Stanford School of Medicine
Cardiovascular Medicine– In the Department of Medicine

Percutaneous Myocardial Revascularization

Transmyocardial laser revascularization (TMR or TMLR) was conceived to treat patients with refractory angina or "end-stage" coronary disease . It was inspired by the reptilian circulation, which supplied blood directly to the myocardium from the ventricular cavity via a network of branching channels without the need for epicardial vessels. TMR procedure creates a multitude of transmural myocardial channels using a CO2 laser via an open thoracotomy approach with the aim of improving myocardial perfusion. Percutaneous transmyocardial laser revascularization (PMR , PTMR or PMLR) is now a feasible catheter-based procedure using a Ho:YAG laser, which reduces the perioperative risk

Background

In the 1980s, pioneering work by Mirhoseini et al 1,2 in a canine infarct model demonstrated the myocardial protective effects of CO2 laser created transmyocardial channels.

TMR

In 1988, Mirhoseini et al 3 reported the first human TMR series using adjunctive CO2 laser TMR with coronary bypass surgery (CABG) in 12 patients. Follow-up stress thallium imaging demonstrated improved perfusion in the treated segments and patent channels on left ventriculography. However, these benefits were not distinguishable between the bypass procedure and TMR. TMR sole therapy for refractory angina can significantly reduce angina symptoms , decreased hospital admissions and improved myocardial perfusion but has an associated perioperative mortality of 9% 4. A prospective , multicenter randomized trial of TMR versus maximum medical management in 162 patients demonstrated significantly reduced hospitalization at 3 months (20% vs. 43%) and improved angina without significant increase in mortality 5. For "end-stage " CAD patients, TMR is an effective method of angina relief with an almost immediate benefit which persists to at least 1 year post-procedure but which has a significant perioperative mortality risk.

How Does it Work?

The exact mechanism of action of TMR/PMR remains poorly understood. Patent channels are seen as long as 3 years post-procedure 6,7 and occluded as early as 1 day 8,9. More likely mechanisms are angiogenesis 10,11 and denervation 12,13.

PMR (PMLR)

An open thoracotomy with a general anesthetic is required with a CO2 laser TMR procedure which accounts for the increased periprocedural risks. This is related to the inability to transmit CO2 laser energy via a flexible fiberoptic system unlike a Holmium:Yittrium-aluminium-garnet (Ho:YAG) laser. Jeevanandam et al 14 and Yano et al 15 created nontransmural channels from the endocardium in canines using a Ho:YAG laser. At Stanford University, Kim and colleagues16 advanced the percutaneous approach using a novel endovascular system in a canine model. PMR has now been used in human clinical trials.

Currently, PMR systems under investigation include:

  1. CardioGenesis PMRä (CardioGenesis Corporation, Sunnyvale, CA)

    A braided 9F guiding catheter is employed, allowing a 6F braided laser catheter to enter the left ventricle. The laser catheter has a central 400 mm optical fiber and a 1.75mm lens at the distal tip. The output wavelength of the Ho:YAG laser is 2.1mm and produces 2 J pulses with a peak power of 5.7 kW and a fluence of 83 J/cm2. Pulses are delivered in groups of two at a frequency of 17Hz ("burst").

  2. Eclipse PTMRä (Eclipse Surgical Technologies Inc., Sunnyvale, CA)

    This is very similar to the above system. No lens is attached to the optical fiber tip. This Ho:YAG laser has a wavelength of 2.1 mm and 5 or 15 Hz pulse frequency. The Cardiogenesis and Eclipse companies have merged in latter half of 1998.

  3. NaviStarä (Biosense Inc., Division of Johnson and Johnson, Cordis, Miami,FL)

    This is a 7F steerable catheter system with a unique navigational technology accomplished via electrical and mechanical sensors at the distal tip. A three-dimensional "road map" is produced which offer the additional advantage of myocardial viability detection. The Ho:YAG laser energy is used. This has been renamed direct myocardial revascularization (DMR); human feasibility studies are in progress.

PMR Procedure

The procedure is very similar to any interventional procedure using femoral arterial access. Biplane left ventriculography and coronary angiography are performed to aid target treatment area delineation. A transparent film is taped onto the two video monitors which allow the coronary tree and left ventricular outline to be marked. This "road map" is used to help guide the laser catheter in two planes. The CardioGenesis PMRä guiding catheter is loaded onto a 6F diagnostic catheter and introduced into the left ventricle. After removing the pigtail catheter, the laser catheter is advanced until it exits the guiding catheter and then the extendible optical fiber is positioned onto the endocardium. This coaxial catheter system permits multiple degrees of longitudinal and rotational freedom of movement for tip placement. Once good contact between the laser fiber and the endocardium is achieved, the laser is fired (using the foot control). Typically, two "bursts" of two pulses (2 J per pulse) is delivered to create one channel. The laser delivers bursts approximately 100-150ms after the QRS complex on the electrocardiogram (late systole). Each channel site is then marked on the roadmap in both planes. The laser is retracted and repositioned under fluoroscopy for the next channel site. Care is taken to avoid channel overlapping which increases the possibility of ventricular perforation. Ten to 20 channels are created depending on the area needing treatment (suggested spacing of 1 channel/cm2). When complete, a post-procedure left ventriculogram is performed to assess myocardial function, channels (rarely seen) and undetected perforation. If the post-procedural echocardiogram excludes a pericardial effusion, the patient is discharged the following day.

Potential Risks

In addition to the risks normally associated with a cardiac catheterization procedure, PMR increases the likelihood of left ventricular perforation, pericardial effusion and potential tamponade. Immediate pericardiocentesis may be required. Transient arrhythmias or new bundle branch block may occur.

Contraindications to PMR

Efficacy

To date, little has been published on the effectiveness of PMR. In a feasibility study, there was no major procedural complication or mortality in 30 treated patients 18. Improved angina class was seen at 3 months. Large-scale PMR efficacy studies are ongoing:

The PACIFIC study

Potential Angina Class Improvement From Intramyocardial Channels

This is a large randomized multicenter trial in USA and the UK, comparing PMR (CardioGenesis PMRä system) and maximal medical therapy in 198 patients with Canadian angina class III or IV symptoms . Angina class, exercise tolerance (treadmill test), myocardial perfusion (dipyridamole thallium scan) and quality of life (Seattle angina questionnaire) are assessed at 3, 6 and twelve months post-procedure. Recruitment was complete in July 1998. At the recent AHA'99 meeting in Atlanta, a significant decrease in anginal class (average=1.3) and improved exercise times were noted in the patients who received PMR. 46% of the PMR and 11% of the medicine-only groups had a greater than or equal to 2 anginal class improvement. 71% of the PMR patients ended up with class 0, I, or II angina by the end of the 12-month follow-up. There were eight deaths in the PMR group and three in the medical group (p=NS). These results suggest that PMR is feasible and safe with the potential to improve angina

Conclusion

As a feasible alternative myocardial revascularization technique for the end-stage CAD patient, PMR is awaiting confirmation of its efficacy from current clinical trials. The lower procedural risks of PMR make it more appealing than TMR. This may lead to a broader application, such as in allograft coronary artery disease, or as an adjunct to coronary intervention.

References

1. Mirhoseini M, Cayton MM. Revascularization of the heart by laser. J Microsurg 1981;2:253-260.

2. Mirhoseini M, Muckerheide M, Cayton MM. Transventricular revascularization by laser. Lasers Surg Med 1982;2:187-198.

3. Mirhoseini M, Shelgikar S, Cayton MM. New concepts in revascularization of the myocardium. Ann Thorac Surg 1988;45:415-420.

4. Horvath KA, Cohn LH, Cooley DA, Crew JR, Frazier OH, Griffith BP, Kadipasaoglu K, Lansing A, Mannting F, March R, Mirhoseini MR, Smith C. 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;113:645-654.

5. Allen KB, Fudge TL, Selinger SL, Dowling RD. Prospective randomized multicenter trial of transmyocardial revascularization versus maximal medical management in patients with Class IV angina. Circulation 1997;96(suppl I): I-564.

6. Cooley DA, Frazier OH, Kadipasoglu KA, Pehlivanoglu S, Shannon RL, Angelini P. Transmyocardial laser revascularization: anatomic evidence of long-term channel patency. Tex Heart Inst J 1994;21:220-224.

7. Whittaker P, Rakusan K, Kloner RA. Transmural channels can protect ischemic tissue: assessment of long-term myocardial response to laser- and needle-made channels. Circulation 1996;93:143-152.

8. Krabatsch T, Schaper F, Leder C, Tulsner J, Thalmann U, Hetzer R. Histological findings after transmyocardial laser revascularization. J Card Surg 1996. 11:326-331.

9. Gassler N, Wintzer HO, Stubbe HM, Wullbrand A, Helmchen U. Transmyocardial laser revascularization: histological features in human nonresponder myocardium. Circulation 1997,95:371-375.

10. Kohmoto T, Fisher PE, DeRosa C, Smith CR, Burkhoff D. Evidence of angiogenesis in regions treated with transmyocardial laser revascularization. Circulation 1996;94(Supp II):294.

11. Kohmoto T, DeRosa CM, Yamamoto N, Fisher PE, Failey P,Smith CR, Burkhoff D. Evidence of vascular growth associated with laser treatment of normal canine myocardium. Ann Thorac Surg 1998 65:1360-1367.

12. Whittaker P, Kloner R, Przyklenk K. Laser-mediated transmural myocardial channels do not salvage acutely ischemic myocardium. J Am Coll Cardiol 1993;22:302-309.

13. Kwong KF, Kanellopoulos GK, Nickols JC, Pogwizd SM, Suffitz JE, Schuessler RB, Sundt TM III. Transmyocardial laser treatment denervates canine myocardium. J Thorac Cardiovasc Surg. 1997. 114:883-889

14. Jeevanandam V, Auteri JS, Oz MC, Watkins J, Rose EA, Smith CR. Myocardial revascularization by laser induced channels. Surg Forum 1990; 41:225-227.

15. Yano OJ, Bielefeld MR,Jeevanandam V, Treat MR, Marboe CC, Spotnitz HM, Smith CR :Prevention of acute regional ischemia with endocardial laser channels. Ann Thorac Surg 1993;56:46-53

16. Kim CB, Kesten R, Javier M, Hayase M, Walton AS, Billingham ME, Kernoff R, Oesterle SN. Percutaneous method of laser transmyocardial revascularization. Cathet Cardiovasc Diagn 1997;40:223-228.

17. Kornowski R, Hong MK, Leon MB. Comparison between left ventricular electromechanical mapping and radionuclide perfusion imaging for detection of myocardial viability. Circulation 1998;98:1837-41.

18. Oesterle SN, Reifart N, Meier B, Lauer B, Schuler G. Initial results of laser-based percutaneous myocardial revascularization for angina pectoris. Am J Cardiol 1998;82:659-662.

                                                                       Sidney Lo, MBBS(Hons),FRACP,DDU

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