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Ann Thorac Surg 2002;74:678-683
© 2002 The Society of Thoracic Surgeons

Original article: cardiovascular

Efficacy and safety of on-pump beating heart surgery for valvular disease

Yasushi Matsumoto, MD*a, Go Watanabe, MDb, Masamitsu Endo, MDa, Hisao Sasaki, MDa, Fuminori Kasashima, MDa, Ikuko Kosugi, MDa

a Department of Cardiovascular Surgery, National Kanazawa Hospital, Kanazawa, Japan
b Department of General and Cardio-thoracic Surgery, Kanazawa University School of Medicine, Kanazawa, Japan

Accepted for publication May 1, 2002.

* Address reprint requests to Dr Matsumoto, Department of Cardiovascular Surgery, National Kanazawa Hospital, 1-1 Shimoishibikicho, Kanazawa, 920-8650, Japan
e-mail: matumoto{at}kinbyou.hosp.go.jp


   Abstract
Top
 Abstract
Introduction
 Patients and methods
 Results
 Comment
 References
 
Background. This study was conducted to assess the efficacy and applicability of on-pump beating heart valvular operations using retrograde coronary sinus perfusion.

Methods. A prospective, randomized study was conducted. A total of 50 patients participated in this study after having been allocated to one of two groups. On-pump beating heart valvular operations using retrograde coronary sinus perfusion as myocardial protection were performed in 25 patients (beating heart procedure group: aortic = 8 patients, mitral = 15 patients, double = 2 patients). Twenty-five patients underwent conventional valvular operation using retrograde continuous warm blood cardioplegia (conventional procedure group: aortic = 9 patients; mitral = 13 patients; double = 3 patients). The remaining operative variables and early outcomes of these procedures were compared. In the beating heart procedure group, myocardial tissue oxygen was measured by near infrared spectroscopy, and partial oxygen pressure of coronary sinus perfusion was also measured.

Results. The visual field of the on-pump beating heart was equal to that of conventional valvular operation, and technical accuracy was not compromised. In the beating heart procedure group, tissue oxygen saturation was maintained at 79% ± 2%, and partial oxygen pressure of coronary sinus perfusion blood and returned blood were maintained at 383 ± 29 mm Hg and 38 ± 2 mm Hg, respectively. Postoperative peak creatine kinase-MB (measured every 3 hours postoperatively) and peak troponin T concentrations were significantly lower than those of conventional procedures (17.5 ± 7.8 vs 32.1 ± 9.3 IU/L and 0.12 ± 0.04 vs 0.21 ± 0.06 ng/mL, respectively; p < 0.05). There was no operative mortality and no major complications.

Conclusions. On-pump beating heart valvular operation is a good surgical option, and has advantages because conditions for the heart are more physiologic with beating tonus than with cardioplegia.


   Introduction
Top
 Abstract
 Introduction
Patients and methods
 Results
 Comment
 References
 
Reperfusion injury is a well-known phenomenon that can occur in cardioplegic techniques with cardiopulmonary bypass (CPB) [1]. The consensus among surgeons is that the untoward damaging effect of cardioplegic techniques is reperfusion injury [2]. Therefore, great effort is made to prevent reperfusion injury during such procedures [3–5]. Introduction of off-pump beating heart operations have enabled major technological and procedural advances in coronary artery bypass grafting [6, 7]. We have considered the possibility of conducting valvular operations on the beating heart similarly because the effective way to prevent reperfusion injury is to use methods that do not include a cardioplegic arrest technique. Although presently, valvular operations cannot be performed without using CPB, we can perform an intermediate option that continues to use CPB, but eliminates the ischemic component by keeping the heart beating throughout the operation. In addition to avoiding reperfusion injury, on-pump beating heart valvular operations may have other advantages because of the fact that the heart is under more physiologic conditions than the cardioplegic arrested state with left ventricular beating tonus.

We report on the efficacy and applicability of on-pump beating heart valvular operations using retrograde coronary sinus (CS) perfusion to preserve the myocardium.


   Patients and methods
Top
 Abstract
 Introduction
 Patients and methods
Results
 Comment
 References
 
A total of 50 patients participated in this prospective clinical study after having been allocated to follow 2 groups randomly and underwent elective valvular operations at the Department of Cardiovascular Surgery of National Kanazawa Hospital. Surgical procedure and the design of this study were explained to all patients who gave signed consent after approval by the Ethics Committee of National Kanazawa Hospital.

On-pump beating heart valvular operations using retrograde CS perfusion as the myocardial protection were performed in 25 patients (11 men and 14 women; mean age, 65.3 ± 9.3 years) with 8 mitral and 15 aortic valvular diseases (2 patients had double valvular disease) (Table 1, beating heart procedure). Also 25 patients underwent conventional valvular operations using retrograde continuous warm blood cardioplegia (9 men and 16 women; mean age, 64.8 ± 7.2 years). This group had 9 mitral, 13 aortic, and 3 double valvular diseases. Clinical data relevant to the operative course of each patient were analyzed. The 23 of 25 patients of the beating heart group and the 24 of 25 patients of the conventional group were classified as New York Heart Association functional class III or IV (with persistent atrial fibrillation, 13 vs 11 patients; or with a previous mitral valve replacement with a bioprosthesis, 1 vs 2 patients). Mean left ventricular ejection fraction of beating heart procedure group was 52.1% ± 13.7%, and that of conventional procedure group was 56.8% ± 15.8%.


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  		Table 1. Preoperative Variables of the Beating Heart Operation Patients and Conventional Operation Patients

 
Surgical procedure
Operations were performed through a median sternotomy. After 300 U/kg of heparin were administered, total CPB was established between the ascending aorta and both venae cava to empty the right atrium. Under normothermia (rectal temperature, 35° to 37°C), CPB pulsatile flow was maintained at the highest pressure that was safely possible, with mean systemic pressure of more than 60 mm Hg. Additional oxygen flow was maintained at 2.5 L/min and 90% concentration. The right atrium was incised parallel to the intraatrial sulcus to expose the ostium of the CS. From the epicardial side of the right atrium, a 4-0 polypropylene purse string suture was made around the ostium of the CS. Subsequently, a three-way (main perfusion, intra-CS pressure measurement, and balloon inflation lines) retrograde perfusion cannula was inserted into the CS, and a tourniquet was applied. The balloon of the retrograde perfusion cannula was inflated and positioned as near as possible to the CS ostium to avoid right ventricular malperfusion. The perfusion cannula was connected to the CPB oxygenated blood perfusion line. Using aortic or left ventricular venting with maximal draining, the aorta was cross clamped and retrograde CS perfusion was started simultaneously (Fig 1). Retrograde CS perfusion flow was maintained at more than 300 mL/min during the surgical procedure, producing an intra-CS mean pressure of approximately 60 mm Hg. Phosphodiesterase III inhibitor (milrinone; 0.5 µg · kg-1 · min-1) was administered into the CS to increase retrograde perfusion flow by inducing vasodilatation.



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  		Fig 1. Schematic drawing of on-pump beating heart valvular operation using retrograde coronary sinus perfusion. (A) Mitral valve procedure. (B) Aortic valve procedure. (AOV = aortic venting; CS = coronary sinus; LVV = left ventricular venting.)

 
Operations on the mitral or aortic valve were performed under good visualization. Transesophageal echocardiography monitoring was performed during each surgical procedure. We were able to assess the results of mitral valve repair under more physiologic conditions with left ventricular beating tonus. We were able to perform the Maze operation (to ablate atrial fibrillation) on the beating heart using radio-frequency energy instead of cryo-coagulation. After each procedure, cardiac cavities were filled with saline, the aortic vent was opened, and air evacuation was confirmed carefully by the transesophageal echocardiography monitoring. The aortic clamp was released, and the retrograde CS perfusion cannula was removed. The anesthetic regimen was the same as that used in our conventional valvular procedures, and all patients remained ventilated in the intensive care unit for 4 to 6 hours postoperatively. Concentrations of creatine kinase MB isozyme and peak troponin T were routinely checked postoperatively (measured at every 3 hours after operation). Creatine kinase MB isozyme activity was determined by immuno-inhibition using an appropriate antibody (Cica Liquid; Kanto kagaku, Japan) (upper reference limit 25 IU/L at 25°C), and troponin T was measured by a commercial enzyme-linked immunosorbent assay (Elecsys Troponin T; Roche Diagnostics, Mannheim, Germany) (upper reference limit 0.1 ng/mL).

Myocardial tissue oxygen measurement
Intraoperatively, partial oxygen pressure (PCO2) of the CS perfusion blood and the blood from the aortic vent were measured every 15 minutes during CS perfusion in all 25 patients. In aortic procedures, PCO2 was measured using returning blood from the coronary ostia instead of blood from the aortic vent. Simultaneously, myocardial tissue oxygen was measured by three-wavelength near infrared spectroscopy, using a probe specially designed for the heart (PSA-500; Biomedical Science, Kanazawa, Japan) [8]. Near infrared light passes through tissues easily and is significantly absorbed by oxygenated and deoxygenated hemoglobin, which have distinctly different absorption spectra in the near infrared region. This difference in absorption spectra can be used to measure changes in the tissue concentration of oxygen. The probe contains 3 light-emitting diodes as light sources and 3 pairs of silicone photodiodes to detect the intensity of reflected light. The probe was used with a suction stabilizing system to avoid intraoperative handling, and was attached to the anterior surface of the right ventricle. Optical information from a myocardial tissue depth of 2.5 to 5.0 mm was obtained. The near infrared signal was analyzed using a set of algorithms that solve for oxygenated and deoxygenated hemoglobin. Tissue oxygen saturation (SO2) was calculated by dividing oxygenated hemoglobin by the sum of oxygenated and deoxygenated hemoglobin. We also evaluated the early outcomes of the patients of both groups.

Statistical analysis
Continuous variables were expressed as mean ± standard deviation, and statistical analysis was performed using Student’s t test to detect significant (p < 0.05) differences between measured variables. Categorical variables, expressed as percentages, were analyzed using Pearson’s {chi}2 test or Fisher’s exact test.


   Results
Top
 Abstract
 Introduction
 Patients and methods
 Results
Comment
 References
 
Intraoperatively, retrograde CS perfusion and aortic venting facilitated good visualization of the operative field. All operations were performed without difficulty. As mentioned above, we were able to test the results of mitral valvuloplasty under more physiologic conditions than cardioplegic arrested state. Initially, mean retrograde CS perfusion flow was 380 ± 36 mL/min at a CS pressure of 60 mm Hg. With intra-CS administration of phosphodiesterase III inhibitor, mean retrograde CS perfusion flow significantly increased to 418 ± 42 mL/min at a CS pressure of 60 mm Hg. Figure 2 shows the serial changes in SO2 of myocardial tissue and PO2 of CS perfusion blood and the returned blood from aortic venting (in aortic procedures, PO2 of returned blood from the coronary ostia was measured). Myocardial SO2 was 80% ± 2% before aortic clamping, then it decreased to 78% ± 1% immediately after aortic clamping, and then according to the start of the retrograde CS perfusion, it quickly rose to 79% ± 2%, at which it was maintained throughout the rest of the procedure. PO2 of CS perfusion blood and returned blood were maintained at 383 ± 29 mm Hg and 38 ± 2 mm Hg, respectively.



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  		Fig 2. Serial changes in myocardial tissue oxygen saturation (SO2) and partial oxygen pressure (PO2) of coronary sinus (CS) perfusion blood and returned blood from aortic venting. Myocardial SO2 before aortic clamping was 80% ± 2%, slightly decreased to 78% ± 1% immediately after aortic clamping, and then quickly rose to 79% ± 2%, at which it remained throughout the procedure. PO2 of CS perfusion blood and returned blood were maintained at 383 ± 29 mm Hg and 38 ± 2 mm Hg, respectively. 60 minutes, n = 25; 75 minutes, n = 18; 90 minutes, n = 9. (NIRS = near infrared spectroscopy; Pre = before retrograde CS perfusion.)

 
The remaining operative variables are shown in Table 2. The mean total cardiopulmonary bypass time (105 ± 31 minute) and mean retrograde CS perfusion time (68 ± 11 minute) were well tolerated, even by patients with low left ventricular function. All patients remained hemodynamically stable, with minimal need for pharmacologic inotropic support. The mean total dose of dopamine required by patients who underwent beating heart valvular operations was 78.6 ± 57.8 mg, whereas the mean total dose required for conventional valvular operations was 318.1 ± 142.4 mg. No further deterioration of organ function occurred in patients with preexisting kidney or central nervous system dysfunction. Peak creatine kinase MB concentrations after beating heart operations (measured every 3 hours) were within normal limits (17.5 ± 7.8 IU/L) and were significantly lower than those of conventional valvular operations (32.1 ± 9.3 IU/L). Postoperative peak troponin T concentrations of the beating heart valvular operation patients and conventional valvular operation patients were 0.12 ± 0.04 ng/mL and 0.21 ± 0.06 ng/mL, respectively.


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  		Table 2. Operative Variables of the Beating Heart Operation Patients and Conventional Operation Patients

 
Right ventricular function was assessed by transesophageal echocardiography and no abnormal finding was noted.

There was no operative mortality and no occurrence of major complications such as low output syndrome, bleeding requiring reexploration, cerebral infarction, perioperative myocardial infarction, and mediastinitis.


   Comment
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
References
 
Although major technological advances have been made in myocardial protection during cardiac operations over the past decade, perioperative adverse effects caused by myocardial ischemia have not been completely eliminated. Even with continuous warm blood cardioplegia, which is considered the best form of myocardial protection because it keeps the heart in an aerobic state, some degree of postoperative myocardial stunning still occurs [9]. Cardiac dysfunction may be caused by myocardial edema intrinsic to the diastolic state of the arrested heart [10]. Thus, cardioplegic arrest techniques will inevitably produce some degree of reperfusion injury. In contrast, keeping the heart beating results in less myocardial edema and better cardiac function [10]. To perform beating heart valvular operations, we adopted a procedure in which oxygenated blood is supplied to the heart in a retrograde fashion through the coronary venous system from the CS ostium. Oxygenated blood is perfused from the CS and flows through the coronary venous system, capillaries, and then out the atrial end, just as with retrograde blood cardioplegia.

In the present study, postoperative levels of creatine kinase MB, troponin T, and required levels of catecholamine were significantly lower in the beating heart patients. Consistent with these results is the present finding that maintenance of the heart in a beating state throughout the operation results in less damage than cardioplegic arrest, even when blood cardioplegia is used in a continuous fashion. Intraoperative monitoring showed that retrograde CS perfusion maintained myocardial SO2 at levels almost identical to preoperative physiologic values throughout the procedure, and that PO2 of CS perfusion blood and returned blood was maintained at 383 ± 29 mm Hg and 38 ± 2 mm Hg, respectively. This difference in PO2 values indicates that an aerobic myocardial environment was maintained by retrograde CS perfusion.

Despite motion of the heart, the on-pump and well-decompressed state of the heart caused by cardiac venting resulted in quality of visual field equal to that of conventional valvular operations, and technical accuracy was not compromised. Moreover, in cases of mitral valvuloplasty, the three-dimensional architecture of the beating heart provided a good opportunity to examine the mitral valve under more physiologic conditions than cardioplegic arrested state, before, during, and after completion of the repair. With conventional techniques, the mitral valve is in a motionless, flaccid state that may not accurately reflect its function in the beating heart.

We were able to perform intraoperative electrophysiologic examination of the beating heart during the procedure to ablate atrial fibrillation. First, we performed pulmonary vein isolation (the simpler method of elimination of atrial fibrillation) [11] with monitoring of intrapulmonary venous potentials. In cases in which atrial fibrillation was not eliminated by pulmonary vein isolation, we were able to perform the full Maze procedure on the beating heart using radio-frequency energy [12] instead of cryo-coagulation.

When considering the applicability of on-pump beating heart valvular operations, retrograde myocardial perfusion is a very important factor. Retrograde CS perfusion as a method of myocardial preservation is not novel. In 1956, Lillehei and colleagues [13] reported a case of an aortic valve operation using this technique with retrograde CS perfusion flow at 125 mL/min. In recent years, this procedure has not been used because of advances in cardioplegic arrest technique. However, beating heart valvular operations using retrograde CS perfusion may be revived as a surgical option for valvular disease. The advantages of retrograde CS perfusion include: (1) avoidance of injury and postcannulation ostial stenosis of the coronary arteries; (2) performance of surgical procedures (especially aortic procedures) without interruption; (3) a long period of continuous oxygenated blood delivery, which maintains beating of the heart and appropriate pH, and allows effective delivery of substrates or drugs and removal of acid metabolites; and (4) more uniform oxygenated blood distribution in the presence of coronary artery stenosis or obstruction.

The optimal level of retrograde CS perfusion flow is unknown. Resting coronary blood flow in humans averages approximately 225 mL per minute, which is about 0.7 to 0.8 mL per gram of heart muscle, or 4% to 5% of total cardiac output [14]. However patients with a hypertrophied heart (eg, patients with valvular disease) require high flow rates of retrograde perfusion for adequate myocardial protection, thus necessitating the use of high pressures during retrograde CS perfusion. Therefore, we maintained the highest possible safe level of CS perfusion flow (minimum, 300 mL/min; mean, 418 ± 42 mL/min) to avoid adverse effects of hypoperfusion.

The optimal safe perfusion pressure during retrograde CS perfusion is closely related to CS perfusion flow. High pressure is required to maintain more than 300 ml/min CS perfusion flow. Because initial experiments by Beck and colleagues [15] and others on working, beating dog hearts showed that hemorrhage occurs at pressures greater than 40 to 60 mm Hg, it has generally been recommended that CS pressure be kept below these levels. In an experimental study of retrograde CS perfusion by Eke and colleagues [16], they found that CS pressure up to 120 mm Hg caused no extravasation of blood into the myocardium in a vented and arrested heart. Under microscopic examination, their heart tissue slices showed normal structures. Because the present procedures were performed in vented, beating, unburdened hearts, we believe that the coronary sinus was able to withstand somewhat higher pressure (60 to 80 mm Hg) during retrograde heart perfusion than the range described previously. Also, we used phosphodiesterase III inhibitor as a vasodilator to increase CS perfusion flow. We found no complications related to retrograde CS perfusion, even at a pressure of 60 mm Hg [17], and we maintained a high perfusion rate.

In this procedure, removal of air after aortic declamping is important. The air evacuation was performed using the remained aortic venting tube continuously until the end of cardiopulmonary bypass. The air removal was confirmed by monitoring with transesophageal echocardiography. No episode of air embolism was experienced in our study.

In the present patients, there was no failure of CS perfusion. However, in other series, we experienced a patient with malperfusion. The patient had repeated ventricular fibrillation during retrograde perfusion despite the cardioversion. Retrograde coronary sinus perfusion flow rate at that time was only 180 mL/min and SO2 fell to approximately 50%. So we immediately abandoned the beating heart procedure and used antegrade cardioplegic arrest technique. If ventricular fibrillation is observed during the beating heart procedure, this technique should be abandoned because malperfusion is strongly suggested.

Also, when retrograde CS perfusion could not have been continued, we would have been able to switch from retrograde CS perfusion to retrograde continuous warm blood cardioplegia. However, if myocardial malperfusion is suspected, it may be better to use antegrade infusion of cardioplegia. The most important points of this procedure are to maintain high coronary sinus perfusion flow rate and to keep adequate venting.

The present results indicate that an on-pump beating heart valvular operation is a good surgical option for valvular disease. The advantages of on-pump beating heart valvular operations are due to the fact that the heart is under more physiologic conditions than cardioplegic arrested state with left ventricular beating tonus, thus eliminating adverse effects of global myocardial ischemia produced from reperfusion injury. However the efficacy of this procedure requires further study using larger prospective randomized trials comparing this method with cardioplegic arrest methods.


   References
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 References
 

  1. Weman S.M., Karhunen P.J., Penttila A., Jarvinen A.A., Salminen U.S. Reperfusion injury associated with one-fourth of deaths after coronary artery bypass grafting. Ann Thorac Surg 2000;70:807-812.[Abstract/Free Full Text]
  2. Allen B.S., Okamoto F., Buckberg G.D., Bugyi H., Leaf J. Studies of controlled reperfusion after ischemia XIII. Reperfusion conditions: critical importance of total ventricular decompression during regional reperfusion. J Thorac Cardiovasc Surg 1986;92:605-612.[Abstract]
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  4. Ikonomidis J.S., Rao V., Weisel R.D., Hayashida N., Shirai T. Myocardial protection for coronary bypass grafting: the Toronto hospital perspective. Ann Thorac Surg 1995;60:824-832.[Abstract/Free Full Text]
  5. Mauny M.C., Kron I.L. The physiologic basis of warm cardioplegia. Ann Thorac Surg 1995;60:819-823.[Abstract/Free Full Text]
  6. Calafiore A.M., Giammarco D.G., Teodori G., et al. Left anterior descending coronary artery grafting via left anterior small thoracotomy without cardiopulmonary bypass. Ann Thorac Surg 1996;61:1658-1665.[Abstract/Free Full Text]
  7. Benetti F.J., Maselli G., Wood M., Geffner L. Direct myocardial revascularization without extracorporeal circulation. Experience in 700 patients. Chest 1991;100:312-316.[Abstract/Free Full Text]
  8. Kawasuji M., Yasuda T., Tomita Y., Sakakibara N., Takemura H., Watanabe Y. Near-infrared monitoring of myocardial oxygenation during intermittent warm blood cardioplegia. Eur J Cardiothorac Surg 1997;12:236-241.[Abstract]
  9. Misare B.D., Krukenkamp B.D., Lazer Z.P., Levitsky S.L. Recovery of postischemic contractile function is depressed by antegrade warm continuous blood cardioplegia. Ann Thorac Surg 1993;105:37-44.
  10. Mehlhorn U., Allen S.J., Adamus D.L., Davis K.L., Gogola G.R., Warters R.D. Cardiac surgical conditions induced by ß-blockade: effect on myocardial fluid balance. Ann Thorac Surg 1996;62:143-150.[Abstract/Free Full Text]
  11. Sueda T., Imai K., Ishi O., Orihashi K., Wtari M., Okada K. Efficacy of pulmonary vein isolation for the elimination of chronic atrial fibrillation in cadiac valvular surgery. Ann Thorac Surg 2001;71:1189-1193.[Abstract/Free Full Text]
  12. Pasic M., Bergs P., Muller P., et al. Intraoperative radifrequency Maze ablation for atrial fibrillation: the Berlin modification. Ann Thorac Surg 2001;72:1484-1491.[Abstract/Free Full Text]
  13. Lillehei C.W., DeWall R.A., Gott V.L., Varco R.L. The direct vision correction of calcific aortic stenosis by means of a pump-oxygenator and retrograde coronary sinus perfusion. Disease of the Chest 1956;30:123-131.
  14. Guyton A.C., Hall J.E. Muscle blood flow and cardiac output during exercise: the coronary circulation and ischemic heart disease. Textbook of medical physiology, chapter 21, 10th ed. Philadelphia: Saunders, 2000:223-224.
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