ATS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Vincent A. Scavo
Robert J. Morelock
Thomas G. Sharp
John W. Brown
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Vijay, P.
Right arrow Articles by Brown, J. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vijay, P.
Right arrow Articles by Brown, J. W.

Ann Thorac Surg 1998;66:1934-1938
© 1998 The Society of Thoracic Surgeons

Original Articles

Donor cardiac troponin T: a marker to predict heart transplant rejection

Palaniswamy Vijay, PhDa, Vincent A. Scavo, MDa, Robert J. Morelock, MDa, Thomas G. Sharp, MDa, John W. Brown, MDa

a Section of Cardiothoracic Surgery, Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana USA

Address reprint requests to Dr Vijay, Department of Surgery, Indiana University School of Medicine, 545 Barnhill Dr, EH 215, Indianapolis, IN 46202-5125
e-mail: (pvijay{at}iupui.edu)

Presented at the Thirty-fourth Annual Meeting of The Society of Thoracic Surgeons, New Orleans, LA, Jan 26–28, 1998.


   Abstract
Top
 Abstract
Introduction
 Material and methods
 Results
 Comment
 References
 
Background. Noninvasive methodologies have shown poor sensitivity in predicting rejection when compared to serial endomyocardial biopsies. We studied the potential role of donor blood troponin T (Tn-T) as a marker for predicting heart transplant rejection.

Methods. Blood cardiac Tn-T was measured from 16 heart donors. Transplant rejection and cardiac function in the recipients were monitored for 1 year.

Results. When data were analyzed based on donor blood Tn-T levels, 6 patients who received hearts from donors with low Tn-T (<0.45 ± 0.1 ng/mL) showed no rejection, and patients whose hearts came from donors with higher Tn-T (6.01 ± 0.81 ng/mL) developed episodes of high-grade rejection (3A) within 38.5 ± 2.1 days after transplantation. Eight patients who received hearts from donors with intermediate levels of Tn-T (3.57 ± 0.55 ng/mL) showed mild rejection (grade 1). All recipients had qualitatively normal left ventricular systolic function by serial echocardiography. The mean donor ischemic time was 169 ± 47 minutes.

Conclusions. The quality of the donor heart is an important prognostic factor in heart transplantation. It may be possible to identify severely damaged donor organs before transplantation and avoid their use or to develop more aggressive strategies for reducing recurrent acute rejection episodes in high-risk patients.


   Introduction
Top
 Abstract
 Introduction
Material and methods
 Results
 Comment
 References
 
Cardiac transplantation is now a widely accepted treatment for end-stage myocardial failure. Approximately 2,000 heart transplants are performed annually in the United States alone [1]. Immediate mortality resulting from heart transplantation is decreasing, and long-term survival has been increasing. However, the donor pool has not increased as rapidly as the pool of potential recipients leading to a shortage of organ donors. Prescreening of donor hearts for both structural abnormalities and biochemical function may be helpful in maximizing successful outcomes after transplantation.

Histologic evaluation of serial endomyocardial biopsies performed at fixed time intervals after cardiac transplantation is the universal method for detection of cardiac rejection and assessment of the adequacy of antirejection therapy. One of the widely used markers of myocardial injury, the creatine kinase MB isoenzyme, has not been of much use in detecting myocardial damage attributable to rejection because of its lack of specificity and the time frame in which it is released [2]. The lack of highly specific noninvasive techniques has led other investigators to look for alternative markers of myocardial injury. Several studies have shown that specific proteins present only in the myocardium can be used as indicators of muscle damage occurring in the heart. Troponin T (Tn-T) and troponin I (Tn-I) of the tropomyosin complex located on the thin filaments of the muscle contractile apparatus [3, 4] are two such proteins that are released into the blood during episodes of cell injury or necrosis. They are thus potentially useful as markers to determine the quality of a donor heart [5]. The release of troponins into the recipient’s blood after transplantation has previously been evaluated as a marker of transplant rejection [6, 7]. We investigated the potential role of circulating donor Tn-T as a predictive marker for early heart transplant rejection.


   Material and methods
Top
 Abstract
 Introduction
 Material and methods
Results
 Comment
 References
 
Sixteen patients who underwent heart transplantation between 1995 and 1996 at either Riley Hospital for Children or Indiana University Hospital, Indianapolis, Indiana, were included in this study. Eligibility for inclusion was determined by the availability of donor serum for troponin assay. All protocols were approved by the Institutional Review Board of Indiana University School of Medicine, Indianapolis, Indiana.

Patient characteristics
The characteristics of the heart transplant recipients are given in Table 1. There were 7 male and 9 female patients with a mean age (± S.D.) of 40 ± 22 years (range, 0.2 to 63 years) who required heart transplant for various forms of cardiomyopathies. Four pediatric transplant recipients are included in this study: aged 2 months and 2, 3, and 12 years.


View this table:
[in this window]
[in a new window]
  		Table 1. Heart Transplant Recipient Demographics

 
Donor organ procurement and blood collection
Donor hearts were harvested after obtaining consent from parent or legal guardian under United Network for Organ Sharing (UNOS) guidelines using a standard protocol. Briefly, a long midline incision was made and the pericardium was opened. The heart was examined for evidence of any cardiac injury, congenital anomalies, or acquired heart disease. The ascending aorta was dissected and mobilized as far as the takeoff of the innominate artery. The superior vena cava was completely mobilized. The inferior vena cava was encircled with a heavy ligature. A purse-string suture was placed on the ascending aorta for infusion of cardioplegic solution. The aorta was cross-clamped, blood samples were collected, and then cardioplegic solution was infused. The cardioplegic solution (Plegisol, Abbott Laboratories, North Chicago, IL) contains 110 mEq/L sodium, 160 mEq/L chloride, 16 mEq/L potassium, 2.4 mEq/L calcium, and 32 mEq/L magnesium. Ten milliliters of 8.4% sodium bicarbonate was added to 1,000 mL of the solution to adjust the pH to 7.8. The inferior vena cava and the right superior pulmonary vein were partially divided to allow the escape of warm blood from the heart. Ice-cold saline was poured into the pericardium. The apex of the heart was then elevated, and the left and right pulmonary veins were divided. The right and left pulmonary arteries were divided near the bifurcation, the aorta was transected, and after the pericardial reflections were cut, the heart was removed. The heart was placed in plastic bag containing ice-cold saline and transported under sterile conditions. Donor blood samples were prepared by separating the plasma and storing at -70°C until Tn-T assays were performed.

Heart transplantation
Orthotopic cardiac transplantation was performed in a standard fashion. The left atrial cuff of the donor heart was sutured to the remnant of the recipient left atrium using a running 3-0 monofilament suture. The right atrial anastomosis was then performed in a similar manner. The pulmonary artery and aortic anastomoses were then carried out in an end-to-end fashion with running monofilament suture. Topical cooling of the heart was maintained by filling each of the atrial chambers with ice-cold saline and placing iced slush in the pericardium during implantation.

Clinical follow-up after heart transplantation
Cardiac function of the transplanted heart was assessed by two-dimensional echocardiography immediately after transplantation and then every 3 months for the first year.

Graft rejection was monitored by routine endomyocardial biopsy at 2 weeks after transplant, then at 3-month intervals if no rejection was seen. Additional biopsies were obtained at the end of treatment for a high-grade rejection episode and at 1 to 2 months for untreated low-grade rejection. Biopsies were obtained from right ventricle through the right internal jugular vein. Three separate 3.0-mm3 samples were obtained and fixed in 10% phosphate-buffered formalin. Standard biopsy grading criteria were used, which defines scores from 0 to 4, where grade 0 is negative, grades 1A and 1B consist of minimal or mild lymphocytic infiltrates, grade 2 shows focal moderate rejection, and grades 3A, 3B, and 4 show moderate to severe rejection [8]. A standard immunosuppressive regimen for pediatric and adult heart transplant recipients was administered as reported previously [9].

Troponin-T assay
Samples of donor plasma were collected at the time of organ harvest and stored frozen until assayed. Cardiac Tn-T was determined using a kit available from Boehringer Mannheim Corp. (Indianapolis, IN). The assay is based on the dual monoclonal antibody ELISA "sandwich" principle [10], with streptavidin-coated polystyrene tubes as the solid phase. Biotinylated cardiospecific anti-troponin T monoclonal antibody M7, and peroxidase-labeled anti-troponin T monoclonal antibody 1B10 were used as capture and labeled antibodies, respectively. The sandwich complex in the presence of substrates 2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonate) and hydrogen peroxide form a dark green cation, which can be measured at 405 nm, and whose concentration is directly proportional to the Tn-T present in the sample.

Statistical analysis
Data analysis was performed using CSS Statistica (Statsoft, Tulsa, OK) statistical package. Continuous variables such as rejection episodes and Tn-T levels were analyzed by linear regression. Comparison of pump times was performed by analysis of variance (Tukey test). All assays were performed in triplicate. Mean and standard deviations were calculated and p values less than 0.05 were considered significant.


   Results
Top
 Abstract
 Introduction
 Material and methods
 Results
Comment
 References
 
Patient grouping
The patients were divided into three groups on the basis of the Tn-T level in the heart donor’s blood at the time of organ harvest. Group 1 patients (n = 6) received hearts from donors who had blood Tn-T levels less than 1 ng/mL, group 2 (n = 8) from donors with blood Tn-T levels greater than or equal to 1 ng/mL but less than 5 ng/mL, and similarly group 3 (n = 2) from donors whose blood Tn-T levels were greater than 5 ng/mL.

Cause of death of donors
The UNOS records were obtained for each of the heart donors and their cause of death was noted. In group 1, there was death due to a motor vehicle accident resulting in head trauma in two donors, a fall with head injury in one donor, and head trauma of unknown cause in one donor. Two hearts came from donors whose cause of death was listed only as brain death. In group 2, two had only brain death listed, one had cerebral edema, one died of an intracranial bleed, two suffered head trauma in motor vehicle accidents, one sustained a gunshot wound to the head, and one died of unknown causes. In group 3, one donor sustained a head injury in a motor vehicle accident and one died of a gunshot wound.

Troponin-T and rejection
The results are given in Table 2. Group 1 patients received hearts from donors who had blood Tn-T levels of 0.45 ± 0.1 ng/mL. Group 2 recipient hearts came from donors whose blood Tn-T levels averaged 3.57 ± 0.6 ng/mL, whereas group III hearts were from donors with Tn-T levels of 6.01 ± 0.8 ng/mL. The levels of Tn-T were significantly different between the groups (p = 0.0001).


View this table:
[in this window]
[in a new window]
  		Table 2. Donor Blood Tn-T Levels and Recipient Transplant Follow-up

 
Group 1 patients, after 1 year of follow-up, showed no signs of rejection. In group 2, 5 patients exhibited grade 1A rejection with their first episode occurring within 36 ± 7.2 days after transplantation. An average of 5.4 rejection episodes per patient occurred over the course of 1 year. Three patients showed grade 1B rejection with the first episode occurring within 29 ± 8.1 days of transplantation and an average of four episodes in the first year. The recipients who received hearts from donors with the highest blood Tn-T levels (6.01 ± 0.8 ng/mL) showed moderate to severe rejection (3A) within 38 ± 2.1 days after operation. They averaged two significant episodes of rejection in the first year after transplantation despite antirejection therapy. These patients were treated with high-dose prednisone (1 mg · kg-1 · day-1) for 14 days and a repeat endomyocardial biopsy was then done. If rejection persisted with the same grade of rejection the regimen was continued, otherwise prednisone levels were tapered back to a maintenance dose of 0.4 mg · kg-1 · day-1.

There were 3 pediatric patients in group 1 and 1 in group 3. Because of the possibility of an influence of age on the incidence of rejection, the data were analyzed with and without the pediatric patients. The association between Tn-T levels and rejection episodes did not change when pediatric patients were excluded from the analysis (adults only: no rejection, Tn-T 0.43 ± 0.13; grade 1, 3.57 ± 0.55; grade 3A, 5.44; all, including pediatric patients: no rejection, Tn-T 0.45 ± 0.1; grade 1, 3.57 ± 0.55; grade 3A, 6.01 ± 0.81).

In the entire cohort of patients, linear regression analysis between donor plasma Tn-T levels and the highest grade of rejection during the first year showed a highly significant correlation (R = 0.973, adjusted R = 0.943, p < 0.001), suggesting a strong association between the donor Tn-T and rejection episodes seen in transplant recipients (Table 3 ).


View this table:
[in this window]
[in a new window]
  		Table 3. Profile of Transplant Recipients

 
Hemodynamic data
Donor organ ischemic times were similar among all three groups with no statistically significant differences (group 1 183 ± 61 versus group 2 164 ± 41, p = 0.510 and group 1 183 ± 61 versus group 3 148 ± 2.1, p = 0.469). The pump time was significantly shorter for group III than either of the other two groups (115.5 ± 15, 110 ± 17, and 76.5 ± 12 in groups 1, 2, and 3, respectively, p = 0.016 and p = 0.036 for group 3 versus group 1 and group 3 versus group 2).

Cardiac function was assessed using left ventricular diameter, left ventricular area, intraventricular septal thickness, left ventricular posterior wall thickness (diastolic), and left atrial diameter (systolic) as measured by echocardiography (Table 4 ). No significant differences were found in these parameters between the groups and echocardiography was reported to show qualitatively normal left ventricular systolic function in all patients.


View this table:
[in this window]
[in a new window]
  		Table 4. Results of Echocardiographya

 

   Comment
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
References
 
Shortages in organ donors for cardiac transplantation have led to the suggestion that criteria for donor selection should be liberalized [11]. However, several studies have indicated that either preoperative donor myocardial injury or perioperative ischemic injury to the transplanted heart result in poorer short-term and long-term outcomes in heart transplant recipients [12, 13]. Accurate methods of predicting functional outcomes after heart transplant are needed to maximize utilization of the available donor pool.

Several previous studies have looked at the release of cardiac-specific proteins into the blood after transplantation. Tn-T has been shown to be released into the recipient’s blood for up to 3 months after transplantation [14, 15]. Although minor fluctuations did occur with rejection episodes, the levels of Tn-T did not consistently correlate with clinical episodes of acute rejection.

In a population of 18 infant (<1 year) recipients, Grant and colleagues [7] measured Tn-I in 19 heart donors and showed a significant relationship between the Tn-I concentration in the donor sera before harvest and the subsequent occurrence of fatal primary graft failure. All of the hearts that were harvested from donors with Tn-I levels <3.1 ng/mL were associated with successful transplantation. In contrast, 5 of the 8 hearts from donors with elevated Tn-I (3.2 to 71.5 ng/mL) developed intractable graft failure suggesting severe ischemic damage in the donor heart before harvest. Graft failure occurred early and no evidence of rejection was reported on pathologic analysis.

In another study, involving 100 adult cardiac donors, elevated circulating concentrations of cardiac Tn-T were shown to be associated with a severe decrease in cardiac function as measured by echocardiography, suggesting that severe and potentially irreversible myocardial cell damage might have occurred [16]. The Tn-T concentrations were significantly higher in patients with a severe decrease (<=30%) in left ventricular ejection fraction area.

In contrast to these findings, we were unable to detect any differences in left ventricular function after transplantation between patients who received hearts from donors with low or elevated Tn-T levels. We were, however, able to show an association between increased Tn-T in the donor blood and episodes of acute cellular rejection detected on serial myocardial biopsies. The onset of rejection was generally greater than 1 month after transplant. Thus, all of our patients survived through the period where acute graft failure was observed in other reports.

Cardiopulmonary bypass times varied considerably between the groups, with a significant difference between groups 1 and 3. This leads to the possibility that greater damage from nonspecific ischemic insult occurred in group 1 than in group 3. This is unlikely to have influenced our results, however, as the longest ischemic times (and thus the potential for greater intraoperative damage) were in the group with the lowest levels of rejection. This also suggests that ischemic injury alone is not the explanation for our findings.

The mechanism of accelerated rejection in recipients of hearts from donors with elevated Tn-T is not entirely clear. We can speculate that it could be a manifestation of one of three phenomena: increased vascular permeability allowing early post-transplant infiltration of activated recipient lymphocytes into the interstitium of the donor heart, activation of nonspecific inflammatory mediators that then lead to increased expression of donor histocompatibility antigens, or an increase in passenger leukocytes from the donor that then interact aggressively with recipient lymphocytes to cause rejection. Minor degrees of damage to the donor heart may not necessarily be associated with dramatic changes in overall cardiac function but could alter either the expression of donor antigens or the integrity of the vascular basement membrane. Cardiac endothelial cell activation after myocardial damage can result in release of inflammatory cytokines and vascular endothelial growth factor, a potent chemoattractant for T-lymphocytes [17]. Early after injury this could result in localization of donor T-lymphocytes and macrophages in the heart in an attempt to repair or remove damaged tissues. These cells would be expected to interact vigorously with recipient lymphocytes in the presence of a damaged endothelial basement membrane. After transplantation, continued release of cytokines might independently attract high affinity cytotoxic T-cells from the recipient, which could participate directly in transplant rejection.

Because the quality of the donor’s heart is an important prognostic factor in heart transplantation, the determination of donor Tn-T may be useful to heart transplant teams as they assess potential donors. High concentrations of Tn-T might lead to either rejection of the organ donor or to a higher intensity immunosuppressive regimen for the recipient. A single determination of Tn-T can be obtained within 2 hours and would cost approximately $20.00 to perform. This may help to protect recipients from both early and long-term cardiac graft failures based on a risk assessment predicted by the extent of donor heart injury as defined by Tn-T.


   References
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 References
 

  1. O’Connell J.B., Bourge R.C., Driscoll D.J., Morgan J.P., Rose E.A., Uretsky F. Cardiac transplantation: recipient and medical follow–up. Circulation 1992;86:1061-1078.[Free Full Text]
  2. Apple F.S. Diagnostic use of CK–MM and CK–MB isoforms for detecting myocardial infarction. Clinics Lab Med 1989;9:643-653.
  3. Katus H.A., Remppis A., Looser S., Hallermeier K., Scheffold T., Kuebler W. Enzyme linked immunoassay of cardiac troponin T for the detection of acute myocardial infarction in patients. J Mol Cell Cardiol 1989;21:1349-1353.[Medline]
  4. Adams J.E., III, Bodor G.S., Davila–Roman V.G. Cardiac troponin I. A marker with high specificity for cardiac injury. Circulation 1993;88:101-106.[Abstract/Free Full Text]
  5. Katagiri T., Kobayashi Y., Sasai Y., Toba K., Niitani H. Alternations in cardiac troponin subunits in myocardial infarction. Jpn Heart J 1981;22:653-664.[Medline]
  6. Darracott–Cankovic S., Stovin P.G.I., Wheeldon D., Wallwork J., Wells F., English T.A.H. Effect of donor heart damage on survival after transplantation. Eur J Cardiothorac Surg 1989;3:525-532.[Abstract]
  7. Grant J.W., Canter C.E., Spray T.M., et al. Elevated donor cardiac troponin I. A marker of acute graft failure in infant heart recipients. Circulation 1994;90:2618-2621.[Free Full Text]
  8. Billingham M.E., Cary N.R.B., Hammond E.H., et al. A working formulation for the standardization of nomenclature in the diagnosis of heart and lung rejection: Heart Rejection Study Group. J Heart Transplant 1990;8:587-593.
  9. Brown J.W., Turrentine M.W., Kesler K.A., et al. Triple–drug immunosuppression for heart transplantation in infants and children. J Heart Lung Transplant 1993;12(6 Pt 2):S265-S274.[Medline]
  10. Katus H.A., Looser S., Hallermeier K., et al. Development and in vitro characterization of a new immunoassay of cardiac troponin T. Clin Chem 1992;38:386-393.[Abstract/Free Full Text]
  11. Zimmermann R., Baki S., Dengler T.J., et al. Troponin T release after heart transplantation. Br Heart J 1993;69:395-398.[Abstract/Free Full Text]
  12. Jeevanandam V., Furukawa S., Prendergast T.W., et al. Standard criteria for an acceptable donor are restricting heart transplantation. Ann Thorac Surg 1996;62:1268-1275.[Abstract/Free Full Text]
  13. Fyfe B., Loh E., Winters G.L., et al. Heart transplantation–associated perioperative ischemic myocardial injury. Morphological features and clinical significance. Circulation 1996;93:1133-1140.[Abstract/Free Full Text]
  14. Gaudin P.B., Rayburn B.K., Hutchins G.M., et al. Peritransplant injury to the myocardium associated with the development of accelerated atherosclerosis in heart transplant recipients. Am J Surg Pathol 1994;18:338-346.[Medline]
  15. Alexis J.D., Lao C.D., Selter J.G., et al. Cardiac troponin T: a noninvasive marker for heart transplant rejection?. J Heart Lung Transplant 1998;17:395-398.[Medline]
  16. Riou B., Dreux S., Roche S., et al. Circulating cardiac troponin T in potential heart transplant donors. Circulation 1995;92:409-414.[Abstract/Free Full Text]
  17. Torry R.J., Labarrere C.A., Torry D.S., et al. Vascular endothelial growth factor expression in transplanted human hearts. Transplantation 1995;60:1451-1457.[Medline]



This article has been cited by other articles:


Home page
 Canadian J. AnesthesiaHome page
D. J. Kutsogiannis, G. Pagliarello, C. Doig, H. Ross, and S. D. Shemie
Medical management to optimize donor organ potential: review of the literature: [Traitement medical pour optimaliser le potentiel de don d'organe : une revue documentaire].
Can J Anesth, August 1, 2006; 53(8): 820 - 830.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
J. G. Zaroff, B. R. Rosengard, W. F. Armstrong, W. D. Babcock, A. D'Alessandro, G. W. Dec, N. M. Edwards, R. S. Higgins, V. Jeevanandum, M. Kauffman, et al.
Consensus Conference Report: Maximizing Use of Organs Recovered From the Cadaver Donor: Cardiac Recommendations March 28-29, 2001, Crystal City, Va
Circulation, August 13, 2002; 106(7): 836 - 841.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
N. Parekh, B. Venkatesh, D. Cross, A. Leditschke, J. Atherton, W. Miles, A. Winning, A. Clague, and C. Rickard
Cardiac troponin I predicts myocardial dysfunction in aneurysmal subarachnoid hemorrhage
J. Am. Coll. Cardiol., October 1, 2000; 36(4): 1328 - 1335.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
J. R. Anderson and D. W. Holt
The role of cardiac troponin T to predict heart transplant rejection.
Ann. Thorac. Surg., September 1, 1999; 68(3): 1121 - 1122.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Vincent A. Scavo
Robert J. Morelock
Thomas G. Sharp
John W. Brown
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Vijay, P.
Right arrow Articles by Brown, J. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vijay, P.
Right arrow Articles by Brown, J. W.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
ANN THORAC SURG ASIAN CARDIOVASC THORAC ANN EUR J CARDIOTHORAC SURG
J THORAC CARDIOVASC SURG ICVTS ALL CTSNet JOURNALS