- Email: [email protected]
Aortic Valve Disease With Concomitant Proximal Aorta Dilation: Surgical Strategy
1502
CORRESPONDENCE
1. We chose to focus on the results of one surgeon as this was the patient population available to us for the purposes of this project. These patients were accumulated consecutively over a period of months. We are seeking to expand our study with more surgeons, institutions, and patients. 2. We would agree that intrathoracic physiology is likely altered to a greater degree after extended resection when compared with more limited resections. Although this data was not included in this article, we have not yet found an increased incidence of aspiration or dysphagia based on extent of pulmonary resection. 3. Although we would have preferred to avoid patients with the mentioned preoperative comorbidities, this was simply not possible, as it would have greatly reduced our patient population. Also, these are rather common preoperative comorbidities for this patient population, so to have omitted them would have given an unsatisfactory representation of the true incidence of disease. 4. Ismail and colleagues [1] are correct in stating that we did not specifically gather data in regard to the nature of the head and neck malignancy in this series of patients. For a more complete review on this topic, please see the excellent work of Herrera and colleagues [3]. There were no patients with either primary brain tumors or metastatic lesions to the brain in this series of patients. 5. As previously stated, we plan to expand the scope of this research to include more surgeons, patients, and institutions. I am sure that Dr Ismail would agree in excluding patients with esophageal resection from this research as it is an entire topic unto itself and has been researched extensively. Again, we thank Ismail and colleagues [1] for their insight and interest. William Brent Keeling, MD Keith Eric Sommers, MD Department of Surgery H. Lee Moffit Cancer and Research Center University of South Florida 12902 Magnolia Dr Tampa, FL 33612 e-mail: [email protected]; [email protected]
References
MISCELLANEOUS
1. Ismail MF, El-Refael Hammad RI, El-Sayed Sersar SI, ElGhoneimy YAF. Aspiration after thoracotomy (letter). Ann Thorac Surg 2008;85:1501. 2. Keeling WB, Lewis V, Blazick E, Maxey TS, Garrett JR, Sommers KE. Routine evaluation for aspiration after thoracotomy for pulmonary resection. Ann Thorac Surg 2007;83: 193– 6. 3. Herrera LJ, Correa AM, Vaporciyan AA, et al. Increased risk of aspiration and pulmonary complications after lung resection in head and neck cancer patients. Ann Thorac Surg 2006;82:1982–7; discussion 1987– 8.
Aortic Valve Disease With Concomitant Proximal Aorta Dilation: Surgical Strategy To the Editor: We read with utmost interest the article by Reece and colleagues [1], in which an aggressive strategy toward concomitant dilata© 2008 by The Society of Thoracic Surgeons Published by Elsevier Inc
Ann Thorac Surg 2008;85:1500 – 6
tion of the proximal aorta in patients with aortic valve disease was strongly recommended, even in moderately dilated aortas (ie, with a diameter exceeding 5.0 cm). To further support this thesis, we would like to report our personal experience with a cohort of 38 patients with slightly dilated proximal aortas (from 40 to 55 mm) and aortic valve disease that for several reasons were not submitted to any surgical procedure beside aortic valve replacement, and were subsequently followed-up over time (follow-up median duration: 36 months) [2]. Briefly, we identified three different behaviors of the proximal aorta during the follow-up: (1) no significant change, (2) increased growth velocity of the aortic diameter without reaching the limit of 55 mm (ie, the commonly accepted indication to an ascending aorta replacement), and (3) increase of the proximal aorta reaching 55 mm or actual rupture. Two patients fell in the second group with a mean growth velocity of 1.1 and 1.5 mm per year, and therefore entered a close-interval follow-up protocol. Five of 36 early survivors reached an aortic diameter of 55 mm or larger (third group), and were subsequently operated on (1 with acute rupture). The only predictive factor associated with a velocity growth exceeding 1 mm per year was the preoperative diameter (R ⫽ 0.60; p ⫽ 0.0004). A more complex polynomial fitting in the regression model demonstrated an abrupt increase of growth velocity in the aorta with a preoperative diameter of 50 mm or more (R ⫽ 0.83; p ⬍ 0.0001). Therefore, we advocated replacement (or at least a reduction plasty) of the ascending aorta at a level of approximately 48 to 50 mm, even in patients with no additional well-known risk factors, as the presence of a bicuspid aortic valve or a Marfan syndrome. Once it was demonstrated that the combined operation could be performed without an additional risk, carrying the important advantage of eliminating the threat for later reoperations [1], we believe that an aggressive approach should be strongly suggested when dealing with the quite common setting of concomitant aortic valve and proximal aorta disease. Patients with additional risk factors should probably be submitted to ascending aorta replacement or repair even at lower levels of dilation (ie, at approximately 43 to 45 mm). Just one word of caution might be used in the case of isolated aortic stenosis with mild dilatation of the ascending aorta, and that is, in our experience, the immediate resolution of the fluid-dynamics that led to aortic expansion by means of the valve replacement might be sufficient to prevent further dilatation. In patients with prevalent aortic regurgitation, the volume overload of the proximal aorta persists after valve replacement, thus perpetuating the hemodynamic harm to the aortic wall. Actually, in our series, the aortic growth velocity was ⫺0.6 ⫾ 1.5 mm per year in patients with prevalent stenosis, and 1.4 ⫾ 4.8 mm per year in patients with prevalent regurgitation. However, this difference was only marginally significant, with p ⫽ 0.10 [2]. Carlo Bassano, MD, PhD Luigi Chiariello, MD Department of Cardiac Surgery Tor Vergata University Viale Oxford 84 Rome 00133, Italy e-mail: [email protected]
References 1. Reece TB, Singh RR, Stiles BM, et al. Replacement of the proximal aorta adds no further risk to aortic valve procedures. Ann Thorac Surg 2007;84:473– 8. 0003-4975/08/$34.00
Ann Thorac Surg 2008;85:1500 – 6
Reply To the Editor: We would like to thank Dr Bassano and Dr Chiariello for their kind comments [1] on our article regarding the aggressive replacement of the ascending aorta in patients undergoing aortic valve procedures [2]. Their experience supports the approach we presented. Their data provide further support that dilatation may indicate that the interstitium of the vessel wall is abnormal and therefore is prone to further dilatation. We agree that this dilatation is an indication for replacement, which we would prefer over aortoplasty, of the dilated ascending aorta in patients undergoing aortic valve procedures. T. Brett Reece, MD University of Colorado 12631 E 17th Ave, Rm 6602, MS C310 Aurora, CO 80045 e-mail: [email protected] Irving L. Kron, MD Thoracic and Cardiovascular Surgery University of Virginia Charlottesville, Virginia 22908 e-mail: [email protected]
References 1. Bassano C, Chiariello L. Aortic valve disease with concomitant proximal aorta dilation: surgical strategy (letter). Ann Thorac Surg 2008;85:1502–3. 2. Reece TB, Singh RR, Stiles BM, et al. Replacement of the proximal aorta adds no further risk to aortic valve procedures. Ann Thorac Surg 2007;84:473– 8.
Proteasome Inhibitors in Myocardial Ischemia, Some Concerns To the Editor: I read with great interest the article by Stansfield and coworkers [1] that reports observations suggesting that pretreatment of mice with the proteasome inhibitor, PS-519, decreases postischemic infarct size and preserves cardiac function through a mechanism that might be linked to changes in nuclear factor kappa B (NFB) signaling. Considering the critical role of the ubiquitin proteasome system in cardiac pathophysiology [2], this is an important study; however, certain issues with the experimental design, as well as interpretation of these studies require comment. There is concern that simply showing changes in IB levels and phosphorylation of p65 without measuring levels of total p65 may not be reflective of changes in activity of NFB. For these changes to be meaningful, transcriptional activity of NFB must be assessed, which is usually done by means of an electrophoretic mobility shift assay. However, of greater concern is the lack of assessment of proteasome activity in at least peripheral blood cells, if not in cardiac tissue. Without this data, it is unclear if a single dose of PS-519 had any effect on proteasome activity in any tissue (cardiac or blood), and thus if any of the observed effects are even related to proteasome © 2008 by The Society of Thoracic Surgeons Published by Elsevier Inc
1503
inhibition, or if these are extracardiac effects. The authors cite Zollner and coworkers [3] study as the source of this treatment protocol, which examined proteasome inhibition in the inflammatory processes. At issue is that Zollner and coworkers [3] first measured proteasome activity only after 4 days of treatment, not 1 dose, and that only 20S-proteasome or the non-ATPdependent activity was determined, which may not be reflective of the ATP-dependent degradation of ubiquitinated proteins by the 26S-proteasome [4]. For optimal interpretation of these studies, the authors should have assessed activity of the 26Sproteasome in both peripheral blood cells and heart. We have recently published a modification of the standard technique for analysis of both ATP-dependent and non-ATP-dependent activities of the proteasome in cardiac tissue, which simplifies this procedure [4]. The need for accurate assessment of proteasome activity is further exemplified by studies that show that proteasome may become dysfunctional as a result of myocardial ischemia [5]. Considering that significant inhibition of the proteasome is known to induce cellular apoptosis in a variety of tissues, including the heart [6], the wisdom of adding additional inhibition on top of pre-existing dysfunction is questionable. Using the isolated perfused heart preparation, which allows for assessment of direct effect of proteasome inhibitors on function, we have consistently observed that these compounds at best have little or no effect and may worsen postischemic function (reviewed in [2]), an observation recently confirmed by another group [7]. It is certainly conceivable that under the right conditions, the extracardiac anti-inflammatory effects of proteasome inhibition [3] could be beneficial. However, in light of a recent case report [8] of cardiac toxicity after bortezomib (Velcade; Millenium Pharmaceuticals Inc, Cambridge, MA) treatment for multiple myeloma, the prudent course would be to suggest caution before proposing use of proteasome inhibitors to treat myocardial infarction. Saul R. Powell, PhD The Feinstein Institute for Medical Research The Albert Einstein School of Medicine Department of Medicine The Long Island Jewish Medical Center 270-05 76th Ave Room B-387 New Hyde Park, NY 11042 e-mail: [email protected]
References 1. Stansfield WE, Moss NC, Willis MS, Tang R, Selzman C. Proteasome inhibition attenuates infarct size and preserves cardiac function in a murine model of myocardial ischemiareperfusion injury. Ann Thorac Surg 2007;84:120 –5. 2. Powell SR. The ubiquitin proteasome system in cardiac physiology and pathology. Am J Physiol Heart Circ Physiol 2006; 291:1–19. 3. Zollner TM, Podda M, Pien C, Elliott PJ, Kaufmann R, Boehncke WH. Proteasome inhibition reduces superantigenmediated T cell activation and the severity of psoriasis in a SCID-hu model. J Clin Invest 2002;109:671–9. 4. Powell SR, Davies KJA, Divald A. Optimal determination of heart tissue 26S proteasome activity requires maximal stimulating concentrations of ATP. J Mol Cell Cardiol 2007;42: 265–9. 5. Powell SR, Wang P, Katzeff HL, et al. Oxidized and ubiquitinated proteins may predict recovery of postischemic cardiac function. Essential role of the proteasome. Antioxid Redox Signal 2005;7:538 –5. 0003-4975/08/$34.00
MISCELLANEOUS
2. Bassano C, Fratticci L, Del Giudice C, et al. Ectasia of the ascending aorta at the time of aortic valve surgery: replace or relax? Italian Heart J 2005;6:968 –71.
CORRESPONDENCE
CORRESPONDENCE
1. We chose to focus on the results of one surgeon as this was the patient population available to us for the purposes of this project. These patients were accumulated consecutively over a period of months. We are seeking to expand our study with more surgeons, institutions, and patients. 2. We would agree that intrathoracic physiology is likely altered to a greater degree after extended resection when compared with more limited resections. Although this data was not included in this article, we have not yet found an increased incidence of aspiration or dysphagia based on extent of pulmonary resection. 3. Although we would have preferred to avoid patients with the mentioned preoperative comorbidities, this was simply not possible, as it would have greatly reduced our patient population. Also, these are rather common preoperative comorbidities for this patient population, so to have omitted them would have given an unsatisfactory representation of the true incidence of disease. 4. Ismail and colleagues [1] are correct in stating that we did not specifically gather data in regard to the nature of the head and neck malignancy in this series of patients. For a more complete review on this topic, please see the excellent work of Herrera and colleagues [3]. There were no patients with either primary brain tumors or metastatic lesions to the brain in this series of patients. 5. As previously stated, we plan to expand the scope of this research to include more surgeons, patients, and institutions. I am sure that Dr Ismail would agree in excluding patients with esophageal resection from this research as it is an entire topic unto itself and has been researched extensively. Again, we thank Ismail and colleagues [1] for their insight and interest. William Brent Keeling, MD Keith Eric Sommers, MD Department of Surgery H. Lee Moffit Cancer and Research Center University of South Florida 12902 Magnolia Dr Tampa, FL 33612 e-mail: [email protected]; [email protected]
References
MISCELLANEOUS
1. Ismail MF, El-Refael Hammad RI, El-Sayed Sersar SI, ElGhoneimy YAF. Aspiration after thoracotomy (letter). Ann Thorac Surg 2008;85:1501. 2. Keeling WB, Lewis V, Blazick E, Maxey TS, Garrett JR, Sommers KE. Routine evaluation for aspiration after thoracotomy for pulmonary resection. Ann Thorac Surg 2007;83: 193– 6. 3. Herrera LJ, Correa AM, Vaporciyan AA, et al. Increased risk of aspiration and pulmonary complications after lung resection in head and neck cancer patients. Ann Thorac Surg 2006;82:1982–7; discussion 1987– 8.
Aortic Valve Disease With Concomitant Proximal Aorta Dilation: Surgical Strategy To the Editor: We read with utmost interest the article by Reece and colleagues [1], in which an aggressive strategy toward concomitant dilata© 2008 by The Society of Thoracic Surgeons Published by Elsevier Inc
Ann Thorac Surg 2008;85:1500 – 6
tion of the proximal aorta in patients with aortic valve disease was strongly recommended, even in moderately dilated aortas (ie, with a diameter exceeding 5.0 cm). To further support this thesis, we would like to report our personal experience with a cohort of 38 patients with slightly dilated proximal aortas (from 40 to 55 mm) and aortic valve disease that for several reasons were not submitted to any surgical procedure beside aortic valve replacement, and were subsequently followed-up over time (follow-up median duration: 36 months) [2]. Briefly, we identified three different behaviors of the proximal aorta during the follow-up: (1) no significant change, (2) increased growth velocity of the aortic diameter without reaching the limit of 55 mm (ie, the commonly accepted indication to an ascending aorta replacement), and (3) increase of the proximal aorta reaching 55 mm or actual rupture. Two patients fell in the second group with a mean growth velocity of 1.1 and 1.5 mm per year, and therefore entered a close-interval follow-up protocol. Five of 36 early survivors reached an aortic diameter of 55 mm or larger (third group), and were subsequently operated on (1 with acute rupture). The only predictive factor associated with a velocity growth exceeding 1 mm per year was the preoperative diameter (R ⫽ 0.60; p ⫽ 0.0004). A more complex polynomial fitting in the regression model demonstrated an abrupt increase of growth velocity in the aorta with a preoperative diameter of 50 mm or more (R ⫽ 0.83; p ⬍ 0.0001). Therefore, we advocated replacement (or at least a reduction plasty) of the ascending aorta at a level of approximately 48 to 50 mm, even in patients with no additional well-known risk factors, as the presence of a bicuspid aortic valve or a Marfan syndrome. Once it was demonstrated that the combined operation could be performed without an additional risk, carrying the important advantage of eliminating the threat for later reoperations [1], we believe that an aggressive approach should be strongly suggested when dealing with the quite common setting of concomitant aortic valve and proximal aorta disease. Patients with additional risk factors should probably be submitted to ascending aorta replacement or repair even at lower levels of dilation (ie, at approximately 43 to 45 mm). Just one word of caution might be used in the case of isolated aortic stenosis with mild dilatation of the ascending aorta, and that is, in our experience, the immediate resolution of the fluid-dynamics that led to aortic expansion by means of the valve replacement might be sufficient to prevent further dilatation. In patients with prevalent aortic regurgitation, the volume overload of the proximal aorta persists after valve replacement, thus perpetuating the hemodynamic harm to the aortic wall. Actually, in our series, the aortic growth velocity was ⫺0.6 ⫾ 1.5 mm per year in patients with prevalent stenosis, and 1.4 ⫾ 4.8 mm per year in patients with prevalent regurgitation. However, this difference was only marginally significant, with p ⫽ 0.10 [2]. Carlo Bassano, MD, PhD Luigi Chiariello, MD Department of Cardiac Surgery Tor Vergata University Viale Oxford 84 Rome 00133, Italy e-mail: [email protected]
References 1. Reece TB, Singh RR, Stiles BM, et al. Replacement of the proximal aorta adds no further risk to aortic valve procedures. Ann Thorac Surg 2007;84:473– 8. 0003-4975/08/$34.00
Ann Thorac Surg 2008;85:1500 – 6
Reply To the Editor: We would like to thank Dr Bassano and Dr Chiariello for their kind comments [1] on our article regarding the aggressive replacement of the ascending aorta in patients undergoing aortic valve procedures [2]. Their experience supports the approach we presented. Their data provide further support that dilatation may indicate that the interstitium of the vessel wall is abnormal and therefore is prone to further dilatation. We agree that this dilatation is an indication for replacement, which we would prefer over aortoplasty, of the dilated ascending aorta in patients undergoing aortic valve procedures. T. Brett Reece, MD University of Colorado 12631 E 17th Ave, Rm 6602, MS C310 Aurora, CO 80045 e-mail: [email protected] Irving L. Kron, MD Thoracic and Cardiovascular Surgery University of Virginia Charlottesville, Virginia 22908 e-mail: [email protected]
References 1. Bassano C, Chiariello L. Aortic valve disease with concomitant proximal aorta dilation: surgical strategy (letter). Ann Thorac Surg 2008;85:1502–3. 2. Reece TB, Singh RR, Stiles BM, et al. Replacement of the proximal aorta adds no further risk to aortic valve procedures. Ann Thorac Surg 2007;84:473– 8.
Proteasome Inhibitors in Myocardial Ischemia, Some Concerns To the Editor: I read with great interest the article by Stansfield and coworkers [1] that reports observations suggesting that pretreatment of mice with the proteasome inhibitor, PS-519, decreases postischemic infarct size and preserves cardiac function through a mechanism that might be linked to changes in nuclear factor kappa B (NFB) signaling. Considering the critical role of the ubiquitin proteasome system in cardiac pathophysiology [2], this is an important study; however, certain issues with the experimental design, as well as interpretation of these studies require comment. There is concern that simply showing changes in IB levels and phosphorylation of p65 without measuring levels of total p65 may not be reflective of changes in activity of NFB. For these changes to be meaningful, transcriptional activity of NFB must be assessed, which is usually done by means of an electrophoretic mobility shift assay. However, of greater concern is the lack of assessment of proteasome activity in at least peripheral blood cells, if not in cardiac tissue. Without this data, it is unclear if a single dose of PS-519 had any effect on proteasome activity in any tissue (cardiac or blood), and thus if any of the observed effects are even related to proteasome © 2008 by The Society of Thoracic Surgeons Published by Elsevier Inc
1503
inhibition, or if these are extracardiac effects. The authors cite Zollner and coworkers [3] study as the source of this treatment protocol, which examined proteasome inhibition in the inflammatory processes. At issue is that Zollner and coworkers [3] first measured proteasome activity only after 4 days of treatment, not 1 dose, and that only 20S-proteasome or the non-ATPdependent activity was determined, which may not be reflective of the ATP-dependent degradation of ubiquitinated proteins by the 26S-proteasome [4]. For optimal interpretation of these studies, the authors should have assessed activity of the 26Sproteasome in both peripheral blood cells and heart. We have recently published a modification of the standard technique for analysis of both ATP-dependent and non-ATP-dependent activities of the proteasome in cardiac tissue, which simplifies this procedure [4]. The need for accurate assessment of proteasome activity is further exemplified by studies that show that proteasome may become dysfunctional as a result of myocardial ischemia [5]. Considering that significant inhibition of the proteasome is known to induce cellular apoptosis in a variety of tissues, including the heart [6], the wisdom of adding additional inhibition on top of pre-existing dysfunction is questionable. Using the isolated perfused heart preparation, which allows for assessment of direct effect of proteasome inhibitors on function, we have consistently observed that these compounds at best have little or no effect and may worsen postischemic function (reviewed in [2]), an observation recently confirmed by another group [7]. It is certainly conceivable that under the right conditions, the extracardiac anti-inflammatory effects of proteasome inhibition [3] could be beneficial. However, in light of a recent case report [8] of cardiac toxicity after bortezomib (Velcade; Millenium Pharmaceuticals Inc, Cambridge, MA) treatment for multiple myeloma, the prudent course would be to suggest caution before proposing use of proteasome inhibitors to treat myocardial infarction. Saul R. Powell, PhD The Feinstein Institute for Medical Research The Albert Einstein School of Medicine Department of Medicine The Long Island Jewish Medical Center 270-05 76th Ave Room B-387 New Hyde Park, NY 11042 e-mail: [email protected]
References 1. Stansfield WE, Moss NC, Willis MS, Tang R, Selzman C. Proteasome inhibition attenuates infarct size and preserves cardiac function in a murine model of myocardial ischemiareperfusion injury. Ann Thorac Surg 2007;84:120 –5. 2. Powell SR. The ubiquitin proteasome system in cardiac physiology and pathology. Am J Physiol Heart Circ Physiol 2006; 291:1–19. 3. Zollner TM, Podda M, Pien C, Elliott PJ, Kaufmann R, Boehncke WH. Proteasome inhibition reduces superantigenmediated T cell activation and the severity of psoriasis in a SCID-hu model. J Clin Invest 2002;109:671–9. 4. Powell SR, Davies KJA, Divald A. Optimal determination of heart tissue 26S proteasome activity requires maximal stimulating concentrations of ATP. J Mol Cell Cardiol 2007;42: 265–9. 5. Powell SR, Wang P, Katzeff HL, et al. Oxidized and ubiquitinated proteins may predict recovery of postischemic cardiac function. Essential role of the proteasome. Antioxid Redox Signal 2005;7:538 –5. 0003-4975/08/$34.00
MISCELLANEOUS
2. Bassano C, Fratticci L, Del Giudice C, et al. Ectasia of the ascending aorta at the time of aortic valve surgery: replace or relax? Italian Heart J 2005;6:968 –71.
CORRESPONDENCE