HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Amram Cohen Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cohen, A. Articles by Schachner, A. Search for Related Content PubMed PubMed Citation Articles by Cohen, A. Articles by Schachner, A.

J Thorac Cardiovasc Surg 1995;109:574-581
© 1995 Mosby, Inc.

SURGERY FOR ACQUIRED HEART DISEASE

Chronic obstructive pulmonary disease in patients undergoing coronary artery bypass grafting

Holon and Tel Aviv, Israel

Received for publication March 10, 1994. Accepted for publication August 15, 1994. Address for reprints: Arieh Schachner, MD, Department of Cardiovascular Surgery, Edith Wolfson Medical Center, P.O. Box 5, Holon 58100, Israel.

Abstract

The purpose of this study was to evaluate the effect of chronic obstructive pulmonary disease on patients undergoing coronary artery bypass grafting. Between June 1991 and June 1993, 651 patients underwent coronary artery bypass grafting: 37 patients (group I) had significant chronic obstructive pulmonary disease. These patients were compared with 37 matched control subjects (group II). Comparison of the groups was made with regard to postoperative morbidity and mortality. Quality of life of survivors was compared at the last follow-up. More patients in group I had preoperative arrhythmias (8 versus 1, p = 0.014). Group I patients had lower values of forced expiratory volume in 1 second (1.366 ± 0.032 L versus 2.335 ± 0.49 L, p < 0.0001), lower oxygen tension (63.5 ± 8.2 versus 79.1 ± 13.4 mm Hg, p = 0.001), and higher carbon dioxide tension (44.8 ± 6.5 mm Hg versus 39.7 ± 3.6 mm Hg, p = 0.001). After operation patients in group I had a longer hospital stay (8.1 ± 3.6 days versus 6.6 ± 1.7 days, p = 0.0236) and longer intensive care unit stay (2.64 ± 0.9 days versus 1.23 ± 0.49 days, p = 0.0001). More patients in group I required prolonged intubation (7 versus 1, p = 0.0278) and reintubation (5 versus 1, p = 0.088). More patients in group I had significant arrhythmias (27 versus 9, p < 0.0001). During a 16-month follow-up period, five patients in group I died, whereas none in group II died (p = 0.0271). Four deaths were related to arrhythmias. More group I patients were not functionally improved by the operation (17 versus 3, p = 0.0056). The results of coronary artery bypass grafting in patients with significant chronic obstructive pulmonary disease were not favorable in midterm follow-up. A major cause for morbidity and mortality was postoperative arrhythmias. (J THORACCARDIOVASCSURG1995; 109: 574-81)

Chronic obstructive pulmonary disease (COPD) is common among patients undergoing coronary artery bypass grafting (CABG). ¹ COPD has been considered as a risk factor for early mortality in patients undergoing CABG, and forced expiratory volume (FEV₁ ) has been shown to be an independent risk factor for early mortality. ² However, there has been no systematic evaluation of the patterns for morbidity or mortality in patients with COPD undergoing CABG. Furthermore, midterm follow-up has not been reported in this population. To address these questions, we evaluated our population with COPD undergoing CABG.

PATIENTS AND METHODS

Between June 1991 and June 1993, 651 patients underwent CABG at our institution. Of these, 37 patients (group I) were considered to have significant COPD. To be included in group I, the patient had to be actively treated and followed up for COPD in the pulmonary clinic. Further, the referring physician had to consider the COPD as dominant or codominant to the ischemic heart disease. These patients were compared with a population of 37 patients (group II) matched for age, sex, ejection fraction, and date of operation. Because there were no repeat operations in any of the group I patients, those undergoing reoperation were excluded from group II. For this study, heavy smoking was defined as more than 15 cigarettes per day for more than 5 years.

The groups were evaluated for preoperative and operative characteristics. The postoperative course, including length of intensive care unit stay, total hospitalization, morbidity, and 30-day mortality, were evaluated.

During hospitalization, all patients were monitored continuously for arrhythmias. A bedside electronic monitor was used when the patients were in the intensive care unit. When they were on the ward, they were monitored by telemetry to a control nursing station. Significant arrhythmias were considered to be those that occurred for more than 1 minute, those with malignant potential, or those that caused hemodynamic compromise.

All patients in both groups or their families were contacted between July 1 and August 1, 1993. All survivors were assessed in our clinic to evaluate the postoperative course. This evaluation included a history of all readmissions to the hospital and their causes. Patients were asked to assess their present quality of life as compared with their preoperative state. This evaluation encompassed exercise capability, breathing difficulty, and the ability to perform desired tasks.

All patients had chest roentgenograms taken before operation and at the last follow-up. These were evaluated by a radiologist unfamiliar with the patients' clinical status. In evaluating the chest roentgenograms for COPD, the radiologist observed the posteroanterior and lateral films for evidence of retrosternal emphysema, flattened diaphrams, hyperexpansion of the lungs, and pulmonary vascularity. A significant finding in any of these categories was considered to be radiologic evidence for COPD.

The postoperative films were examined for evidence of a new elevated diaphram and other pulmonary complications.

Pulmonary function tests were done in all patients in group I before operation and in all but one of the survivors at the last follow-up. In group II, 12 patients had both preoperative and follow-up pulmonary function tests.

Statistical analysis.
For the comparison of categorical parameters between the two groups, the ² test was used. When the groups were too small, Fisher's exact test was used. For the determination of significant differences between the groups for quantitative parameters, a two-sample t test was applied. To analyze relationships between two continuous parameters, Pearson's correlation analysis was applied.

RESULTS

Preoperative characteristics.
Preoperative characteristics of the patients in groups I and II are shown in Table I. There were no significant differences in the demographic data for the two groups. Operative risk factors including diabetes, previous myocardial infarction, unstable angina, and ventricular ejection fraction were similar in the two groups. There were more significant arrhythmias before admission in group I (Table I). These consisted of atrial fibrillation (4), ventricular tachycardia (1), and multiple ventricular premature beats (VPBs) (>8/min) or multifocal VPBs (3). More patients had been previously hospitalized for shortness of breath in group I (Table I). In 21 of the 29 hospitalized patients (group I), it was unclear whether the origin was cardiac or pulmonary. In the nine patients hospitalized before operation in group II, the shortness of breath was clearly cardiac in origin.

Of the late deaths, two were also related to arrhythmias. One patient, with poor ejection fraction, was readmitted to the hospital 2 months after discharge with atrial fibrillation and heart failure. He died during the hospitalization of multiple organ failure. The third patient had acute atrial fibrillation 4 weeks after operation. Concurrent with the arrhythmia, dense right-sided hemiplegia developed. She died after 3 weeks of hospitalization. The fourth patient died 10 months after operation. She had been hospitalized four times for shortness of breath and died of respiratory insufficiency.

Morbidity.
During the follow-up period, there were significantly more complications among group I patients. Twenty-four of the 37 patients were rehospitalized after CABG, with a total of 44 hospital admissions. Fourteen patients were hospitalized multiple times (Fig. 1). Readmissions were due to respiratory symptoms (n = 31), arrhythmias (n = 5), recurrent ischemia (n = 2), uncontrolled diabetes (n = 1), mediastinitis (n = 3), superficial wound infection (n = 1), and uncontrolled hypertension (n = 1). Four patients with arrhythmias had significant sequelae. These included two patients who required femoral embolectomy for emboli that occurred during atrial fibrillation. One patient had right hemiparesis that totally resolved, and one had transient monocular blindness concurrent with atrial arrhythmias. In all instances, the patients were in atrial fibrillation on readmission to the hospital, whereas they had been discharged from the cardiac service in normal sinus rhythm. In group II, there were 12 readmissions to the hospital because of respiratory symptoms (n = 3), arrhythmias (n = 2), recurrent ischemia (n = 1), diabetes (n = 1), superficial wound infection (n = 3), uncontrolled hypertension (n = 1), and lung cancer (n = 1).

View larger version (20K): [in this window] [in a new window]   Fig. 1. Comparison of number of hospital admissions and causes of admission in patient population during follow-up period.

The results of our quality of life evaluation are shown in Fig 2. Of the 32 surviving patients in group I, 12 (37%) believed that their physical abilities to do desired tasks were reduced after the operation, 15 patients subjectively felt an improvement, and 5 remained unchanged. In group II, 34 (91.9%) patients believed that the operation had improved their conditions, 1 felt worse, and 2 remained unchanged (p = 0.0056).

View larger version (20K): [in this window] [in a new window]   Fig. 2. Results of quality-of-life questionnaire showing patients' assessment of quality of life at last follow-up compared with preoperative status.

COPD and atherosclerotic cardiovascular disease commonly occur among the same patient population. ¹ The importance of the cardiovascular reserve in patients undergoing pulmonary resection is recognized. ³ The effect of respiratory reserve on patients undergoing CABG is not well delineated. Our hypothesis was that a limited pulmonary reserve is a major cause of poor immediate and intermediate results in patients undergoing CABG.

Definition of COPD.
Attempts have been made to establish COPD as a risk factor for mortality in patients undergoing CABG. ^4-6 The Society of Thoracic Surgeons established COPD as an operative risk factor, ⁵ and the Cleveland Clinic Score has alloted COPD a value of 1. ⁶ The Veterans Administration showed patients undergoing CABG with an FEV₁ less than 1.25 L to have a significantly higher acute mortality rate. ² However, detailed analysis of the influence of COPD on patients undergoing CABG has not been done.

Part of the problem is defining significant COPD. Whereas the definition of severe COPD is well established with the use of laboratory parameters, these patients are clearly too ill to undergo CABG. ^7,8 In an attempt to overcome this problem, we elected to define our population on the basis of clinical criteria, as described in the Patients and methods section. The laboratory and radiologic data from this group of patients confirmed that the patients in this group had moderate to severe COPD. Our clinical definition was sufficiently broad to include 5.7% of our CABG population. It was specific enough that when this group of patients with clinical COPD was compared with the control group, the highly significant effect of COPD was evident.

Arrhythmias.
The association of COPD with an increased incidence of ventricular and supraventricular arrhythmias is well established. ^9,10 This was confirmed by our study with a higher incidence of preoperative arrhythmia in group I patients. Arrhythmias, especially supraventricular arrhythmias, are common after CABG. ^11,12 Risk factors known to be associated with the development of these arrhythmias include increased age and withdrawal from ß-blockers. ^13,14 Other factors, including arterial blood gas levels, have been studied as potential risk factors for supraventricular arrhythmias after CABG, but no correlation has been found. ^14,15 COPD has been identified as a risk factor for postoperative atrial arrhythmias in a recent study, but COPD is not defined in that paper. ¹⁶

There was a large increase in the number of patients with significant arrhythmias in group I, implicating clinical COPD as a risk factor for arrhythmias after CABG. Furthermore, ventricular fibrillation and tachycardia developed only in group I patients. Hemodynamic compromise because of arrhythmias occurred only in group I patients, and arrhythmias in this group were a major cause of morbidity and mortality.

Hemodynamic compromise with atrial fibrillation has previously been associated with poor left ventricular systolic and diastolic function, hypertrophied myocardium, ischemic myocardium, and duration of arrhythmia. ¹⁷ Atrial fibrillation after CABG is usually benign and of short duration, and the CABG itself has greatly reduced the ischemic jeopardy of the myocardium. ¹⁷ Our data implicate COPD as a risk factor for hemodynamic compromise during atrial arrhythmia in patients after CABG.

Pulmonary complications.
Increased postoperative pulmonary morbidity in patients with COPD is documented. ¹⁸ In patients undergoing CABG, the effects of sternotomy and bypass on pulmonary function will reduce FEV₁ in the postoperative period to two thirds the amount of its preoperative value. ^18,19 In patients with COPD, this acute postoperative reduction in FEV₁ will accentuate their underlying condition to increase postoperative morbidity. As such, our findings of increased reintubation, length of intubation, and length of hospital stay in group I are all consistent with data from previous reports. ^18,20

Infection.
There were three episodes of mediastinitis in group I and none in group II. Chronic pulmonary disease has been documented as a risk factor for mediastinitis after CABG. ^21,22

Mortality.
Over a mean of 14 months of follow-up, there was a significant difference in the mortality between groups. An FEV₁ of less than 1.25 L has been shown to increase the risk of acute mortality. ² Intermediate mortality and an analysis of the causes of death have not been previously reported. Our analysis shows that the major cause of mortality was arrhythmia: 4 of 5 patients who died had arrhythmia as the direct or precipitating cause of death. The lethal arrhythmias were distributed equally between the immediate postoperative period and follow-up period. It should also be noted that 23 of our patients had an FEV₁ greater than 1.25 L. This again emphasizes the need to use clinical COPD as the risk factor and not a single laboratory value associated with the disease.

Quality of life.
It is frequently difficult to differentiate cardiac from pulmonary causes of dyspnea. ²³ Thus a patient with COPD who is seen with shortness of breath as a manifestation of cardiac disease may not have the symptoms alleviated by CABG. In addition, injury to the pulmonary system during CABG may result in alleviation of the cardiac symptoms and exacerbation of pulmonary symptoms, resulting in little symptomatic benefit to the patient.

Our analysis seems to confirm this concern. In group I, 24 patients had to be rehospitalized during the follow-up period. Further, only 15 believed that their physical condition improved after CABG; 12 believed that it worsened. This contrasts with the results in group II, whose patients enjoyed the results of CABG as previously described in the literature. ²⁴

Thus, on the basis of the data collected, our impression is that the following conclusions are warranted: (1) Clinical COPD is a significant factor for morbidity and mortality after CABG, (2) a large portion of the morbidity and mortality may be due to an increase in significant postoperative arrhythmias, and (3) the clinical benefits of CABG reported in the literature are significantly reduced among this patient population.

We suggest the following recommendations: (1) Because of high (or higher) mortality and reduced benefit, indications for CABG in this group of patients should be restricted and (2) postoperative prophylaxis against arrhythmias should be used in this group of patients and maintained indefinitely.

Acknowledgments

This article was prepared in consultation with Eliezer Jucha, who performed the statistical calculations, and with the technical assistance of Sally Esakov.

Footnotes

From the Departments of Cardiovascular Surgery^a and Radiology,^b Edith Wolfson Medical Center, Holon, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

References

1. Lippman ML, Goldberg SK, Walkerstein MD. Pulmonary complications of open heart surgery. In: Kolter MN, Alfieri A. eds. Cardiac and noncardiac complications of open heart surgery: prevention, diagnosis, treatment. Mt Kisco, NY: Futura, 1992:239-79.
   
2. Grover FL, Hammermeister KE, Burchfiel C. Initial report of Veterans Administration peroperative risk assessment study for cardiac surgery. Ann Thorac Surg 1990;50:12-26.[Abstract]
   
3. Morice RC, Peters EJ, Ryan MB, Putnam JB, Ali MK, Roth JA. Exercise testing in the evaluation of patients at high risk for complications from lung resection. Chest 1992;101:356-61.[Abstract/Free Full Text]
   
4. Naunheim KS, Fiore AC, Wadley JJ, et al. The changing profile of the patient undergoing coronary artery bypass surgery. J Am Coll Cardiol 1988;11:494-8.[Abstract]
   
5. Kouchoukos NT, Ebert PA, Grover FL, Lindesmith GG. Report of the ad hoc committee on risk factors for coronary artery bypass surgery. Ann Thorac Surg 1988;45:348-9.[Abstract]
   
6. Loop FD, Higgins TL, Panda R, Pearce G, Estafanous FG. Myocardial protection during cardiac operations. J THORAC CARDIOVASC SURG 1992;104:608-18.[Abstract]
   
7. Nocturnal Oxygen Treatment Trial Group. Continuous or nocturnal oxygen treatment in hypoxemic chronic obstructive lung disease. Ann Intern Med 1980;93:391-8.
   
8. Timms RM, Khaja FU, Williams GW, Nocturnal Oxygen Treatment Trial Group. Hemodynamic response to oxygen treatment in chronic obstructive lung disease. Ann Intern Med 1985;102:29-36.
   
9. Sideris DA, Katsadoros DP, Valianos G, Assioura A. Type of cardiac dysrhythmias in respiratory failure. Am Heart J 1975;89:32-5.[Medline]
   
10. Incalzi RA, Pistelli R, Fuso L, Cocchi A, Bonetti MG, Giordano A. Cardiac arrhythmias and left ventricular function in respiratory failure from chronic obstructive pulmonary disease. Chest 1990;97:1092-7.[Abstract/Free Full Text]
    
11. Mohr R, Smolinsky A, Goor DA. Prevention of supraventricular tachyarrhythmia with low-dose propranolol after coronary bypass. J THORAC CARDIOVASC SURG 1981;81:840-5.[Abstract]
    
12. Vecht RJ, Nicolaides EP, Ikweuke JK, Liassides C, Cleary J, Cooper WB. Incidence and prevention of supraventricular tachyarrhythmias after coronary bypass surgery. Int J Cardiol 1986;13:125-34.[Medline]
    
13. Leitch JW, Thomson D, Baird DK, Harris PJ. The importance of age as a predictor of atrial fibrillation and flutter after coronary artery bypass grafting. J THORAC CARDIOVASC SURG 1990;100:338-42.[Abstract]
    
14. Salazar C, Fishman W, Friedman S, et al. Beta-blockade treatment for supraventricular tachyarrhythmias after coronary surgery: A propranolol withdrawal syndrome? Angiology 1979;30:816-9.
    
15. Suttorp MJ, Kingma JH, Joe Gin RMT, et al. Efficacy and safety of low- and high-dose sotalol versus propranolol in the prevention of supraventricular tachyarrhythmias early after coronary artery bypass operations. J THORAC CARDIOVASC SURG 1990;100:921-6.[Abstract]
    
16. Creswell LL, Schuessler RB, Rosenbloom M, Cox JL. Hazards of postoperative atrial arrhythmias. Ann Thorac Surg 1993;56:539-49.[Abstract]
    
17. Turlapti R, Greenspan AM. Supraventricular arrhythmias following coronary artery bypass grafting. In: Kolter MN, Alfieri A, eds. Cardiac and noncardiac complications of open heart surgery: prevention, diagnosis, treatment. Mt Kisco, NY: Futura, 1992:74.
    
18. Cain HD, Stevens PM, Adaniya R. Preoperative pulmonary function and complications after cardiovascular surgery. Chest 1979;76:130-5.[Abstract/Free Full Text]
    
19. Cohen AJ, Moore P, Jones C, et al. Effect of internal mammary harvest on postoperative pain and pulmonary function. Ann Thorac Surg 1993;56:1107-9.[Abstract]
    
20. Jackson CV. Preoperative pulmonary function evaluation. Arch Intern Med 1988;148:2120-7.[Abstract/Free Full Text]
    
21. Demmy TL, Park SB, Liebler GA, et al. Recent experience with major sternal wound complications. Ann Thorac Surg 1990;49:458-62.[Abstract]
    
22. Newman LS, Szczukowski LC, Bain RP, Pelino CA. Suppurative mediastinitis after open heart surgery: a case control study of risk factors. Chest 1988;94:546-53.[Abstract/Free Full Text]
    
23. Nery LE, Wasserman K, French W, Oren A, Davis JA. Contrasting cardiovascular and respiratory responses to exercise in mitral valve to chronic obstructive pulmonary diseases. Chest 1983;83:446-53.[Abstract/Free Full Text]
    
24. Booth DC. Quality of life after bypass surgery for unstable angina. Circulation 1991;83:87-95.[Abstract/Free Full Text]
    

This article has been cited by other articles:

				Z. I. Khalpey, R. B. Ganim, and J. D. Rawn Postoperative Care of Cardiac Surgery Patients Card. Surg. Adult, January 1, 2008; 3(2008): 465 - 486. [Full Text]

				S. Sivalingam, S. Rathinam, A. Ajis, and C. M.R. Satur Nurse-Led Preoperative Screening and Targeted Optimization of Pulmonary Dysfunction in Patients Undergoing Cardiac Surgery Ann. Thorac. Surg., August 1, 2007; 84(2): 683 - 685. [Abstract] [Full Text] [PDF]

				E. Kuralay, F. Cingoz, S. Kilic, C. Bolcal, C. Gunay, U. Demirkilic, and H. Tatar Supraventricular tachyarrythmia prophylaxis after coronary artery surgery in chronic obstructive pulmonary disease patients (early amiodarone prophylaxis trial) Eur. J. Cardiothorac. Surg., February 1, 2004; 25(2): 224 - 230. [Abstract] [Full Text] [PDF]

				B. Medalion, M. G. Katz, A. J. Cohen, E. Hauptman, L. Sasson, and A. Schachner Long-term Beneficial Effect of Coronary Artery Bypass Grafting in Patients With COPD Chest, January 1, 2004; 125(1): 56 - 62. [Abstract] [Full Text] [PDF]

				Y. Deng, K. Byth, and H. S. Paterson Phrenic nerve injury associated with high free right internal mammary artery harvesting Ann. Thorac. Surg., August 1, 2003; 76(2): 459 - 463. [Abstract] [Full Text] [PDF]

				M. De Feo, R. Gregorio, A. Della Corte, C. Marra, C. Amarelli, A. Renzulli, R. Utili, and M. Cotrufo Deep sternal wound infection: the role of early debridement surgery Eur. J. Cardiothorac. Surg., June 1, 2001; 19(6): 811 - 816. [Abstract] [Full Text] [PDF]

				M. De Feo, A. Renzulli, G. Ismeno, R. Gregorio, A. Della Corte, R. Utili, and M. Cotrufo Variables predicting adverse outcome in patients with deep sternal wound infection Ann. Thorac. Surg., January 1, 2001; 71(1): 324 - 331. [Abstract] [Full Text] [PDF]

				A. J. Cohen, M. G. Katz, G. Frenkel, B. Medalion, D. Geva, and A. Schachner Morbid Results of Prolonged Intubation After Coronary Artery Bypass Surgery Chest, December 1, 2000; 118(6): 1724 - 1731. [Abstract] [Full Text] [PDF]

				K. A. Eagle, R. A. Guyton, R. Davidoff, G. A. Ewy, J. Fonger, T. J. Gardner, J. P. Gott, H. C. Herrmann, R. A. Marlow, W. C. Nugent, et al. ACC/AHA guidelines for coronary artery bypass graft surgery: A report of the American College of Cardiology/ American Heart Association task force on Practice Guidelines (Committee to revise the 1991 Guidelines for Coronary Artery Bypass Graft Surgery) J. Am. Coll. Cardiol., October 1, 1999; 34(4): 1262 - 1347. [Full Text] [PDF]

				M. Engoren, N. F. Buderer, A. Zacharias, and R. H. Habib Variables predicting reintubation after cardiac surgical procedures Ann. Thorac. Surg., March 1, 1999; 67(3): 661 - 665. [Abstract] [Full Text] [PDF]

				C. C. Canver, R. D. Nichols, and G. M. Kroncke Influence of age-specific lung function on survival after coronary bypass Ann. Thorac. Surg., July 1, 1998; 66(1): 144 - 147. [Abstract] [Full Text] [PDF]

				M. G. Katz, R. Katz, A. Schachner, and A. J. Cohen Phrenic Nerve Injury After Coronary Artery Bypass Grafting: Will It Go Away? Ann. Thorac. Surg., January 1, 1998; 65(1): 32 - 35. [Abstract] [Full Text] [PDF]

				C. Y. Bitkover and B. Gardlund Mediastinitis After Cardiovascular Operations: A Case-Control Study of Risk Factors Ann. Thorac. Surg., January 1, 1998; 65(1): 36 - 40. [Abstract] [Full Text] [PDF]

				A. J. Cohen, M. G. Katz, R. Katz, D. Mayerfeld, E. Hauptman, and A. Schachner Phrenic Nerve Injury After Coronary Artery Grafting: Is It Always Benign? Ann. Thorac. Surg., July 1, 1997; 64(1): 148 - 153. [Abstract] [Full Text]

This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Amram Cohen Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cohen, A. Articles by Schachner, A. Search for Related Content PubMed PubMed Citation Articles by Cohen, A. Articles by Schachner, A.