| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J Thorac Cardiovasc Surg 2002;123:845-854
© 2002 The American Association for Thoracic Surgery
General Thoracic Surgery (GTS) |
From the Pulmonarya and Thoracic Surgeryb Divisions, University Hospital of Zurich, Switzerland.
Supported by Grant No. 3200-043358;95.1 from the Swiss National Science Foundation, and by the Zurich Lung League.
Received for publication May 5, 2001. Revisions requested July 11, 2001; revisions received Aug 6, 2001. Accepted for publication Aug 15, 2001. Address for reprints: Walter Weder, MD, Division of Thoracic Surgery, University Hospital of Zürich, Rämistrasse 100, CH-8091 Zurich, Switzerland (E-mail: walter.weder{at}chi.usz.ch).
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionAppendix: DiscussionReferences |
|---|
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionAppendix: DiscussionReferences |
|---|
1-5 and, more recently, a few prospective, randomized, controlled trials 6-8 have demonstrated a relief of dyspnea and an improvement in lung function, exercise tolerance, and quality of life after lung volume reduction surgery (LVRS) for emphysema. The amount of improvement is variable and may depend on various factors, including cause and morphologic types of emphysema, preoperative lung function, and amount of resected emphysematous lung tissue.
Certain authors have stressed that patients with distinct regional differences in tissue destruction (ie, with markedly heterogeneous emphysema) on computed tomographic (CT) scanning, perfusion scintigraphy, or both profit most from LVRS because nonfunctional areas identified by means of imaging techniques are the ideal targets for resection. 9,10 In previous analyses we corroborated this concept, but more important, we were able to demonstrate that even patients with a uniform pattern of emphysematous destruction (ie, a homogenous type) had significant and clinically relevant improvement after the operation. 11,12 Because data on long-term outcome after LVRS are scant and have not been analyzed with regard to the potential effects of emphysema morphology, we prospectively investigated the initial gain and the subsequent loss of lung function over several years after LVRS in patients with various degrees of emphysema heterogeneity.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionAppendix: DiscussionReferences |
|---|
2 As described previously, 13 patients with nonbullous pulmonary emphysema were included when they were severely symptomatic despite optimal medical therapy, had severe airflow obstruction (forced expiratory volume in 1 second [FEV1] of < 40% of predicted value), and had pulmonary hyperinflation (residual volume [RV] of > 200% of predicted value, RV/total lung capacity of > 0.60). Severely impaired carbon dioxide diffusing capacity (<20% of predicted value) and significant coronary artery disease represented the major exclusion criteria for the current study. No systematic rehabilitation was performed at our center before or after the operation, but the majority of patients had undergone rehabilitation at other institutions before referral. The study was approved by the hospital ethics committee, and informed consent was obtained from the patients.
Surgical intervention
LVRS was performed by means of bilateral, video-assisted, stapled (buttressed or nonbuttressed with bovine pericardium according to the protocol of a previous study 14) resection of approximately 30% of lung volume. 1 Target areas were identified, by means of analysis of the CT scans and perfusion scintiscans, as the lung zones with the most pronounced emphysematous alteration and the greatest reduction in perfusion. In addition, target areas were selected on the basis of visual observation of areas with delayed resorption atelectasis during the surgical intervention. 12 Patients were operated on in the supine position if resection in the upper lobes was planned. For lower lobe resections, patients were placed in a lateral decubitus position and turned to the other side after completion of the first side.
Measurements
Clinical evaluation
Spirometry, whole-body plethysmography, and measurement of carbon monoxide diffusing capacity were performed (6200 Autobox; SensorMedics, Yorba Linda, Calif) according to standard criteria after inhalation of 2 puffs of albuterol. Arterial blood for blood gas analysis was obtained while the patient was sitting and breathing room air. Cotinine concentration of the urine was determined as a marker for smoking. 15 For the purpose of the current analysis, a patient was considered a smoker if his or her urinary cotinine concentration was greater than 1000 mg/L, if greater than 5% of his or her hemoglobin was saturated with carbon monoxide, or if he or she reported regular cigarette smoking.
For assessment of the 6-minute walking distance, the patients walked along the same hospital hallway without supplemental oxygen. Severity of dyspnea was graded by the American Thoracic Society modified Medical Research Council (MRC) dyspnea score, with a scale ranging from 1 to 4. 16 Baseline and follow-up examinations were performed within 1 month before LVRS, at 3 and 6 months after LVRS, and every 6 months thereafter.
Imaging techniques
Preoperative chest CT examinations were performed on a Somatom plus 4 scanner (Siemens, Erlangen, Germany) with a high-resolution technique by using an increment of 15 mm and a slice thickness of 1 mm at 140 kV and 11 mA. Heterogeneity of emphysema distribution was graded according to our semiquantitative staging system, which comprises 3 degrees 11:
Lung perfusion scans were also obtained as a help for identification of target areas in cases with homogeneous emphysema distribution on CT scans. 12
Data analysis and statistics
Summary statistics are presented as medians and quartile ranges because certain variables were not normally distributed. 17 To perform statistical comparisons, data were logarithmically transformed to obtain a normal distribution, as confirmed with the Kolmogorov-Smirnov statistic. 18 Changes in variables over time within and among the 3 groups of patients with different emphysema heterogeneity were evaluated by analysis of variance, followed by Newman-Keuls multiple comparisons where appropriate. Correlation of baseline variables with changes in FEV1 after LVRS were performed by means of multiple linear regression analyses.
In each patient, elapsed time after the operation when the individual maximal value of FEV1 (FEV1max) was reached was noted, along with the corresponding gain in FEV1. The maximal gain was defined as the difference between the maximal minus the preoperative value of FEV1 and expressed in liters and in percentages of the preoperative value. Graphic display of the individual time course of FEV1 after FEV1max suggested an exponential decay. The decrease in FEV1 in the first year after the operation and the median yearly decrease over subsequent years were determined to capture this phenomenon numerically. Elapsed time from the operation to the time when FEV1 had fallen below FEV1max minus half the maximal gain was also computed. Furthermore, the decline of FEV1 was modeled by fitting an exponential equation to the data of each individual patient according to the following equation:
FEV1 (t) = FEV1max · e-t/
,
where t corresponds to the time elapsed since FEV1max and to the time constant of the exponential decay. The half-life of FEV1 expresses the time when FEV1 reaches the value of 0.5 times FEV1max. It is calculated as follows:
Half-life = ln (0.5/).
Data from individual patients were included only if more than 4 observations were available and if the regression of predicted versus observed data was statistically significant.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionAppendix: DiscussionReferences |
|---|
1-antitrypsin (Pi ZZ) deficiency. Chest CT scoring revealed markedly heterogeneous emphysema distribution in 51, intermediately heterogeneous emphysema distribution in 37, and homogeneous emphysema distribution in 27 patients. Preoperative FEV1 was greater in the group with markedly heterogeneous emphysema distribution (median FEV1, 0.81 L) than in the other 2 groups (Table 2).
However, the medians in FEV1 expressed as a percentage of predicted values (range, 25%-27%) were not statistically different among groups.
|
|
|
19) was 29% (quartile range, 19%-39%).
In Table 1
the course of lung function, walking distance, and dyspnea is summarized for all patients and grouped according to the length of postoperative observation. In the first year after the operation, FEV1 measured in absolute volume units fell by a median of 0.24 L per year (quartile range, 0.11-0.43). The median decrease in FEV1 expressed as a percentage of the individual maximal value was 22% per year (quartile range, 12%-36%) in the first postoperative year. Over subsequent years, the median annual decline was significantly reduced to 0.09 L per year (quartile range, 0.05-0.15 L per year; n = 80; P < .00001), corresponding to a yearly relative loss of FEV1 of 9% per year (quartile range, 4%-16% per year; n = 80; P < .0005 vs first year values). After a median duration of 12 months after the operation (quartile range, 9-24 months; n = 100 patients), half of the gain of FEV1 was lost (ie, FEV1 had fallen from FEV1max to below the value of FEV1max minus half the maximal gain).
In 60 patients in whom an exponential function could be fitted to the decay in FEV1, there was a close match of predicted value with observed data (median coefficients of determination r2 = 0.88; quartile range, 0.82-0.95; P < .05). Figure 1 shows the changes in FEV1 over the individual times of follow-up.
The estimated time for FEV1 to fall back to the preoperative value was 38 months (quartile range, 21-64 months; Figures 1 and 2).
The half-life of FEV1 (ie, the time required for FEV1 to fall to 50% of its initial maximal value) was estimated at 63 months (quartile range, 45-87; Figure 2). Neither resumption of smoking after the operation (documented in 14 patients at any time during their follow-up) nor 1-antitrypsin deficiency (present in 11 patients) had a statistically significant effect on the decline in FEV1 after the operation, as assessed by the measures mentioned above.
|
|
data are presented according to CT morphologic emphysema heterogeneity. The loss of follow-up was not statistically different among the 3 groups. The relative decrease in RV (1 - RV after LVRS/RV before LVRS) was 32% (quartile range, 23%-42%) in the group with markedly heterogeneous emphysema, 28% (quartile range, 19%-39%) in the group with intermediately heterogeneous emphysema, and 22% (quartile range, 19%-31%; P < .5 vs markedly heterogeneous) in the group with homogeneous emphysema. The functional gain was greatest in the group with markedly heterogeneous emphysema, but in patients with intermediately heterogeneous and homogeneous emphysema, significant functional and symptomatic improvements were also achieved (Table 2).
Figure 1 provides a graphic display of the initial gain and subsequent loss of FEV1 in the 3 groups of patients with different emphysema morphologic patterns. The absolute and relative gain in FEV1 (in liters and in percentage of preoperative value, respectively) was greatest in markedly heterogeneous emphysema. There was a trend for a greater subsequent loss of FEV1 (in absolute volume units [ie, liters]) in markedly heterogeneous emphysema during the first and subsequent years compared with intermediately heterogeneous or homogeneous emphysema. However, neither the time until 50% of the individual gain was lost nor the relative decline (in percentage) over the first and subsequent years nor the half-life of FEV1 differed among groups of patients with different emphysema morphologic patterns (Table 3, Figures 1 and 2).
The baseline values and follow-up values at 3, 12, 24, 36, and 48 months after LVRS for diffusing capacity, blood gases (PaO2 and PaCO2), 6-minute walking distance, and MRC dyspnea scores did not statistically differ among the 3 groups with different emphysema morphologic patterns, and the values are listed for the entire cohort in Table 1. Data for the groups with different emphysema heterogeneity are therefore not shown.
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionAppendix: DiscussionReferences |
|---|
).
Short-term results after LVRS
The short-term outcome achieved in the current study compares favorably with results achieved in other centers. With a value of less than 2%, the perioperative mortality was at the lower end of the range of 0% 20 to 6% to 17% 8 reported by others. Dyspnea decreased in all patients by at least 2 points on the MRC scale. In the entire cohort of 115 patients (Table 1), the significant reduction of lung volume, reflected by the 29% median decrease in RV, 19 was associated with a median gain in FEV1 of 43%. This is similar to the mean increase in FEV1 of 51% reported for 150 patients by Cooper and colleagues. 3 In our 51 patients with markedly heterogeneous emphysema, FEV1 increased even more (ie, by 63%; Table 3), which is close to the mean increase in FEV1 of 60% in 90 patients with heterogeneous emphysema treated with bilateral videothoracoscopic LVRS by Brenner and coworkers. 4 In the 2 randomized studies for which the relative gain in FEV1 was reported, the corresponding values were less than 30% 20 and 53%, 7 respectively.
We were able to further substantiate our previous findings of a significant and clinically relevant functional and symptomatic benefit from LVRS in a larger number of patients with completely diffuse, homogenous emphysema followed over longer time periods than in the earlier reports. 11,12 The significant differences in short-term outcome among groups of patients classified according to emphysema heterogeneity by means of visually scoring the chest CT illustrates the clinical relevance of our simple grading system 11 and underlines an effect of morphologic factors on the success of LVRS. Nevertheless, the association of emphysema heterogeneity with favorable functional outcome is relatively modest and may, in part, be related to a greater extent of resection by the surgeon in heterogeneous emphysema, if target areas are clearly visualized on the CT.
Evolution of symptoms and function over several years
Our data suggest that dyspnea is persistently relieved after LVRS in the majority of patients over at least 48 months (Table 1). Median walking distance also remained increased above preoperative levels over this time period. On the other hand, airflow obstruction and hyperinflation began to deteriorate after maximal improvement within 3 to 6 months after the operation. Within the first year after LVRS, the median loss of FEV1 in our entire cohort (n = 91 patients followed up over the first year) was 0.24 L. This is consistent with a previous report 4 of a mean decline in FEV1 of 0.255 L per year (n = 90 patients, mean follow-up of 420 days after the operation). Because this result 4 reflects the slope of the linear regression of FEV1 versus time in patients with a mean follow-up that was close to 1 year, the resulting mean loss of FEV1 is comparable with the decrease in FEV1 documented in the first year in our cohort (Table 3).
Observation of changes in lung function over several years suggested a nonlinear course (Table 1). This was analyzed in greater detail for FEV1, which declined much more rapidly in the first than in subsequent years after LVRS (ie, group medians of the fall were between 0.16 and 0.32 L per year initially and between 0.06 and 0.12 L per year in the later course; P < .0005 vs fall in the first year; Table 3). This indicates that long-term trends in FEV1 after LVRS can not be derived by means of linear extrapolation of the early postoperative course. Instead, graphic representation and statistical analysis confirmed an exponential decay (Figures 1 and 2). In an individual patient FEV1 closely followed the course predicted by the following general equation: FEV1 (at a given time [t] after the peak value) = Maximal postoperative FEV1 · e-t/individual time constant
A median of 88% in the variability of FEV1 could be explained accordingly, suggesting that the exponential function may provide a useful guide in the assessment and counseling of patients after LVRS. It is conceivable that our exponential model, which is different from the linear polynomial equation applied to describe the effects of smoking cessation and inhalation therapy on the course of FEV1, 21 performed well in capturing the much more striking effect of a surgical intervention such as LVRS.
Interestingly, the characteristics of exponential decay in FEV1, such as the observed time to half the initial gain in FEV1 (measured in 100 of 115 patients, Table 3) or the estimated half-life of FEV1 (computed for 60 patients) did not statistically differ among the 3 groups with different emphysema morphologic patterns (Figure 2). Because the exponential decay was fitted to data of patients with a follow-up of at least 21 months after the maximal postoperative FEV1 only (ie, postoperative observation 
2 years after LVRS) and because of mortality (16/115 patients at 2 years after LVRS) and losses to follow-up (9/115 patients at 2 years), the subgroup of 60 patients in whom this analysis could be performed may reflect a certain bias toward a more favorable course and, obviously, is representative for survivors over this time period only. Nevertheless, the prediction derived from 60 patients together with the time until half of the gain in FEV1 was lost (measured in 100 patients) may still be typical for the time course of the decay in FEV1 in many patients who undergo LVRS.
Conclusions
We confirmed that heterogeneity of emphysema distribution graded visually on the chest CT correlates with the degree of functional improvement in the first few months after LVRS. The early rate of decline in FEV1 from the maximal value in the first year after the operation was significantly greater than that in subsequent years, according to an exponential decay. Therefore, our data, obtained in a fairly large number of patients over several years, illustrate that the course of lung function in intermediate and long-term survivors of LVRS may be more favorable than previously expected from linear extrapolations of short-term observations.
|
Appendix: Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionAppendix: DiscussionReferences |
|---|
Dr Weder's report confirms the long-term benefit produced by LVRS and suggests that maybe the restrictive selection criteria we have adhered to in the past might be somewhat relaxed. Because LVRS is a palliative procedure and because emphysema is an unrelenting and progressive disease, much of the controversy surrounding LVRS centers on how much benefit is produced, how long it lasts, and for which patients the magnitude and the duration of benefit justifies the risk to the patient and the cost to the payer.
On the basis of short-term data, others have suggested that the rate of decline in lung function after LVRS might somehow be accelerated, but Dr Weder's thoughtful analysis demonstrates that the benefit persists for years. This is consistent with our own recent analysis of 5 years' follow-up on our first 200 patients, showing that, on average, the benefit persists for 5 years or more and that it takes at least 3 years for half of the improvement in the FEV1 to be lost.
Dr Weder's results have again confirmed that the patients with a heterogeneous pattern of destruction benefit the most from LVRS, but his analysis suggests that the loss of benefit follows a similar logarithmic decay for each of the 3 different morphologic patterns he has identified.
I have 3 questions.
The first relates to your selection process. In your manuscript you noted that you had 51 patients with a more ideal heterogeneous pattern, and 27 patients in this series had the more diffuse homogeneous pattern, and yet we see 3 or 4 patients with a homogeneous pattern for every one we see with a more favorable pattern. How do you select among those patients, and specifically, because the morphologic patterns that you have demonstrated are based on regional differences and not absolute severity, do you tend to shy away from the patients with homogeneous severe destruction?
The second and third questions relate to the results. In all patients LVRS produces improved mechanics by reducing hyperinflation, and this is reflected in a reduction in RV and an improvement in the FEV1. But in patients with heterogeneous disease, it may also improve gas exchange by redistributing ventilation, and this is reflected in the improvement in PO2 and the reduction in oxygen requirements. Did you, in your series, see less benefit in terms of gas exchange improvement in the patients with a homogeneous pattern?
Finally, your analysis and that of most of us is focused primarily on the FEV1, but I increasingly believe that the long-term benefits of volume reduction may have more to do with a reduction in the hyperinflation, as reflected in the RV, than it does with the improvement in the FEV1. Have you any thoughts on that matter or have you analyzed the follow-up in RV in a similar fashion?
Dr Weder. Thank you very much for these 3 questions. The first question concerns the selection of patients with more homogeneous disease and whether we are more selective in picking them. We select patients with no distinct target areas for resection only if all selection criteria are fulfilled. We are especially strict in excluding patients with a very low functional reserve—expressed by carbon monoxide diffusion capacity below 20% predicted or an FEV1 below 20% predicted. Additionally, the information from the visual analysis of the CT scan is included. Unfortunately, the radiologic criteria of a too destroyed and almost vanished lung are not defined with respect to lung volume reduction surgery. Therefore, some patients might also be excluded from surgery based on the clinical judgment of a radiologically too destroyed lung.
The second point concerns changes in gas exchange with regard to the morphology. You suspect that patients with markedly heterogeneous emphysema show much more improvement in terms of gas exchange. In fact, we found a trend of more improvement only in heterogeneous disease but no significant difference between the 3 morphologic groups.
The last question regards the measurement of FEV1 as the best indicator for qualifying this procedure. Again, many of us have observed patients who claimed a clear benefit from this procedure without having a great change in FEV1 and the only improved parameter being a reduction in hyperinflation. However, most groups, including us, would like to see an improvement in FEV1, since this parameter is most widely used to validate lung function.
|
Footnotes |
|---|
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionAppendix: DiscussionReferences |
|---|
This article has been cited by other articles:
|
|
 |
|
  W. Weder, M. Tutic, D. Lardinois, W. Jungraithmayr, S. Hillinger, E. W. Russi, and K. E. Bloch Persistent Benefit From Lung Volume Reduction Surgery in Patients With Homogeneous Emphysema Ann. Thorac. Surg., January 1, 2009; 87(1): 229 - 237. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Moser, I. Opitz, W. Zhai, V. Rousson, E.W. Russi, W. Weder, and D. Lardinois Autologous fibrin sealant reduces the incidence of prolonged air leak and duration of chest tube drainage after lung volume reduction surgery: a prospective randomized blinded study. J. Thorac. Cardiovasc. Surg., October 1, 2008; 136(4): 843 - 849. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Tacconi, E. Pompeo, D. Forcella, M. Marino, D. Varvaras, and T. C. Mineo Lung Volume Reduction Reoperations Ann. Thorac. Surg., April 1, 2008; 85(4): 1171 - 1177. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. S. Naunheim, D. E. Wood, Z. Mohsenifar, A. L. Sternberg, G. J. Criner, M. M. DeCamp, C. C. Deschamps, F. J. Martinez, F. C. Sciurba, J. Tonascia, et al. Long-Term Follow-Up of Patients Receiving Lung-Volume-Reduction Surgery Versus Medical Therapy for Severe Emphysema by the National Emphysema Treatment Trial Research Group Ann. Thorac. Surg., August 1, 2006; 82(2): 431 - 443. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Tutic, D. Lardinois, S. Imfeld, S. Korom, A. Boehler, R. Speich, K. E. Bloch, E. W. Russi, and W. Weder Lung-volume reduction surgery as an alternative or bridging procedure to lung transplantation. Ann. Thorac. Surg., July 1, 2006; 82(1): 208 - 213. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kushibe, M. Takahama, T. Tojo, T. Kawaguchi, M. Kimura, and S. Taniguchi Assessment of pulmonary function after lobectomy for lung cancer - upper lobectomy might have the same effect as lung volume reduction surgery. Eur. J. Cardiothorac. Surg., June 1, 2006; 29(6): 886 - 890. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Venuta, T. de Giacomo, E. A. Rendina, A. M. Ciccone, D. Diso, A. Perrone, D. Parola, M. Anile, and G. F. Coloni Bronchoscopic Lung-Volume Reduction With One-Way Valves in Patients With Heterogenous Emphysema Ann. Thorac. Surg., February 1, 2005; 79(2): 411 - 416. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. C. Mineo, E. Pompeo, D. Mineo, P. Rogliani, C. Leonardis, and I. Nofroni Results of unilateral lung volume reduction surgery in patients with distinct heterogeneity of emphysema between lungs J. Thorac. Cardiovasc. Surg., January 1, 2005; 129(1): 73 - 79. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Tutic, K. E. Bloch, D. Lardinois, T. Brack, E. W. Russi, and W. Weder Long-term results after lung volume reduction surgery in patients with {alpha}1-antitrypsin deficiency J. Thorac. Cardiovasc. Surg., September 1, 2004; 128(3): 408 - 413. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E.W. Russi, K.E. Bloch, and W. Weder Lung volume reduction surgery: what can we learn from the National Emphysema Treatment Trial? Eur. Respir. J., October 1, 2003; 22(4): 571 - 573. [Full Text] [PDF]
|
|
|
|
 |
|
 National Emphysema Treatment Trial Research Group A Randomized Trial Comparing Lung-Volume-Reduction Surgery with Medical Therapy for Severe Emphysema N. Engl. J. Med., May 22, 2003; 348(21): 2059 - 2073. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. F. Gelb and R. J. McKenna Jr Lung Volume Reduction Surgery Update Chest, April 1, 2003; 123(4): 975 - 977. [Full Text] [PDF]
|
|
|
|
|
|
A. M. Ciccone, B. F. Meyers, T. J. Guthrie, G. E. Davis, R. D. Yusen, S. S. Lefrak, G. A. Patterson, and J. D. Cooper Long-term outcome of bilateral lung volume reduction in 250 consecutive patients with emphysema J. Thorac. Cardiovasc. Surg., March 1, 2003; 125(3): 513 - 525. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 |
