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© 2003 European Association of Cardio-Thoracic Surgery
Quantification of microembolic signals during transmyocardial laser revascularization
a Clinic of Cardiac Surgery, University Clinic of Luebeck, Ratzeburger Allee 160, 23538 Luebeck, Germany
* Corresponding author. Tel.: +49-451-500-2108; fax: +49-451-500-2051 Received December 29, 2002; received in revised form April 8, 2003; accepted April 11, 2003
Transmyocardial laser revascularization (TMLR) is known to induce cerebral microembolic signals (MES). We quantified laser induced MES in patients undergoing TMLR during cardiopulmonary bypass for coronary artery bypass grafting (group A) and during TMLR treatment alone (group B). The total number of MES during a single laser application with identical energy was significantly higher in group A compared to group B (  ). Also the peak of MES occurred significantly later in group A ( ). An increase of laser energy was associated with an increase in numbers of MES particular in group B ( ). Different TMLR modalities generate different amounts of cerebral microembolic signals. Thus, adjustment of TMLR to these modalities may reduce potentially harmful cerebral microemboli and warrants further evaluation.
Key Words: Transcranial Doppler; Transmyocardial laser revascularization; Microembolic signals
Therapy of patients with coronary artery disease (CAD) not treatable with conventional revascularization techniques remains a major challenge to cardiovascular medicine. Transmyocardial laser revascularization (TMLR) has emerged to a promising alternative during the mid 90ths [1]. Although an increase in myocardial blood flow to the lasered ischemic regions at least in the clinical setting is questionable [2], angina pectoris is significantly reduced, leading to improved quality of life. The exact mechanism underlying this clinical improvement is unknown, ranging from placebo effect, denervation, angiogenesis, and increased perfusion [3–5]. There is, however, general consensus, that the attractive theory of blood flow through open laser channels did not come true in practice. Nevertheless, TMLR is regaining increasing attention especially because alternative strategies for this group of patients are still in the developmental stages and the number of patients with endstage CAD is increasing. Recently, the US Food and Drug Administration has approved TMLR. Thus, research in this field needs to be advanced to optimize clinical results, but also to define procedure related risks. One of these potential risks are microemboli generated by the interaction of laser with myocardial tissue and blood. Microemboli, reaching the cerebral circulation, can be detected by transcranial Doppler ultrasound (TCD) as microembolic signals (MES). They have been correlated to impaired neurological outcome in carotid artery disease, as well as cardiac surgery [6]. Indeed, cerebral microemboli have also been demonstrated to occur during TMLR [7,8] and, theoretically, might have a negative effect on cerebral function following TMLR as well. In this context, it is essential to get more knowledge about the quantity of MES in relation to several procedural variations of TMLR. Therefore, this study was performed to measure the amount of MES generated by TMLR in relation to laser energy and the mode of TMLR application -TMLR in combination with coronary artery bypass grafting (CABG) or TMLR alone.
2.1. Patients Following approval by the institutional review board, ten patients with severe CAD gave informed consent and were included into the study. Indication for myocardial revascularization was based on clinical criteria and angiographic findings. Patients undergoing TMLR were under maximal antianginal medication and still symptomatic at least CCS class III (Canadian Cardiovascular Society). They had at least one ischemic myocardial area related to one coronary vessel which was not graftable due to severe diffuse coronary sclerosis with a target vessel diameter less than 1 ml, multiple stenosis and bad vessel wall quality. Eight patients received a combined procedure with TMLR and CABG (group A), in two patients TMLR was performed as a sole therapy (group B), because there was no graftable coronary artery at all. All patients received a complete supra-aortal color-coded duplex sonography to exclude significant stenosis of the brain supplying arteries. Table 1 shows patients demographic and perioperative data.
2.2. Methods 2.2.1. Transcranial Doppler sonography MES were detected by a transcranial Doppler ultrasound device (MultiDop X4 with TCD 8 software; DWL Elektronische Geräte GmbH, Sipplingen, Germany) with a 64 point fast Fourier transformation processor. During the TMLR procedures, the right and left middle cerebral artery was insonated through a temporal bone window using two 2 MHz ultrasound probes The probes were fixated by means of an elastic band around the patients head with the patient being in an upper body position. Sample volume length was set at 10 mm with a depth between 46 and 55 mm and an ultrasound intensity of 20 mW/cm2. Criteria to identify the basal cerebral arteries in transcranial ultrasound investigations [9], as well as criteria to identify MES and their discrimination from artefacts [10] have been described previously. During cardiopulmonary bypass (CPB) TCD monitoring showed a continuous signal caused by the heart-lung-machine. Therefore, detection of TMLR related MES during CPB were analyzed when systolic signal peaks were greater than 3 cm/s of the CPB related flow pattern occurred indicating an effective systolic ejection. Doppler signals were recorded on separate tapes with a digital audio recorder (DTC-690, Sony Germany GmbH, Cologne, Germany).
2.2.2. Surgical technique 2.3. Data analysis All TCD tapes were analyzed off-line by the same experienced observer using the Fast Fourier transformation processor by watching the signals on the screen and listening to the signals over a headphone. MES were defined according the definitions of Ringelstein et al. [11]. To discriminate clusters of MES signals, sections of the Doppler frequency spectrum were straightened out into high resolved sequences with a special audio-software (CoolEdit; Syntrillium Software Corporation, USA) and subsequently analyzed as described above. The number of MES per second after each laser application was counted.
Results were expressed in mean±standard deviation or as median with a 95% confidence interval. Correlation of laser energy and MES were analyzed using the Spearman correlation coefficient. The Mann–Whitney U-test was used to compare the temporal appearance of maximum MES rates. The Wilcoxon test was used to compare MES rates between matched pairs of equal laser energy in both groups. A
Clinically, one patient in group A developed a transient delivery postoperatively, another patient in group B died on the 11th postoperative day due to cardiac failure. 3.1. Number of MES The total number of microembolic events were 0–25 MES per second (1.3±3.0) and 0–183 MES per laser application (28.4±38.5), respectively.3.2. Influence of CPB on MES The number of MES in group A was significant higher compared to the number of MES in group B (mean 44.7±43.6, median 32 MES in group A versus mean 12.8±9.5, median 11 MES in group B,). Also time related occurrence differed significantly in both groups (Fig. 1).
3.3. Influence of laser energy on MES In both groups an increase of laser energy was associated with an increase in numbers of MES (Figs. 2a,b), this was most evident in group B ( ).
This study demonstrates the influence of laser energy and CPB on the occurrence of cerebral MES in patients undergoing TMLR. The microembolic load was positively correlated to laser energy. Furthermore, the number of MES was increased, when TMLR was performed during CPB. Because MES have been shown to be associated with an increase of adverse neurological outcome after cardiac operations [6] and cerebral injury is associated with an increase in mortality, length of hospitalization, and use of postoperative care facilities [12], new strategies are necessary to prevent such injuries. In conventional CABG certain factors have been made responsible for an increase of MES such as setting and removal of the cross clamp choice of cardioplegic solutions, type of oxygenators and associated cerebral artery disease [13]. As MES also occur in high numbers in patients treated with TMLR [7,8], combination of TMLR and CABG may increase the risk of microembolic events. Although MES induced by TMLR using an Excimer Laser seems to be predominantly of gaseous nature [8], their clinical relevance is still unclear, because even gaseous emboli have been shown to cause cerebral injury [14]. Using a high power CO2 laser could be even more harmful in terms of the structure of microemboli, is composed of a mixture of gaseous and solid ablation products.
We were able to quantify laser induced MES by using a new method for discriminating single MES in clusters of microemboli, following TMLR applications. Interestingly, we found a varying number of MES after TMLR. Especially in patients of group B, where laser therapy was performed without CPB, the number of MES was related to laser energy ( This study has its limitations. The number of patients especially in group B is small and results could be patient related. However, the total number of laser applications was high and laser effects were homogeneous. In conclusion, the clinical impact of MES in patients undergoing TMLR still needs to be evaluated. However, as long as these microemboli are suspicious of being a potential risk with adverse cerebral outcome, we advocate to decrease the number of MES. This could be achieved by adjusting laser energy to the lowest level that allows myocardial perforation and by performing TMLR after termination of CPB. doi:10.1016/S1569-9293(03)00079-3
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Abstract
1. Introduction
500. Extracorporal circulation was maintained using non-pulsatile flow and a membrane oxygenator (Milite 7000 or Spiral-Gold; Baxter, USA). TMLR was performed on the beating heart with an 800 Watts CO2-laser (PLC Medical Systems, Milford, MA, USA) after the bypass surgery was completed with the patients still being on the heart-lung-machine. Laser channels were created with a density of one channel per cm2 and laser energy was set individually depending on TCD measurements (see 
was considered to be statistically significant. 
). (b) Microembolic signals (MES) in correlation to laser energy in patients undergoing transmyocardial laser revascularization without cardiopulmonary bypass (