Ann Thorac Surg 1999;68:1681-1685
© 1999 The Society of Thoracic Surgeons
Original Articles
Antegrade/retrograde cardioplegia for valve replacement: a prospective study
François Dagenais, MDa,
L. Conrad Pelletier, MDa,
Michel Carrier, MDa
a Department of Surgery, Montreal Heart Institute, University of Montreal, Montreal, Quebec, Canada
Address reprint requests to Dr Carrier, Montreal Heart Institute, 5000 Bélanger St E, Montreal, PQ H1T 1C8, Canada
e-mail: carrier{at}icm.umontreal.ca
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Abstract
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Background. From 1994 to 1996, 75 patients undergoing valve replacement were randomized to antegrade (36 patients, group 1) or antegrade/retrograde (39 patients, group 2) administration of cold blood cardioplegia.
Methods. Groups were comparable for age, sex, valve disease, and ventricular dysfunction. The aortic valve was replaced in 27 patients from group 1 and 24 patients from group 2, the mitral valve in 8 and 15 patients, and 1 patient in group 1 underwent double valve replacement (p = not significant).
Results. Lengths of cardiopulmonary bypass and aortic cross-clamp averaged, respectively, 10 minutes (p = not significant) and 12 minutes (p = < 0.05) shorter in group 2. Total amount of cardioplegia solution infused averaged 1,279 ± 406 mL and 1,341 ± 379 mL (p = not significant), respectively, in groups 1 and 2, and the period of infusion averaged 44% and 72% (p = < 0.01) of the total period of aortic cross-clamping. No death occurred in group 1 compared to two in group 2 (p = not significant). The perioperative myocardial infarction and stroke rates were comparable in both groups. Peak enzyme release at 24 hours was similar both for creatine kinase-MB fraction (26 versus 37 IU/L) and for troponin T (2.1 versus 2.5 IU/L).
Conclusions. Our study shows no significant advantage of the antegrade/retrograde administration of cardioplegia over the antegrade route in routine valvular replacement, other than a slightly shorter aortic cross-clamping time.
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Introduction
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Most patients with severe aortic valvular heart disease and mitral regurgitation have left ventricular hypertrophy. Left ventricular hypertrophy increases myocardial metabolic demand during ischemic arrest, thus rendering the heart more susceptible to ischemia during cardiac operations [1]. In addition, the increased ventricular wall thickness found in the hypertrophied heart as well as the elevated left ventricular end-diastolic pressure contribute to further decrease subendocardial perfusion [2]. Therefore, use of a cardioplegia solution offering optimal myocardial protection is fundamental in patients undergoing valve replacement.
The advent of blood cardioplegia in the clinical field of cardiac surgery has definitely reduced operative mortality and morbidity, especially in complex cardiac procedures [3, 4]. Blood cardioplegia, either cold or warm, retrograde or antegrade, has been extensively studied for coronary artery bypass grafting [5–8]. Studies evaluating blood cardioplegia during valvular procedures are unfortunately frequently limited by their retrospective nature and the heterogeneity of the patients included in the series. Although retrograde cardioplegia has been widely advocated for valve replacement by different investigators [9–11], no specific data compares prospectively the effects of an antegrade cold blood cardioplegia to a retrograde cold blood perfusion. To assess this issue we conducted a prospective randomized study among patients undergoing valve replacement procedures comparing the value and benefits of an antegrade cold blood induction followed by a nearly continuous retrograde administration to an intermittent antegrade cold blood infusion.
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Patients and methods
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From 1994 to 1996, 75 patients undergoing valve replacement procedures at the Montreal Heart Institute were randomly assigned to an intermittent antegrade cold blood cardioplegia (antegrade group) or an antegrade cold blood induction followed by nearly continuous retrograde cold blood infusion (antegrade/retrograde group). A consent form, approved by the Institutional Ethics Review Board, was signed by the patient after explanation given by the research coordinator. Treatment allocation was by sealed envelope and occurred after the patient’s arrival in the operating room. There were 36 patients randomized in the antegrade group and 39 patients in the antegrade/retrograde group (Table 1). Exclusion criteria were as follow: emergent operation and complex valve procedures requiring prolonged aortic cross-clamp time.
Surgical technique
Procedures were conducted using standard techniques. Through a median sternotomy, cardiopulmonary bypass was instituted through cannulation of the ascending aorta and the right atrium with a two-stage venous cannula. For aortic valve procedures, the left ventricle was vented through the right superior pulmonary vein. The antegrade cardioplegia solution was infused through a large-bore double-lumen needle in the ascending aorta and directly within the coronary ostia after initial arrest. In the retrograde group, blind intubation of the coronary sinus with a 14F self-expandable balloon catheter (Research Medical Inc, Midvale, UT) was successful in 32 of 36 patients (89%). Thus, 4 patients within the retrograde group were perfused exclusively in an antegrade fashion. The cardioplegia solution was formulated as follow: 1 L of Ringer’s lactate containing either 80 mmol (high K) or 40 mmol (low K) of potassium, 20 g of mannitol, 80 g of lidocaine, and 1.9 mL of 8.4% sodium bicarbonate solution with a pH of 7.4. Two inflow lines were installed for mixing of the cardioplegia solution with blood from the arterial circuit (Baxter Corp, Santa Ana, CA). In both groups, after cross-clamping of the ascending aorta, 300 to 500 mL of cold blood (4°C) cardioplegia (pressure, < 250 mm Hg) was infused to obtain an electromechanical arrest. In 4 patients of the antegrade group, cardiac standstill was impossible to achieve through the antegrade route and required implantation of a retrograde coronary sinus catheter. For the antegrade group, diastolic arrest was maintained through the antegrade route by intermittent infusions (maximum interval, 15 minutes) of low or high potassium cardioplegia depending on reappearance of electrical activity. Within the antegrade/retrograde group, after antegrade cardiac arrest, maintenance cold blood cardioplegia was delivered in the coronary sinus by a nearly continuous infusion of 150 mL/min (coronary sinus perfusion pressure, < 40 mm Hg). Retrograde cardioplegia was discontinued only to optimize surgical visibility. To enhance right ventricular preservation, a topical frosted pad was applied on its surface throughout the cross-clamp period. Whenever coronary bypass procedures were indicated, distal anastomosis was completed before the valve replacement, and proximal anastomosis was executed during the reperfusion period. No cardioplegia was infused through the saphenous vein grafts. Before release of the aortic cross-clamp, 200 mL of warm blood cardioplegia was infused in both groups, either by the antegrade or the retrograde route.
Outcome measures
Primary end points of the study was the serum levels of troponin T after valve replacements. Blood samples for determination of serum levels of total creatine kinase (CK), CK-MB fraction, and troponin T were obtained 1, 3, 6, 12, 24, and 48 hours after operation. Electrocardiograms were taken preoperatively, after arrival to the intensive care unit, and on postoperative days 1, 2, and 3. A diagnosis of perioperative myocardial infarction was established when two of the following criteria were met: (1) new Q wave or loss of R wave progression in the anterior chest leads; (2) serum CK-MB activity more than 100 IU/L 12 to 24 hours postoperatively; or (3) a positive myocardial pyrophosphate scan (performed only in presence of an abnormal CK-MB increase with an unchanged electrocardiogram).
Secondary end points were hospital mortality, myocardial infarction rate, and requirement of inotropic agents after weaning of cardiopulmonary bypass and postoperative heart failure.
Measurement of biochemical markers
The serum CK level (normal range, 24 to 195 IU/L), as well as the CK-MB catalytic activity (normal range, 0 to 30 IU/L) was measured by standard methods using reagents and a Hitachi 717 analyzer from Boehringer-Mannheim (Mannheim, Germany). The serum cardiac troponin T concentration (normal range, 0 to 0.02 µg/L) was analyzed by an enzyme immunoassay using reagents and an ES300 analyzer from Boehringer-Mannheim.
Data analysis
The study sample size in each group was based on a projected decrease of 50% in the mean maximum value of postoperative troponin T serum level, as reported in a previous study [8], with an 
error of 0.05, a ß error of 0.20, and a power of 80%.
Data are expressed as mean ± standard deviation. Analysis of continuous data was performed with an unpaired Student’s t test, whereas categoric data were done with a 
2 test. Analysis of variance for repeated measures was performed to test differences in CK-MB release and troponin T release between groups. Level of significance was set at 95%. Groups were analyzed according to an "intention to treat" protocol.
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Results
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Patient characteristics
The preoperative profiles of the patients were comparable among the two groups except for a significant (p < 0.05) increase in coronary artery disease within the antegrade cardioplegia group (Table 1). Patients were considered at high risk when one of the following were present: New York Heart Association functional class III, IV, severe left ventricular dysfunction (ejection fraction, < 30%), concomitant coronary artery disease, severe pulmonary hypertension (systolic pressure, > 60 mm Hg), age more than 70 years, or chronic renal failure (creatinine level, > 150 mmol/L).
Operative data
Type of valvular replacement was similar between both groups (Table 2). Although, the duration of cardiopulmonary bypass of both groups showed a nonsignificant difference, aortic cross-clamp time was significantly decreased in the antegrade/retrograde group compared to the antegrade group (p < 0.05). In each group 67% of patients returned spontaneously to a normal sinus rhythm after weaning from cardiopulmonary bypass. Six patients in the antegrade group and 8 patients in the antegrade/retrograde group necessitated a temporary pacemaker after completion of operation (p = not significant). Total blood losses averaged 1,067 ± 1,131 mL in the antegrade group and 1,425 ± 1,664 mL in the antegrade/retrograde group (p = not significant).
Cardioplegia-related data
The total volume of administered cardioplegia was similar for both groups (Table 3). On the other hand, the total duration of cardioplegia infusion was significantly higher (p < 0.01) in the antegrade/retrograde group (50 ± 20 minutes; 73% of cross-clamp time) compared to the antegrade group (36 ± 23 minutes; 44% of cross-clamp time). Minimal septal temperature, minimal core temperature, as well as maximal potassium levels were comparable between groups.
Postoperative morbidity and mortality
Two hospital deaths attributable to a low cardiac output syndrome were encountered in the antegrade/retrograde group (Table 4). No death occurred with the antegrade group. Criteria of myocardial infarction were observed in 3 patients of the antegrade group and 2 patients of the antegrade/retrograde group (p = not significant). Postoperative increase in total CK, CK-MB, and troponin T were similar between groups at all time intervals (Figs 1–3). Five patients (14%) of the antegrade group and 4 patients (10%) of the antegrade/retrograde group underwent early surgical reexploration for mediastinal hemorrhage or tamponade (p = not significant). Inotropic support after operation was required in 9 patients of the antegrade group and 11 patients of the antegrade/retrograde group. One patient of the antegrade/retrograde group necessitated an intraaortic balloon pump. Clinical or radiologic signs of congestive heart failure were observed in 5 patients of each group (2 of which in the antegrade/retrograde group died). Supraventricular arrhythmias, mainly atrial fibrillation, occurred in 14 patients of the antegrade group and 17 patients of the antegrade/retrograde group (p = not significant). Incidence of ventricular arrhythmias, mostly premature ventricular beats were comparable among both groups: 11 patients in the antegrade group and 8 in the antegrade/retrograde group (p = not significant). One patient of each group developed a stroke in the postoperative period.
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Fig 1. Postoperative total creatine kinase (CK) release for both study groups (mean ± standard deviation).
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Fig 2. Postoperative creatine kinase-MB fraction (CK-MB) release for both study groups (mean ± standard deviation).
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Comment
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This is a prospective randomized study comparing the administration of intermittent antegrade cold blood cardioplegia to antegrade cold blood cardioplegia induction followed by retrograde cold blood maintenance in patients with valve replacement. Our study focuses principally on measurement of indicators of global heart preservation assessed by CK-MB and troponin T levels. No significant advantage regarding perioperative mortality or morbidity was observed other than a shorter aortic cross-clamp time for the antegrade/retrograde group.
Clinical application of retrograde perfusion of metabolic substrates was proposed by Gott and colleagues in 1957 [12]. Initially, retrograde perfusion was instituted to obviate the maldistribution of antegrade cardioplegia in the presence of severe proximal coronary artery stenoses. However, experimental and clinical data with retrograde infusates have documented underperfusion of specific cardiac regions especially the right ventricle [13, 14]. On the other hand, other researchers, using high flow rates, showed adequate right ventricle protection during retrograde cardioplegia perfusion [15, 16]. Numerous factors possibly influence retrograde cardioplegia distribution. Optimal retrograde catheter positioning remains debated. Theoretically, distal positioning of the retrograde cannula may obstruct tributaries of the coronary sinus, mainly the posterior interventricular vein, therefore, decreasing perfusion of the interconnecting veins [9]. Proponents of retrograde perfusion emphasize the necessity to use high flow rates to ensure uniform cardioplegia distribution. Ikonomidis and colleagues [17], in a prospective randomized trial, observed maintenance of an aerobic metabolism with flow rates more than 200 mL/min. Unfortunately, high flow rates through the coronary sinus are often limited by a high coronary sinus pressure. Pressures above 40 mm Hg may induce myocardial edema, perivascular hemorrhage, or direct injury to the sinus. Furthermore, presence of venovenous shunts and thebesian channels draining in the right ventricle may contribute to locoregional malperfusion with retrograde perfusion. Albeit potential problems of distribution, retrograde cardioplegia has significant advantages over antegrade perfusion, especially for valvular operations. Obviation of operative interruptions, reduced risk of aortic root air, as well as the possibility to flush coronary debris is a major advantage associated with retrograde cardioplegia delivery during valvular operations. On the other hand, antegrade delivery is easy, induces a rapid electromechanical cardiac arrest, and assures uniform distribution in the presence of normal coronary arteries. However, aortic insufficiency, possible coronary ostial injury or emboli, as well as the necessity to interrupt the operative procedure for administration are major drawbacks of antegrade cardioplegia in valvular procedures.
Left ventricular hypertrophy found in valvular heart patients increases metabolic demands during ischemic arrest. Moreover, right ventricular hypertrophy, which is often present in patients with mitral disease, dictates a necessity of a homogenous cardioplegia distribution to ensure adequate global myocardial preservation. For the aforementioned reasons reliance solely on retrograde perfusion for protection of the hypertrophied heart may be deleterious. However, excellent clinical results have been reported using continuous retrograde cardioplegia in the hypertrophied heart [9, 11, 18, 19]. Jin and colleagues [20], using transesophageal M-mode echocardiography and high-fidelity left ventricular recording among patients undergoing aortic valve replacement, documented an increased preservation of the myocardial physiologic response and function with antegrade/retrograde cold blood cardioplegia compared to continuous warm retrograde cardioplegia or antegrade crystalloid cardioplegia. Buckberg and colleagues [21] have proposed an integrated approach using antegrade/retrograde delivery, warm/cold blood cardioplegia, and intermittent/continuous perfusion in the management of patients with valvular heart disease. Chitwood and colleagues [22] showed excellent clinical outcomes in valvular patients requiring a mean cross-clamp time of 113 minutes using an antegrade cardioplegic induction followed by retrograde maintenance.
Our study was conducted using cold blood cardioplegia. We favor cold blood cardioplegia over the warm temperature for its security advantages, especially when dealing with protection of the hypertrophied heart of valvular patients. Furthermore, no prospective randomized study up to date has demonstrated a benefit of warm blood cardioplegia in terms of decreasing perioperative mortality or myocardial infarction rate during valvular replacement procedures.
In conclusion, our study demonstrates equivalent release of myocardial marker of ischemia and similar clinical outcome of a strategy of intermittent antegrade cold blood cardioplegia compared to a cold blood cardioplegia antegrade induction followed by a continuous retrograde maintenance among a low-to-moderate risk population undergoing valve replacement procedures. The antegrade/retrograde approach is, however, technically convenient and decreases significantly the aortic cross-clamp time.
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Accepted for publication April 30, 1999.
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Abstract
Introduction
