You are in: eMedicine Specialties > Thoracic Surgery > Cardiac Transmyocardial Laser RevascularizationArticle Last Updated: Jun 8, 2006AUTHOR AND EDITOR INFORMATIONSection 1 of 10
  Author: Shabir Bhimji, MD, PhD, Locum Cardiothoracic and Vascular Surgeon, Saudi Arabia and Middle East Hospitals Shabir Bhimji is a member of the following medical societies: American Cancer Society, American College of Chest Physicians, American Lung Association, and Texas Medical Association Editors: Jeffrey C Milliken, MD, Chief, Division of Cardiothoracic Surgery, University of California at Irvine Medical Center; Clinical Professor, Department of Surgery, University of California at Irvine School of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Shreekanth V Karwande, MBBS, Chair, Professor, Department of Surgery, Division of Cardiothoracic Surgery, University of Utah School of Medicine and Medical Center; Rajalaxmi McKenna, MD, FACP, Consulting Staff, Department of Medicine, Southwest Medical Consultants, SC, Good Samaritan Hospital, Advocate Health Systems; Mary C Mancini, MD, PhD, Director of Cardiothoracic Transplantation, Professor, Department of Surgery, Louisiana State University Health Sciences Center Author and Editor Disclosure Synonyms and related keywords: TMLR, transmyocardial revascularization, TMR, laser, angina, angiogenesis, endothelialization, neovascularization, laser channels, carbon dioxide laser, CO2 laser, sympathetic denervation, amphibian hearts, coronary artery disease, CAD, angina pectoris, direct revascularization procedure, chronic angina INTRODUCTIONSection 2 of 10
  Background Despite advances in both medical and surgical management of coronary artery disease, many patients remain symptomatic after conventional therapies have been exhausted. Typically, these patients continue to have chest pain while on maximal medical therapy, and most are at an extraordinary risk for surgical intervention. Transmyocardial laser revascularization (TMLR) is based on the use of a high-powered carbon dioxide or other laser that interjects a strong energy pulse into the left ventricle, vaporizing the ventricular muscle and creating a transmural channel with a 1-mm diameter. The procedure can be used to create channels along the free left ventricular wall but not the septum. These channels are placed 1 cm apart in the ischemic myocardium. TMLR is performed to improve myocardial oxygenation, eliminate or reduce angina, and improve the patient's cardiovascular function. The carbon dioxide laser is triggered to the ECG to prevent arrhythmias (ventricular tachycardia). Cardiopulmonary bypass (CPB) is not required, and the patient is not heparinized. TMLR is a less invasive procedure, and it is appropriate for minimally invasive surgical incisions. Blood transfusions are rarely required, and recovery appears to be faster and less traumatic. Clinical trials currently in progress are investigating the benefits of TMLR compared with continued medical management for patients with angina who are not candidates for either percutaneous coronary angioplasty or coronary artery bypass grafting (CABG). To date, the studies on TMLR show marked decreases in angina and improved functional status for patients with chronic angina. The precise physiologic mechanism for the efficacy of TMLR is not thoroughly understood. Initially, blood was presumed to flow to the intraventricular chambers through the newly created channels. Today, whether this is the exact mechanism by which myocardial blood flow is improved remains unclear. Although unproven, one postulation is that angiogenesis (growth of new blood vessels) may occur in response to the myocardial tissue injury caused by the laser energy; this may be the process that eventually leads to improved myocardial oxygenation. History The first attempts at improving myocardial blood supply were designed to increase collateral circulation from extracardiac sources. In 1935, Beck used a burr to drill holes into the epicardium and pericardium, intending to stimulate ingrowth of new vessels into the ischemic myocardium. In 1941, Schlesinger and Zoll observed that intramyocardial arterioles were not prone to arteriosclerosis. This prompted Vineberg to implant the left internal mammary artery (LIMA) directly onto the myocardium with the purpose of developing collaterals between the LIMA and the intramyocardial arterioles. Although the first patient to undergo the Vineberg procedure died 2 days later, the LIMA was demonstrated to be widely patent at autopsy. Vineberg later created an intramyocardial tunnel prior to LIMA implantation, and patency of these grafts was documented 2 decades later. In 1965, Sen et al studied the benefits of transmyocardial channels produced with needle punctures. Using a canine model, they placed numerous needle punctures in an ischemic area subtended by an occluded left anterior descending artery. They showed that the acupuncture-created channels resulted in decreased mortality, increased long-term survival, and decreased infarct size. Although patent channels were identified at 8 weeks, no evidence suggested that the channels had developed an endothelial cell lining, thus confirming successful rearterialization. In 1968, Sen et al described marked improvements in patients with chronic angina following transmyocardial revascularization. These initial data supported attempts to improve myocardial perfusion by creating mechanisms for a direct flow of blood from the ventricular cavity to the myocardium, thus mimicking the anatomy of the reptilian heart, in which much of the myocardium is perfused with blood directly from the ventricular cavity. During the next 2 decades, numerous studies were undertaken to evaluate the effects of needle-created transmyocardial channels in revascularizing ischemic myocardium. However, much of this research received little attention because it was not considered nearly as promising as the emerging techniques involving direct myocardial revascularization, such as CABG and angioplasty. The development of laser energy sources in the 1980s stimulated investigators to restudy myocardial acupuncture. In 1981, Mirhoseini and Cayton demonstrated that the carbon dioxide laser could generate small transmyocardial channels in the ischemic myocardium of a dog. In 1983, Mirhoseini et al used TMLR on a patient with coronary artery disease. They used a carbon dioxide laser in conjunction with CABG to treat a hypokinetic area of the left ventricle. The patient did well, with normal ventricular function demonstrated during a postoperative nuclear scan. These initial clinical studies provided further impetus for the use of TMLR. Since the early 1990s, carbon dioxide laser systems have been used to perform TMLR in humans, with excellent results. Mechanisms of TMLR Initially, researchers believed 2 components were necessary to the success of TMLR for revascularizing myocardium. The first was thought to be a physical effect; TMLR channels were thought to remain patent secondary to the high intraluminal pressure within the left ventricle. These patent channels would become small sinuses from which diffusion could occur deep within the once-ischemic myocardium and from which cardiac capillaries could communicate and draw oxygen. This subject has been an area of significant debate, and histologic data are controversial. Some researchers have observed patency in these channels for a 2-week period, followed by complete occlusion in humans. In animal models, postoperative patency has been achieved for more than 12 months. Studies by Gassler et al describe the histologic features of TMLR at autopsy at various time intervals. These studies showed that no patent channels were created and that endothelialization did not occur. Thus, they concluded that the histologic steps following TMLR are much like those of wound healing following necrosis, resulting in a fibrous scar. The clinical response to TLMR in these patients prior to death was not described in this report. Stimulated by the ongoing debate over the long-term patency of laser channels, several centers have reported results of histologic analyses of tissues from patients who died after TMLR. To date, no researchers have reported patent channels from clinical material. Early development of a capillary network has been observed, but the results have not been consistent. Some believe that angiogenesis resulting from the inflammatory response, as opposed to the patent channel hypothesis, may be the reason for improved perfusion. The other component to successful TMLR is based on the hypothesis that the laser channels activate wound repair mechanisms, thus resulting in increased angiogenesis. This is supported by Gassler et al, who noted extensive capillary networks around the laser-created channels in histology sections from a patient 150 days after surgery. The formation of a fibrous scar and the development of capillary networks suggest that the laser actually necroses myocytes, thus initiating an inflammatory response that, in turn, results in angiogenesis and improved myocardial microperfusion. The idea regarding the success of TMR is that the process of using a laser to create channels in the ischemic area of the left ventricle actually causes denervation of the myocardium. Sundt and Kwong (1999) noticed a significant decrease in patient symptoms after TMR therapy. Using the holmium:YAG laser, they performed laser revascularization in canine hearts. Microscopic analysis revealed that laser treatment of the heart tissue might damage or even destroy nerve fibers, and, thus, reduce the symptoms of angina. However, if this were the sole reason for the success of TMR initially, the long-term outcomes would not be positive, as the original problem of ischemic myocardium would continue to worsen. Denervation may play a role in the success of TMR, depending on the type of laser utilized, but the positive effects of denervation are in addition to the increased blood flow that occurs over time related to the other mechanisms of action that make TMR a successful therapy. INDICATIONSSection 3 of 10
Although no absolute indications have been described for the application of TMLR, several studies have provided some necessary guidelines. Most patients have diffuse disease, either locally or globally, such that no target vessel is available for either percutaneous transluminal coronary angioplasty or bypass grafting. Furthermore, the appropriate patient is symptomatic from disease in an area of the myocardium that is not treatable by conventional techniques and has not responded to maximal medical therapy. Prior to undertaking TMLR, a nuclear perfusion scan is obtained, the results of which must show evidence of reversible ischemia. Patients with infarcted or scarred tissue are not suitable candidates for TMLR. Patients should have reasonable ventricular function, with left ventricular ejection fractions above 20%. Historically, patients enrolled in TMLR clinical trials had severe coronary artery disease with Canadian Heart Association class III or IV angina despite maximal medical therapy. The patients had a left ventricular ejection fraction above 20% and were on maximal antianginal therapy. CONTRAINDICATIONSSection 4 of 10
The reported mortality rate (7-10%) following TMLR is a significant cause for caution. Risk-factor assessment has shown that patients with unstable angina and poor myocardial function are at relatively greater risk. If patients have an ejection fraction greater than 30% and chronic stable angina, their risk may be minimized. In addition, patients must have a viable region of the myocardium for TMLR. Patients with scarred or infarcted tissue are not appropriate candidates. Patients with severe adhesions from prior coronary artery bypass surgery can have significant bleeding if a median sternotomy approach is used; therefore, in these patients, a left anterior thoracotomy may be an alternative. TREATMENTSection 5 of 10
Preoperative preparationAlthough clinical trials studying the effects of TMLR differ in protocol, eligible patients are provided information regarding the potential benefits and risks of this procedure. A complete history, physical examination, chest radiograph, and echocardiogram are performed. Regions of the left ventricle to be treated by TMLR are identified based on ischemic areas noted on the preoperative thallium scan image. The surgical team does not have to wear special protective gowns during TMLR, but eyes must be shielded with special glasses. The patient must be prepared and draped just as if he or she was undergoing any open heart procedure. Most patients have a Swan-Ganz catheter and arterial line placed for monitoring. In any reoperative case, external defibrillator pads are applied prior to making the incision. Surgical procedureTMLR is performed with the patient under general anesthesia without the use of CPB or anticoagulation. A double-lumen endotracheal tube is used to allow for selective ventilation of the right lung, thus affording better exposure of the heart during the procedure. For monitoring, all patients need an ECG, arterial pressure monitoring, a Swan-Ganz catheter, and transesophageal echocardiography (TEE). The heart is approached via an anterolateral thoracotomy through the fifth and sixth intercostal space, and the pericardium is opened. Because most of these patients have had prior surgery, all dense adhesions must be carefully excised. In some patients in Europe who have not had previous operations, the thoracoscopic approach has been used. The energy level for the laser is usually set at 15-60 J, corresponding to a pulse duration of 20-50 milliseconds. The laser probe is placed in contact with the epicardium and fired, thus vaporizing the myocardium in its path and creating a 1-mm wide channel that extends from the surface of the heart to the ventricular cavity. TMLR can be performed with a carbon dioxide or a holmium:YAG laser. Carbon dioxide lasers can deliver up to 1000 W of energy through the myocardium. ECG electrodes are used to synchronize the pulsed carbon dioxide to fire with the R wave (corresponding to end diastole), thus minimizing the risk of ventricular arrhythmias. TEE is used to confirm channel creation when transmural penetration is successful. On the TEE image, steam or bubbles are visualized. The holmium:YAG laser transmits energy through optical fibers. Because the energy is more readily dissipated, 3-4 firings are usually required to pass through the entire myocardium. Regardless of the type of laser used, the laser energy vaporizes the myocardial tissue. One channel is created for approximately every square centimeter of ischemic myocardium; thus, a total of 20-40 channels are usually required. Bleeding from the epicardial surface stops quickly, although local pressure or a suture may occasionally be required to achieve hemostasis. Once the desired number of channels has been created and hemostasis has been obtained, chest tubes are placed in the pericardial cavity and the incision is closed. An intraoperative TEE study is performed to exclude any injury to the mitral valve apparatus or the septum. After 25-40 channels are drilled, the pericardium is loosely reapproximated. The chest is then closed in the usual fashion for a small thoracotomy, and the patient is returned to the intensive care unit. Postoperative care is extremely critical, particularly in regard to the maintenance of the appropriate perfusion pressure in the patient's coronary arterial system. Alternative laser sources A number of different laser technologies have been developed while studies with the carbon dioxide laser are completing US Food and Drug Administration–approved trials. The entire experience described herein has been gained only with the carbon dioxide laser. Other laser technologies are not coordinated with the ECG and therefore may not protect against ventricular arrhythmias. Additionally, the other laser technologies do not produce high energy; therefore, they do not protect against perichannel burns and other forms of tissue destruction around the channels. Postoperative careAll patients who undergo TMLR are treated in the same manner as patients undergoing any open heart surgery procedure. All patients are transferred to the intensive care unit and weaned off the respirator. Postoperative hemodynamics are monitored, and pressor drips are tapered accordingly. The average stay in the intensive care unit is generally 1 day, and then patients are transferred to a monitored floor bed. Because of the limited incision, shortened procedure, and nonuse of the CPB machine, most patients recuperate rapidly. The average stay in the hospital is approximately 2-3 days. The hospital stay is extended for patients who develop supraventricular arrhythmias, which must be controlled prior to discharge. RESULTSSection 6 of 10
Short-term clinical experience Numerous studies have reported on the use of TMLR. In most patients, preoperative and postoperative evaluations include a positron emission tomography scan, dobutamine echocardiography, thallium stress test, radionuclide ventriculography, and an exercise treadmill test to evaluate the results of TMLR. Thallium dipyridamole scans and dobutamine stress echocardiograms have shown an overall definite, statistically significant reduction in the severity and extent of ischemic myocardium and improvements in resting function and contractile reserve. The initial report by Mirhoseini et al on 12 patients whose conditions were refractory to medical treatment and who were not candidates for either CAGB or angioplasty revealed no deaths, and all patients improved both clinically and based on nuclear scan findings. This initial report and subsequent follow-up eventually led to phase 2 trials. Frazier et al reported the use of TMLR in 21 patients with medically refractory, chronic stable angina who were not candidates for traditional revascularization procedures. This study showed a concomitant reduction in antianginal medications and cardiac-related hospital admissions. Without question, the most dramatic clinical effect of TMLR has been a significant reduction in angina pectoris. In patients with either stage III or IV angina by the Canadian Heart Association Classification, the perioperative mortality rate was 9%. Postoperatively, most patients improved to class II or better. Remarkably, much of this benefit was observed immediately after the operation. In multicenter studies, one third of patients reported complete relief of angina, whereas two thirds experienced at least a 2-class reduction in symptoms. In addition, the admission rate for angina pectoris in multicenter series dropped significantly in patients treated with TMLR. Note that myocardial perfusion, as determined by single-photon emission computed tomography scanning, was significantly improved in ischemic areas that had received TMLR. Recent long-term studies have unequivocally demonstrated the superiority of TMLR in decreasing angina. Five-year follow-up of patients who had refractory class IV angina and were not candidates for conventional therapy demonstrated significantly increased Kaplan-Meier survival estimates in patients randomized to TMLR. The significant angina relief observed 12 months after sole TMLR therapy was sustained long-term and continued to be superior to that observed for patients maintained on continual medical management alone. Improvements in myocardial perfusion after TMLR have been less convincing than its impact on clinical symptoms. Thus far, study findings are not uniform, with most showing no difference between baseline and 12-month studies of ejection fraction using nuclear studies. TMLR has also been used in cardiac transplantation patients who have accelerated graft atherosclerosis documented by angiography findings. Recent reports indicate that TMLR provides excellent relief of angina in these patients. Clinical trials are currently under way in many centers in the United States and Europe. CABG combined with TMLR Over the last few years, increasing evidence has shown that TMLR may be more useful as a hybrid procedure when used in combination with CABG. Several randomized studies have shown that the combination of TMLR and CABG has more clinical benefit than TMLR or CABG alone. In a prospective, randomized trial that involved 263 patients who were not completely revascularized with CABG alone, the addition of TMLR to conventional CABG provided superior anginal relief compared with CABG alone. Other studies have shown similar results. When TMR was used (both alone and in combination with CABG), much improvement was noted on the anginal score, exercise tolerance, and left ventricular function 6 months after the procedure. In summary, most studies have shown that TMLR, as an adjunct to CABG in selected patients with limited options, may improve hospital outcomes. Postoperative follow-up care TMLR is no longer an experimental procedure. Most trials have been completed, and long-term follow up data are being collected. Regular follow-up care includes a history, a physical examination, and an evaluation of angina and quality of life. A series of tests, including echocardiograms, thallium scans, and exercise tolerance tests, are regularly performed. Whether TMLR has a significant impact on overall mortality in this patient population remains to be determined. Patient education For excellent patient education resources, visit eMedicine's Circulatory Problems Center and Heart Center. Also, see eMedicine's patient education articles Angina Pectoris and Coronary Heart Disease. COMPLICATIONSSection 7 of 10
In more than 1500 patients, intraoperative analysis has documented little morbidity. In the postoperative period, occasional supraventricular tachycardia, pleural effusions, and incisional pain from the thoracotomy have been observed. Because perfusion pressure determines perfusion of the collateral coronary circulation, maintaining adequate perfusion pressure until the patient has recovered completely is important. Hypotension must be avoided, and myocardial support with the use of intra-aortic balloon pumping is sometimes required. Postoperative myocardial infarctions have been reported and are associated with a mortality rate of 8-10%. Mortality also appears to be correlated with the left ventricular ejection fraction in all the national studies, with highest early and late mortality in patients with worse left ventricular function. CLINICAL TRIALSSection 8 of 10
Most clinical studies show that TMLR, regardless of the type of laser used, results in profound and almost immediate improvement in angina pectoris among patients with inoperable coronary artery disease. This improvement appears to be sustained throughout the first year. TMLR also offers advantages over CABG in that it does not require arresting the heart or CPB. The mechanisms by which these clinical benefits are achieved remain unknown. The patency of laser channels in the long-term has not been convincingly demonstrated with any consistency. The hypothesis that TMLR stimulates angiogenesis is becoming increasingly popular but remains unproved. With the predominant clinical effect being relief of angina, other authorities have considered the possibility that denervation of the heart occurs with or without any meaningful revascularization. A recent review of TMLR by the Food and Drug Administration recommended that TMLR not be considered experimental because the latest data support its efficacy and safety. Clinical trials are in progress that randomize patients to continued medical therapy or to TMLR. Trials are also under way that compare TMLR with reoperative CABG. Other studies are examining the use of TMLR in combination with CABG surgery. If combination TMLR and CABG therapy proves beneficial, TMLR could be used in areas where bypass grafting is not possible. TMLR may prove helpful in the treatment of cardiac transplantation patients with diffuse atherosclerosis. Also, TMLR will most likely be performed using minimally invasive approaches in the future. Clinical trials will soon begin using TMLR via the endocardial approach. TMLR performed using the endocardial approach creates transmural channels through the myocardium, initiated at the endocardial surface and extended toward the pericardium, using the holmium:YAG laser. The obvious benefit of this technique is that it can be performed via a percutaneous approach in the cardiac catheterization laboratory and that it obviates the need for surgery. Current clinical investigations are evaluating alternative energy sources potentially adaptable to endovascular applications. The final use of this type of treatment, whether delivered percutaneously or surgically, will be determined only when the results of prospectively randomized trials of maximum medical therapy versus TMLR are available and the impact of this therapy on survival and symptom relief are known. Although the future is uncertain, research efforts continue to strive for new and improved options for treating patients with inoperable chronic angina. FUTURESection 9 of 10
Although CABG is effective in many patients, some are not candidates for direct revascularization procedures. In the last few years, TMLR has elicited significant interest in the treatment of otherwise surgically untreatable coronary artery disease. The results of several large clinical studies show marked improvements in angina. These improvements appear instantaneously after TMLR and are sustained. In most cases, a comparable improvement in exercise tolerance occurs. Regional myocardial perfusion also may be improved, but this has not been convincingly confirmed on thallium scintigram images. The mechanism by which TMLR works still remains unknown. The marked improvement in patients with chronic angina has led the Food and Drug Administration to approve TMLR for such use. In addition to the carbon dioxide laser energy source, trials of alternative devices using the YAG and excimer lasers are currently under way. The latter 2 sources use fiberoptic technology and are currently being evaluated for percutaneous approaches. REFERENCESSection 10 of 10
Transmyocardial Laser Revascularization excerpt Article Last Updated: Jun 8, 2006 |
