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Troponin elevation after radiofrequency catheter ablation of atrial fibrillation: Relevance to AF substrate, procedural outcomes, and reverse structural remodeling Kentaro Yoshida, MD,* Yoshiaki Yui, MD,† Akira Kimata, MD,* Naoya Koda, MD,* Jo Kato, MD,* Masako Baba, MD,* Masako Misaki, MD,* Daisuke Abe, MD,* Chiho Tokunaga, MD,* Shinji Akishima, MD,* Yukio Sekiguchi, MD,† Hiroshi Tada, MD,‡ Kazutaka Aonuma, MD,† Noriyuki Takeyasu, MD* From the *Division of Cardiovascular Medicine, Ibaraki Prefectural Central Hospital, Kasama, Japan, † Division of Cardiovascular Medicine, University of Tsukuba, Tsukuba, Japan, and ‡Division of Cardiovascular Medicine, University of Fukui, Yoshida-gun, Japan. BACKGROUND Although radiofrequency ablation creates myocardial necrosis leading to troponin T (TnT) release into the systemic circulation, the significance of TnT elevation after atrial fibrillation (AF) ablation is unknown. OBJECTIVE To demonstrate a possible mechanism of reverse structural remodeling in the left atrium (LA) by evaluating postprocedural TnT elevation. METHODS This study included 106 patients with an enlarged LA (paroxysmal AF, n ¼ 43; persistent AF, n ¼ 63). All patients underwent pulmonary vein isolation alone in the index procedure. Left atrial volume indexed to body surface area (LAVi) was measured by echocardiography before ablation and 6 months after sinus rhythm restoration. Patients were divided into responders (n ¼ 53) and nonresponders (n ¼ 53) based on a cutoff value of 23% reduction in LAVi. The TnT level was measured 12 hours postprocedure. RESULTS LAVi decreased from 43 ⫾ 13 to 33 ⫾ 12 mL/m2 (P o .0001). The TnT level was higher in responders than in nonresponders (1.31 ⫾ 0.34 μg/L vs 0.88 ⫾ 0.29 μg/L; P o .0001) and correlated linearly with percent reduction in LAVi (R ¼ .54;
Introduction Cardiac troponin T (TnT), an intracellular protein involved in the regulation of cardiac muscle contraction, was initially identified as a sensitive indicator of myocardial damage particularly associated with myocardial infarction. Recent advances in assay technology have led to a refinement in the clinical ability to quantify cardiomyocyte injury1 and in the prediction of mortality risk in the general population.2 An increase in the TnT level is also known to occur after various Address reprint requests and correspondence: Dr Kentaro Yoshida, Division of Cardiovascular Medicine, Ibaraki Prefectural Central Hospital, 6528 Koibuchi, Kasama, Ibaraki 309-1793, Japan. E-mail address: [email protected].
1547-5271/$-see front matter B 2014 Heart Rhythm Society. All rights reserved.
P o .0001). Also in multivariate analysis, the TnT level was the only independent predictor for responders (odds ratio 90.1; 95% confidence interval 14.95–543.3; P o .0001). The TnT level in patients who required a repeat procedure (n ¼ 30) was lower than that in patients who did not require a repeat procedure only in the persistent AF group (0.92 ⫾ 0.38 μg/L vs 1.16 ⫾ 0.37 μg/L; P ¼ .01). CONCLUSION Greater elevation of the TnT level was related both to favorable outcomes after ablation and to greater reversal of structural remodeling. Postprocedure, the TnT level may be reflective of the preservation of healthy LA myocardium. KEYWORDS Atrial fibrillation; Catheter remodeling; Structural remodeling; Troponin
ablation;
Reverse
ABBREVIATIONS AF ¼ atrial fibrillation; eGFR ¼ estimated glomerular filtration rate; LA ¼ left atrium/left atrial; LAVi ¼ left atrial volume indexed to body surface area; MRI ¼ magnetic resonance imaging; PV ¼ pulmonary vein; TnT ¼ troponin T (Heart Rhythm 2014;0:0–7) rights reserved.
I
2014 Heart Rhythm Society. All
types of cardiac electrophysiological procedures, such as cardioversion, device therapy, and catheter ablation.3–5 Although radiofrequency ablation energy creates localized lesions and myocardial necrosis leading to TnT release into the systemic circulation, the significance of an increase in the TnT level after ablation of atrial fibrillation (AF) remains undetermined. With regard to AF substrate, reversal of structural remodeling in the left atrium (LA) occurs to a different degree after restoration of sinus rhythm, which is in contrast to the uniform reversal of electrical remodeling.6–8 Reverse structural remodeling may more likely occur in patients who have a relatively healthy LA with less fibrosis.8,9 In this study, we focused on the increase in the TnT level in patients http://dx.doi.org/10.1016/j.hrthm.2014.04.015
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undergoing pulmonary vein (PV) isolation alone as a treatment of drug-resistant AF and hypothesized that greater postprocedural increase in the TnT level predicts greater reversal of structural remodeling because more TnT would be released by radiofrequency ablation in a healthy LA than in a “sick” LA, in which the myocardium had degenerated into fibrous tissue.
Methods Study participants The study participants comprised 106 consecutive patients with an enlarged LA volume of Z30 mL/m2 who underwent PV isolation alone at the index procedure.10 Forty-three patients had paroxysmal AF, and 63 patients had persistent AF. According to the HRS/EHRA/ECAS consensus statement,11 paroxysmal AF is defined as recurrent AF (Z2 episodes) that terminates spontaneously within 7 days and persistent AF is defined as recurrent AF that is sustained for Z7 days. Coronary artery disease was ruled out in all patients by coronary angiography performed in conjunction with the ablation procedure. Patients with structural heart disease or chronic kidney disease (estimated glomerular filtration rate [eGFR] o60 mL/min per 1.73 m2) were excluded from the study. Patients with atrial tachycardia or long-standing persistent AF (continuous AF of 41 year’s duration)11 were also excluded because additional ablation beyond PV isolation, such as linear ablation and continuous fractionated atrial electrogram ablation, is considered to enhance procedural efficacy for those atrial tachyarrhythmias.11 All antiarrhythmic drug therapies were discontinued 4–5 half-lives before the procedure except for amiodarone, which was discontinued 8 weeks beforehand. The study protocol was approved by the local institutional review board, and all patients provided their informed written consent.
Data acquisition Blood samples for the measurement of the TnT level were collected 1 day before the procedure and 12 hours after the completion of the procedure. The TnT level was measured with a Cobas e411 analyzer (Roche Diagnostics, XXXX, XX). The 99th percentile of a healthy reference population has been determined to be 0.014 μg/L. To evaluate the degree of LA reverse remodeling, transthoracic echocardiography (Vivid 7, GE Healthcare, Horten, Norway) was performed 1 day before the procedure and 6 months after the final ablation procedure by sonographers blinded to any electrophysiological and laboratory data. The LA volumes were measured by using the biplane method on apical 2- and 4-chamber views during end systole.12
Electrophysiology study and catheter ablation A 7-F 14-pole dual-site mapping catheter (Irvine Biomedical Inc, Irvine, CA) was positioned in the coronary sinus and the low lateral wall of the right atrium throughout the procedure. Two long sheaths (SL0, AF Division, St Jude Medical,
Heart Rhythm, Vol 0, No 0, Month 2014 Minnetonka, MN) were advanced into the LA. After PV angiography, a decapolar ring catheter (Lasso, Biosense Webster, Diamond Bar, CA) was placed in the PVs. An open-irrigated 3.5-mm-tip deflectable catheter (ThermoCool, Biosense Webster) was used for mapping and ablation. Bipolar electrograms were displayed and recorded at filter settings of 30–500 Hz during the procedure (EP-WorkMate, St Jude Medical). The LA and PVs were constructed with a 3-dimensional electroanatomic mapping system (CARTO, Biosense Webster). The ipsilateral PV antrum was circumferentially ablated under fluoroscopic, 3-dimensional cardiac computed tomography, and CARTO guidance by 2 operators (K.Y. and Y.S.). Circumferential lesions were created in a point-by-point manner, and dragging was limited as much as possible. This technique allowed us to accurately assess local electrogram amplitude and morphology and the impedance drop during ablation as indicators of catheter-tissue contact.13 The carina region between the superior and inferior PVs was ablated in all patients.14 Radiofrequency energy was delivered at a power of 20 W at the posterior aspect, 15 W at the sites adjacent to the esophagus, and 25–30 W at the anterior aspect of the PV antrum. The maximum irrigation flow rate was 30 mL/min, and the maximum temperature was 42ºC. The procedural end point was PV isolation as confirmed by the Lasso catheter. Biphasic external cardioversion was used to restore sinus rhythm if AF was still present after ablation.
Postablation care and follow-up Patients were discharged with warfarin prescription for Z4 days after ablation and were seen in an outpatient clinic 2 and 6 weeks after hospital discharge and every 2 months thereafter. Holter (DSC-3300, Nihon Kohden, Tokyo, Japan) and frequent electrocardiographic recordings using a manually activated event recorder (HCG-901, Omron, Kyoto, Japan) were undertaken for a duration of 1 month before the 6-month follow-up visit. Treatment success was defined as freedom from all atrial tachyarrhythmias in the absence of antiarrhythmic drug therapy after a 2-month blanking period.
Definition of LA reverse remodeling Patients were divided into 2 groups according to the extent of decrease in left atrial volume indexed to body surface area (LAVi): responders, with a reduction in LAVi of Z23%, which was the mean and median percent reduction in LAVi; and nonresponders, with a reduction in LAVi of o23% or an increase during the follow-up period.
Statistical analysis Continuous variables are expressed as mean ⫾ SD and were compared by using the Student t test or paired t test. The Mann-Whitney test was used for continuous variables that were highly skewed. Categorical variables were compared by using the χ2 test. Correlation analysis was calculated by using the Pearson correlation test. Multivariate logistic regression analysis was performed to identify the possible
127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 Q7 158 159 160 161 162 163 164 165 166 167 168 169 170 171 Q8 172 173 174 175 176 177 178 179 180 181 182 183
Yoshida et al
P = 0.08 P
Troponin elevation after radiofrequency catheter ablation of atrial fibrillation: Relevance to AF substrate, procedural outcomes, and reverse structural remodeling Kentaro Yoshida, MD,* Yoshiaki Yui, MD,† Akira Kimata, MD,* Naoya Koda, MD,* Jo Kato, MD,* Masako Baba, MD,* Masako Misaki, MD,* Daisuke Abe, MD,* Chiho Tokunaga, MD,* Shinji Akishima, MD,* Yukio Sekiguchi, MD,† Hiroshi Tada, MD,‡ Kazutaka Aonuma, MD,† Noriyuki Takeyasu, MD* From the *Division of Cardiovascular Medicine, Ibaraki Prefectural Central Hospital, Kasama, Japan, † Division of Cardiovascular Medicine, University of Tsukuba, Tsukuba, Japan, and ‡Division of Cardiovascular Medicine, University of Fukui, Yoshida-gun, Japan. BACKGROUND Although radiofrequency ablation creates myocardial necrosis leading to troponin T (TnT) release into the systemic circulation, the significance of TnT elevation after atrial fibrillation (AF) ablation is unknown. OBJECTIVE To demonstrate a possible mechanism of reverse structural remodeling in the left atrium (LA) by evaluating postprocedural TnT elevation. METHODS This study included 106 patients with an enlarged LA (paroxysmal AF, n ¼ 43; persistent AF, n ¼ 63). All patients underwent pulmonary vein isolation alone in the index procedure. Left atrial volume indexed to body surface area (LAVi) was measured by echocardiography before ablation and 6 months after sinus rhythm restoration. Patients were divided into responders (n ¼ 53) and nonresponders (n ¼ 53) based on a cutoff value of 23% reduction in LAVi. The TnT level was measured 12 hours postprocedure. RESULTS LAVi decreased from 43 ⫾ 13 to 33 ⫾ 12 mL/m2 (P o .0001). The TnT level was higher in responders than in nonresponders (1.31 ⫾ 0.34 μg/L vs 0.88 ⫾ 0.29 μg/L; P o .0001) and correlated linearly with percent reduction in LAVi (R ¼ .54;
Introduction Cardiac troponin T (TnT), an intracellular protein involved in the regulation of cardiac muscle contraction, was initially identified as a sensitive indicator of myocardial damage particularly associated with myocardial infarction. Recent advances in assay technology have led to a refinement in the clinical ability to quantify cardiomyocyte injury1 and in the prediction of mortality risk in the general population.2 An increase in the TnT level is also known to occur after various Address reprint requests and correspondence: Dr Kentaro Yoshida, Division of Cardiovascular Medicine, Ibaraki Prefectural Central Hospital, 6528 Koibuchi, Kasama, Ibaraki 309-1793, Japan. E-mail address: [email protected].
1547-5271/$-see front matter B 2014 Heart Rhythm Society. All rights reserved.
P o .0001). Also in multivariate analysis, the TnT level was the only independent predictor for responders (odds ratio 90.1; 95% confidence interval 14.95–543.3; P o .0001). The TnT level in patients who required a repeat procedure (n ¼ 30) was lower than that in patients who did not require a repeat procedure only in the persistent AF group (0.92 ⫾ 0.38 μg/L vs 1.16 ⫾ 0.37 μg/L; P ¼ .01). CONCLUSION Greater elevation of the TnT level was related both to favorable outcomes after ablation and to greater reversal of structural remodeling. Postprocedure, the TnT level may be reflective of the preservation of healthy LA myocardium. KEYWORDS Atrial fibrillation; Catheter remodeling; Structural remodeling; Troponin
ablation;
Reverse
ABBREVIATIONS AF ¼ atrial fibrillation; eGFR ¼ estimated glomerular filtration rate; LA ¼ left atrium/left atrial; LAVi ¼ left atrial volume indexed to body surface area; MRI ¼ magnetic resonance imaging; PV ¼ pulmonary vein; TnT ¼ troponin T (Heart Rhythm 2014;0:0–7) rights reserved.
I
2014 Heart Rhythm Society. All
types of cardiac electrophysiological procedures, such as cardioversion, device therapy, and catheter ablation.3–5 Although radiofrequency ablation energy creates localized lesions and myocardial necrosis leading to TnT release into the systemic circulation, the significance of an increase in the TnT level after ablation of atrial fibrillation (AF) remains undetermined. With regard to AF substrate, reversal of structural remodeling in the left atrium (LA) occurs to a different degree after restoration of sinus rhythm, which is in contrast to the uniform reversal of electrical remodeling.6–8 Reverse structural remodeling may more likely occur in patients who have a relatively healthy LA with less fibrosis.8,9 In this study, we focused on the increase in the TnT level in patients http://dx.doi.org/10.1016/j.hrthm.2014.04.015
55 56 57 58 59 60 61 62 63 64 65 66 67 68 69
2 70 71 72 73 74 75 76 77 78 79 80 81 82 Q5 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112Q6 113 114 115 116 117 118 119 120 121 122 123 124 125 126
undergoing pulmonary vein (PV) isolation alone as a treatment of drug-resistant AF and hypothesized that greater postprocedural increase in the TnT level predicts greater reversal of structural remodeling because more TnT would be released by radiofrequency ablation in a healthy LA than in a “sick” LA, in which the myocardium had degenerated into fibrous tissue.
Methods Study participants The study participants comprised 106 consecutive patients with an enlarged LA volume of Z30 mL/m2 who underwent PV isolation alone at the index procedure.10 Forty-three patients had paroxysmal AF, and 63 patients had persistent AF. According to the HRS/EHRA/ECAS consensus statement,11 paroxysmal AF is defined as recurrent AF (Z2 episodes) that terminates spontaneously within 7 days and persistent AF is defined as recurrent AF that is sustained for Z7 days. Coronary artery disease was ruled out in all patients by coronary angiography performed in conjunction with the ablation procedure. Patients with structural heart disease or chronic kidney disease (estimated glomerular filtration rate [eGFR] o60 mL/min per 1.73 m2) were excluded from the study. Patients with atrial tachycardia or long-standing persistent AF (continuous AF of 41 year’s duration)11 were also excluded because additional ablation beyond PV isolation, such as linear ablation and continuous fractionated atrial electrogram ablation, is considered to enhance procedural efficacy for those atrial tachyarrhythmias.11 All antiarrhythmic drug therapies were discontinued 4–5 half-lives before the procedure except for amiodarone, which was discontinued 8 weeks beforehand. The study protocol was approved by the local institutional review board, and all patients provided their informed written consent.
Data acquisition Blood samples for the measurement of the TnT level were collected 1 day before the procedure and 12 hours after the completion of the procedure. The TnT level was measured with a Cobas e411 analyzer (Roche Diagnostics, XXXX, XX). The 99th percentile of a healthy reference population has been determined to be 0.014 μg/L. To evaluate the degree of LA reverse remodeling, transthoracic echocardiography (Vivid 7, GE Healthcare, Horten, Norway) was performed 1 day before the procedure and 6 months after the final ablation procedure by sonographers blinded to any electrophysiological and laboratory data. The LA volumes were measured by using the biplane method on apical 2- and 4-chamber views during end systole.12
Electrophysiology study and catheter ablation A 7-F 14-pole dual-site mapping catheter (Irvine Biomedical Inc, Irvine, CA) was positioned in the coronary sinus and the low lateral wall of the right atrium throughout the procedure. Two long sheaths (SL0, AF Division, St Jude Medical,
Heart Rhythm, Vol 0, No 0, Month 2014 Minnetonka, MN) were advanced into the LA. After PV angiography, a decapolar ring catheter (Lasso, Biosense Webster, Diamond Bar, CA) was placed in the PVs. An open-irrigated 3.5-mm-tip deflectable catheter (ThermoCool, Biosense Webster) was used for mapping and ablation. Bipolar electrograms were displayed and recorded at filter settings of 30–500 Hz during the procedure (EP-WorkMate, St Jude Medical). The LA and PVs were constructed with a 3-dimensional electroanatomic mapping system (CARTO, Biosense Webster). The ipsilateral PV antrum was circumferentially ablated under fluoroscopic, 3-dimensional cardiac computed tomography, and CARTO guidance by 2 operators (K.Y. and Y.S.). Circumferential lesions were created in a point-by-point manner, and dragging was limited as much as possible. This technique allowed us to accurately assess local electrogram amplitude and morphology and the impedance drop during ablation as indicators of catheter-tissue contact.13 The carina region between the superior and inferior PVs was ablated in all patients.14 Radiofrequency energy was delivered at a power of 20 W at the posterior aspect, 15 W at the sites adjacent to the esophagus, and 25–30 W at the anterior aspect of the PV antrum. The maximum irrigation flow rate was 30 mL/min, and the maximum temperature was 42ºC. The procedural end point was PV isolation as confirmed by the Lasso catheter. Biphasic external cardioversion was used to restore sinus rhythm if AF was still present after ablation.
Postablation care and follow-up Patients were discharged with warfarin prescription for Z4 days after ablation and were seen in an outpatient clinic 2 and 6 weeks after hospital discharge and every 2 months thereafter. Holter (DSC-3300, Nihon Kohden, Tokyo, Japan) and frequent electrocardiographic recordings using a manually activated event recorder (HCG-901, Omron, Kyoto, Japan) were undertaken for a duration of 1 month before the 6-month follow-up visit. Treatment success was defined as freedom from all atrial tachyarrhythmias in the absence of antiarrhythmic drug therapy after a 2-month blanking period.
Definition of LA reverse remodeling Patients were divided into 2 groups according to the extent of decrease in left atrial volume indexed to body surface area (LAVi): responders, with a reduction in LAVi of Z23%, which was the mean and median percent reduction in LAVi; and nonresponders, with a reduction in LAVi of o23% or an increase during the follow-up period.
Statistical analysis Continuous variables are expressed as mean ⫾ SD and were compared by using the Student t test or paired t test. The Mann-Whitney test was used for continuous variables that were highly skewed. Categorical variables were compared by using the χ2 test. Correlation analysis was calculated by using the Pearson correlation test. Multivariate logistic regression analysis was performed to identify the possible
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P = 0.08 P
