International Journal of Cardiology 172 (2014) e359–e360
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Long-term predictive value of copeptin after acute myocardial infarction: A cardiac magnetic resonance study Sebastian Johannes Reinstadler a, Gert Klug a, Hans-Josef Feistritzer a, Johannes Mair a, Michael Schocke b, Wolfgang-Michael Franz a, Bernhard Metzler a,⁎ a b
University Clinic of Internal Medicine III, Cardiology, Innsbruck Medical University, Austria Department of Radiology, Innsbruck Medical University, Austria
a r t i c l e
i n f o
Article history: Received 18 December 2013 Accepted 30 December 2013 Available online 16 January 2014 Keywords: Copeptin ST-segment elevation myocardial infarction Cardiac magnetic resonance
Circulating copeptin, the C-terminal portion of the vasopressin precursor molecule, is an established marker of acute stress. Multiple studies demonstrated an association of copeptin with disease severity and progression in different patient populations such as stroke, pneumonia and acute myocardial infarction (AMI) [1]. Recently, we have shown that copeptin correlated with acute and 4-month infarct size and myocardial function in patients after ST-segment elevation AMI (STEMI) [2]. Moreover, copeptin was shown to identify patients with low risk for the development of adverse remodeling at 4 months after STEMI. In this study, the assessment of cardiac morphology, function and infarct size was done by contrast-enhanced cardiovascular magnetic resonance imaging (CMR), which is the method of choice to determine the above mentioned parameters [3]. Nevertheless, it is unknown, whether the association between early copeptin levels and AMI size and function is maintained beyond a mid-term follow-up of 4 months. Because of lack of long-term follow-up data we investigated the relationship between copeptin levels and 12 month myocardial infarct size and functional parameters. Forty-one STEMI patients successfully treated with primary percutaneous coronary intervention (p-PCI) were included as described previously [2]. Blood samples were collected at 2 days (IQR = 1–3) after
⁎ Corresponding author at: University Clinic of Internal Medicine III, Cardiology, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck, Austria. Tel.: +43 512 504 81315; fax: +43 512 504 22767. E-mail address: [email protected] (B. Metzler). 0167-5273/$ – see front matter © 2014 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.12.301
STEMI. Plasma copeptin levels were measured by an established immunofluorescent assay (Thermo Fisher Scientific, B.R.A.H.M.S., Henningsdorf, Germany) [4]. All participants underwent CMR within the first week after STEMI and 12 months thereafter. CMR scans were performed on a 1.5 Tesla AVANTO-scanner (Siemens, Erlangen, Germany) according to a standardized protocol published previously [5,6]. Infarct size was evaluated on late gadolinium enhanced images. Left ventricular volumes and function were measured by cine true-FISP sequences. Statistical analysis was performed using the SPSS 19.0.0 (IBM, Armonk, NY, USA) software for Windows. Pearson or Spearman rank correlations were calculated as appropriate. To calculate the predictive value of copeptin for the occurrence of adverse remodeling, receiver operating characteristic curve analysis was performed. An increase in end-diastolic volume ≥20% was defined as a surrogate marker of adverse remodeling. A two-tailed p-value b 0.05 was considered to indicate statistical significance. The study was approved by the local ethical committee and informed consent was obtained from all patients. The median copeptin concentration was 10.3 pmol/l (IQR = 5.8– 13.2). The mean infarct size at baseline was 18.2 ± 10.0% of left ventricular myocardial mass (LVMM) and 10.8 ± 6.7% of LVMM 12 months thereafter (significant difference; p b 0.01). The mean left ventricular ejection fraction (LVEF) was 55 ± 11% at baseline and 54 ± 12% at 12 months (difference not significant; p N 0.05). Copeptin levels were positively correlated to baseline (r = 0.42, p = 0.006) and 12 month infarct size (r = 0.40, p = 0.011). There were also significant correlations for copeptin with baseline stroke volumes (r = −0.48, p = 0.002) and 12 month end-systolic volumes (r = 0.32, p = 0.039). No correlation was found between copeptin and baseline end-systolic and end-diastolic volumes or 12 month end-diastolic volumes and stroke volume (all p N 0.07). Copeptin was significantly related to acute and 12 month LVEF (r = − 0.49, p = 0.001, baseline; r = − 0.36, p = 0.022, 12 months; Fig. 1). Moreover, patients with a preserved LVEF (N60%, n = 15) at 12 months after STEMI showed a significant lower baseline copeptin value than patients with a reduced LVEF (b60%, n = 26) at follow-up (7.3 pmol/l vs. 12.2 pmol/l, p = 0.013). Finally, we made a distinction between patients with (n = 5) and without (n = 36) adverse remodeling 12 months after the acute event. The AUC of copeptin (0.67, 95% CI 0.47 to 0.86) with the optimal cut-off level of 11.8 pmol/l showed 60% sensitivity and 69% specificity for the prediction of remodeling at 12 month follow-up. This is the first study, showing that copeptin levels are significantly correlated with 12 month infarct size and LVEF in patients treated
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Fig. 1. Linear correlation between plasma copeptin and baseline (r = −0.49, p = 0.001, A) as well as 12 months (r = −0.36, p = 0.022), B) left ventricular ejection fraction in patients after acute STEMI (n = 41).
with p-PCI for STEMI. In addition, copeptin only moderately predicts the occurrence of adverse remodeling over a period of up to 1 year after STEMI. After STEMI, both infarct mass and myocardial function will dynamically change over time [7]. These parameters can be assessed accurately by CMR [3] and have been shown to strongly correlate with poor outcome [8]. We found that baseline copeptin concentrations were significantly correlated with acute and 12 month infarct size. Moreover, copeptin was related with LVEF at baseline and follow-up. This data suggests a potential role of copeptin as a longterm predictor of myocardial function after acute STEMI treated with p-PCI. Adverse remodeling occurs frequently after STEMI and is associated with higher morbidity and mortality [9]. Copeptin was shown to be a predictor for the risk of adverse remodeling 4 months after acute myocardial infarction [2]. In this study, baseline copeptin was also a moderate predictor for the occurrence of adverse remodeling at 12 months. To conclude, copeptin has the potential to be a useful biomarker for prediction of long-term myocardial function and thus potential outcome. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology.
References [1] Yalta K, Yalta T, Sivri N, Yetkin E. Copeptin and cardiovascular disease: a review of a novel neurohormone. Int J Cardiol Sep 1 2013;167(5):1750–9. [2] Reinstadler SJ, Klug G, Feistritzer HJ, et al. Association of copeptin with myocardial infarct size and myocardial function after ST segment elevation myocardial infarction. Heart Oct 2013;99(20):1525–9. [3] Klug G, Metzler B. Assessing myocardial recovery following ST-segment elevation myocardial infarction: short- and long-term perspectives using cardiovascular magnetic resonance. Expert Rev Cardiovasc Ther Feb 2013;11(2):203–19. [4] Reichlin T, Hochholzer W, Stelzig C, et al. Incremental value of copeptin for rapid rule out of acute myocardial infarction. J Am Coll Cardiol Jun 30 2009;54(1):60–8. [5] Mayr A, Klug G, Schocke M, et al. Late microvascular obstruction after acute myocardial infarction: relation with cardiac and inflammatory markers. Int J Cardiol Jun 14 2012;157(3):391–6. [6] Mayr A, Mair J, Schocke M, et al. Predictive value of NT-pro BNP after acute myocardial infarction: relation with acute and chronic infarct size and myocardial function. Int J Cardiol Feb 17 2011;147(1):118–23. [7] Pokorney SD, Rodriguez JF, Ortiz JT, Lee DC, Bonow RO, Wu E. Infarct healing is a dynamic process following acute myocardial infarction. J Cardiovasc Magn Reson 2012;14:62. [8] Lonborg J, Vejlstrup N, Kelbaek H, et al. Final infarct size measured by cardiovascular magnetic resonance in patients with ST elevation myocardial infarction predicts longterm clinical outcome: an observational study. Eur Heart J Cardiovasc Imaging Apr 2013;14(4):387–95. [9] Bolognese L, Neskovic AN, Parodi G, et al. Left ventricular remodeling after primary coronary angioplasty: patterns of left ventricular dilation and long-term prognostic implications. Circulation Oct 29 2002;106(18):2351–7.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Long-term predictive value of copeptin after acute myocardial infarction: A cardiac magnetic resonance study Sebastian Johannes Reinstadler a, Gert Klug a, Hans-Josef Feistritzer a, Johannes Mair a, Michael Schocke b, Wolfgang-Michael Franz a, Bernhard Metzler a,⁎ a b
University Clinic of Internal Medicine III, Cardiology, Innsbruck Medical University, Austria Department of Radiology, Innsbruck Medical University, Austria
a r t i c l e
i n f o
Article history: Received 18 December 2013 Accepted 30 December 2013 Available online 16 January 2014 Keywords: Copeptin ST-segment elevation myocardial infarction Cardiac magnetic resonance
Circulating copeptin, the C-terminal portion of the vasopressin precursor molecule, is an established marker of acute stress. Multiple studies demonstrated an association of copeptin with disease severity and progression in different patient populations such as stroke, pneumonia and acute myocardial infarction (AMI) [1]. Recently, we have shown that copeptin correlated with acute and 4-month infarct size and myocardial function in patients after ST-segment elevation AMI (STEMI) [2]. Moreover, copeptin was shown to identify patients with low risk for the development of adverse remodeling at 4 months after STEMI. In this study, the assessment of cardiac morphology, function and infarct size was done by contrast-enhanced cardiovascular magnetic resonance imaging (CMR), which is the method of choice to determine the above mentioned parameters [3]. Nevertheless, it is unknown, whether the association between early copeptin levels and AMI size and function is maintained beyond a mid-term follow-up of 4 months. Because of lack of long-term follow-up data we investigated the relationship between copeptin levels and 12 month myocardial infarct size and functional parameters. Forty-one STEMI patients successfully treated with primary percutaneous coronary intervention (p-PCI) were included as described previously [2]. Blood samples were collected at 2 days (IQR = 1–3) after
⁎ Corresponding author at: University Clinic of Internal Medicine III, Cardiology, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck, Austria. Tel.: +43 512 504 81315; fax: +43 512 504 22767. E-mail address: [email protected] (B. Metzler). 0167-5273/$ – see front matter © 2014 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.12.301
STEMI. Plasma copeptin levels were measured by an established immunofluorescent assay (Thermo Fisher Scientific, B.R.A.H.M.S., Henningsdorf, Germany) [4]. All participants underwent CMR within the first week after STEMI and 12 months thereafter. CMR scans were performed on a 1.5 Tesla AVANTO-scanner (Siemens, Erlangen, Germany) according to a standardized protocol published previously [5,6]. Infarct size was evaluated on late gadolinium enhanced images. Left ventricular volumes and function were measured by cine true-FISP sequences. Statistical analysis was performed using the SPSS 19.0.0 (IBM, Armonk, NY, USA) software for Windows. Pearson or Spearman rank correlations were calculated as appropriate. To calculate the predictive value of copeptin for the occurrence of adverse remodeling, receiver operating characteristic curve analysis was performed. An increase in end-diastolic volume ≥20% was defined as a surrogate marker of adverse remodeling. A two-tailed p-value b 0.05 was considered to indicate statistical significance. The study was approved by the local ethical committee and informed consent was obtained from all patients. The median copeptin concentration was 10.3 pmol/l (IQR = 5.8– 13.2). The mean infarct size at baseline was 18.2 ± 10.0% of left ventricular myocardial mass (LVMM) and 10.8 ± 6.7% of LVMM 12 months thereafter (significant difference; p b 0.01). The mean left ventricular ejection fraction (LVEF) was 55 ± 11% at baseline and 54 ± 12% at 12 months (difference not significant; p N 0.05). Copeptin levels were positively correlated to baseline (r = 0.42, p = 0.006) and 12 month infarct size (r = 0.40, p = 0.011). There were also significant correlations for copeptin with baseline stroke volumes (r = −0.48, p = 0.002) and 12 month end-systolic volumes (r = 0.32, p = 0.039). No correlation was found between copeptin and baseline end-systolic and end-diastolic volumes or 12 month end-diastolic volumes and stroke volume (all p N 0.07). Copeptin was significantly related to acute and 12 month LVEF (r = − 0.49, p = 0.001, baseline; r = − 0.36, p = 0.022, 12 months; Fig. 1). Moreover, patients with a preserved LVEF (N60%, n = 15) at 12 months after STEMI showed a significant lower baseline copeptin value than patients with a reduced LVEF (b60%, n = 26) at follow-up (7.3 pmol/l vs. 12.2 pmol/l, p = 0.013). Finally, we made a distinction between patients with (n = 5) and without (n = 36) adverse remodeling 12 months after the acute event. The AUC of copeptin (0.67, 95% CI 0.47 to 0.86) with the optimal cut-off level of 11.8 pmol/l showed 60% sensitivity and 69% specificity for the prediction of remodeling at 12 month follow-up. This is the first study, showing that copeptin levels are significantly correlated with 12 month infarct size and LVEF in patients treated
e360
S.J. Reinstadler et al. / International Journal of Cardiology 172 (2014) e359–e360
Fig. 1. Linear correlation between plasma copeptin and baseline (r = −0.49, p = 0.001, A) as well as 12 months (r = −0.36, p = 0.022), B) left ventricular ejection fraction in patients after acute STEMI (n = 41).
with p-PCI for STEMI. In addition, copeptin only moderately predicts the occurrence of adverse remodeling over a period of up to 1 year after STEMI. After STEMI, both infarct mass and myocardial function will dynamically change over time [7]. These parameters can be assessed accurately by CMR [3] and have been shown to strongly correlate with poor outcome [8]. We found that baseline copeptin concentrations were significantly correlated with acute and 12 month infarct size. Moreover, copeptin was related with LVEF at baseline and follow-up. This data suggests a potential role of copeptin as a longterm predictor of myocardial function after acute STEMI treated with p-PCI. Adverse remodeling occurs frequently after STEMI and is associated with higher morbidity and mortality [9]. Copeptin was shown to be a predictor for the risk of adverse remodeling 4 months after acute myocardial infarction [2]. In this study, baseline copeptin was also a moderate predictor for the occurrence of adverse remodeling at 12 months. To conclude, copeptin has the potential to be a useful biomarker for prediction of long-term myocardial function and thus potential outcome. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology.
References [1] Yalta K, Yalta T, Sivri N, Yetkin E. Copeptin and cardiovascular disease: a review of a novel neurohormone. Int J Cardiol Sep 1 2013;167(5):1750–9. [2] Reinstadler SJ, Klug G, Feistritzer HJ, et al. Association of copeptin with myocardial infarct size and myocardial function after ST segment elevation myocardial infarction. Heart Oct 2013;99(20):1525–9. [3] Klug G, Metzler B. Assessing myocardial recovery following ST-segment elevation myocardial infarction: short- and long-term perspectives using cardiovascular magnetic resonance. Expert Rev Cardiovasc Ther Feb 2013;11(2):203–19. [4] Reichlin T, Hochholzer W, Stelzig C, et al. Incremental value of copeptin for rapid rule out of acute myocardial infarction. J Am Coll Cardiol Jun 30 2009;54(1):60–8. [5] Mayr A, Klug G, Schocke M, et al. Late microvascular obstruction after acute myocardial infarction: relation with cardiac and inflammatory markers. Int J Cardiol Jun 14 2012;157(3):391–6. [6] Mayr A, Mair J, Schocke M, et al. Predictive value of NT-pro BNP after acute myocardial infarction: relation with acute and chronic infarct size and myocardial function. Int J Cardiol Feb 17 2011;147(1):118–23. [7] Pokorney SD, Rodriguez JF, Ortiz JT, Lee DC, Bonow RO, Wu E. Infarct healing is a dynamic process following acute myocardial infarction. J Cardiovasc Magn Reson 2012;14:62. [8] Lonborg J, Vejlstrup N, Kelbaek H, et al. Final infarct size measured by cardiovascular magnetic resonance in patients with ST elevation myocardial infarction predicts longterm clinical outcome: an observational study. Eur Heart J Cardiovasc Imaging Apr 2013;14(4):387–95. [9] Bolognese L, Neskovic AN, Parodi G, et al. Left ventricular remodeling after primary coronary angioplasty: patterns of left ventricular dilation and long-term prognostic implications. Circulation Oct 29 2002;106(18):2351–7.
