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Eur J Cardiothorac Surg 1998;14:S82-S87
© 1998 Elsevier Science NL

Minimally invasive coronary surgery: surgical considerations and assessment of cardiac troponin I

Gérard Babatasia,*, Massimo Massettia, Patrick Natafb, Sabine Fradina, Denis Agostinia, Gilles Grolliera, Jean-Louis Gerarda, André Khayata

a Thoracic and Cardiovascular Surgery Department, Departement of Biochemistry A, University Hospital CHU Caen, Cote de Nacre, 14033 Caen, France
b Thoracic and Cardiovascular Surgery, CCN, 32 rue des Moulins Gémeaux, 93207 St. Denis, France

* Corresponding author. Tel.: +33 2 31064457; fax: +33 2 31064521.


    Abstract
 Top
 Abstract
 1. Introduction
 2. Material and methods
 3. Results
 4. Discussion
 References
 
Objective: Minimally invasive coronary artery bypass grafting (MICABG) using internal thoracic artery (ITA) without median sternotomy and cardiopulmonary bypass (CPB) become a viable option for the management of proximal left anterior descending artery (LAD) disease. Recent studies have demonstrated that cardiac troponine I (cTnI), a new highly specific diagnostic marker of cardiomyocyte damage, is a reliable marker of cardiac ischemia during heart operations under CPB. Methods: Between February 1996 and April 1997, 14 patients (10 males, 4 females aged 41–68) underwent MICABG with single-vessel bypass grafting for LAD stenosis (n=9) or occlusion (n=5). Video-assisted surgery with left anterior mini-thoracotomy was performed in ten patients and vertical parasternal thoracotomy in the other four. cTnI was measured before LAD occlusion (T0), during anastomosis (T1) and 10 min (T2), 6 h (T3), 24 h (T4), 48 h (T5), 72 h (T6) after coronary reperfusion. Assay methods used a specific enzyme-linked immunosorbent autoanalyzer (Stratus) in peripheral venous blood. Control coronary angiography was performed in all patients. Results: There were no operative complications, no reoperations for bleeding. cTnI concentrations were expressed in ng/ml±SD. Mean cTnI level was <3.85±1 ng/ml (range 0–32.8). Values were: T0=0, T1=0.5±0.1, T2=1.15±0.2, T3=2.16±0.6, T4=1.5±0.3, T5=0.6±0.02, T6=0.4±0.01. Angiography showed patent grafts in 12 patients. A `no flow situation' was demonstrated in a cardiac symptom-free patient, with reestablishment of flow on repeat angiogram at 6 months. In the other case, early ITA graft occlusion in a patient with two-vessel disease was correlated with a higher cTnI concentration (17.8 ng/ml). Percutaneous angioplasty was performed on the right coronary artery, complicated with dissection and cardiac failure. This patient died 3 months after the MICABG despite ventricular assist device. Conclusion: cTnI did not increase during and after coronary artery occlusion and local immobilization of the heart. It can be used to evaluate postoperative myocardial damage on the beating heart using MICABG.

Key Words: Cardiac troponin I • Minimally invasive cardiac surgery • Perioperative myocardial damage • Video-assisted coronary surgery


    1. Introduction
 Top
 Abstract
 1. Introduction
 2. Material and methods
 3. Results
 4. Discussion
 References
 
Myocardial revascularization by means of the internal thoracic artery (ITA) has regained support because the long-term patency and the patient survival have been shown to be superior to that with coronary bypass using the saphenous vein [8]. The majority of coronary bypass are performed under cardiopulmonary bypass (CPB), with a significant incidence of serious complications including stroke, renal failure, aortic injury, respiratory failure and coagulation abnormalities [16]. Some of these are directly associated with CPB as systematic heparinization, cannulations and aortic cross-clamping. Maintenance of CPB induces a systemic inflammatory response with coagulation abnormalities, hemodilution and potential risk of air and microembolization [12]. Nevertheless, CPB provides safety on coronary anastomosis with myocardial protection, cardioplegic arrest and bloodless field. There has been a revival of interest in performing coronary bypass on beating heart without CPB [4]. As the surgical technique of minimally invasive coronary artery bypass grafting (MICABG) is in its early stages, the selection criteria are continually being re-evaluated [12]. To provide a safe surgical technique with a steady and bloodless field on beating heart, different techniques have been evaluated so far: ischemic myocardial preconditioning with interrupted flow for 2 min followed by 2 min of relaxation and reperfusion [14], a square metal stabilizer or `octopus' device [6], prolonged sinus pause induced with intravenous adenosine.

Creatine kinase MB isoenzyme (CK-MB) has become the biochemical marker of choice [5]for diagnosing myocardial infarction (MI). However, limitations of CK-MB measurement such as delayed response and short duration of elevation following MI as well as lack of specificity necessitate the finding of a more suitable diagnostic marker. Elevations of cardiac specific troponin I (cTnI) have been reported to be highly specific for myocardial injury [1, 13]. The specificity of this marker is higher than of that of other commonly used analytes for MI such as total creatine kinase, CK-MB and myoglobin. Particularly useful applications of cTnI are in the determination of MI in patients with chronic renal failure and in those suspected of perioperative MI [2]. In addition to its excellent cardiac specificity, its earlier rise remaining elevated for several days following myocardial damage.

The aim of the study was to report the results of a series of patients on whom revascularization of the LAD was performed using minimally invasive coronary surgery on the beating heart and to evaluate the usefulness of cardiac troponin I as diagnostic criteria of perioperative infarction.


    2. Material and methods
 Top
 Abstract
 1. Introduction
 2. Material and methods
 3. Results
 4. Discussion
 References
 
2.1 Patient population
Between February 1996 and April 1997, a group of 14 patients were scheduled for revascularization of the LAD by means of the left internal thoracic artery (ITA) using minimally invasive surgical technique. The group included ten men and four women with a mean age of 52±6 years (range 41–68 years). All patients were symptomatic with persistent angina despite maximal medical therapy. Five patients demonstrated a history of anterior non-transmural myocardial infarction with 201-thallium single-photon emission computer tomography (SPECT) study showing myocardial viability. Coronary angiography revealed a proximal stenosis of the LAD in eight patients and occlusion of the LAD in five cases. In one case, two-vessel disease was imaged (LAD and right coronary artery). Percutaneous transluminal coronary angioplasty (PTCA) had been performed in four patients associated with stent placement in two cases. The left ventricular ejection fraction ranged from 0.30 to 0.70 (mean ejection fraction: 0.61±0.09). Informed medical consent was obtained from the patient and the family members before the operation. Patients with aortic valve insufficiency were excluded.

2.2 Surgical technique
The operating room is configured as for a standard CABG. The CPB pump is set up but not primed, although the perfusion team remains immediately available. Radial artery catheter and pulmonary artery catheter (Baxter Health, Irvine, CA) with continuous cardiac output and mixed venous oxygen saturation measurement were performed. The anesthetic goals are similar for both minithoracotomy or left vertical parasternal surgical approaches. A double-lumen endotracheal Carlens tube was systematically performed for one-lung ventilation to deflate the left lung, enhancing ITA harvesting. The additional use of simultaneous monitoring of lead II and lateral precordial (V4–V5) electrocardiograph leads makes ischemic detection highly probable and increases the sensitivity of detecting an ischemic event to 96%. Analysis of the ST segment was helpful. In three cases, additional trans-esophageal echocardiography (TEE) was performed as indicator of intraoperative ischemia by early detection of regional wall abnormalities.

2.2.1 Video assisted coronary artery bypass grafting (10 patients)
Thoracoscopic harvesting of the ITA was performed according to the technique previously reported by Patrick Nataf et al., with some minor modifications [17]. The patient is placed in the supine position with slight lateral tilt of the left hemithorax helped by an inflatable pillow. External defibrillator pads are placed on the patient. Thoracoports are made in the fourth and sixth intercostal spaces along the medial axillary line and at the level of the fifth intercostal space on the anterior axillary line. After deflation of the left lung, dissection of the pedicle of the ITA is done with diathermy, avoiding skeletonization. Dissection is extended downward until the fifth costal cartilage. After completing the dissection, general heparinization was given (1.5 mg/kg). Papaverin solution was gently injected through the irrigation system towards the ITA. At this time of operation, the ITA was not tied or sectioned. Using the port through the fifth intercostal space, a 4–5 cm left anterior thoracotomy was carefully performed without rib excision. The left ITA was then identified beside the sternal border and the distal segment was isolated and dissected until the sixth costal cartilage with the help of the thoracoscope. The distal end of the pedicle was clipped and withdrawn from the thoracotomy.

2.2.2 Left vertical parasternal thoracotomy (4 patients)
The patient is placed in the supine position. This anterior mediastinotomy approach required careful dissection of the costal cartilage to avoid injury of the underlying ITA trunk. Harvesting of the ITA is difficult without the help of thoracoscopic instruments. The distal limit of the dissection need only be one interspace beyond the lower margin of the incision.

2.2.3 Coronary anastomosis
Stay sutures are placed on the edge of the opened pericardium facilitating the direct vision of the lad. Ischemic preconditioning of the myocardium was performed by encircling the target vessel with elastic vessel loop and interrupting flow for 2–5 min, followed by 2–5 min of relaxation and reperfusion. The coronary artery was identified with looping sutures (4/0 polypropylene). To facilitate motionless of the coronary artery anastomotic area, a hand-held square metal stabilizer in order to restrict cardiac movement to a single plane was used in the first nine patients. A new device including retractor-fixed stabilizer (autosuture, elancourt, france) was recently used for the last five patients, allowing a perfect immobilization of the anastomotic site which made the anastomosis easy and smooth. Since this time, no pharmacological drugs were administrated to reduce heart rate during anastomosis. The anastomotic area was cleared of blood by air pressure. The anastomosis was performed with uninterrupted sutures of 8/0 surgilene (davis and geck, france) on the beating heart in all patients. Five milliliters of fibrin glue (thrombin 500 iu/ml, immuno ag, vienna, austria) were injected around the anastomosis.

2.3 Measurements of cardiac markers proteins
Serial venous blood samples were drawn just before coronary artery occlusion (T0), during anastomosis (T1) and after reperfusion at 10 min (T2), 6 hours (T3), 24 h (T4), 48 h (T5) and 72 h (T6). cTnI concentrations were measured by a rapid, sensitive, fluorometric enzyme immunoassay sandwich technique which employs two monoclonal antibodies (Mab) specific for the TnI cardiac isotype (Stratus II, Dade, Maurepas, France). The time from assay initiation to the result was 8–10 min. Each test sample was incubated with Mab 2B1.9 (specific for cTnI) for 10 min.

2.4 Follow-up
All patients were followed up at the outpatient department after the postoperative period (1 month) in the cardiac rehabilitation center and at the end of the 6 postoperative months. Coronary angiography and Doppler flow evaluation was systematically performed at the sixth day before discharged from hospital. 201-Thallium SPECT was performed in all patients at the time of the second control. The follow-up was 100% complete and ranged from 21 days to 14 months (mean: 6.2 months).


    3. Results
 Top
 Abstract
 1. Introduction
 2. Material and methods
 3. Results
 4. Discussion
 References
 
There was no operative mortality. Results including preoperative, operative and postoperative data are summarized in Table 1 . No operative complication was found. No reoperation for bleeding was necessary. No wound infection was noted. Evolution of mean cTnI concentration is shown in Fig. 1 (median and interquartile range; ng/ml). The average time spent for harvesting the ITA was 63.2±10.1 min (range: 25–154 min). Selected angiography confirmed the patency of the mammary grafts in 12 patients without stenosis of the distal LAD or of the anastomosis (Fig. 2 ). None of those patients showed any adverse cardiac responses to exercise testing. The mean cTnI level was <3.85±1 ng/ml (range 0–32.8). In one case, internal mammary artery graft was found to be non-functional. Despite this finding, the patient did not complain of any symptoms and in agreement with his cardiologist, medical therapy without redo surgery was planned for 3 months. A repeat angiographic study was then performed 4 months after MICABG and showed that the ITA graft regained patency. In the third patient of the series, a 49-year-old woman, results of cTnI concentrations were at T0 and T1: 0 ng/ml, T2: 2.5 ng/ml, T3: 4.5 ng/ml, T4: 23.8 ng/ml, T5: 32.8 ng/ml and T6: 17.8 ng/ml. There was a significant difference in cTnI concentration between the results of this patient and the 13 other patients (Fig. 1). Control angiography confirmed occlusion of the mammary artery graft. No other signs of myocardial ischemia, based on ECG and TEE, were detected in the early post-operative period. After an initial uneventful postoperative course, she complained of recurrent angina and for this reason underwent repeat angiography at 3 months. Poor distal coronary bed was shown on LAD and progression of proximal right coronary artery (RCA) disease was demonstrated. Coronary dissection progressed during PTCA of proximal RCA and required ventricular assist device (Medos pneumatic pulsatile system) for heart failure. Unfortunately this patient died 5 days later of septicemic shock.


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Table 1. Clinical data and results (14 patients)
 

Figure 1
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Fig. 1. Cardiac troponin I (cTnI) concentration time courses in MICABG group. Concentrations of cTnI are significantly higher in patient 3 (occluded ITA graft) than in the 13 other patients.

 

Figure 2
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Fig. 2. Selective angiography of the left internal thoracic artery shows the anastomosis on the left anterior descending artery.

 
Transthoracic echocardiograms indicated adequate left ventricular performance with ejection fractions of 0.35–0.75 (mean: 0.64). The mean postoperative hospital stay in cardiac unit was 7±2 days (6–10 days). Longer hospitalization was mainly due to routine repeat angiography. At follow-up, 13 patients are alive and are free of cardiac symptoms. 201-Thallium SPECT showed no residual ischemia in any patient. All patients were satisfied with the cosmetic wound of the left minithoracotomy.


    4. Discussion
 Top
 Abstract
 1. Introduction
 2. Material and methods
 3. Results
 4. Discussion
 References
 
Patients selected for MICABG [18]include those with single-vessel disease, particularly LAD unplanned for PTCA (unsuccessful or impossible: occluded artery). Others have combined MICABG with PTCA for the management of multiple vessel disease [12]. Several complications and disadvantages continue to arise with the use of CPB and cardioplegic arrest. Potential advantages of MICABG arise from the avoidance of CPB, which results in a reduced rate of postoperative complications such as stroke, bleeding or arrhythmias [7]. Additionally, deep sternal wound infections due to the sternotomy approach decreased. Rapid postoperative recovery and reduced in the average length of hospital stay have been noted [7, 18]. Different techniques of minimally invasive coronary artery bypass surgery have already been described [7, 15, 18, 19]. According to Nataf et al. [17], we have used the thoracoscopic approach, in the majority of the cases. Compared with the four patients in whom the ITA was harvested through the anterior mediastinotomy, we found that the thoracoscopic approach allowed an easily and safe dissection of the ITA from the subclavian artery to the sixth costal cartilage. Potential disadvantages may be anticipated. The operation is technically more difficult to perform, given the smaller operative view, the moving anastomotic target on the beating heart and the potential difficulty in conversion to conventional sternotomy. For the last five patients, we have used mechanical cardiac stabilizers providing a motionless operative field while the rest of the heart contracts normally. This retractor-fixed stabilizer allows perfect exposure and reduction in cardiac motion for precise anastomosis.

In addition, it may be more difficult to reliably detect clinically significant ischemia. Decreasing the heart rate by using an esmolol infusion [17], adenosine bolus or use of myocardial preconditioning [14]before coronary artery occlusion renders the heart more resistant to ischemic injury. Decreases in CO and SVO2 or wall-motion abnormalities TEE are not helpful in those patients for detecting myocardial ischemia [11]. The variable results reported in the extensive literature on this topic probably reflect the difficulties of diagnosing myocardial injury perioperatively [10, 11, 16].

The analysis of the two patients of the series in whom the initial control angiography shown ITA graft occlusion revealed several interesting features. In the first case, the poor distal coronary bed was probably responsible for cessation of flow through the internal thoracic artery. Development of collateral circulation or the vasoactive therapy could decrease resistance, with re-establishment of flow at a later time [3]. cTnI concentrations were always below 2 ng/ml in this patient, who was symptom-free in the postoperative period. In the second case, cTnI concentrations peaked at 6 h and remained higher until 72 h, so selective angiogram of the left ITA was performed on the third day and confirmed graft thrombosis.

The usefulness of immunoenzyme assays of cTnI in order to detect myocardial damage is now well established [1, 2, 13]. The troponin complex is composed of troponin I (TnI), troponin T (TnT) and troponin C (TnC). TnI, a contractile protein, is the component which inhibits the ATPase activity of myosin which blocks myosin from movement along the filament. It is not found in skeletal muscle during neonatal development or during adulthood, even after acute or chronic injury is present. There are molecular forms of Troponin I with unique amino acid sequences in slow- and fast-twitch cardiac muscle. Thus, unlike both MB creatine kinase and other troponin proteins, cTnI is produced only in myocardium throughout the development. CTnI is the only known molecular marker of myocardial injury that is not expressed in regenerating skeletal muscle [2]. For this reason, it is not elevated in plasma from patients with acute or chronic muscle disease unless a cardiac injury has occurred. The immunoenzymometric assays developed by Stratus II (Dade) are compatible with emergency testing and allows the detection of cTnI within 10 min. Recent published data [2]have demonstrated that the measurement of a highly sensitive, cardiac-specific marker such as cTnI is an accurate method to confirm or exclude the diagnosis of perioperative cardiac injury, simpler and more cost effective than the routine use of echocardiography. Etievent et al. [9]found a positive correlation between aortic cross-clamping time and cTnI level in a group of patients undergoing aortic valve replacement, proving that this protein is a marker of myocardial ischemia. CTnI has been shown to be a reliable tool in diagnosing early AMI or perioperative micro-AMI undetectable by electrocardiogram or common serum enzymes. In our study, cTnI concentration of the third patient (Fig. 1) demonstrated higher levels since the sixth hour. Higher levels of cTnI legitimate angiographic control. Elevations of cTnI persisted for 2 days and more. Our strategy was to obtain a preoperative (before coronary artery occlusion) value for comparison with postoperative values. Some studies [9, 13]reported that cTnI peaks below 3.7 ng/ml 12–48 h after CPB exclude perioperative myocardial infarction with high probability. Retrospective analysis of the cTnI concentrations during and after MICABG, in our group of patients, showed that coronary anastomosis on the beating heart did not increase myocardial damage. Collateral circulation developed in the setting of chronic coronary occlusion may be efficient for myocardial preservation during short periods such as coronary anastomosis. A refined method for the detection of perioperative infarction should improve the ability to predict which patients are at high-risk of an infarction and to determine if coronary angiographic control is necessary in the early postoperative period of MICABG. Early patency of the internal mammary artery reflects its ability to remain open in low-flow situations. Care must be exercised to avoid any situation in which competitive flow may occur. `Occlusion' of an internal thoracic artery graft may be reversible [18], and a specific biochemical marker of myocardial damage could be helpful. The cTnI immunoassay confirmed the feasibility and safety of coronary anastomosis on the beating heart during minimally invasive coronary operations.


    Acknowledgments
 
We are indebted to A. Lotti, A. Gringore, M. Tasle, P. Lebreton, F. Flais, M. Nivaud, R. Deredec and C. Zerr for collaborative efforts during anesthaetic management.


    References
 Top
 Abstract
 1. Introduction
 2. Material and methods
 3. Results
 4. Discussion
 References
 

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