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(Chest. 1999;115:135-139.)
© 1999 American College of Chest Physicians

Can Retrograde Cardioplegia Alone Provide Adequate Protection for Cardiac Valve Surgery?*

Nirupama G. Talwalkar, MD, FCCP; Gerald M. Lawrie, MD, FCCP; Nan Earle, BS and Michael E. DeBakey, MD, FCCP

* From the Division of Cardiothoracic Surgery, Baylor College of Medicine, Methodist Hospital, Houston, TX.


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
 References
 
Background: When aortic insufficiency is present, antegrade delivery of cardioplegia requires coronary cannulation. Use of retrograde cardioplegia simplifies administration. The efficacy of the retrograde route alone in ensuring adequate myocardial protection may be assessed by the clinical outcome.

Methods and results: We used closed transatrial coronary sinus perfusion as the sole method of cardioplegia delivery in 100 patients who underwent valve operations, either isolated or combined with coronary (n = 24), ascending aortic aneurysm (n = 8), or other procedures. Eighty-one patients were in New York Heart Association (NYHA) Class III or IV; 23 had undergone previous heart operations; 23 were admitted from the coronary care unit (CCU); and 20 had left ventricular ejection fraction (LVEF) of <= 40%. Operative mortality was 2%. An intra-aortic balloon pump was required in eight patients. On univariate analysis, perioperative use of inotropes (n = 26) was related to age >= 70 years (p = 0.02), COPD (p = 0.05), pulmonary hypertension (p = 0.005), higher NYHA Class (p = 0.0006), preoperative heart failure (p = 0.006), lower LVEF (p = 0.0003), urgency (p = 0.00001), admission from the CCU (p = 0.006), repeat operation (p = 0.03), coronary artery disease (p = 0.02), and longer ischemic (p = 0.02) and bypass times (p = 0.0003). On multivariate stepwise logistic regression analysis, use of inotropes was related to preoperative lower LVEF (p = 0.02) and urgency of operation (p = 0.0002). Perioperative complications included ventricular arrhythmia in six, heart block in one, renal dysfunction in nine, and stroke in two patients; no patient had myocardial infarction.

Conclusion: Good clinical results can be obtained by using retrograde cardioplegia alone without prior doses of antegrade cardioplegia in all valve operations.

Key Words: myocardial protection • retrograde cardioplegia • valve operations


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 Conclusion
 References
 
The strategy of sequential use of antegrade and retrograde cardioplegia has been increasingly applied by many for myocardial protection during ischemic arrest.1 Recently, we started using closed transatrial retrograde coronary sinus perfusion as the exclusive means of cardioplegia delivery in all valve operations, including those with previous operations or concomitant coronary, aortic, or other procedures. The purpose of this retrospective study is to evaluate the clinical outcome with this strategy.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 Conclusion
 References
 
In 2 years between January 1993 and April 1995, 100 consecutive patients on our service at the Methodist Hospital underwent cardiac valve operations, either isolated or combined with other procedures. For all patients, cardioplegia was given only retrogradely by closed transatrial cannulation of the coronary sinus, without adjunctive antegrade perfusion. There were 59 men and 41 women with a mean age of 63 years (range, 23 to 88 years). Forty one patients were >= 70 years old. A custom database was created using Data Tree MUMPS (DT.MAX Intersystems; Cambridge, MA). Patient data were collected from hospital charts. This study was approved by our institutional review board in November 1995. Informed consent was obtained from all patients or relations. Charts were reviewed regarding the preoperative profile of the patients (Table 1 ), associated conditions, medications, diagnoses, etiology, indications for operation, cardiac rhythm, operative procedures (Table 2 ), intraoperative factors (Table 3 ), and postoperative complications. Perioperative myocardial infarction (MI) was said to be present when one of the following was observed: (1) new Q waves on ECG; (2) creatine kinase-MB (CK-MB) index of > 8; (3) CK-MB of > 50 with ECG changes; or (4) CK-MB of > 70 without ECG changes. Renal dysfunction was considered present when the serum creatinine level was > 167 nmol/L (1.8 mg/dL), and the parameter that confirmed hepatic dysfunction was a serum bilirubin level > 17 nmol/L (1 mg/dL). Operative mortality was defined as death occurring within 30 days of operation or before discharge from the hospital.


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  		Table 1. Patient Profile

 

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  		Table 2. Operative Procedures

 

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  		Table 3. Mean, Standard Deviations, and Ranges of Variables

 
Operative Technique
Median sternotomy was done in all patients. A membrane oxygenator (Sarns Turbo, Model 9443; Cardiovascular Systems Department, 3M Health Care; Ann Arbor, MI) was used. A total cardiopulmonary bypass (CPB) was established using bicaval cannulation with snaring and ascending aortic return. The left ventricle was drained with a sump catheter via the right superior pulmonary vein. Moderate systemic hypothermia (rectal temperature, 27° to 32°C) and hemodilution (hematocrit, 20 to 25%) were maintained during CPB.

A crystalloid cardioplegic solution, Plegisol (Abbott; North Chicago, IL), which is a sterile nonpyrogenic, isotonic formulation of water for injection, was used as a core solution to which was added the buffer—10 mL of 8.4% sodium bicarbonate injection (10 mEq each of sodium and bicarbonate) per liter. The buffered admixture contains the following electrolytes (per liter): Ca2+ 2.4 mEq, Mg2+ 32 mEq, K+ 16 mEq, Na+ 120 mEq, Cl- 160 mEq, and bicarbonate (HCO-) 10 mEq; osmolar concentration, 324 mOsmol/liter (calc); pH 7.8 (approximate).

After cross clamping the aorta, a liter of cold (4°C) buffered Plegisol was given via a size-14 French retroplegia cannula with a smooth self-inflating retention balloon (Research Medical; Midvale, UT) introduced into the coronary sinus by using a closed transatrial technique, while maintaining a coronary sinus pressure of < 20 mm Hg. This resulted in a rapid diastolic arrest of the heart within 30 to 50 s. Valve repair and/or replacement, and concomitant procedures if any, were carried out. As the patients were rewarmed to normothermia, 1 L of warm (35° to 37°C) cardioplegia (Plegisol with 20 mEq of sodium bicarbonate, 10 mEq of K+, and 50 mL of 50% dextrose) was given retrograde just before removing the aortic cross clamp. Patients were weaned off CPB, and the operation was concluded.

Concomitant coronary artery bypass grafting (CABG) was done during single aortic cross clamping. Femoral artery-bicaval bypass was used in a patient who underwent prosthetic aortic valve replacement concomitant with tube graft replacement of the ascending aorta and the transverse arch under profound hypothermia and circulatory arrest, with retrograde cerebral perfusion via a superior vena caval cannula.

A St. Jude Medical prosthetic valve was used as the prosthetic valve of choice in all patients who had valve replacement, except for six in whom a Carpentier-Edward bioprosthetic valve was used (one of them was a Jehovah's Witness), and one in whom an aortic root homograft was used. All patients had a Swan-Ganz catheter placed after induction of anesthesia for intra- and postoperative monitoring. The right atrial and ventricular pressures remained satisfactory during operation with no evidence of new tricuspid regurgitation, indicating adequate protection of the right ventricle with retrograde cardioplegia.

Statistical Methods
Statistical analysis was performed using Bio Medical Data Program (BMDP Statistical Software; University of Southern California; Los Angeles, CA) to identify the pre- and intraoperative risk factors associated with the need for perioperative inotropes. The univariate analysis was done using the {chi}2 test for categorical variables, and a pooled t-test was used for continuous variables. Since the variances were significantly different, the Welch F test was used for LVEF, instead of a pooled t-test. The variables analyzed by the univariate method include factors listed in Tables 1 through 3, age, sex, body surface area, preoperative medications, cardiac rhythm, renal dysfunction, degree of hypothermia, use of an intra-aortic balloon pump (IABP), intra-/perioperative ventricular arrhythmia, and conduction disturbances requiring treatment. Systemic hypertension, diabetes, gender, and factors with p < 0.05 on univariate analysis were tested by forward and backward stepwise logistic regression analysis. The significance was calculated by the method of maximum likelihood.

Univariate analysis was also applied to pre- and intraoperative factors to assess their predictive value for the occurrence of perioperative complications.


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 Conclusion
 References
 
Preoperatively, 44 patients had nonsinus rhythm. The diagnoses of the valve lesions (isolated/mixed) that needed operation included aortic stenosis in 42, aortic incompetence in 19, mitral stenosis in 14, mitral incompetence in 45, and tricuspid incompetence in 4. Twenty-three patients had undergone one or more previous cardiac or ascending aortic operations. In some patients the main indication for operation was coronary artery disease (CAD)/blocked grafts/aneurysm of the ascending aorta, and in these patients the valve operation was performed as a concomitant procedure (Table 2 ). Two patients had concomitant replacement of permanent pacemakers.

Intraoperatively, 7 patients needed sequential atrioventricular pacing for heart block; 8 required IABP; and 26 were on inotropes at the time of leaving the operating room. There was no incidence of coronary sinus injury due to retrograde cardioplegia catheterization. The median hospital stay was 10 days.

Operative Mortality
Two patients died. Both were > 70 years of age and had emergency operations, preoperative low cardiac output, and multiple problems. Both required IABP and died of multisystem failure.

Perioperative Need for Inotropes
This was noted in 26 patients. The results of univariate and multivariate analysis of pre- and intraoperative determinants of the need for inotropes are summarized in Table 4 and Table 5 . On univariate analysis, a history of medication with diuretics (p = 0.004) or angiotensin-converting enzyme inhibitors (p = 0.05) and preoperative high pulmonary artery systolic (p = 0.005), diastolic (p = 0.0008), and mean (p = 0.02) pressures significantly increased the inotropic need. Diabetes was only marginally significant (p = 0.07), but systemic hypertension was not at all significant. When 12 preoperative factors (age >= 70, hypertension, diabetes, CAD, endocarditis, repeat operation, urgency, NYHA Class IV, admission from CCU, renal dysfunction, LVEF <= 40%, IABP) were analyzed by univariate method, it was evident that the presence of more than three of these factors substantially increased the necessity (p = 0.0002) of inotropic support before leaving the operating room, and the significance was higher when more than five factors were present (p = 0.00001).


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  		Table 4. Determinants of Need for Perioperative Inotropic Support: Univariate Analysis

 

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  		Table 5. Determinants of Need for Perioperative Inotropic Support: Multivariate Logistic Regression Analysis*

 
Although the IABP (p = 0.00001), postbypass low cardiac output (p = 0.0001), and postbypass cardiac index (p = 0.0004) were highly significant predictors, we did not include them in the multivariate analysis because low cardiac output is the very reason that determines the need for inotropes and, therefore, must be present as such. It is noteworthy that, although a total of 26 patients needed perioperative inotropes, only 10 of them required it for > 24 h, and thus, could be said to have had a true low cardiac output syndrome. In the remaining 16 patients, inotropes were needed for < 24 h, which signified a transient postbypass hemodynamic instability rather than a true low output.

Perioperative Myocardial Infarction
None of the patients in this series showed any clinical/electrocardiographic/cardiac enzymatic evidence of myocardial infarction in the perioperative period.

Perioperative Complications
Eighteen patients had renal dysfunction after operation, but it had been noted before operation in nine patients. Thirty patients had supraventricular arrhythmia, six had ventricular arrhythmia, one had a heart block, and one needed a permanent pacemaker. Eighteen had coagulopathy, and two of them required reopening for bleeding.

When preoperative COPD, other respiratory problems, and history of smoking were grouped together as one variable, they significantly increased the perioperative respiratory complications (p = 0.01), which occurred in 26 patients.

All preoperative and intraoperative variables were analyzed separately by the univariate method to assess their predictive value for the risk of developing each of the perioperative complications. The incidence of perioperative heart failure, including congestive heart failure and left ventricular failure, was found to be significantly increased by advanced age (p = 0.003), CAD (p = 0.005), and urgency of operation (p = 0.00001). Of the 46 patients who had heart failure before operation, 17 (37%) did not show evidence of it after operation. Of the 34 patients who were noted to have perioperative heart failure, 29 (85%) had it prior to surgery, and only 5 (15%) developed it after surgery as a result of coagulopathy, blood transfusion, and respiratory and renal complications.


   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
Conclusion
 References
 
Closed transatrial retrograde coronary sinus cardioplegia2 ,3 ,4 is an effective and safe method of cardioplegia delivery in valve operations. Its specific advantages in the presence of aortic insufficiency and occluded left anterior descending coronary artery have been noted in previous reports.1 ,4 ,5 ,6 ,7 ,8 ,9 ,10 ,11 We used it exclusively in all valve operations (with concomitant procedures, if any) without prior antegrade cardioplegia and had good clinical outcome. Delay in the onset of diastolic arrest is considered a disadvantage of using cardioplegia solely by the retrograde method, in contrast to rapid diastolic arrest achieved by antegrade method. However, this feature of retrograde method does not seem to have clinically detectable adverse effects on the operative outcome, as evident by previous reports5 ,12 ,13 ,14 and our present results. The efficacy of intraoperative myocardial protection may be assessed clinically by: (1) operative mortality; (2) prevalence of intra- or perioperative myocardial infarction, suspected clinically and confirmed by electrocardiographic or enzymatic evidence; (3) requirement of IABP or inotropic support at the time of leaving the operating room; and (4) significant ventricular arrhythmias and conduction disturbances postbypass and in the perioperative period.

There were only two operative deaths in our series; both occurred in patients who had been in a deleterious condition before operation, with more than five incremental risk factors predicting perioperative low cardiac output status. None of the patients in the series suffered perioperative MI; these include patients who had concomitant CABG and also those in whom primary indication for operation was unstable angina.

Eight percent of patients had true low cardiac output syndrome and required IABP. All these patients had been in a compromized cardiac state before operation with more than five conditions that posed incremental risk for hemodynamic instability. Transient instability, which required inotropes for less than 24 h, occurred in 13% of patients, all of whom had more than three incremental risk factors. Our incidence of postbypass and perioperative ventricular arrhythmias, conduction disturbances, and the need for inotropes compared favorably with previous reports.4 ,5 ,6 ,11

It is noteworthy that there was a high proportion of seriously ill patients in our series. 50% were in NYHA Class IV, 45% had urgent or emergent operations, 23% had previous operations, many had multiple comorbid risk factors, and 36% had concomitant operations, including CABG. The high number of patients in NYHA Class IV reflects those in the high-risk category referred from or rejected by other centers or states. Unlike some other studies,11 repeat operations, concomitant CABG, and low LVEF did not preclude the exclusive use of retrograde cardioplegia in this study. We did not find it necessary to use adjunctive antegrade cardioplegia in such cases.

The highly precarious state of many patients prior to operation with multiple comorbid conditions and dysfunctions contributed to perioperative complications, prolonged ventilatory support, and longer hospital stay. In 85% of patients with perioperative heart failure, it was not a new development, but had existed prior to surgery. Advanced age, CAD, and urgency of operation significantly increased heart failure and requirement of inotropic support. Respiratory complications also had a very strong correlation with pre-existing compromized respiratory status and smoking.

Our goal was to find out whether exclusive use of retrograde cardioplegia can provide adequate myocardial protection in valve operations. It was not our objective to do a comparative analysis with the use of antegrade cardioplegia alone or as an adjuvant. This, along with the small sample size and the retrospective nature of the study, are the limitations of our series.


   Conclusion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
References
 
This study shows that retrograde cardioplegia alone without adjuvant antegrade cardioplegia can be safely and effectively used in all valve operations, including: procedures with single or multiple valves, in combination with procedures with coronary or ascending aortic aneurysm, and others. It has obvious advantages in the presence of aortic insufficiency. Low operative mortality, absence of perioperative MI, and low, acceptable prevalence of ventricular arrhythmias/conduction disturbances and hemodynamic instability requiring inotropic support in the immediate perioperative period are the clinical markers indicative of adequate myocardial protection. Preoperative high-risk factors significantly increase perioperative complications, which, in a majority of cases, are related to the pre-existing debilitating state rather than a new development. The clinical outcome of the exclusive use of retrograde cardioplegia in all valve operations is encouraging.


   Footnotes
 
Correspondence to: Gerald M. Lawrie, MD, Methodist Hospital, 6560 Fannin, Suite 1842, Houston, TX 77030

Abbreviations: CABG = coronary artery bypass grafting; CAD = coronary artery disease; CPB = cardiopulmonary bypass; IABP = intra-aortic balloon pump; LVEF = left ventricular ejection fraction; MI = myocardial infarction; NYHA = New York Heart Association

Received for publication December 11, 1997. Accepted for publication June 27, 1998.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusion
 References
 

  1. Buckberg, GD (1988) Antegrade cardioplegia, retrograde cardioplegia, or both? Ann Thorac Surg 45,589-590[ISI][Medline]
  2. Diehl, JT, Eichhorn, EJ, Konstam, MA, et al (1988) Efficacy of retrograde coronary sinus cardioplegia in patients undergoing myocardial revascularization: a prospective randomized trial. Ann Thorac Surg 45,595-602[Abstract]
  3. Drinkwater, DC, Laks, H, Buckberg, GD (1990) A new simplified method of optimizing cardioplegia delivery without right heart isolation. J Thorac Cardiovasc Surg 100,56-64[Abstract]
  4. Gundry, SR, Sequiera, A, Razzouk, AM, et al (1990) Facile retrograde cardioplegia: transatrial cannulation of the coronary sinus. Ann Thorac Surg 50,882-887[Abstract]
  5. Menasche, P, Subayi, JB, Piwnica, A (1990) Retrograde coronary sinus cardioplegia for aortic valve operations: a clinical report on 500 patients. Ann Thorac Surg 49,556-563[Abstract]
  6. Mentzer, RM, Barner, H (1990) In discussion of: Menasche P, Subayi JB, Piwnica A. Retrograde coronary sinus cardioplegia for aortic valve operations: a clinical report on 500 patients. Ann Thorac Surg 49,556-564
  7. Bonchek, LI (1988) In discussion of: Diehl JT, Eichhorn EJ, Konstam MA, et al. Efficacy of retrograde coronary sinus cardioplegia in patients undergoing myocardial revascularization: a prospective randomized trial. Ann Thorac Surg 45,595-602
  8. Salerno, TA, Houck, JP, Barrozo, CAM, et al (1991) Retrograde continuous warm blood cardioplegia: a new concept in myocardial protection. Ann Thorac Surg 51,245-247[Abstract]
  9. Aronson, S, Lee, BK, Liddicoat, JR, et al (1991) Assessment of retrograde cardioplegia distribution using contrast echocardiography. Ann Thorac Surg 52,810-814[Abstract]
  10. Menasche, P, Subayi, JB, Veyssie, L, et al (1991) Efficacy of coronary sinus cardioplegia in patients with complete coronary artery occlusions. Ann Thorac Surg 51,418-423[Abstract]
  11. Noyez, L, van Son, JA, van der Werf, T, et al (1993) Retrograde versus antegrade delivery of cardioplegic solution in myocardial revascularization: a clinical trial in patients with three-vessel coronary artery disease who underwent myocardial revascularization with extensive use of the internal mammary artery. J Thorac Cardiovasc Surg 105,854-863[Abstract]
  12. Guiraudon, GM, Campbell, CS, McLellan, DG (1986) Retrograde coronary sinus versus aortic root perfusion with cold cardioplegia: randomized study of levels of cardiac enzymes in 40 patients. Circulation 74(Suppl 3),105-115[Abstract/Free Full Text]
  13. Fiore, AC, Naunheim, KS, Kaiser, GC (1989) Coronary sinus versus aortic root perfusion with blood cardioplegia in elective myocardial revascularization. Ann Thorac Surg 47,684-688[Abstract]
  14. Vinas, JF, Fewel, JG, Arom, KV, et al (1979) Effects of systemic hypothermia on myocardial metabolism and coronary blood flow in the fibrillating heart. J Thorac Cardiovasc Surg 77,900-907[Abstract]



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