, 25 ⬍0.0001 Kaski JC. Ischemia modified albumin is a sensitive marker of myocardial ischemia after percutaneous coronary intervention. Circulation 2003;107:2403–2405. 5. Garrido IP, Roy D, Calvino R, Vazquez-Rodriguez JM, Aldama G, Cosin-Sales J, Quiles J, Gaze DC, Kaski JC. Comparison of ischemia-modified albumin levels in patients undergoing percutaneous coronary intervention for unstable angina pectoris with versus without coronary collaterals. Am J Cardiol 2004;93: 88 –90. 6. Bar-Or D, Winkler JV, Vanbenthuysen K, Harris L, Lau E, Hetzel FW. Reduced albumin-cobalt binding with transient myocardial ischemia after elective percutaneous transluminal coronary angioplasty: a preliminary comparison to creatine kinase-MB, myoglobin, and troponin I. Am Heart J 2001;141:985–991. 7. Christenson RH, Duh SH, Sanhai WR, Wu AH, Holtman V, Painter P, Branham E, Apple FS, Murakami M, Morris DL. Characteristics of an albumin cobalt binding test for assessment of acute coronary syndrome patients: a multicenter study. Clin Chem 2001;47:464 –470. 8. Wu AH, Morris DL, Fletcher DR, Apple FS, Christenson RH, Painter PC. Analysis of the albumin cobalt binding (ACB) test as an adjunct to cardiac troponin I for the early detection of acute myocardial infarction. Cardiovasc Toxicol 2001;1:147–151. 9. Sinha MK, Roy D, Collinson PO, Kaski JC. Role of “ischemia modified albumin”, a new biochemical marker of myocardial ischaemia, in the early diagnosis of acute coronary syndromes. Emerg Med J 2004;21:29 –34. 10. Morrow DA, de Lemos JA, Sabatine MS, Antman EM. The search for a biomarker of cardiac ischemia. Clin Chem 2003;49:537–539. 11. del Rey JM, Madrid AH, Valino JM, Rubi J, Mercader J, Moro C, Ripoll E. Cardiac troponin I and minor cardiac damage: biochemical markers in a clinical model of myocardial lesions. Clin Chem 1998;44:2270 –2276. 12. Madrid AH, del Rey JM, Rubi J, Ortega J, Gonzalez Rebollo JM, Seara JG, Ripoll E, Moro C. Biochemical markers and cardiac troponin I release after radiofrequency catheter ablation: approach to size of necrosis. Am Heart J 1998;136:948 –955. 13. Katritsis D, Hossein-Nia M, Anastasakis A, Poloniecki I, Holt DW, Camm AJ, Ward DE, Rowland E. Use of troponin-T concentration and kinase isoforms for quantitation of myocardial injury induced by radiofrequency catheter ablation. Eur Heart J 1997;18:1007–1013. 14. Erdogan A, Carlsson J, Grumbrecht S, Kostin S, Schulte B, Schlapp M, Neuzner J, Pitschner HF. Electrochemical potentials during radiofrequency energy delivery: a new method to control catheter ablation of arrhythmias. Europace 2001;3:201–207. 15. Roy D, Quiles J, Sinha M, Aldama G, Gaze D, Kaski JC. Effect of direct current cardioversion on ischemia modified albumin levels in patients with atrial fibrillation. Am J Cardiol 2004;93:366 –368. 16. Iuliano L, Pratico D, Greco C, Mangieri E, Scibilia G, FitzGerald GA, Violi F. Angioplasty increases coronary sinus F2-isoprostane formation: evidence for in vivo oxidative stress during PTCA. J Am Coll Cardiol 2001;37:76 –80.
VOL. 94
JULY 15, 2004
albumin (IMA) is a new marker of transient myocardial ischemia. We and othIersschemia-modified have recently shown that IMA levels are elevated 1,2
3–5
6
after percutaneous coronary intervention (PCI) as a result of ischemia-reperfusion injury. IMA levels have been also shown to correlate with the magnitude and duration of PCI-induced myocardial ischemia.3 In the clinical setting, IMA has been shown to be a sensitive marker of cardiac ischemia in patients presenting with suspected acute coronary syndrome.1,7–9 The biochemical mechanism by which serum albumin is modified by ischemia, resulting in the formation of IMA, is unclear. It is speculated that oxidative processes associated with ischemia-reperfusion and organ injury may lead to N-terminus modification that results in a reduced binding capacity for cobalt cations.10 Radiofrequency (RF) catheter ablation is a widely used treatment for cardiac arrhythmias but results in a detectable injury to the myocardium, which is unrelated to ischemia-reperfusion injury per se.11 The present study sought to evaluate the effects of RF catheter ablation on serum levels of IMA. •••
We assessed 24 consecutive patients (16 men; mean age 54 years, range 30 to 74) who underwent RF catheter ablation for arrhythmias and 8 control patients (4 men; mean age 55 years, range 44 to 74) who underwent diagnostic electrophysiologic studies but no ablation procedures from April to November 2003. The study was approved by the local research ethics committee, and all patients gave written informed consent. Patients were excluded if they had experienced myocardial infarctions or unstable angina or if they had undergone coronary artery bypass surgery or coronary angioplasty in the 6 months before the study and if they had symptomatic peripheral vascular disFrom Cardiological Sciences and Chemical Pathology, St. George’s Hospital Medical School; and the Department of Basic Sciences, The Royal Veterinary College, London, United Kingdom. Dr. Kaski’s address is: Cardiological Sciences, St. George’s Hospital Medical School, Cranmer Terrace, London SW17 0RE, United Kingdom. Email: [email protected]. Manuscript received February 2, 2004; revised manuscript received and accepted March 25, 2004.
234
©2004 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 94 July 15, 2004
ease, renal failure, or a history of cerebrovascular disease. In the 2 groups of patients, the electrophysiologic study was performed with the patients in a nonsedated fasting state, using conventional techniques of intracardiac recording and pacing. Three sheaths (6Fr, 7Fr, and 8Fr) were inserted into the right femoral vein. Depending on the substrate for ablation, 2 to 4 multipolar catheters were introduced from the femoral vein. A femoral artery catheter was introduced for left accessory pathways. RF catheter ablation was performed in a unipolar, temperature-guided mode using either a 4-or 8-mm tip ablation electrode. Peripheral venous blood samples were obtained, and serum was used for the measurement of cardiac troponin T, creatine kinase, and IMA at baseline, 30 minutes, and 8 to 10 hours after ablation and the electrophysiologic study. IMA samples were frozen at ⫺70°C ⱕ2 hours after the procedure and stored until measurement. Serum IMA was measured by the albumin cobalt binding test on a Roche Cobas MIRA PLUS instrument (ABX Ltd., London, United Kingdom). The albumin cobalt binding test method has been validated and described in previous studies.8 The total interassay coefficient of variation was 4.9% to 7.5% at 72.54 to 140.16 U/ml for quality control material. For human serum pools, the total coefficient of variation was 5.3% to 8.8% at 95.07 to 97.35 U/ml, respectively. Cardiac troponin T was measured by electrochemiluminescence with an Elecsys 1010 analyzer (Roche Diagnostics, Lewes, West Sussex, United Kingdom, and levels ⬎0.05 g/L were considered to represent a positive result. Creatine kinase was measured on the Synchron LX 20 system (Beckman-Coulter, High Wycombe, United Kingdom) using the N-acetyl-Lcysteine method. The reference range was 30 to 210 U/L for creatine kinase. A 12-lead electrocardiogram was recorded before and after the procedure in every patient. Electrocardiographic changes were also recorded when new persistent ST-segment depression or elevation ⱖ0.2 mV or new T-wave inversion developed in ⱖ2 contiguous leads during RF ablation or the electrophysiologic study, as assessed by continuous electrocardiographic monitoring. The results for normally distributed continuous variables are expressed as the mean values ⫾ SD, and continuous variables with non-normal distribution are presented as the median values (interquartile interval). Continuous variables were tested for normal distribution with the Kolmogorov-Smirnov goodness-of-fit 0002-9149/04/$–see front matter doi:10.1016/j.amjcard.2004.03.073
FIGURE 1. Comparison of IMA, creatine kinase (CPK), and troponin T (TnT) levels in patients after ablation and the electrophysiologic study. *p <0.05 compared with baseline.
test for normality. IMA values were normally distributed. We used Pearson’s or Spearman’s test as appropriate to explore correlations between study variables and the duration of the ablation procedure. We used a repeated-measures analysis of variance test to assess IMA, creatine kinase, and cardiac troponin T values at every different time point and to adjust for the duration of the procedures. Statistical analyses were conducted with a commercially available software package (SPSS version 11, SPSS, Inc., Chicago, Illinois), and p values ⬍0.05 were considered statistically significant. In the control group, the electrophysiologic study was carried out to induce atrial flutter in 5 patients, ventricular tachycardia in 2 patients, and supraventricular tachycardia in 1 patient. Arrhythmias were induced in all patients during the procedure, except 1 patient with a diagnosis of supraventricular tachycardia. With respect to the ablation target, 9 patients had atrial fibrillation (37.5%), 7 had atrial flutter (29.2%), 5 had supraventricular tachycardia (20.8%; nodal reentry), 2 had ventricular tachycardia (8.3%), and 1 had an accessory pathway (4.2%). The mean procedure duration was 463 ⫾ 124 minutes, and mean screening time was 25 ⫾ 14 minutes. No patients had ischemic ST-T electrocardiographic changes during or after the procedure. Mean IMA levels were higher 30 minutes after ablation (96 ⫾ 18 U/ml compared with 81 ⫾ 13 U/ml at baseline, p ⫽ 0.01) and returned to preablation levels at 8 hours (81⫾ 15, p ⫽ 0.5, compared with baseline; Figure 1). There were no significant differences in IMA levels among patients with the different arrhythmias being studied (Figure 2). IMA levels were related to total screening time (r ⫽ 0.55, p ⫽ 0.005; Figure 3). Levels of creatine kinase and cardiac troponin T were elevated 30 minutes after ablation and remained significantly elevated at 8 hours (Table 1 and Figure 1). In the control group, there was no significant difference between mean IMA values (77
FIGURE 2. Comparison of IMA levels in patients who underwent ablation for different arrhythmias. Data are adjusted for the duration of the procedures. *p <0.05 compared with baseline; atrial flutter p ⴝ 0.1 and nodal reentry tachycardia p ⴝ 0.07.
FIGURE 3. The relation between IMA levels and screening time.
⫾ 16 U/ml before the electrophysiologic study compared with 77 ⫾ 16 U/ml 30 minutes afterward). Levels of creatine kinase and cardiac troponin T also remained unchanged from baseline values in control patients. •••
This study showed for the first time that IMA levels increase in patients after RF catheter ablation. It may be suggested that IMA was increased after ablation as a consequence of cardiac muscle damage as IMA elevation followed those of creatine kinase and troponin T. It has been suggested that increases in IMA could be attributed to oxidative processes related to organ injury,10 and our study using RF ablation appears to substantiate this. Levels of cardiac troponin T were elevated 30 minutes after the ablation procedure, which agrees with previous studies.11–13 Thus, ablation causes rapid focal myocardial necrosis, which is different from the gradual development of myocardial necrosis that occurs in ischemia-reperfusion injury.11 Thermal injury of myocardial cells occurs during RF catheter ablation and leads to a rapid release of BRIEF REPORTS
235
TABLE 1 Comparison of Biochemical Markers Depending on the Performance of an Ablation Procedure Electrophysiologic Testing (n ⫽ 8) Age (yrs) Men Study time (min) Screening time (mins) IMA (U/ml) Baseline 30 min 8 hours Cardiac troponin T (g/L) Baseline 30 min 8h Creatine kinase (U/L) Baseline 30 min 8h
Ablation Procedure (n ⫽ 24)
55 ⫾ 9 4 (50%) 36 ⫾ 10 0
54 16 97 25
⫾ 14 (67%) ⫾ 31 ⫾ 14
77 ⫾ 16 77 ⫾ 16 78 ⫾ 14
81 ⫾ 96 ⫾ 81 ⫾
0.009 ⫾ 0.003 0.01 ⫾ 0.000 0.01 ⫾ 0.000
0.01 ⫾ 0.27 ⫾ 0.49 ⫾
69 ⫾ 24 67 ⫾ 21 71 ⫾ 26
84 ⫾ 92 ⫾ 117 ⫾
Data are expressed as means ⫾ SDs.
electrolytes and free radicals from intracellular sites.14 Elevated levels of IMA in the absence of myocardial necrosis have also been observed after direct-current cardioversion, and it has been speculated that this may be a consequence of cardiac or skeletal muscle ischemia.15 It is believed that the underlying biochemical mechanism of IMA formation is damage to the Nterminus of albumin by reactive oxygen species, acidosis, membrane energy-dependent sodium, and calcium pump disruptions, resulting in a reduced metalbinding capacity of albumin.1 The results of our study are intriguing because despite the lack of evidence of ischemia in our patients, the transient elevation of IMA was observed, suggesting reduced cobalt binding secondary to direct myocardial injury. It can be speculated that the underlying mechanism is damage to the N-terminus by reactive oxygen species or disruption at the cellular level. IMA levels were also correlated with the total screening time. It is possible that patients with longer screening times underwent more complex procedures requiring greater numbers of RF applications and resulting in more oxidative stress and therefore higher IMA levels. Interestingly, the kinetics of IMA showed a similar pattern to that previously observed in the PCI model. IMA is a consistent marker of ischemia in patients who develop myocardial ischemia during PCI.4 PCI offers a clinical model of ischemia-reperfusion characterized by an increase in oxidative stress.16 Although as a model system, PCI is different from RF catheter ablation, the present findings suggest that the
236 THE AMERICAN JOURNAL OF CARDIOLOGY姞
p Value 0.8 0.4 ⬍0.0001 ⬍0.0001
underlying mechanism resulting in IMA production may be similar and involve albumin modification by reactive oxygen species.
1. Bar-Or D, Lau E, Winkler JV. A novel assay for cobalt-albumin binding and its potential as a marker for myocardial ischemia—a preliminary report. J Emerg Med 2000;19:311–315. 2. Bhagavan NV, Lai EM, Rios PA, Yang J, Ortega13 0.5 Lopez AM, Shinoda H, Honda SA, Rios CN, Sugiyama 18 0.01 CE, Ha CE. Evaluation of human serum albumin cobalt 15 0.5 binding assay for the assessment of myocardial ischemia and myocardial infarction. Clin Chem 2003;49: 581–585. 0.0 0.6 3. Quiles J, Roy D, Gaze D, Garrido IP, Avanzas P, 0.2 ⬍0.0001 Sinha M, Kaski JC. Relation of ischemia-modified al0.3 ⬍0.0001 bumin (IMA) levels following elective angioplasty for stable angina pectoris to duration of balloon-induced 32 0.2 myocardial ischemia. Am J Cardiol 2003;92:322–324. 25 0.02 4. Sinha MK, Gaze DC, Tippins JR, Collinson PO, 25 ⬍0.0001 Kaski JC. Ischemia modified albumin is a sensitive marker of myocardial ischemia after percutaneous coronary intervention. Circulation 2003;107:2403–2405. 5. Garrido IP, Roy D, Calvino R, Vazquez-Rodriguez JM, Aldama G, Cosin-Sales J, Quiles J, Gaze DC, Kaski JC. Comparison of ischemia-modified albumin levels in patients undergoing percutaneous coronary intervention for unstable angina pectoris with versus without coronary collaterals. Am J Cardiol 2004;93: 88 –90. 6. Bar-Or D, Winkler JV, Vanbenthuysen K, Harris L, Lau E, Hetzel FW. Reduced albumin-cobalt binding with transient myocardial ischemia after elective percutaneous transluminal coronary angioplasty: a preliminary comparison to creatine kinase-MB, myoglobin, and troponin I. Am Heart J 2001;141:985–991. 7. Christenson RH, Duh SH, Sanhai WR, Wu AH, Holtman V, Painter P, Branham E, Apple FS, Murakami M, Morris DL. Characteristics of an albumin cobalt binding test for assessment of acute coronary syndrome patients: a multicenter study. Clin Chem 2001;47:464 –470. 8. Wu AH, Morris DL, Fletcher DR, Apple FS, Christenson RH, Painter PC. Analysis of the albumin cobalt binding (ACB) test as an adjunct to cardiac troponin I for the early detection of acute myocardial infarction. Cardiovasc Toxicol 2001;1:147–151. 9. Sinha MK, Roy D, Collinson PO, Kaski JC. Role of “ischemia modified albumin”, a new biochemical marker of myocardial ischaemia, in the early diagnosis of acute coronary syndromes. Emerg Med J 2004;21:29 –34. 10. Morrow DA, de Lemos JA, Sabatine MS, Antman EM. The search for a biomarker of cardiac ischemia. Clin Chem 2003;49:537–539. 11. del Rey JM, Madrid AH, Valino JM, Rubi J, Mercader J, Moro C, Ripoll E. Cardiac troponin I and minor cardiac damage: biochemical markers in a clinical model of myocardial lesions. Clin Chem 1998;44:2270 –2276. 12. Madrid AH, del Rey JM, Rubi J, Ortega J, Gonzalez Rebollo JM, Seara JG, Ripoll E, Moro C. Biochemical markers and cardiac troponin I release after radiofrequency catheter ablation: approach to size of necrosis. Am Heart J 1998;136:948 –955. 13. Katritsis D, Hossein-Nia M, Anastasakis A, Poloniecki I, Holt DW, Camm AJ, Ward DE, Rowland E. Use of troponin-T concentration and kinase isoforms for quantitation of myocardial injury induced by radiofrequency catheter ablation. Eur Heart J 1997;18:1007–1013. 14. Erdogan A, Carlsson J, Grumbrecht S, Kostin S, Schulte B, Schlapp M, Neuzner J, Pitschner HF. Electrochemical potentials during radiofrequency energy delivery: a new method to control catheter ablation of arrhythmias. Europace 2001;3:201–207. 15. Roy D, Quiles J, Sinha M, Aldama G, Gaze D, Kaski JC. Effect of direct current cardioversion on ischemia modified albumin levels in patients with atrial fibrillation. Am J Cardiol 2004;93:366 –368. 16. Iuliano L, Pratico D, Greco C, Mangieri E, Scibilia G, FitzGerald GA, Violi F. Angioplasty increases coronary sinus F2-isoprostane formation: evidence for in vivo oxidative stress during PTCA. J Am Coll Cardiol 2001;37:76 –80.
VOL. 94
JULY 15, 2004