Sustained angina relief 5 years after transmyocardial laser revascularization with a CO(2) laser.

BACKGROUND: Although transmyocardial laser revascularization (TMR) has provided symptomatic relief of angina over the short term, the long-term efficacy of the procedure is unknown. Angina symptoms as assessed independently by angina class and the Seattle Angina Questionnaire (SAQ) were prospectively collected up to 7 years after TMR. METHODS: Seventy-eight patients with severe angina not amenable to conventional revascularization were treated with a CO(2) laser. Their mean age was 61+/-10 years at the time of treatment. Preoperatively, 66% had unstable angina, 73% had had >/=1 myocardial infarction, 93% had undergone >/=1 CABG, 42% had >/=1 PTCA, 76% were in angina class IV, and 24% were in angina class III. Their average pre-TMR angina class was 3.7+/-0.4. RESULTS: After an average of 5 years (and up to 7 years) of follow-up, the average angina class was significantly improved to 1.6+/-1 (P=0.0001). This was unchanged from the 1.5+/-1 average angina class at 1 year postoperatively (P=NS). There was a marked redistribution according to angina class, with 81% of the patients in class II or better, and 17% of the patients had no angina 5 years after TMR. A decrease of >/=2 angina classes was considered significant, and by this criterion, 68% of the patients had successful long-term angina relief. The angina class results were further confirmed with the SAQ; 5-year SAQ scores revealed an average improvement of 170% over the baseline results. CONCLUSIONS: The long-term efficacy of TMR persists for >/=5 years. TMR with CO(2) laser as sole therapy for severe disabling angina provides significant long-term angina relief.

Intraoperative arrhythmias and tissue damage during transmyocardial laser revascularization.

BACKGROUND: Transmyocardial laser revascularization creates transmural channels to improve myocardial perfusion. Different laser sources and ablation modalities have been proposed for transmyocardial laser revascularization. We investigated the incidence of cardiac arrhythmias and laser-tissue interactions during transmyocardial laser revascularization of normal porcine myocardium with three different lasers. METHODS: We used a continuous-wave, chopped CO2 laser (20 J/pulse, 15 ms/pulse) synchronized with the R wave; a holmium:yttrium aluminum garnet (Ho:YAG) laser (2 J/pulse, 250 micros/pulse, 5 Hz); and a xenon-chloride (excimer, Xe:Cl) laser (35 mJ/pulse, 20 ns/pulse, 30 Hz). Each laser was used 30 times as the sole modality in four consecutive pigs, yielding 120 channels. RESULTS: The average number of pulses needed to create a channel was 1, 11 +/- 4, and 37 +/- 8 for the CO2, Ho:YAG, and Xe:Cl lasers, respectively. All Ho:YAG and Xe:Cl channels had premature ventricular contractions. Ventricular tachycardia occurred in 70% of the Xe:Cl and 60% of the Ho:YAG channels. Only 36% of the CO2 channels had premature ventricular contractions, and only 3% of the CO2 channels had ventricular tachycardia (p < 0.001 versus Ho:YAG and Xe:Cl). Ho:YAG channels were highly irregular: each had a 0.6-mm-wide central zone surrounded by a ring of coagulation necrosis (diameter, 1.84 +/- 0.67 mm) with effaced cellular architecture in a thin hemorrhagic zone. The Xe:Cl sections exhibited the same patterns on a smaller scale (diameter, 0.74 +/- 0.18 mm). The CO2 channels were straight and well demarcated. The zone of structural and thermal damage extended over half the channel's diameter, measuring 0.52 +/- 0.25 mm. CONCLUSIONS: During transmyocardial laser revascularization, the CO2 laser synchronized with the R wave is significantly less arrhythmogenic than the Ho:YAG and Xe:Cl lasers not synchronized with the R wave. In addition, the interaction of the CO2 laser with porcine cardiac tissue is significantly less traumatic than that of the Ho:YAG and the Xe:Cl lasers.

Transmyocardial laser revascularization: effect of laser parameters on tissue ablation and cardiac perfusion.

Dr. Mahmood Mirhoseini from Milwaukee, WI, transformed transmyocardial revascularization (TMR) into transmyocardial laser revascularization (TMLR) more than 2 decades ago. The controversial nature of this laser procedure and the prospect of its successful application to refractory cases of chronic debilitating angina have created spirited interest in TMLR. As a natural component of this interest, various laser modalities have been proposed and employed during the performance of the TMLR procedure both in the experimental and the clinical setting. However, it is the nature of laser-tissue interactions that is primarily responsible for the long-term fate of the channels, the angiogenesis that occurs in the vicinity of these laser channels, and the resulting increase (if any) in myocardial perfusion. These interactions with tissue are, in turn, determined by laser variables such as photonic absorption and scattering by the target tissue, pulse energy and duration, and the peak power generated. The CO2 laser has the advantages of producing high-energy pulses that create a transmural channel with a single pulse, low-peak power that minimizes structural tissue trauma, and high photonic absorption to minimize thermal damage. The holmium:YAG and excimer lasers, in turn, have the advantage of being coupled to a fiber optic catheter for transluminal endocardial delivery. Importantly, long-term clinical and perfusional data showing a cause and effect relationship between the use of TMLR and these end-points are available for the CO2 laser only. Prospective randomized trials are, therefore, warranted to delineate the use of each laser modality in relation to that of the CO2 laser in the TMLR setting.

Transmyocardial laser revascularization. Does it have a role in the treatment of ischemic heart disease?

Transmyocardial laser revascularization, with or without coronary artery bypass grafting, is an alternative modality for complete revascularization in selected patients with coronary artery disease. Arguably, this modality works by shunting left ventricular blood directly into the ischemic myocardium via laser-mediated transmural channels. In clinical trials, drilling of laser channels has been strongly correlated with long-term improvement of angina, but a causal relationship has not yet been documented. For now, the usefulness of transmyocardial laser revascularization and the nature of its mechanism remain controversial. Some researchers question the existence of myocardial sinusoids altogether. Others question the physiologic possibility of moving blood from the left ventricular cavity into the myocardium against a pressure gradient. Further questions concern the possible routes through which the additional blood gains access to the myocardium; the difficulty of objectively documenting improved myocardial perfusion after transmyocardial laser revascularization; and the nature of the mechanism responsible for the observed clinical benefit. This article examines the different aspects of this controversy and discusses the current status of transmyocardial laser revascularization, as well as possible future directions.

Transmyocardial laser revascularization in allograft coronary artery disease.

We used transmyocardial laser revascularization to treat accelerated cardiac allograft atherosclerosis in 2 patients. One patient received transmyocardial laser revascularization as sole therapy, the other as an adjunct to coronary artery bypass grafting. The systolic function improved in both patients, although the patient who had adjunctive transmyocardial laser revascularization died of systemic infection and renal failure on postoperative day 55. The second patient is alive and well 1 1/2 years after the laser procedure. We discuss 4 other patients who received transmyocardial laser revascularization treatment elsewhere in the United States. Transmyocardial laser revascularization has the potential to become important in the treatment of transplant atherosclerosis. Randomized clinical trials are warranted to assess the efficacy of transmyocardial laser revascularization in this setting.

Transmyocardial laser revascularization: histopathological findings.

Transmyocardial laser revascularization (TMLR) is a new surgical technique clinically tested in patients with advanced severe coronary arteriosclerosis when classic routine treatment by medicaments, percutaneous transluminal coronary angioplasty (PTCA), or aorto-coronary bypass surgery does not improve symptoms of ischemic heart disease. During the procedure high-energy CO 2 laser performs 35-40 transmyocardial channels via left-sided thoracotomy. Channels are drilled from the epicardial side of the heart through the myocardium into the left ventricle cavity. Impulses are synchronized with EKG (diastole), the channel diameter is about 1 mm. Transmural laser penetration is confirmed by intraoperative transesophageal echocardiography (TEE). This technique is based on a theory that channels allow blood supply from left ventricle directly into the intramyocardial vessels (possibly capillaries) and so improve oxygenation of ischemic myocardium. Presented are gross and microscopic findings in a 75-year-old woman who suffered from classic class IV angina with shortness of breath. She had a history of an inferior myocardial infarct, ventricular tachyarrhythmia, aorto-coronary bypass, and mitral valvuloplasty. Her ejection fraction by echocardiography was 25%. Angiographically, she had multiple occlusions of native coronary arteries and diffuse distal stenosis in the graft of the left internal mammary artery (LIMA) to the left anterior descending coronary artery (LAD). Thirty six of forty laser pulses were confirmed by TEE as transmural. The patient died suddenly of ventricular fibrillation 5 days after TMLR surgery. The autopsy was performed 6 hours after death. After cross-sectioning of the heart all the laser-bored channels were found partially or completely filled by fibrin and cell infiltrate composed mainly of polymorphonuclear leukocytes. Patent channels were found within myocardial scars, channels performed through viable myocardium appeared to be partially collapsed and occluded.

Refractory angina pectoris in end-stage coronary artery disease: evolving therapeutic concepts.

Refractory angina pectoris in coronary artery disease is defined as the persistence of severe anginal symptoms despite maximal conventional antianginal combination therapy. Further, the option to use an invasive revascularization procedure such as percutaneous coronary balloon angioplasty or aortocoronary bypass grafting must be excluded on the basis of a recent coronary angiogram. This coronary syndrome, which represents end-stage coronary artery disease, is characterized by severe coronary insufficiency but only moderately impaired left ventricular function. Almost all patients demonstrated severe coronary triple-vessel disease with diffuse coronary atherosclerosis, had had one or more myocardial infarctions, and had undergone aortocoronary bypass grafting (70% of cases). We present three new approaches with antiischemic properties: long-term intermittent urokinase therapy, transcutaneous and spinal cord electrical nerve stimulation, and transmyocardial laser revascularization.

Laser-tissue interaction during transmyocardial laser revascularization.

BACKGROUND: The clinical procedure known as transmyocardial revascularization has recently seen its renaissance. Despite the promising preliminary clinical results, the associated mechanisms are subject to much discussion. This study is an attempt to unravel the basics of the interaction between 800-W CO2 laser radiation and biological tissue. METHODS: Time-resolved flash photography was used to visualize the laser-induced channel formation in water and in vitro porcine myocardium. In addition, laser-induced pressures were measured. Light microscopy and birefringence microscopy were used to assess the histologic characteristics of laser-induced thermal damage. RESULTS: The channel depth increased logarithmically with time (ie, with pulse duration) in water and porcine myocardium. Pressure measurements showed the occurrence of numerous small transients during the laser pulse, which corresponded with channel formation, as well as local and partial channel collapse during the laser pulse. Twenty millimeters of myocardium was perforated in 25 ms. Increasing the pulse duration had a small effect on the maximum transversable thickness, but histologic analysis showed that thermal damage around the crater increased with increasing pulse duration. CONCLUSIONS: Several basic aspects of the interaction of high-power CO2 laser radiation with myocardial tissue and tissue phantoms were studied in vitro. Although the goal of this study was not to unravel the mechanisms responsible for the beneficial effects of transmyocardial revascularization, it provided important information on the process of channel formation and collapse and tissue damage.

Long- and short-term effects of transmyocardial laser revascularization in acute myocardial ischemia.

BACKGROUND AND OBJECTIVE: This study examined the effect of transmyocardial laser revascularization (TMLR) on infarct size and global and regional left ventricular (LV) function. STUDY DESIGN/MATERIALS AND METHODS: Acute ischemia was induced in 24 dogs by ligating the left anterior descending artery. TMLR was done through a left thoracotomy in 12 dogs. The 12 control dogs had ligation only. Global and regional LV function were measured before ligation, then at 6 hours or 3 months after ligation. We calculated the volumetric ratio of damaged myocardium to myocardium at risk (Vd/Vr). RESULTS: At 6 hours, global compensation despite regional dyskinesia was universal; Vd/Vr was the same in control and TMLR dogs. At 3 months, global function during stress was significantly higher in TMLR dogs than in control dogs (P < .05); regional contractions were synergic only in TMLR dogs; mean Vd/Vr was significantly lower in TMLR dogs. CONCLUSION: TMLR limits infarct expansion and improves long-term global and regional function after acute ischemia.

Transmyocardial laser revascularization: clinical experience with twelve-month follow-up.

We are investigating a new technique for myocardial revascularization in which an 800 W carbon dioxide laser is used to drill 1 mm diameter channels into a beating heart after left thoracotomy. Clotting occludes the channels on the subepicardium, and in the long-term setting, blood from the left ventricular cavity flows through these channels to perfuse the ischemic subendocardium. To test the efficacy of this technique in a preliminary clinical trial, we used it as sole therapy for 21 consecutive patients. All patients had hibernating myocardium, reduced coronary flow reserve, or both, had distal diffuse coronary artery disease, and had angina refractory to normal therapy. Eight patients were excluded from follow-up because of death (n=5), rerevascularization (n=2), or diaphragmatic paralysis resulting in postoperative respiratory incapacity (n=1). In the remaining 13 patients available for follow-up, the mean angina class (Canadian Cardiovascular Society) was 3.7 +/- 0.4 before operation and 1.8 +/- 0.6 12 months after operation (p < 0.01). Mean resting left ventricular ejection fraction was 48% +/- 10% before operation and 50% +/- 8% at 12-month follow-up. At 12 months, resting mean subendocardial/subepicardial perfusion ratio had increased by 20% +/- 9% in septal regions treated by laser but decreased by 2% +/- 5% in untreated regions (n=11, p <.001). These results suggest that revascularization by this laser technique positively affects subregional myocardial perfusion and may result in clinical benefits for patients with reversible myocardial ischemia. Studies to date have not demonstrated significant changes in global and regional ventricular contractile function.

Myocardial revascularization with laser. Preliminary findings.

BACKGROUND: We assessed the transmyocardial laser revascularization (TMLR) as sole therapy in patients with symptomatic coronary artery disease refractory to interventional or medical treatment. METHODS AND RESULTS: Thirty-one patients were evaluated with positron emission tomography (PET), dobutamine echocardiography, 201Tl single-photon emission computed tomography (201Tl-SPECT), and multigated acquisition radionuclide ventriculography (MUGA). TMLR was performed in 21 patients who had demonstrable ischemia in viable myocardium. The mean Canadian Cardiovascular Society (CCS) angina class was 3.70 +/- 0.7 (4 patients with unstable angina). Untreated septal segments were used as controls. At 3 months, (n = 15 patients), the mean CCS angina class was to 2.43 +/- 0.9 (P < .05). On dobutamine echocardiography, the mean resting wall motion score index was improved by 16% in lased segments (P < .03 vs control), and mean LVEF at peak stress increased by 19% (P = NS vs baseline). On 201Tl-SPECT, perfusion of lased and nonlased segments did not change. On PET, the mean ratio of subendocardial to subepicardial perfusion (SEn/SEp) increased 14% over baseline (P < .001 vs control). At 6 months (n = 15 patients), the mean CCS angina class was 1.7 +/- 0.8 (P < .05). The mean resting wall motion score index was up by 13% in lased segments (P < .05 vs control). Resting LVEF was unchanged. Stress LVEF increased 21% (P = NS vs baseline). Myocardial perfusion remained unchanged by 201Tl-SPECT. On PET, 36% of the lased segments were better, and 25% were worse compared with baseline. The resting SEn/SEp by PET was up 21% (P < .001 vs control). All deaths (two perioperative and three late) occurred in patients with preoperative congestive heart failure. Two patients required repeat revascularization of new coronary lesions. CONCLUSIONS: These results suggest that TMLR improves anginal status, relative endocardial perfusion, and cardiac function in patients who do not have preoperative congestive heart failure.

Transmyocardial laser revascularization. Anatomic evidence of long-term channel patency.

Transmyocardial laser revascularization, a new surgical technique, is being tested in patients with chronic obstructive coronary artery disease that is refractory to conventional revascularization techniques and to maximal medical therapy. During the operation, which is performed on the beating heart through a left thoracotomy, a high-energy CO2 laser is used to bore transmural channels (1 mm in diameter) into the left ventricle. Each high-energy laser pulse is delivered during end diastole and transects the heart within 10 to 60 msec. The operation is based on the theory that blood will flow directly from the left ventricle into the channels and then into the myocardial vascular plexus. Restoring perfusion should alleviate ischemia in potentially viable myocardium and improve ventricular function. Recently, one of our patients died 3 months after transmyocardial laser revascularization of causes unrelated to the operation. Histologic analysis enabled us to obtain, for the 1st time, anatomic evidence of patent laser channels. Routine staining of cardiac tissue with hematoxylin and eosin revealed multiple patent channels, running perpendicular to and interconnecting with the native vasculature. Although reactive fibrous scar tissue had caused narrowing of the original laser tract, the channels had endothelialized and they contained red blood cells. These findings suggest that the laser channels were functional. We report this interesting case and briefly discuss the anatomic and physiologic phenomena involved in establishing camerosinusoidal blood flow by use of transmyocardial laser revascularization.

Determination of the role of cuticular carbohydrates in the hemocompatibility of Dirofilaria immitis (Nematoda).

We have partially characterized surface glycoproteins of the canine heartworm, Dirofilaria immitis. Histochemical studies indicated the presence of neutral and acidic mucopolysaccharides at the blood-cuticle interface. Fluorescein isothiocyanate-conjugated lectin binding patterns suggested the presence of alpha-D-glucosyl and/or alpha-D-mannosyl, beta-galactosyl, N-acetylneuraminyl and N-acetylated-D-hexosaminyl (sialic and glucuronic acids, respectively) terminal residues among the constituent sugars of the glycocalyx. An additional goal of this study was to assess the significance of each carbohydrate in parasite hemocompatibility by using scanning electron microscopy, internal reflection infrared spectroscopy, and comprehensive contact angle measurements. Each carbohydrate identified in the glycocalyx was selectively cleaved with the appropriate exoglycosidase. Heart-worms bearing native and enzyme-altered surfaces were exposed to platelet-rich canine plasma. Activation and aggregation of platelets were significantly increased on enzyme-treated surfaces as compared with native surfaces. Enzyme-induced cleavage of carbohydrate residues was associated with an increase in critical surface tension or a loss in cuticular structural integrity or both. Hemocompatibility of the heartworm cuticle depends on the retention of a stable saccharide-rich layer that minimizes interaction with plasma proteins and platelets; thus, carbohydrate residues on the glycocalyx may contribute to parasite hemocompatibility. The presence of similar low-critical-surface-tension coatings with high mechanical integrity may impart thromboresistance to other polyphenolic or chitinous substances.

Human intraperitoneal response to a left ventricular assist device with a Ti-6AI-4V alloy surface.

The soft tissue reaction to long-term implantation of an intraperitoneal left ventricular assist device (LVAD) was investigated. The HeartMate 1000 (Thermo Cardiosystems, Inc., Woburn, MA) is a pneumatically driven blood pump with smooth titanium alloy (Ti-6AI-4V) outer surfaces that is placed intraperitoneally in the left upper quadrant and sutured to the anterior abdominal wall. It is being used currently as a bridge to cardiac transplant, which sometimes requires extended support times. We examined the tissue capsule that formed around the rigid circular pump housing of four LVADs (duration of implant: 61, 86, 128, and 153 days) for gross, histologic, immunohistochemical, and ultrastructural analysis. Immunostaining was performed using monoclonal and polyclonal antibodies against cytoskeletal tissue markers (vimentin, desmin, alpha-smooth muscle actin), T and B lymphocytes, carcinoembryonic antigen, factor VIII, and cytokeratins (CAM 5.2 AE1/AE3, 34 beta E12, and 35 beta H11). Direct fluorescent immunolabeling for fibrinogen was also performed to characterize cell and tissue type. Histologic analysis of the 3 to 4 mm thick capsule with white, glistening inner surfaces showed fibrovascular tissue with multipotential subserosal cells (MSCs), capillary endothelium, collagen, and a few mononuclear infiltrates. The immunohistochemical profile of the MSCs differed from myofibroblasts despite a morphologic similarity. Transmission electron microscopy revealed abundant rough endoplasmic reticulum and peripherally arranged myofilaments within the spindle shaped cells. It was hypothesized that capsule formation was initiated by fibrin deposition, followed by proliferation of MSCs and subsequent formation of fibrovascular tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Preliminary results of intraoperative excimer laser angioplasty: phase 1: an adjunct to coronary artery bypass surgery.

The excimer laser underwent phase I clinical trials at three centers to determine its safety for intraoperative coronary laser angioplasty as an adjunct to coronary artery bypass grafting. A 308-nm Xenon-Chloride, pulsed-wave excimer laser was used to perform angioplasty in 30 patients undergoing coronary artery bypass surgery. Forty vessels (30 patients) were treated, in which the extent of occlusion ranged from 30% to 100%, with complete occlusion in 40% of all vessels. Improvement in vessel luminal caliber was achieved in 33 (79%) vessels, with perforations occurring in 4 (12%) vessels, 2 of which required surgical repair. The lumens of the remaining 8 (19%) vessels were not enlarged, and 2 (5%) of these vessels were perforated. Luminal enlargement was most often achieved in totalled occluded vessels in which 16/17 (94%) were recanalized. No patients died within 30 days postoperatively. Five patients demonstrated biochemical and electrocardiographic evidence of myocardial injury 48 hr postoperatively, and one patient died of cardiac arrest 139 days postoperatively. On the basis of these results, we believe that excimer laser angioplasty can be performed safely to improve coronary luminal patency, even in totally occluded vessels, in an operative setting. The long-term value of this procedure remains to be elucidated.