2232
CORRESPONDENCE
From 1999 through 2010, 12,113 patients underwent various types of cardiac surgical procedures at the Feiring Heart Clinic. Survival was established through the Norwegian National Registry, and the follow-up was 100% complete. The mean follow-up time was 7.4 years (range, 0 to 14.3 years). The total time at risk for the whole cohort was 89,268 patient-years. The number of all-cause deaths was 2,962 (24.9%). Figure 1 depicts survival after univariable analyses. The risk seemed to increase at AST above 100 U/L and the higher the AST level is. However, after multivariable adjustments by use of Cox regression, the hazard ratio (HR) was significantly increased only in group 5 (HR 2.11; 95% confidence interval 1.65 to 2.71; p < 0.001). Thus, the cutoff point in our series is at AST more than 300 U/L (group 5), whereas in the previous study the hazard ratio was also increased in groups 3 and 4 after multivariable adjustments. The difference might in some respect be explained by the previous study’s inclusion of only patients with coronary artery bypass grafting, whereas our series was a case mix of various cardiac operations. AST is a nonspecific cardiac marker. More specific markers such as creatinine kinase myocardial band or troponins seem to predict a worse prognosis to a higher extent than was found in our study on AST [3]. Sven M. Almdahl, MD, PhD Department of Cardiac Surgery Feiring Heart Clinic Feiring, Norway Department of Cardiothoracic and Vascular Surgery University Hospital of North Norway 9038 Tromsø, Norway e-mail: [email protected] Terje Veel, MD, PhD Department of Cardiac Surgery Feiring Heart Clinic Feiring, Norway
Ann Thorac Surg 2014;97:2228–34
In the comment by Almdahl and colleagues [1], the results of their multivariate Cox regression analysis showed that the hazard ratio (HR) is only significantly increased when the AST is greater than 300 U/L. As the authors also addressed, the difference in the results might be that their study included various types of cardiac surgical procedures. In our study, only patients who underwent isolated CABG were included in the analysis. We are working on an analysis of patients who underwent isolated valve replacement to examine the predictive value of AST for early and late mortality. However, we agree with the authors that AST is not a specific marker for the diagnosis of perioperative myocardial infarction. As we addressed earlier [3], AST measurement can be used as a screening method for perioperative myocardial infarction and therefore help in early detection and treatment of the adverse effects of this serious complication [3]. Astrid G. M. van Boxtel, MD Albert H. M. van Straten, MD, PhD Mohamed A. Soliman Hamad, MD, PhD Department of Cardiothoracic Surgery Catharina Hospital Michelangelolaan 2 Postbus 1350, 5602 ZA Eindhoven The Netherlands e-mail: [email protected]
References 1. Almdahl SM, Veel T, Mølstad P. Aspartate aminotransferase and survival after cardiac surgical procedures (letter). Ann Thorac Surg 2014;97:2231–2. 2. van Boxtel AGM, Bramer S, Soliman Hamad MA, van Straten AHM. Perioperative serum aspartate aminotransferase level as a predictor of survival after coronary artery bypass grafting. Ann Thorac Surg 2012;94:1492–8. 3. van Boxtel AGM, van straten AHM, Bramer S, Soliman Hamad MA. Reply: Can aspartate aminotransferase diagnose peri-operative myocardial infarction? Ann Thorac Surg 2013;96:740.
Per Mølstad, MD, PhD Department of Cardiology Feiring Heart Clinic Feiring, Norway
References
MISCELLANEOUS
1. van Boxtel AGM, Bramer S, Soliman Hamad MA, van Straten AHM. Perioperative serum aspartate aminotransferase level as a predictor of survival after coronary artery bypass grafting. Ann Thorac Surg 2012;94:1492–8. 2. Deb S, Fremes S. Invited commentary. Ann Thorac Surg 2012;94:1498–9. 3. Domanski MJ, Mahaffey K, Hasselblad V, et al. Association of myocardial enzyme elevation and survival following coronary artery bypass graft surgery. JAMA 2011;305:585–91.
Reply To the Editor: We would like to thank Dr Almdahl for his comment [1] on our study [2]. In our study, we presented the correlation between increased postoperative aspartate aminotransferase (AST) levels and higher risk for early and late mortality after isolated coronary artery bypass grafting (CABG). AST was identified as an independent predictor for early and late mortality after CABG. Ó 2014 by The Society of Thoracic Surgeons Published by Elsevier Inc
Is Microplegia Superior to Regular Blood Cardioplegia During Coronary Artery Bypass Grafting? To the Editor: We read with great interest the recent article by Dr Algarni and colleagues [1] that reported a retrospective study comparing microplegia with standard 8:1 blood cardioplegia in patients undergoing isolated coronary artery bypass graft (CABG) surgery. They should be congratulated for their excellent work on this issue. Standard diluted cardioplegia and whole blood cardioplegia (microplegia) are commonly used to arrest and protect the heart during some kinds of heart surgery. Microplegia retain all the advantages of blood cardioplegia (e.g., superior oxygen-carrying capacity, better osmotic properties and antioxidant capability) without the potential disadvantages of hemodilution [2, 3]. However, the clinical advantage of microplegia remains uncertain. In this retrospective study, the authors compared diluted blood cardioplegia (8 blood to 1 crystalloid) with microplegia (at least 66 blood to 1 crystalloid) using a propensity score method, and they concluded that microplegia was associated with a lower incidence of postoperative low cardiac output syndrome. However, according to our unpublished data of a meta-analysis comparing diluted blood 0003-4975/$36.00
Ann Thorac Surg 2014;97:2228–34
cardioplegia with microplegia, there was no statistical significance concerning incidence of postoperative low output syndrome (relative risk [RR], 0.95; 95% confidence interval [CI] 0.55–1.62), rate of spontaneous return to sinus rhythm (RR, 1.64; 95% CI, 0.61–4.41), and perioperative myocardial infarction (RR, 0.62; 95% CI, 0.19– 2.08). The only difference between these two groups was the volume of cardioplegia (weighted mean difference, –514.79; 95% CI, –705.37 to –324.21) used during surgery. The authors thought that standard diluted cardioplegia could cause myocardial edema compared with microplegia; however, they might have ignored the fact that microplegia could cause coronary artery endothelium dysfunction [4]. In addition, the potential consequence of endothelium dysfunction is a predisposition to postoperative cardiac dysfunction, thrombosis, or larger infarction size. It is likely that myocardial edema and endothelium dysfunction are the two countervailing forces between the two groups that produced equal rates of postoperative low output syndrome in the surgical setting. Although the results could be the same with using these kinds of cardioplegia, another benefit of microcardioplegia is its lack of extra volume to dilute the pump system. It could be used as a part of blood conservation during cardiopulmonary compared with diluted cardioplegia. More evidence from large, randomized, controlled trials is needed to settle the dispute and to determine which one is better and more suitable for CABG patients. Bing Gong Yanhua Sun Zhe Zheng Bingyang Ji, MD Department of Cardiac Surgery State Key Laboratory of Cardiovascular Disease Fuwai Hospital, National Center for Cardiovascular Diseases Chinese Academy of Medical Sciences and Peking Union Medical College Beijing, China Department of Cardiopulmonary Bypass State Key Laboratory of Cardiovascular Disease, Fuwai Hospital National Center for Cardiovascular Diseases Chinese Academy of Medical Sciences and Peking Union Medical College Beijing, China e-mail: [email protected]
CORRESPONDENCE
2233
rigorous statistical methods to adjust for confounding [2]. We used the propensity score analysis to account for confounders [3]. We realize, however, the limitations of propensity score analysis, as stated in the discussion section of our paper. Although the propensity score can account for known confounders that are included in the multivariable model, it does not account for unknown confounders [4]. Moreover, despite control of all of the known confounders, the effect of the time trend is a potential confounder that might not have been controlled adequately in our study. In addition, our results do not imply causality as many unknown and subtle changes in perioperative management may have been associated with the improved results found between 2001 and 2006. Nonetheless, our operative techniques and postoperative management remained similar during the time of these two cohorts. We agree that it is still possible, at least theoretically, that the lower prevalence of low cardiac output syndrome in the microplegia group is due to unknown confounders for which the propensity score analysis did not account. A randomized clinical trial will be required to determine the potential benefits of microplegia conclusively. Until then, however, we believe that our study provides credible evidence of the benefit of microplegia compared with diluted blood cardioplegia. Regarding the potential association between microplegia and endothelial dysfunction, we are not aware of any study that demonstrated credible evidence in this regard. We look forward to reading the authors’ meta-analysis comparing diluted blood cardioplegia with microplegia once it is published. Khaled D. Algarni, MD, MHSc Richard D. Weisel, MD, FRCSC Christopher A. Caldarone, MD, FRCSC Manjula Maganti, MSc Katherine Tsang, RN, MN Terrence M. Yau, MD, FRCSC Department of Cardiac Surgery University of Toronto 196 Westmount Rd North Apartment 216 Waterloo, Ontario, Canada N2L 3G5 e-mail: [email protected]
References 1. Algarni KD, Weisel RD, Caldarone CA, Maganti M, Tsang K, Yau TM. Microplegia during coronary artery bypass grafting was associated with less low cardiac output syndrome: a propensity-matched comparison. Ann Thorac Surg 2013;95: 1532–8. 2. Menasche P. Blood cardioplegia: Do we still need to dilute? Ann Thorac Surg 1996;62:957–60. 3. Menasche P, Touchot B, Pradier F, Bloch G, Piwnica A. Simplified method for delivering normothermic blood cardioplegia. Ann Thorac Surg 1993;55:177–8. 4. Guru V, Omura J, Alghamdi AA, Weisel R, Fremes SE. Is blood superior to crystalloid cardioplegia? A meta-analysis of randomized clinical trials. Circulation 2006;114(1 Suppl):I331–8.
Reply To the Editor: We thank Gong and colleagues for their comments [1]. Our study is the first study that compared microplegia and diluted blood cardioplegia with a large sample size and with the application of Ó 2014 by The Society of Thoracic Surgeons Published by Elsevier Inc
1. Gong B, Sun Y, Zheng Z, Ji B. Is microplegia superior to regular blood cardioplegia during coronary artery bypass grafting? (letter). Ann Thorac Surg 2014;97:2232–3. 2. Algarni KD, Weisel RD, Caldarone CA, Maganti M, Tsang K, Yau TM. Microplegia during coronary artery bypass grafting was associated with less low cardiac output syndrome: a propensitymatched comparison. Ann Thorac Surg 2013;95:1532–8. 3. Parson LS. Reducing bias in a propensity score matched-pair sample using greedy matching techniques. Proceedings of the Twenty-sixth Annual SAS Users Group International Conference, Long Beach, CA, 2001. 4. Rubin DB. The design versus the analysis of observational studies for causal effects: parallels with the design of randomized trials. Stat Med 2007;26:20–36.
Retrograde Cardioplegia for Myocardial Protection During Arterial Switch Operation To the Editor: We read with great interest the article by Bojan and colleagues [1] in which they described myocardial protection techniques for the 0003-4975/$36.00
MISCELLANEOUS
References
CORRESPONDENCE
From 1999 through 2010, 12,113 patients underwent various types of cardiac surgical procedures at the Feiring Heart Clinic. Survival was established through the Norwegian National Registry, and the follow-up was 100% complete. The mean follow-up time was 7.4 years (range, 0 to 14.3 years). The total time at risk for the whole cohort was 89,268 patient-years. The number of all-cause deaths was 2,962 (24.9%). Figure 1 depicts survival after univariable analyses. The risk seemed to increase at AST above 100 U/L and the higher the AST level is. However, after multivariable adjustments by use of Cox regression, the hazard ratio (HR) was significantly increased only in group 5 (HR 2.11; 95% confidence interval 1.65 to 2.71; p < 0.001). Thus, the cutoff point in our series is at AST more than 300 U/L (group 5), whereas in the previous study the hazard ratio was also increased in groups 3 and 4 after multivariable adjustments. The difference might in some respect be explained by the previous study’s inclusion of only patients with coronary artery bypass grafting, whereas our series was a case mix of various cardiac operations. AST is a nonspecific cardiac marker. More specific markers such as creatinine kinase myocardial band or troponins seem to predict a worse prognosis to a higher extent than was found in our study on AST [3]. Sven M. Almdahl, MD, PhD Department of Cardiac Surgery Feiring Heart Clinic Feiring, Norway Department of Cardiothoracic and Vascular Surgery University Hospital of North Norway 9038 Tromsø, Norway e-mail: [email protected] Terje Veel, MD, PhD Department of Cardiac Surgery Feiring Heart Clinic Feiring, Norway
Ann Thorac Surg 2014;97:2228–34
In the comment by Almdahl and colleagues [1], the results of their multivariate Cox regression analysis showed that the hazard ratio (HR) is only significantly increased when the AST is greater than 300 U/L. As the authors also addressed, the difference in the results might be that their study included various types of cardiac surgical procedures. In our study, only patients who underwent isolated CABG were included in the analysis. We are working on an analysis of patients who underwent isolated valve replacement to examine the predictive value of AST for early and late mortality. However, we agree with the authors that AST is not a specific marker for the diagnosis of perioperative myocardial infarction. As we addressed earlier [3], AST measurement can be used as a screening method for perioperative myocardial infarction and therefore help in early detection and treatment of the adverse effects of this serious complication [3]. Astrid G. M. van Boxtel, MD Albert H. M. van Straten, MD, PhD Mohamed A. Soliman Hamad, MD, PhD Department of Cardiothoracic Surgery Catharina Hospital Michelangelolaan 2 Postbus 1350, 5602 ZA Eindhoven The Netherlands e-mail: [email protected]
References 1. Almdahl SM, Veel T, Mølstad P. Aspartate aminotransferase and survival after cardiac surgical procedures (letter). Ann Thorac Surg 2014;97:2231–2. 2. van Boxtel AGM, Bramer S, Soliman Hamad MA, van Straten AHM. Perioperative serum aspartate aminotransferase level as a predictor of survival after coronary artery bypass grafting. Ann Thorac Surg 2012;94:1492–8. 3. van Boxtel AGM, van straten AHM, Bramer S, Soliman Hamad MA. Reply: Can aspartate aminotransferase diagnose peri-operative myocardial infarction? Ann Thorac Surg 2013;96:740.
Per Mølstad, MD, PhD Department of Cardiology Feiring Heart Clinic Feiring, Norway
References
MISCELLANEOUS
1. van Boxtel AGM, Bramer S, Soliman Hamad MA, van Straten AHM. Perioperative serum aspartate aminotransferase level as a predictor of survival after coronary artery bypass grafting. Ann Thorac Surg 2012;94:1492–8. 2. Deb S, Fremes S. Invited commentary. Ann Thorac Surg 2012;94:1498–9. 3. Domanski MJ, Mahaffey K, Hasselblad V, et al. Association of myocardial enzyme elevation and survival following coronary artery bypass graft surgery. JAMA 2011;305:585–91.
Reply To the Editor: We would like to thank Dr Almdahl for his comment [1] on our study [2]. In our study, we presented the correlation between increased postoperative aspartate aminotransferase (AST) levels and higher risk for early and late mortality after isolated coronary artery bypass grafting (CABG). AST was identified as an independent predictor for early and late mortality after CABG. Ó 2014 by The Society of Thoracic Surgeons Published by Elsevier Inc
Is Microplegia Superior to Regular Blood Cardioplegia During Coronary Artery Bypass Grafting? To the Editor: We read with great interest the recent article by Dr Algarni and colleagues [1] that reported a retrospective study comparing microplegia with standard 8:1 blood cardioplegia in patients undergoing isolated coronary artery bypass graft (CABG) surgery. They should be congratulated for their excellent work on this issue. Standard diluted cardioplegia and whole blood cardioplegia (microplegia) are commonly used to arrest and protect the heart during some kinds of heart surgery. Microplegia retain all the advantages of blood cardioplegia (e.g., superior oxygen-carrying capacity, better osmotic properties and antioxidant capability) without the potential disadvantages of hemodilution [2, 3]. However, the clinical advantage of microplegia remains uncertain. In this retrospective study, the authors compared diluted blood cardioplegia (8 blood to 1 crystalloid) with microplegia (at least 66 blood to 1 crystalloid) using a propensity score method, and they concluded that microplegia was associated with a lower incidence of postoperative low cardiac output syndrome. However, according to our unpublished data of a meta-analysis comparing diluted blood 0003-4975/$36.00
Ann Thorac Surg 2014;97:2228–34
cardioplegia with microplegia, there was no statistical significance concerning incidence of postoperative low output syndrome (relative risk [RR], 0.95; 95% confidence interval [CI] 0.55–1.62), rate of spontaneous return to sinus rhythm (RR, 1.64; 95% CI, 0.61–4.41), and perioperative myocardial infarction (RR, 0.62; 95% CI, 0.19– 2.08). The only difference between these two groups was the volume of cardioplegia (weighted mean difference, –514.79; 95% CI, –705.37 to –324.21) used during surgery. The authors thought that standard diluted cardioplegia could cause myocardial edema compared with microplegia; however, they might have ignored the fact that microplegia could cause coronary artery endothelium dysfunction [4]. In addition, the potential consequence of endothelium dysfunction is a predisposition to postoperative cardiac dysfunction, thrombosis, or larger infarction size. It is likely that myocardial edema and endothelium dysfunction are the two countervailing forces between the two groups that produced equal rates of postoperative low output syndrome in the surgical setting. Although the results could be the same with using these kinds of cardioplegia, another benefit of microcardioplegia is its lack of extra volume to dilute the pump system. It could be used as a part of blood conservation during cardiopulmonary compared with diluted cardioplegia. More evidence from large, randomized, controlled trials is needed to settle the dispute and to determine which one is better and more suitable for CABG patients. Bing Gong Yanhua Sun Zhe Zheng Bingyang Ji, MD Department of Cardiac Surgery State Key Laboratory of Cardiovascular Disease Fuwai Hospital, National Center for Cardiovascular Diseases Chinese Academy of Medical Sciences and Peking Union Medical College Beijing, China Department of Cardiopulmonary Bypass State Key Laboratory of Cardiovascular Disease, Fuwai Hospital National Center for Cardiovascular Diseases Chinese Academy of Medical Sciences and Peking Union Medical College Beijing, China e-mail: [email protected]
CORRESPONDENCE
2233
rigorous statistical methods to adjust for confounding [2]. We used the propensity score analysis to account for confounders [3]. We realize, however, the limitations of propensity score analysis, as stated in the discussion section of our paper. Although the propensity score can account for known confounders that are included in the multivariable model, it does not account for unknown confounders [4]. Moreover, despite control of all of the known confounders, the effect of the time trend is a potential confounder that might not have been controlled adequately in our study. In addition, our results do not imply causality as many unknown and subtle changes in perioperative management may have been associated with the improved results found between 2001 and 2006. Nonetheless, our operative techniques and postoperative management remained similar during the time of these two cohorts. We agree that it is still possible, at least theoretically, that the lower prevalence of low cardiac output syndrome in the microplegia group is due to unknown confounders for which the propensity score analysis did not account. A randomized clinical trial will be required to determine the potential benefits of microplegia conclusively. Until then, however, we believe that our study provides credible evidence of the benefit of microplegia compared with diluted blood cardioplegia. Regarding the potential association between microplegia and endothelial dysfunction, we are not aware of any study that demonstrated credible evidence in this regard. We look forward to reading the authors’ meta-analysis comparing diluted blood cardioplegia with microplegia once it is published. Khaled D. Algarni, MD, MHSc Richard D. Weisel, MD, FRCSC Christopher A. Caldarone, MD, FRCSC Manjula Maganti, MSc Katherine Tsang, RN, MN Terrence M. Yau, MD, FRCSC Department of Cardiac Surgery University of Toronto 196 Westmount Rd North Apartment 216 Waterloo, Ontario, Canada N2L 3G5 e-mail: [email protected]
References 1. Algarni KD, Weisel RD, Caldarone CA, Maganti M, Tsang K, Yau TM. Microplegia during coronary artery bypass grafting was associated with less low cardiac output syndrome: a propensity-matched comparison. Ann Thorac Surg 2013;95: 1532–8. 2. Menasche P. Blood cardioplegia: Do we still need to dilute? Ann Thorac Surg 1996;62:957–60. 3. Menasche P, Touchot B, Pradier F, Bloch G, Piwnica A. Simplified method for delivering normothermic blood cardioplegia. Ann Thorac Surg 1993;55:177–8. 4. Guru V, Omura J, Alghamdi AA, Weisel R, Fremes SE. Is blood superior to crystalloid cardioplegia? A meta-analysis of randomized clinical trials. Circulation 2006;114(1 Suppl):I331–8.
Reply To the Editor: We thank Gong and colleagues for their comments [1]. Our study is the first study that compared microplegia and diluted blood cardioplegia with a large sample size and with the application of Ó 2014 by The Society of Thoracic Surgeons Published by Elsevier Inc
1. Gong B, Sun Y, Zheng Z, Ji B. Is microplegia superior to regular blood cardioplegia during coronary artery bypass grafting? (letter). Ann Thorac Surg 2014;97:2232–3. 2. Algarni KD, Weisel RD, Caldarone CA, Maganti M, Tsang K, Yau TM. Microplegia during coronary artery bypass grafting was associated with less low cardiac output syndrome: a propensitymatched comparison. Ann Thorac Surg 2013;95:1532–8. 3. Parson LS. Reducing bias in a propensity score matched-pair sample using greedy matching techniques. Proceedings of the Twenty-sixth Annual SAS Users Group International Conference, Long Beach, CA, 2001. 4. Rubin DB. The design versus the analysis of observational studies for causal effects: parallels with the design of randomized trials. Stat Med 2007;26:20–36.
Retrograde Cardioplegia for Myocardial Protection During Arterial Switch Operation To the Editor: We read with great interest the article by Bojan and colleagues [1] in which they described myocardial protection techniques for the 0003-4975/$36.00
MISCELLANEOUS
References
