HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Diegeler, A. Articles by Kluge, R. Search for Related Content PubMed PubMed Citation Articles by Diegeler, A. Articles by Kluge, R.

Eur J Cardiothorac Surg 1998;13:392-397
© 1998 Elsevier Science NL

Transmyocardial laser revascularization using the Holium-YAG laser for treatment of end stage coronary artery disease

^a Heartcenter, University of Leipzig, Rußenstraße 19, 04289 Leipzig, Germany
^b Department of Nuclear Medicine, University of Leipzig, 04289 Leipzig, Germany

Received 22 October 1997; received in revised form 12 January 1998; accepted 19 January 1998.

Corresponding author. Tel.: +49 341 8651422; fax: +49 341 8651452; e-mail: diea @ server3.medizin.uni-leipzig.de

	Abstract

Top Abstract Introduction Materials and methods Results Discussion References

 
Objective: Transmyocardial Laserrevascularization (TMLR) is a treatment for end-stage coronary artery disease, that is not eligible for surgery or PTCA. The experience with TMLR using the Holium YAG laser is presented. Methods: Transmyocardial Laserrevascularization (TMLR) was performed in 28 patients with end stage coronary artery disease, using a new Holium YAG Laser. All patients were refractory to a maximum of medical treatment. In 16 patients TMLR was used as the sole therapy with a mean of 28±4 laser created channels (group A). In 12 patients TMLR was combined with coronary artery bypass graft surgery with a mean of 17±2 channels and 1.3±0.2 grafts (group B). Preoperative and postoperative examination included angina classification, exercise test and thallium scan. Results: Postoperative demographics were as follows: (a) age 55–71 years (mean 63.9±6.5 years); (b) Canadian Cardiovascular Society Angina Scale (CCS) mean 3.3±0.5; (c) ejection fraction 35–71% (mean 54±13.7%). All patients had an peri- and postoperative course without major complications and a duration of hospitalization of 8.2±1.9 days. Minor complications were a clinically silent myocardial infarction n=1, atrial arrhythmia n=2 and pneumothorax n=2. A follow-up at 3–12 months was completed in 23 patients (82%). Only one patient died 5 months after surgery (cardiac related death). In all remaining patients CCS had improved with a mean of 1.6±0.3, P<0.01. The exercise tolerance test (bicycle) improved in 17 patients with a mean 26.5±6.5 watt, P<0.01. The ejection fraction did not significantly improve. The repeated thallium scan did not show an improvement of perfusion in the lasered area to a significant level. Subjective benefit from the treatment was confirmed by 21 patients. Conclusion: Based on these results it is concluded that TMLR with the Holium-YAG laser is a safe therapy for the treatment of end stage coronary artery disease. The postoperative clinical results are comparable to that achieved with the CO₂-laser in terms of reducing angina symptoms and improving exercise tolerance and quality of life. However, relief of symptoms is not correlated to objective findings of cardiac function.

Key Words: Transmyocardial laser revascularization • Laser • Holium YAG • Coronary artery disease

	Introduction

Top Abstract Introduction Materials and methods Results Discussion References

 
Transmyocardial revascularization using different laser energy sources has recently gained interest for the treatment of medically refractory angina pectoris in patients who are not eligible for coronary bypass surgery or PTCA. Similar to the blood supply of the snake heart [1], transmyocardial channels were thought to increase the perfusion of the endocardial layer of the myocardium by a direct connection between the left ventricular cavity and intramyocardial sinusoids. Sen and colleagues first brought this concept to clinical use when they reported a new technique of direct myocardial perfusion by the creation of transmyocardial channels by needle acupuncture [2]. Mirhoseini and Cayton [3] introduced laser energy to drill channels through the myocardium to the left ventricular cavity to achieve direct perfusion of the myocardium with oxygenated blood from the left ventricle. Recently a new Holium YAG (Yttrium Argon Garnat) laser has been introduced for transmyocardial revascularization (TMLR). As opposed to CO₂ lasers the Holium YAG laser emits its energy at a wave length of 2100 nm, which can be conducted through a flexible fiber. A prospective clinical study was started in March 1996, which included a follow up period of 1 year. Patients were either treated with TMLR alone (group A) or in combination with a coronary artery bypass graft to a different myocardial area (group B). Results of the first 28 patients were reported.

	Materials and methods

Top Abstract Introduction Materials and methods Results Discussion References

 
From March 1996 to April 1997, 28 patients had transmyocardial revascularization (TMLR) using the Holium YAG Laser (CardioGenesis, Santa Clara, CA). Inclusion criteria for TMLR as the sole therapy were severe angina pectoris class III or IV according to the Canadian Cardiovascular Society (CCS), refractory to medical therapy of at least two antianginal medications on a maximal tolerable dose, ineligible for PTCA or coronary artery bypass grafting (CABG).

Inclusion criteria for TMLR in combination with CABG were demonstrable ischemic reaction in an area of vital myocardium under stress proved by thallium scan. The area had to be ineligible for CABG.

According to these criteria TMLR was performed as the sole therapy in 16 patients (group A) and combined with coronary artery bypass surgery in 12 patients (group B).

Laser source
The Holium YAG Laser delivers a beam with a wave length of 2100 nm. The R-wave triggered energy delivery is pulsed as a triple burst with 350 µs/pulse of duration. At the tip of the flexible probe the laser beam is focused and delivered with an energy of 2 J/pulse. Tissue ablation is performed by a direct contact of the lens at the tip of the probe with the surrounding tissue.

Operative technique
Patients of group A were operated using a left anterior lateral or left posterior lateral thoracotomy. TMLR was performed without using cardiopulmonary bypass (CPB). Single lung ventilation was performed in some but not all patients. After lateral thoracotomy through the 4th intercostal space, the pericardium was opened and the target area was identified on the basis of the preoperative angiography and area which has been determined as being ischemic by thallium scan. Laser channels were drilled by direct contact of the lens of the probe with the myocardium but without manual force. To avoid injury laser channels were created in a distance of at least 5 mm to a major coronary artery and in a distance of 1–1.5 cm² to each other.

Patients of group B were operated using a conventional sternotomy and using Cardiopulmonary bypass (CPB). After median sternotomy, opening of the pericardium and canulation for CPB, coronary artery bypass grafting was performed on the arrested heart using cold antegrade crystalloid cardioplegia. The laser channels were drilled in the same way as described for group A, during reperfusion on CPB.

Postoperative ECG was documented after 6, 12, 18 and 24 h together with CK/CK-MB enzymes. A defined diagnosis of myocardial infarction was made when both criteria were positive. (1) Development of a new abnormal Q-wave not present on the preoperative ECG (Minnesota Code for pathologic Q-waves). (2) Enzymatic changes defined as more than 10% of the ratio of peak CK-MB/peak total CK on three consecutive samples.

According to the protocol, the preoperative and postoperative examination during follow-up included: (a) physical examination; (b) medical history; (c) functional status of angina (classification according to CCS); (d) angina questionnaire (according to The Seattle Angina Questionnaire); (e) ECG; (f) stress ECG (bicycle, 25 watt steps for 2 min each); and (g) stress thallium scan. For stress scintigraphy 90 MBq Tl-201-Cl was administered 4 min after completion of dipyridamole infusion (0.54 mg/kg). Patients had abstained from cardiac related medication and from caffeine and aminophyylline. The next day 90 MBq Tl-201-Cl was injected under resting conditions and under full medication. SPET acquisition was performed 10 min and 4 h p.i. by use of a dual-head camera (ADAC, Vertex, USA). Data were reconstructed iteratively with attenuation correction. For semiquantitative evaluation relative count densities were determined in 12 wall segments (anterior, lateral, inferior and septal wall segments in an apical, a middle and a basal short axis slice). For follow-up studies count rates were related to that of a initially well perfused septal wall segment which was not immediately influenced by the surgical treatment. Follow-up examination were performed after 3, 6, 9 and 12 months, respectively.

	Results

Top Abstract Introduction Materials and methods Results Discussion References

 
Demographics of all 28 patients, which were comparable between both groups, are depicted in Table 1. The mean preoperative angina class according to CCS was 3.3±0.5 for both groups, 3.5 for group A and 3.2 for group B, respectively. The ejection fraction was more than 35% in both groups according to the study protocol.

Complications
The onset of a pneumothorax in each group was due to a technical failure in one and an incorrect removal of a chest tube in another patient. There was one intraoperative myocardial infarction with an typical increase in cardiac enzymes and changes in ECG but without impaired hemodynamics. There was no hospital death. All 28 patients were discharged home and followed-up for a period of 3 months (n=23), 6 months (n=13), 9 months (n=7) and 12 months (n=4). A total of 5 patients, who had surgery less than 3 months ago were contacted by telephone. All of them were alive and well. During follow-up two male patients (group A) died 5 months after surgery with signs of a cardiac related death, which could not be confirmed by autopsy since permission was refused.

The results of follow-up examination are listed in Table 2 and Fig. 1 Fig. 2 , respectively. The mean CCS class was 1.9±0.3 for group A. The improvement compared to preoperative (3.5±0.4) was statistical significant P0.01. For group B CCS class during the follow-up was 1.2±0.3 versus 3.2±0.3 preoperatively P0.01. Patients of group A showed an increase of exercise tolerance to 64.4±14.7 W after 6 months versus 37.9±10.3 watt preoperatively (P<0.05). In group B the increase was up to 92.4±14.7 versus 42.9±10.3 preoperatively (P<0.05). For the postoperative thalium scan results, the signal density was compared as percentage of the density of the septal area, which was valued as 100%. For group A, during pharmacological stress there was a decrease of density 67±17% after 3 and 68±15% after 6 months. Compared with the preoperative value of 73±17% this was statistically significant (P<0.05). After 12 months the density turned to the preoperative value 71±17%. However, under resting conditions, density deminished irreversibly to 76±16 versus 89±15% preoperatively. In group B, the myocardial perfusion increased in the bypassed area up to 90±13 versus 80±21% preoperatively (P<0.05). In the lasered area there was no increase or decrease during stress, 74±18 versus 73±16% but a diminished density under resting conditions, 80±16 versus 87±19% (P<0.05), 3 months after TMLR. This decrease recovered to the initial values after 6 months. Left ventricular function did not change significantly in both groups (Table 2).

View larger version (21K): [in this window] [in a new window]   Fig. 1. Pre- and post-operative angina classification.

View larger version (25K): [in this window] [in a new window]   Fig. 2. Pre- and post-operative exercise tolerance test.

	Discussion

Top Abstract Introduction Materials and methods Results Discussion References

Since Kolessov and Favaloro introduced coronary bypass surgery and Grüntzig introduced coronary angioplasty, these two techniques became the golden standard for the treatment of coronary artery disease. Most alternative techniques, which were performed before this milestones in medicine were abandoned. With an increasing number of patients with diffuse coronary artery disease, not amenable to interventional treatments and refractory to medical treatment, there is renewed interest in alternative treatment modalities.

Most patients, included in this study, had a long history of several treatments including coronary bypass surgery and PTCA. Quality of life was limited by the recurrence of severe angina and severely impaired exercise capacity. The use of laser energy to create transmyocardial channels has been introduced by Mirhoseini and Cayton in 1981 [11]. This concept was based on studies done by Sen in the sixties, when he used a transmyocardial puncture for immediate myocardial revascularization [2]. These channels were thought to create a direct connection between the left ventricular cavity and the intramyocardial sinusoids mimicking direct myocardial perfusion as it is known from snakes and some reptiles. The laser energy was thought to create transmyocardial channels in an atraumatic way, so that long term patency could be expected [12] [13]. The theory of direct myocardial perfusion through laser created channels as the underlying mechanism for the clinical improvement after TMLR is still not revoked but most recent reports demonstrated an early occlusion of at least most of the channels after surgery in canine-long term studies or at human autopsy studies [14] [15].

Despite the fact that the underlying mechanisms are not clarified yet [16], the clinical improvement after TMLR has been demonstrated in several clinical trials using CO₂ lasers [3] [12] [17] [18] [19] [20] [21] [22] [23]. As compared to the CO₂ laser, the Holium YAG laser has some advantages in terms of handling. Firstly, the probe is flexible and any target area of the myocardium is easily attainable. Secondly, the energy is delivered as a pulsed triple burst of 350 µs. Usually three to four bursts are needed for transmyocardial perforation. This gives more control than a high energy one-shot perforation applied with the CO₂ laser. Thirdly, the energy release is triggered by ECG, thus no severe ventricular arrhythmia was observed during the procedure performed without cardiopulmonary bypass.

Compared to the results of different centers using the CO₂ laser or the Eximer laser; the results demonstrate the same clinical outcome after TMLR. Thus, the clinical benefit is not related to the kind of laser. The different depth of acute injury created by the different laser energies [24] [25] may also be of minor importance, since it has to be considered that patency of the channel is probably not the underlying mechanism for the clinical benefit. Burkhoff and colleges demonstrated angiogenesis not only in the channel remnants but also in the surrounding myocardium as a reaction to the injury [14]. Nevertheless, no significant data are currently available that demonstrate an improved myocardial perfusion by angiogenesis. In contrast to the results of Horvath and colleges, who demonstrated a decrease in the number of segments with reversible perfusion defects in the treated area by a technetium sestamibi scan [21] these improvements could not be demonstrated in the study by using a thallium scan. Moreover, in some patients the early scan after 3 months showed a depression of the signal density in the lasered area compared to the unlasered septum. This depression was normalized after 12 months in most of these patients but only to the level of preoperative signal density. Another interesting observation was, that this signal depression was minor in the patients of group B, in which TMLR was performed in combination with coronary bypass grafting to a different myocardial area. This phenomena may be attributed to better perfusion of existing collateral by the new graft. Although thallium scan may not be sophisticated enough to reflect minor changes in myocardial perfusion, at least in this limited study myocardial perfusion did not increase in the lasered area soon after TMLR but decreased in some patients. Furthermore, there was no correlation between the clinical outcome and the results of thallium scan in the patients. Other mechanisms such as cardiac microinfarction, nerval ablation or a change of molecular pathways between ischemia and the onset of angina may be responsible for the clinical response in absence of increased perfusion. However, the clinical benefit of TMLR in the treatment of angina pectoris is still important facing otherwise therapy refractory coronary artery disease. As a positive response to therapy was defined by an improvement of two angina classes according to the CCS scale, the overall success rate was 75% (11/12) in patients treated with TMLR alone (group A) and 91.6% (11/12) in patients with a combined treatment of CABG and TMLR (group B). This is reflected by an improvement of exercise tolerance, which improved in both group and was slightly significant, P=0.047 in group A and P=0.037 in group B. This improvement was confirmed by the subjective benefit of quality of life not only during the time soon after surgery but during the entire duration of follow-up, usually with a slight additional improvement after 6 months.

Furthermore the result of the study demonstrates that transmyocardial laser revascularization is a safe therapy. Despite the severe underlying disease there was no intraoperative death in both groups. The intra- and postoperative course was uneventful apart from one uncertain myocardial infarction without clinical symptoms and two pneumothoraces which were not related to the laser procedure itself. TMLR should be used only in patients with stable chronic angina. The leading symptom of the disease should be angina pectoris rather than dyspnoe or other signs of myocardial insufficiency. In one patient major coronary artery, which supplies the myocardium may increase the safety of the procedure. Since no acute improvement of perfusion after the creation of transmyocardial channels is believed, patients with unstable angina might be at increased risk for the procedure. As such patients were excluded in the study, hospital mortality was low as compared to other reports.

Despite good peri- and postoperative results, two patients of group A, who were nearly symptom free after TMLR died of a cardiac related dead. Thus, some questions remain unanswered. The underlying mechanisms for the release of angina symptoms have been not investigated yet. Based on the results, the patients with end-stage coronary artery diseased are still facing myocardial ischemia after TMLR, even if they do not develop angina. The question is, does TMLR target the ischemic myocardial disease or only the angina symptoms. This leads to the next question, are patients at more risk during exercise if myocardial perfusion is not improved after TMLR but warning symptoms are not developed. If so, this would have an influence on the long term survival after TMLR. The opposite could be true as well. As a result of the improved exercise tolerance, patients may continue exercise if they develop no angina symptoms and repeated myocardial ischemia could be a stimulus for angiogenesis and new collateral vascularization. Thus, myocardial perfusion may improve secondary to TMLR as likewise collateralization is improved during exercise in some patients having peripheral occlusive vascular disease. Based on the results, the maximal tolerable medical treatment should not be reduced after TMLR, even if patients are without angina symptoms.

In summary, the study demonstrates that transmyocardial laser revascularization with the Holium YAG laser is a safe and effective therapy in patients with severe angina pectoris, which is therapy refractory by other means. The benefit is related to a decrease of angina symptoms and an increase of exercise tolerance rather than an improvement of myocardial perfusion or function.

	References

Top Abstract Introduction Materials and methods Results Discussion References

 

1. Wearn J.T., Mettier S.R., Klumpp T.G. The nature of the vascular communications between the coronary arteries and the chamber of the heart. Am Heart J 1933;9:143-164.
2. Sen P.K., Udwadia T.E., Kinare S.G., Parulkar G.B. Transmyocardial acupuncture. J Thorac Cardiovasc Surg 1950;50:181-189.
3. Mirhoseini M., Cayton M.M., Shelgikar S., Fisher J.C. Laser myocardial revascularization. Lasers Surg Med 1986;6:459-461.[Medline]
4. Beck C.S. The development of a new blood supply to the heart by operation. Ann Surg 1935;102:801-813.[Medline]
5. Massimo C., Boffi L. Myocardial revascularization by new method of carring blood directly from the left ventricular cavity into the coronary circulation. J Thorac Cardiovasc Surg 1957;34:257-264.
6. O’Saughnessy L. An experimental method of providing a collateral circulation to the heart. Br J Surg 1936;23:665-670.
7. O’Shaughnessy L. Surgical treatment of cardiac ischemia. Lancet 1937;23:185-194.
8. Vineberg A.M. Development of an anastomosis between the coronary vessels and a transplanted internal mammary artery. Can Med Assoc J 1946;55:117-119.
9. Vineberg A.M. Evidence that revascularization by ventricular-internal mammary artery implants increases longevity: 24 year, 9 months follow-up. J Thorac Cardiovasc Surg 1975;70:381-397.[Abstract]
10. Walter P., Hundeshagen H., Borst H.G. Treatment of acute myocardial infarction by transmural blood supply from the ventricular cavity. Eur Surg Res 1971;3:130-138.[Medline]
11. Mirhoseini M., Muckerheide M., Cayton M.M. Transventricular revascularization by laser. Lasers Surg Med 1982;2:187-198.[Medline]
12. Okada M., Ikuta H., Shimizu K., Horii H., Nakamura K. Alternative method of myocardial revascularization by laser: experimental and clinical study. Kobe J Med Sci 1986;32:151-161.[Medline]
13. Owen E., et al. Observation on the effects of CO₂-laser on rat myocardium. Microsurgery 1984;5:140.[Medline]
14. Burkfoff D., Fisher P., Apfelbaum M., Kohmoto T., DeRosa C.M., Smith C.R. Histological appearance of transmyocardial laser channels after 4 1/2 weeks. Ann Thorac Surg 1996;61:1532-1535.[Abstract/Free Full Text]
15. Kohmoto T., Fisher P.E., Gu A., Zhu S.M., Yano O.J., Spotnitz H.M., Smith C.R., Burkhoff D. Does blood flow through Holium:YAG transmyocaedial laser channels?. Ann Thorac Surg 1996;61:861-868.[Abstract/Free Full Text]
16. Landreneau R., Nawarawong W., Laughlin H., Ripperger J., Brown O., McDaniel W., McKnown D., Curtis J. Laser revascularization of the myocardium. Lasers Surg Med 1991;11:35-42.[Medline]
17. Cooley D.A., Frazier O.H., Kadipasaoglu K.A., Pehlivanoglu S., Shannon R.L., Angelini P. Transmyocardial laser revascularization: anatomic evidence of long term channel patency. Texas Heart Inst J 1994;21:220-225.[Medline]
18. Frazier OH, Cooley DA, Kadipasaoglu KA, Pehlivanoglu S, Lindenmeir M, Barasch E, Conger JL, Wilansky S, Moore WH. Myocardial revacularization with laser. Preliminary findings. Circulation 1995;92(9)Suppl II:58–65.
19. Horvath K.A., Mannting F., Cummings N., Shernan S.K., Cohn L.H. Transmyocardial laser revascularization: operative techniques and clinical results at 2 years. J Thorac Cardiovasc Surg 1996;11(5):1047-1053.
20. Horvath K.A., Smith W.J., Laurence R.G., Schoen F.J., Appleyard R.F., Cohn L.H. Recovery and viability of an acute myocardial infarct after transmyocardial laser revascularization. J Am Coll Cardiol 1995;25(1):258-263.[Abstract]
21. Horvath K.A., Cohn L.H., Cooley D.A., Crew J.R., Frazier O.H., Griffith B.P., Kadipasaoglu K., Lansing A., Mannting F., March R., Mirhoseini M.R., Smith C.R. Transmyocardial laser revascularization: results of a multicenter trial with transmyocardial laser revascularization used as sole therapy for end-stage coronary artery disease. J Thorac Cardiovasc Surg 1997;113(4):645-654.[Abstract/Free Full Text]
22. Mirhoseini M., Cayton M.M., Shelgikar S. Transmyocardial laser revascularization. J Am Coll Cardiol 1994;1A:484.
23. Mirhoseini M., Shelgikar S., Cayton M.M. New concepts in revascularization of the myocardium. Ann Thorac Surg 1988;45:415-420.[Abstract]
24. Fleischer K.J., Goldschmidt-Clermont P.J., Fonger J.D., Hutchins G.M., Hruban R.H., Baumgartner W.A. One-months histologic response of transmyocardial laser channels with molecular intervention. Ann Thorac Surg 1996;62:1051-1058.[Abstract/Free Full Text]
25. Jansen E.D., Frenz M., Kadipasaoglu K.A., Pfefer T.J., Altermatt H.J., Motamedi M., Welch A. Laer-tissue interaction during transmyocardial laser revascularization. Ann Thorac Surg 1997;63:640-647.[Abstract/Free Full Text]

This article has been cited by other articles:

				J. Schneider, A. Diegeler, R. Krakor, T. Walther, R. Kluge, and F.W. Mohr Transmyocardial laser revascularization with the holmium:YAG laser: loss of symptomatic improvement after 2 years Eur. J. Cardiothorac. Surg., February 1, 2001; 19(2): 164 - 169. [Abstract] [Full Text] [PDF]

				O. Tjomsland, L. Aaberge, S. M. Almdahl, M. Dragsund, P. Moelstad, K. Saatvedt, and K. Nordstrand Perioperative cardiac function and predictors for adverse events after transmyocardial laser treatment Ann. Thorac. Surg., April 1, 2000; 69(4): 1098 - 1103. [Abstract] [Full Text] [PDF]

				T. Al-Sheikh, K. B. Allen, S. P. Straka, D. A. Heimansohn, R. L. Fain, G. D. Hutchins, S. G. Sawada, D. P. Zipes, and E. D. Engelstein Cardiac Sympathetic Denervation After Transmyocardial Laser Revascularization Circulation, July 13, 1999; 100(2): 135 - 140. [Abstract] [Full Text] [PDF]

				J. W. Jones, S. E. Schmidt, B. W. Richman, C. C. Miller III, K. J. Sapire, D. Burkhoff, and J. C. Baldwin Holmium: YAG laser transmyocardial revascularization relieves angina and improves functional status Ann. Thorac. Surg., June 1, 1999; 67(6): 1596 - 1601. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Diegeler, A. Articles by Kluge, R. Search for Related Content PubMed PubMed Citation Articles by Diegeler, A. Articles by Kluge, R.