International Journal of Cardiology 180 (2015) 129–133

Contents lists available at ScienceDirect

International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard

Mid-regional proadrenomedullin levels predict recurrence of atrial fibrillation after catheter ablation Abdul S. Parwani a,⁎, Stephan von Haehling a, Ana I. Kolodziejski a, Martin Huemer a, Alexander Wutzler a, Philipp Attanasio a, Tatjana Stojakovic b, Hubert Scharnagl b, Wilhelm Haverkamp a, Leif-Hendrik Boldt a a b

Department of Cardiology, Charité — Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Austria

a r t i c l e

i n f o

Article history: Received 20 July 2014 Received in revised form 14 November 2014 Accepted 22 November 2014 Available online 26 November 2014 Keywords: Cather ablation of atrial fibrillation Biomarkers Atrial fibrillation recurrence

a b s t r a c t Background: We evaluated the prognostic value of mid-regional proadrenomedullin (MR-proADM) in atrial fibrillation (AF) patients undergoing radiofrequency ablation. Methods: Plasma concentrations of MR-proADM were measured at baseline and after 12 months in 87 AF patients in whom radiofrequency ablation was performed. The association between MR-proADM and AF recurrence was tested by univariable and multivariable Cox models. Results: In all 87 patients radiofrequency ablation was successfully performed. Of the total population 54% had paroxysmal AF. The mean left ventricular ejection fraction was 54% (minimum 25%). After 12 months of follow-up, 71% of the patients were free of AF recurrence. At baseline, mean MR-proADM in the total population was 0.72 nmol/l ± 0.22. Patients with AF recurrence had significantly higher baseline MR-proADM (0.89 nmol/l ± 0.29) as compared with patients without AF recurrence (0.65 nmol/l ± 0.14; p b 0.001). After 12 months, mean MR-proADM plasma concentration remained higher in patients with AF recurrence (0.81 nmol/l ± 0.22 as compared with patients free of AF 0.54 nmol/l ± 0.20; p b 0.001). Receiver operating characteristic (ROC) curve analysis for MR-proADM yields a specificity of 98% and a sensitivity of 64% with an optimal cut-off value of 0.82 nmol/l to predict recurrence of AF after catheter ablation. In the logistic regression analysis only MR-proADM remained independently predictive for AF recurrence. Conclusion: This is the first study revealing the association between MR-proADM elevation before ablation and poor outcomes after ablation of AF. Larger studies are needed to validate these results. © 2014 Elsevier Ireland Ltd. All rights reserved.

1. Introduction Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in humans [1,2]. Radiofrequency catheter ablation (RFCA) is a standard treatment of symptomatic AF [1]. For paroxysmal AF, catheter ablation is recommended in selected patients as first-line therapy [1]. However, recurrence of AF after RFCA is common, even if patients are selected according to the current guidelines and even if the ablation is performed in experienced centers [2,3]. The reasons for AF recurrence after ablation are not fully understood. Although pulmonary vein reconduction after initial successful isolation is one major factor [1,4,5], atrial structural remodeling probably also plays a major role [5,6]. Stratification of patients prior to RFCA according to the risk of recurrence of AF may help in regulating therapy and in better understanding disease pathophysiology. Therefore, sensitive indicators are needed. ⁎ Corresponding author at: Department of Cardiology, Charité, Campus VirchowKlinikum, Augustenburger Platz 1, 13553 Berlin, Germany. E-mail address: [email protected] (A.S. Parwani).

http://dx.doi.org/10.1016/j.ijcard.2014.11.117 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.

Several studies have reported elevated levels of cardiovascular biomarkers in AF patients [7–10]. Natriuretic peptides such as Nterminal-pro-atrial natriuretic peptide (NT-proANP) and N-terminalpro-B-type natriuretic peptide (NT-proBNP) have been investigated in predicting AF recurrence among patients undergoing RFCA for AF [11, 12]. Studies have reported about NT-proBNP being an independent predictor of AF recurrence after RFCA [13,14]. Adrenomedullin (ADM) is another interesting biomarker that has been shown to be elevated in cardiac diseases, such as atherosclerosis and congestive heart failure [15]. Since ADM has a short plasma halflife, reliable quantification is difficult and technically challenging [15]. Mid-regional pro-adrenomedullin (MR-proADM), an inactive sequence of ADM precursor proADM is more stable and directly reflects levels of the rapidly degraded active peptide ADM [16]. It has been shown that MR-proADM is superior to BNP and NT-proBNP in predicting 90-day mortality in heart failure patients [17,18] or in predicting adverse outcome after acute myocardial infarction [19]. For these reasons we hypothesized, that MR-proADM would add in predicting AF recurrences after AF ablation.

130

A.S. Parwani et al. / International Journal of Cardiology 180 (2015) 129–133

2. Materials and methods 2.1. Study population In this study, we prospectively enrolled 87 consecutive AF patients who were scheduled for RFCA. ECG documentation of AF, information on AF history and clinical parameters were assessed. AF was characterized as paroxysmal when terminating spontaneously within 7 days and persistent when sustained beyond 7 days. Blood tests (including routine laboratory parameters (sodium, potassium, creatinine, C-reactive protein, hemoglobin), NT-proBNP and MR-proADM) were collected at baseline (24 h before the ablation) and 12 months after the ablation. Routine laboratory parameters were measured in the central laboratory of the Charité — Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany. Plasma concentrations of NT-proBNP were measured by electrochemiluminescence on the ElecSys 2010 analyzer (Roche Diagnostics, Indianapolis, Indiana). All included patients gave their written informed consent. The study protocol was in accordance with the Declaration of Helsinki and was approved by the institutional review board of the Charité — Universitätsmedizin Berlin (reference number: EA2/141/13). 2.2. Measurement of MR-proADM Blood samples were collected and centrifuged at 3500 rounds per minute for 15 min. The plasma was stored at −80 °C in plastic freezer vials. Plasma concentrations of MR-proADM were measured from frozen samples in one batch using an automated sandwich chemiluminescence immunoassay on the KRYPTOR System (Thermo Fisher Scientific/BRAHMS GmbH, Hennigsdorf, Germany). The assay's analytical limit of detection is 0.08 nmol/L, and the interassay coefficient of variance is b20% for values N0.12 nmol/L, which is also the reference value for healthy subjects [18]. The assay is linear on dilution with undisturbed recovery of the analyte; EDTA-, heparin-, and citrate-plasma samples are stable for at least 3 days at room temperature, 14 days at 4 °C, and 1 year at −20 °C. 2.3. Radiofrequency catheter ablation All patients underwent left atrial catheter ablation of symptomatic drug-refractory AF. Patients were in a fasting state for at least 8 h and underwent transthoracic and transesophageal echocardiography prior to ablation to exclude left atrial thrombus. After obtaining venous access and double transseptal puncture under fluoroscopic guidance, an open irrigated ablation catheter (Cool Flex, IBI/St. Jude Medical, St. Paul, MN, USA or AlCath flux extra gold, Biotronik, Berlin, Germany) and a circular mapping catheter (Lasso Optima, IBI/St. Jude Medical, Connecticut, USA) were positioned in the left atrium (LA). For reconstruction of LA geometry and electroanatomic guidance, a 3D-mapping system was used (Ensite NavX, St. Jude Medical). Circumferential pulmonary vein isolation (CPVI) was performed in paroxysmal AF. In patients with persistent AF, linear lesions were additionally created on the roof and anterior wall of the LA: RF energy was delivered from the mitral annulus area (11–12 o'clock direction in the left anterior oblique view) to the LA roofline, which joined both superior PVs anteriorly. The ablation was done by an irrigated-tip catheter and a Stockert 70 RF generator (Biosense Webster) with a maximal temperature of 43 °C and maximum power of 35 W. Procedural endpoint was the complete isolation of pulmonary veins (PVs) and bidirectional conduction block at the lines. Bidirectional block in the PVs was verified by the circular and the ablation catheter. Conduction block at the lines was verified by a differential pacing maneuver on either side of the linear lesions after the restoration of sinus rhythm. A temperature probe for monitoring of the esophageal temperature (SensiTherm, St. Jude Medical) was used in all patients. 2.4. Follow-up Patients were followed-up in our outpatient clinic. Follow-up (FU) visits included 12-lead and 72-hour-Holter-ECG at 3, 6 and 12 months after discharge, and MRproADM blood tests at 12 months. Episodes of AF over 30 s were considered to be a recurrence. All patients were instructed to contact our clinic whenever symptoms suggestive of AF recurrence occurred. Antiarrhythmic drugs were continued for three months after ablation and then discontinued. In case of early recurrence of AF with duration N48 h and/or clinical symptoms, direct current cardioversion was performed and additional pharmacological treatment was left to the discretion of the treating physician. If AF occurred within the first three months, the episode was not considered to be a recurrence of AF. If AF occurred more than three months after ablation, it was considered to be a recurrence of AF. 2.5. Statistics Values are expressed as means with standard deviations or counts and percentages as appropriate. We compared quantitative variables between groups with Student's 2-tailed t-test after appropriate adjustment. We used χ2 test or Fisher's exact test as appropriate, for qualitative variables, either categorical or ordered. We relied on univariate analysis or further analyses with stepwise, multivariate binary logistic regression, using a forward model to adjust for potential confounders. A p-value b 0.05 was considered statistically significant. Additional methods included receiver operating characteristic (ROC) curves and the comparison of correlated ROC curves. To evaluate if adding NT-proBNP to the model would increase the predictive value of MR-proADM, ROC curves were constructed

and the areas under the curves (AUC) were compared. Wald confidence intervals were determined for MR-proADM and NT-proBNP at baseline and for the combination of both using a logistic regression model with AF recurrence as the dependent variable and MRproADM and NT-proBNP as independent variables. Statistical analysis was performed with StatView 4.0, (SAS Institute Inc., Berkley, CA, USA).

3. Results Patients were aged 62 years ± 9 and 57 (65%) were men. Patient characteristics are summarized in Tables 1 and 2. A total of 47 (54%) patients had paroxysmal AF and the rest had persistent AF. In the total population, mean left ventricular ejection fraction (LVEF) was 54% ± 9 (minimum 20%). The acute procedural endpoint of pulmonary vein isolation as well as bidirectional block along the lines in patients with persistent AF was achieved in all patients. Mean procedure duration was 154 min ± 43 and mean fluoroscopy time 41 min ± 16. Mean ablation time was 30.5 min ± 10.8 and mean energy delivered 75620 ws ± 25338. There were no significant differences observed between patients with AF recurrence and patients free of AF recurrence in procedure duration, ablation time, total energy application or fluoroscopy time. No steam pops were recognized in any of the groups. No pericardial perforation or pericardial tamponade occurred. 3.1. MR-proADM: serum levels and predictive value Baseline mean MR-proADM in the total population was 0.72 nmol/ l ± 0.22 (minimum/maximum 0.39/1.45 nmol/l). Prior to ablation, mean MR-proADM in patients with paroxysmal AF was 0.66 nmol/l ± 0.17 and in patients with persistent AF 0.78 nmol/l ± 0.25 (p = 0.16). In patients who had an AF recurrence at 12 month FU, mean baseline MR-proADM was 0.89 nmol/l ± 0.29. MR-proADM at baseline was significantly lower in patients free of AF recurrence at 12 month FU (0.65 nmol/l ± 0.14; p b 0.001). MR-proADM plasma concentration 12 months after RFCA was 0.63 nmol/l ± 0.24 when looking at the total population. In patients who had an AF recurrence, mean 12 month MR-proADM was 0.81 nmol/l ± 0.22 and in patients free of AF recurrence it was 0.54 nmol/l ± 0.20 (p b 0.001). Patients free of AF recurrence at 12 months showed a significant reduction of MR-proADM plasma concentration in the FU after 12 months when compared with MR-proADM levels prior to ablation (0.54 nmol/l ± 0.20 vs. 0.65 nmol/l ± 0.14, respectively p = 0.001). ROC curve analysis for MR-proADM yields a specificity of 98% and a sensitivity of 64% with an optimal cut-off value of 0.82 nmol/l to predict recurrence of AF after ablation (Fig. 1).

Table 1 Patient characteristics and AF recurrence.

Mean age in years (SD) Male (group %) BMI mean (SD) CAD (group %) Art. HTN (group %) LVEF % (SD) LA-diameter mm (SD) Paroxysmal AF (group %) Persistent AF (group %)

Total population n = 87

AF recurrence n = 25

Free of AF recurrence n = 62

p-Value⁎

62 (9)

64 (8)

62 (9)

0.48

57 (65%) 28 (5) 28 (24%) 75 (86%)

17 (68%) 29 (5) 10 (40%) 23 (92%)

40 (65%) 28 (4) 18 (29%) 52 (84%)

0.19 0.24 0.30 0.52

54 (9) 44 (7)

50 (10) 47 (7)

55 (7) 44 (5)

0.02 0.03

47 (54%)

10 (40%)

37 (60%)

0.15

40 (46%)

15 (60%)

25 (40%)

0.67

SD: standard deviation, BMI: body mass index, CAD: coronary artery disease, LVEF: left ventricular ejection fraction, LA: left atrium, Art. HTN: arterial hypertension, Paroxy.: paroxysmal, Angio.: angiography. ⁎ p values b 0.05 are printed in bold.

A.S. Parwani et al. / International Journal of Cardiology 180 (2015) 129–133

131

Table 2 Univariable analysis.

AF-heart rate bpm (SD) RR systolic mm Hg (SD) RR diastolic mm Hg (SD) MR-proADM nmol/L (SD) MR-proADM FU nmol/L (SD) NT-proBNP ng/L (SD) Sodium mmol/L (SD) Potassium mmol/L (SD) Creatinine mg/dL (SD) CRP mg/dL (SD) Hemoglobin mg/dL (SD)

Total n = 87

AF recurrence n = 25

Free of AF recurrence n = 62

79 (23) 122 (16) 75 (9) 0.72 (0.22) 0.63 (0.24) 891 (1561) 140 (2.5) 4.2 (0.40) 0.99 (0.21) 1.17 (1.7) 14.1 (1.3)

83 (25) 120 (12) 73 (8) 0.89 (0.29) 0.81 (0.22) 1649 (2561) 140 (2.4) 4.3 (0.40) 1.06 (0.26) 1.44 (1.9) 13.7 (1.2)

78 (23) 121 (17) 76 (9) 0.65 (0.14) 0.54 (0.20) 553 (505) 141 (2.5) 4.2 (0.19) 0.96 (0.19) 1.00 (1.65) 14.3 (1.2)

p-Value⁎ 0.26 0.67 0.14 b0.001 b0.001 0.001 0.16 0.19 0.06 0.34 0.52

SD: standard deviation, bpm: beats per minute, RR: blood pressure, MR-proADM: mid-regional pro-adrenomedullin, NT-proBNP: amino-terminal-pro-B-type natriuretic peptide, Na: sodium, K: potassium, creatinine kinase, CRP: C-reactive protein. ⁎ p values b 0.05 are printed in bold.

Seventeen patients had an MR-proADM value ≥0.82 nmol/l before RFCA. Of these patients, 16 (94%) had an AF recurrence. In the group of patients with an MR-proADM value b 0.82 nmol/l AF recurrence rate was only 13% (9 out of 70 patients). Evaluation of the patients with MR-proADM b 0.82 nmol/l versus patients with MR-proADM N0.82 nmol/l revealed significant differences in LVEF, LA-size and a trend towards persistent AF. Patient with reduced LVEF and/or larger LA size had significantly higher MR-proADM plasma concentrations (Table 3). Adding NT-proBNP levels to the model did not increase the diagnostic performance of MR-proADM.

In 25 patients (29%) with recurrence of AF baseline MR-proADM plasma concentration was significantly higher than those without recurrence of AF. Successful ablation reduced significantly the plasma concentration of MR-proADM 12 months after ablation (Figs. 2 and 3). All other clinical characteristics, proportion of structural heart disease, previous and post-ablation medications and routine laboratory tests showed no significant difference between the patients with and without AF recurrence. Using logistic regression analysis, we found MR-proADM to be the sole independent predictor of AF recurrence after ablation (Table 4). 4. Discussion

3.2. Recurrence of AF Characteristics of patients with and without recurrence of AF are given in Tables 1 and 2. In the FU after 12 months 71% of the patients were free of AF recurrence, and 21% (10/47) of paroxysmal and 38% (15/40) of persistent AF patients had a recurrence. There was no significant difference between these two groups concerning AF recurrence (p = 0.15). LVEF was significantly lower in the AF recurrence group. LA size was significantly larger in AF recurrence group (Table 1).

Fig. 1. Receiver operator characteristic curve analysis for MR-proADM yields a specificity of 98% and a sensitivity of 68%.

Our study is the first study assaying the predictive value of MRproADM in AF patients undergoing RFCA. We demonstrated that MRproADM is elevated above the reference value for healthy subjects and it is independently associated with AF recurrence 12 months after ablation. Its predictive power exceeds that of NT-proBNP, LVEF, and even LA diameter. The optimal value of MR-proADM to predict recurrence of AF after RFCA is ≥0.82 nmol/l. Recurrence of AF after catheter ablation is common. Identification of patients with a low likelihood of long-term restoration of sinus rhythm is therefore crucial. Several factors influencing success of catheter ablation of AF have been discussed: type of AF, age, sleep apnea, hypertension, PV re-conduction, LA size and progression of atrial remodeling [20–22]. Enlarged LA, prolonged AF duration and reduced left atrial function are risk factors and have been used to predict AF recurrence in previous studies [4,5,23,24]. In our study, the pattern of AF (paroxysmal vs. persistent) was not a predictor of AF recurrence, although the small number of patients per group limits this result. Only LA size and LVEF were predictive on single predictor analysis in patients whose ablation had or had not been successful. Age, gender and AF duration were not important in the present cohort in this respect. Atrial structural remodeling is associated with AF recurrence after ablation [25]. These patients show higher degrees of interstitial fibrosis and inflammation [26,27]. A recently published study measuring hs-CRP in patients undergoing AF ablation revealed that high hs-CRP levels were associated with a lower mean bipolar peak-to-peak voltage of the LA [28] as sign of interstitial fibrosis. Adrenomedullin is another interesting biomarker in this regard. It was initially discovered in 1993 by Kitamura et al. [15]. It has a plasma half life of 22 min, and its release yields hypotension via two distinct mechanisms, because pro-adrenomedullin consists of two different peptide products, PAMP (N-terminal proADM 20 peptide) and the mature form of adrenomedullin [29]. The peptide is secreted by endothelial and vascular smooth muscle cells with vasodilating properties, that has been implicated in having effects on microcirculation and endothelial function [30] but its primary sources are the myocardium and the

132

A.S. Parwani et al. / International Journal of Cardiology 180 (2015) 129–133

Table 3 MR-proADM levels and patient characteristics. Total n = 87 Mean age in years (SD) Male (group %) BMI mean (SD) CAD (group %) Art. HTN (group %) LV-EF % (SD) LA-diameter mm (SD) Paroxysmal AF (group %) Persistent AF (group %) AF recurrence (group %)

62 (9) 57 (65%) 28 (5) 28 (24%) 75 (86%) 54 (9) 44 (7) 47 (54%) 40 (46%) 25 (29%)

MR-proADM b 0.8 nmol/l n = 70

MR-proADM ≥ 0.82 nmol/l n = 17

62 (9) 45 (65%) 28 (4) 18 (26%) 56 (81%) 55 (6) 44 (5) 39 (57%) 29 (42%) 9 (13%)

66 (7) 12 (66%) 29 (5) 10 (56%) 18 (100%) 47 (6) 47 (6) 8 (44%) 10 (56%) 16 (94%)

p-Value⁎ 0.077 0.66 0.19 0.08 0.07 0.007 0.017 0.23 0.049 b0.001

SD: standard deviation, BMI: body mass index, CAD: coronary artery disease, LV-EF: left ventricle ejection fraction, LA: left atrium, Art. HTN: arterial hypertension. ⁎ p values b 0.05 are printed in bold.

vascular endothelium [31]. Other tissues that release adrenomedullin include gastrointestinal, respiratory, and endocrine cells, but these are not regarded as primarily important [34]. It has been shown, that the levels of ADM represent patients' disease severity [16]. It is used for the assessment of cardiovascular risk, myocardial injury, and cellular damage. A systemic increase in ADM typically reflects an overflow from local sites of production, mostly caused by endothelial damage (e.g., in chronic heart failure and septic shock) [16]. Therefore, increased levels of MR-proADM are found in patients with more severe cardiac diseases and in respiratory diseases [32]. MR-proADM has been found to be related to hemodynamic alterations and volume load [8,16]. This has also been shown for NT-proBNP. Solheim et al. [14] could show that NT-proBNP correlated with left atrium volume. Therefore we assume that increased levels of MR-proADM reflect increased structural atrial remodeling and atrial hemodynamic changes. The GISSI-AF study, a trial to determine the effect of valsartan in preventing recurrence of AF in patients in sinus rhythm [8], also investigated biomarkers in predicting recurrence of AF. Six cardiovascular markers were assayed in 382 patients. They found that markers of cardiac injury and/or strain and endothelin have a modest but significant predictive value of recurrence of AF, in particular MR-proANP and NTproBNP. Hwang et al. [33] showed that the measurement of NT-proBNP added incremental predictive value to LA size and diastolic function before AF ablation. Other studies have shown that significantly lower NT-proBNP concentration at baseline are seen in patients successfully ablated for AF compared to patients with recurrent AF and that its value decreases significantly after successful restoration of sinus rhythm [12,13,34].

Fig. 2. Baseline MR-proADM levels in patients with and without AF recurrence after 12 months (p b 0.0001).

In line with a study by Solheim et al. [14], NT-proBNP was not a significant predictor of ablation outcome after multivariable adjustment in our study. In the multivariable model, MR-proADM remained the only independent predictor for AF recurrence. MR-proADM may therefore be superior to NT-proBNP as well as LV-EF, LA size or type of AF in predicting AF-recurrences after RFCA.

5. Limitation Major limitation of these studies includes small sample size (b100 patients). This may explain why the pattern of AF was not statistically significant for predicting AF recurrence.

6. Conclusion This is the first study revealing the association between MR-proADM elevation before ablation and poor outcomes after ablation of AF. MRproADM is elevated in AF patients and high levels could predict AF recurrence after RAFC. MR-proADM may optimize stratification of patients suitable for ablation of atrial fibrillation.

Conflict of interest The authors report no relationships that could be construed as a conflict of interest.

Fig. 3. 12 months of follow-up MR-proADM levels in patients with and without AF recurrence after 12 months (p b 0.001).

A.S. Parwani et al. / International Journal of Cardiology 180 (2015) 129–133 Table 4 Mutivariable analysis. Independent predictors of AF recurrence

Multivariable analysis* OR (95% Cl)

p-Value

LV-EF (per 1% increase) Left atrium (per 1 mm increase) NT-proBNP (per 1 ng/l increase) MR-proADM (b0.82 nmol/l)

1.08 (0.97–1.20) 1.04 (0.92–1.17) 1.00 (0.99–1.001) 0.35 (0.01–0.25)

0.18 0.57 0.83 0.0009

Multivariable model included all parameters that were significant in the univariable analysis. LV-EF: left ventricular ejection fraction, left atrium diameter, NT-proBNP and MR-proADM. OR: odds ratio, Cl: confidence interval.

References [1] A.J. Camm, G.Y. Lip, R. De Caterina, et al., 2012 focused update of the ESC guidelines for the management of atrial fibrillation: an update of the 2010 ESC guidelines for the management of atrial fibrillation, Eur. Heart J. 33 (2012) 2719–2747. [2] H. Calkins, K.H. Kuck, R. Cappato, et al., HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design, Heart Rhythm. 9 (2012) 632–696. [3] R. Cappato, H. Calkins, S.A. Chen, et al., Update worldwide survey on the methods, efficacy, and safety of catheter ablation for human atrial fibrillation, Circ. Arrhythm. Electrophysiol. 3 (2012) 32–38. [4] W.H. Sauer, M.L. McKernan, D. Lin, E.P. Gerstenfeld, D.J. Callans, F.E. Marchlinski, Clinical predictors and outcomes associated with acute return of pulmonary vein conduction during pulmonary vein isolation for treatment of atrial fibrillation, Heart Rhythm. 3 (2006) 1024–1028. [5] Y. Sotomi, K. Inoue, N. Ito, et al., Cause of very late recurrence of atrial fibrillation or flutter after catheter ablation for atrial fibrillation, Am. J. Cardiol. 111 (2013) 552–556. [6] L. Cai, Y. Yin, Z. Ling, et al., Predictors of late recurrence of atrial fibrillation after catheter ablation, Int. J. Cardiol. 164 (2013) 82–87. [7] A.S. Parwani, L.H. Boldt, M. Huemer, et al., Atrial fibrillation-induced cardiac troponin I release, Int. J. Cardiol. 168 (2013) 2734–2737. [8] S. Masson, A. Aleksova, C. Favero, et al., GISSI-AF investigators. Predicting atrial fibrillation recurrence with circulating inflammatory markers in patients in sinus rhythm at high risk for atrial fibrillation: data from the GISSI atrial fibrillation trial, Heart 96 (2010) 1909–1914. [9] D.M. Mads, T. Engelmanna, L. Niemann, I.L. Kanstrupa, K. Skagena, J. Godtfredsen, Natriuretic peptide response to dynamic exercise in patients with atrial fibrillation, Int. J. Cardiol. 105 (2005) 31–39. [10] M.K. Chung, D.O. Martin, D. Sprecher, et al., C-reactive protein elevation in patients with atrial arrhythmias. Inflammatory mechanisms and persistence of atrial fibrillation, Circulation 104 (2001) 2886–2891. [11] T. Yamada, Y. Murakami, T. Okada, et al., Plasma atrial natriuretic peptide and brain natriuretic peptide levels after radiofrequency catheter ablation of atrial fibrillation, Am. J. Cardiol. 97 (2006) 1741–1744. [12] J. Fan, H. Cao, L. Su, et al., NT-proBNP, but not ANP and C-reactive protein, is predictive of paroxysmal atrial fibrillation in patients undergoing pulmonary vein isolation, J. Interv. Card. Electrophysiol. 33 (2012) 93–100. [13] D.W. Den Uijl, V. Delgado, L.F. Tops, et al., Natriuretic peptide levels predict recurrence of atrial fibrillation after radiofrequency catheter ablation, Am. Heart J. 161 (2011) 197–203. [14] E. Solheim, M. Kristian Off, P.I. Hoff, et al., N-terminal pro-B-type natriuretic peptide level at long-term follow-up after atrial fibrillation ablation: a marker of reverse atrial remodelling and successful ablation, J. Interv. Card. Electrophysiol. 34 (2012) 129–136.

133

[15] K. Kitamura, K. Kangawa, M. Kawamoto, et al., Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma, Biochem. Biophys. Res. Commun. 192 (1993) 553–560. [16] S. Von Haehling, G.S. Filippatos, J. Papassotiriou, et al., Mid-regional proadrenomedullin as a novel predictor of mortality in patients with chronic heart failure, Eur. J. Heart Fail. 12 (2010) 484–491. [17] A. Gegenhuber, J. Strukc, B. Dieplinger, et al., Comparative evaluation of B-type natriuretic peptide, mid-regional pro-A-type natriuretic peptide, mid-regional pro-adrenomedullin, and Copeptin to predict 1-year mortality in patients with acute destabilized heart failure, J. Card. Fail. 13 (2007) 42–49. [18] A. Maisel, C. Mueller, R. Nowak, et al., Mid-region pro-hormone markers for diagnosis and prognosis in acute dyspnea: results from the BACH (Biomarkers in Acute Heart Failure) trial, J. Am. Coll. Cardiol. 55 (2007) 2062–2076. [19] S.Q. Khan, O.S. Dhillon, R.J. O'Brien, et al., C-terminal provasopressin (Copeptin) as a novel and prognostic Marker in acute myocardial infarction: Leicester Acute Myocardial Infarction Peptide (LAMP) study, Circulation 115 (2007) 2103–2110. [20] R. Weerasooriya, P. Khairy, J. Litalien, et al., Catheter ablation for atrial fibrillation: are results maintained at 5 years of follow-up? J. Am. Coll. Cardiol. 57 (2011) 160–166. [21] F. Ouyang, R. Tilz, J. Chun, et al., Long-term results of catheter ablation in paroxysmal atrial fibrillation: lessons from a 5-year follow-up, Circulation 122 (2010) 2368–2377. [22] A. Arya, G. Hindricks, P. Sommer, et al., Long-term results and the predictors of outcome of catheter ablation of atrial fibrillation using steerable sheath catheter navigation after single procedure in 674 patients, Europace 12 (2010) 173–180. [23] D. Morris, A. Parwani, M. Huemer, et al., Clinical significance of the assessment of the systolic and diastolic myocardial function of the left atrium in patients with paroxysmal atrial fibrillation and low CHADS(2) index treated with catheter ablation therapy, Am. J. Cardiol. 111 (2013) 1002–1011. [24] H. Oral, B.P. Knight, M. Ozaydin, et al., Clinical significance of early recurrences of atrial fibrillation after pulmonary vein isolation, J. Am. Coll. Cardiol. 40 (2002) 100–104. [25] Y. Sato, K. Yoshida, K. Ogata, et al., An increase in right atrial magnetic strength is a novel predictor of recurrence of atrial fibrillation after radiofrequency catheter ablation, Circ. J. 7 (2012) 1601–1608. [26] A. Berruezo, D. Tamborero, L. Mont, et al., Pre-procedural predictors of atrial fibrillation recurrence after circumferential pulmonary vein ablation, Eur. Heart J. 28 (2007) 836–841. [27] S. Miyazaki, T. Kuwahara, A. Kobori, et al., Preprocedural predictors of atrial fibrillation recurrence following pulmonary vein isolation in patients with paroxysmal atrial fibrillation: long-term follow-up results, J. Interv. Card. Electrophysiol. 22 (2011) 621–625. [28] J. Liu, P.H. Fang, S. Dibs, Y. Hou, X.F. Li, S. Zhang, High-sensitivity C-reactive protein as a predictor of atrial fibrillation recurrence after primary circumferential pulmonary vein isolation, Pacing Clin. Electrophysiol. 34 (2011) 398–406. [29] J. Struck, C. Tao, N.G. Morgenthaler, A. Bergmann, Identification of an adrenomedullin precursor fragment in plasma of sepsis patients, Peptides 25 (2004) 1369–1372. [30] T. Eto, J. Kato, K. Kitamura, Regulation of production and secretion of adrenomedullin in the cardiovascular system, Regul. Pept. 112 (2003) 61–69. [31] S.A. Hamid, G.F. Baxter, Adrenomedullin: regulator of systemic and cardiac homeostasis in acute myocardial infarction, Pharmacol. Ther. 105 (2005) 95–112. [32] M.C. Zuur-Telgen, M.G. Brusse-Keizer, P.D. Vandervalk, J. van der Palen, H.A. Kerstjens, M.G. Hendrix, Stable state MR-proadrenomedullin level is a strong predictor for mortality in COPD patients, Chest 145 (2014) 534–541. [33] H.J. Hwang, J.W. Son, B.H. Nam, et al., Incremental predictive value of pre- procedural N-terminal pro-B-type natriuretic peptide for short-term recurrence in atrial fibrillation ablation, Clin. Res. Cardiol. 98 (2009) 213–218. [34] B. Nilsson, P.J. Goetze, X. Chen, S. Pehrson, J.H. Svendsen, Increased NT-pro-B-type natriuretic peptide independently predicts outcome following catheter ablation of atrial fibrillation, Scand. J. Clin. Lab. Invest. 69 (8) (2009) 843–850.

Mid-regional proadrenomedullin levels predict recurrence of atrial fibrillation after catheter ablation.

We evaluated the prognostic value of mid-regional proadrenomedullin (MR-proADM) in atrial fibrillation (AF) patients undergoing radiofrequency ablatio...
511KB Sizes 0 Downloads 7 Views