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Platelets, a major constituent of thrombus, play a crucial role in the pathogenesis of acute ischemic coronary syndromes. The effect of ultraviolet laser emission on platelets within thrombi is unknown. The effects of increasing levels of laser energy on platelets in whole blood were investigated. Blood samples were obtained by aseptic venipuncture and anticoagulated with 3.8% sodium citrate. Samples were exposed to increased levels (0, 30, 45, 60 mJ/mm2; 25 Hz) of ultraviolet excimer laser fluence (308 nm wave-length) and then tested for ADP and collagen induced platelet aggregation, platelet concentration, and for platelet contractile force (PCF) development. Scanning electron microscopy was used to detect laser induced morphologic changes of platelets and by flow cytometric analysis to detect changes in expression of platelet surface antigens p-selectin (CD 62) and glycoprotein IIb/IIIa (CD 43). Exposure to excimer laser energy produced dose dependent suppression of platelet aggregation and force development ("stunned platelets"). ADP aggregation decreased from 8.0+/-1.1 Ohms (mean+/-SEM) to 3.7+/-0.8 Ohms (p<0.001) to 2.7+/-0.6 Ohms (p <0.001) and to 1.8+/-0.5 Ohms (p <0.001) as the laser energy increased from 0 to 30 to 45 to 60 mJ/mm2, respectively. Collagen induced aggregation decreased from 21.4+/-1.4 Ohms to 15.7+/-1.2 Ohms (p <0.001) to 11.7+/-1.1 Ohms (p <0.001) and to 9.9+/-1.0 Ohms (p <0.001), in response to the same incremental range of laser energy. Platelet contractile forces declined from 34,500+/-3700 to 27.800+/-2700 dynes as laser energy increased from 0 to 60 mJ/mm2 (p <0.03). Platelet concentration did not change with increasing laser energy. The expression of platelet surface antigen p-selectin (CD 62) remained stable through increasing levels of laser energy exposures while the percentage of CD 43 positive platelets significantly increased with exposure to laser energy, yet the level of expression did not exceed 0.5% of cells. Thus, aggregation kinetics are altered in platelets exposed to ultraviolet laser energy as manifested by decreased platelet aggregation and reduction in platelet force development capability. The response is dose dependent and most pronounced at higher energy levels such as 60 mJ/mm2.

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Information from histopathologic examination of coronary arterial atherosclerotic plaques treated with in vivo laser energy is sparse. Directional atherectomy provides biopsies for study of tissue changes (injury) due to coronary arterial debulking devices, including laser. Sixteen patients who presented with acute ischemic coronary syndromes underwent debulking of a total of 17 obstructive intracoronary lesions with pulsed-wave holmium:YAG laser (2.1 microm wavelength). Laser was performed with the "pulse and retreat" technique which incorporates slow catheter advancement (0.5-1 mm/s) with controlled emission of energy. Immediately postlasing, directional atherectomy was utilized to obtain irradiated plaque tissue for pathologic examination. Extent of laser-induced tissue injury to plaques was graded as 0 (no tissue damage), 1 (small foci or charring and vacuoles), 2 (large amount of charring, edge disruption and vacuoles) and 3 (extensive tissue damage). Angiographically and clinically, all 17 lesions were successfully debulked with the laser energy (mean 47+/-25 pulses), with a reduction of target lesion percent diameter stenosis from 92+/-6% to 47+/-25%. Adjunct balloon dilations further reduced the target lesions to a final of 10+/-10% stenosis. The histopathologic examination of the lased specimens demonstrated that 13 lesions (76%) had no evidence of laser-induced injury (Grade 0). Four lesions had low-level injury (Grade 1), and none had evidence of Grade 2 or 3 laser-induced trauma. Therefore, a laser debulking technique, which incorporates slow catheter advancement with controlled emission of pulses, does not cause significant injurious effects to the irradiated plaque.

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OBJECTIVE: The mechanism by which transmyocardial laser revascularization relieves angina is not understood. One theory is that laser-induced thermal damage to cardiac nerves results in cardiac denervation. This study examined the acute effects of transmyocardial laser revascularization on reflex responses mediated by cardiac nociceptors, the left ventricular receptors with sympathetic afferent fibers that are thought to mediate anginal chest pain. METHODS: Experiments were performed in 13 chloralose-anesthetized dogs with sinoaortic denervation and vagotomy. Left ventricular receptors with sympathetic afferent fibers were activated by epicardial and intracoronary bradykinin before and 45 minutes after transmyocardial laser revascularization. Reflex responses elicited by bradykinin were quantitated by direct recording of efferent renal sympathetic nerve activity. Transmyocardial laser revascularization was performed in the open-chest model with a hand-held holmium:YAG laser (2.1-microm wavelength). RESULTS: An average of 44.5 +/- 1.0 channels were created. Before transmyocardial laser revascularization, reflex increases in renal sympathetic nerve activity were elicited by both epicardial and intracoronary bradykinin. After transmyocardial laser revascularization, there was no significant attenuation in the reflex responses to either epicardial (before, 66% +/- 8%; after, 100% +/- 24%; P =.19) or intracoronary (before, 124% +/- 37%; after, 108% +/- 25%; P =.44) bradykinin. CONCLUSIONS: Transmyocardial laser revascularization has no significant short-term effect on reflexes mediated by left ventricular receptors with sympathetic afferent fibers in anesthetized dogs. These results indicate that transmyocardial laser revascularization does not acutely interrupt the afferent nerves, which are believed to transmit the perception of anginal pain.

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BACKGROUND: Excimer laser angioplasty is a percutaneous treatment modality for management of selected patients with severe obstructive coronary artery disease. This technology entails application of multifiber catheters that vaporize intra-arterial plaque and thrombus with the 308-nm wavelength light. A coronary laser catheter ("OS") with increased space between its optic fibers (90 microns) at the tip was recently developed. The previous design used a closely packed fiber bundle ("CP") with a smaller space between the fibers (77 microns). We sought to determine the ablation characteristics of the new, OS design. METHODS: Experiments testing the new catheter and comparing it to the existing catheter included: (1) measurement of the laser output beam sizes and divergences; (2) evaluation of particulate matter generation during ablation of atherosclerotic tissue; (3) measurement of ablation hole sizes and tissue penetration rates; (4) histopathologic examination of laser-induced in vivo vessel wall injury. RESULTS: The new OS catheters produce a wider beam with higher divergence than the traditional CP catheters (6.7 degrees vs. 4.7 degrees, respectively). Testing two different levels of energy revealed the generation of a reduced number of particulate matter and shallower penetration depth with the OS catheter compared with traditional CP catheters. The OS catheters created a larger diameter of ablated hole than the CP catheters (for 2.0-mm catheters: 2.7 mm2 vs. 1.5 mm2, respectively, p = 0.01). Lasing with the OS catheters with slow advancement rates (0.2-0.5 mm/sec) resulted in creation of significantly larger-diameter holes than those produced at higher speeds (1-3 mm/sec). The in vivo vessel wall injury scores were similar among the two types of catheters tested. CONCLUSIONS: A new design of spaced optical fibers for coronary laser catheters provides increased tissue ablation in comparison to the traditional closely packed fibers catheter. Slow advancement rates during lasing with the new OS catheter are crucial for achievement of adequate plaque debulking.

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BACKGROUND AND OBJECTIVE: Patients presenting with acute myocardial infarction who fail to respond to standard therapy with thrombolytics or have contraindications for their use oftentimes need revascularization with a mechanical device for removal of an occlusive coronary thrombus and its underlying atherosclerotic plaque. As both thrombi and plaques absorb laser energy in the ultraviolet wavelength (308 nm), we studied the feasibility and safety of excimer laser angioplasty in selective patients with complicated acute myocardial infarction. STUDY DESIGN/MATERIALS AND METHODS: Fifty patients with acute myocardial infarction complicated by continuous chest pain and/or ischemia who had a total of 54 obstructive lesions were treated with percutaneous excimer coronary laser angioplasty (ELCA). A Q-wave myocardial infarction was documented in 56% and a non-Q-wave myocardial infarction in 44%. The baseline left ventricular ejection fraction was reduced at 43 +/- 13% and six patients (12%) presented to the cardiac catheterization laboratory in cardiogenic shock. Twenty-nine patients failed to respond to thrombolytic therapy and 16 had contraindications for thrombolytics and IIb/IIIa receptor antagonists. Following laser debulking, all patients received adjunct balloon dilation and then stents were deployed in 83% of the target lesions. Quantitative coronary arteriography (QCA) was performed at an independent core laboratory. RESULTS: Ninety-eight percent laser success and 100% procedural success were achieved. By QCA the minimal luminal diameter increased from baseline of 0.7 +/- 0.5 to 1.3 +/- 0.5 mm post-lasing and then to 2.0 +/- 0.6 with balloon dilation to a final of 3.0 +/- 0.5 mm. Pre-laser percent stenosis diameter of 77 +/- 17% was reduced to 51 +/- 22% post-laser to 3.0 +/- 17% post-balloon and to a final of 15 +/- 25%. An 83% laser-induced reduction of thrombus burden area was achieved as well as an increase in TIMI flow from baseline of 1.7 +/- 1.1 to 2.8 +/- 0.4 by laser to a 2.9 +/- 0.4 final. There were no deaths, emergency bypass surgery, cerebral vascular accident, neurologic injury, or major perforation. In one case, a laser-induced major dissection was successfully treated by stenting. All 50 patients survived the procedure, improved clinically, and were discharged. CONCLUSION: Application of excimer laser coronary angioplasty is feasible and safe in selected patients with acute myocardial infarction who either fail to respond to thrombolytics or have contraindications to these agents. Intracoronary thrombus at the target lesion can be successfully dissolved with this wavelength laser energy without adverse effect on the procedure results.

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The ultraviolet pulsed excimer laser (308 nm wavelength) is currently the only laser approved by the FDA for percutaneous intervention in patients with ischemic coronary artery disease. The clinical presentation of the treated patients varies from stable and unstable angina to acute myocardial infarction. Potential advantages of excimer laser revascularisation in acute coronary syndromes and in ischaemic obstructive peripheral vascular disease include concomitant plaque debulking and thrombus removal; absence of systemic lytic state; shortened thrombus clearing time and facilitation of adjunct balloon angioplasty and stenting. Improved understanding of laser-tissue interactions and positive clinical outcomes through the use of safe lasing techniques have led to expansion of indications/applications for laser angioplasty. These include stent restenosis, complex lesions and thrombotic stenoses, bifurcation lesions, balloon failure, total occlusions, focal saphenous vein graft lesions and peripheral arterial obstructions. The excimer laser can be effectively utilised in patients with depressed left ventricular ejection fraction and does not require implantation of a temporary pacemaker as no-reflow phenomenon and severe arrhythmias are rarely encountered. Careful case selection, proper utilisation of equipment and incorporation of efficient lasing techniques play a crucial role in effective and safe cardiovascular laser applications.

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Chronic total occlusions in particular, completely obstructed aorto-ostial lesions are among the most challenging targets in interventional cardiology. Excimer laser is a debulking technology for revascularization of complex lesions. Treatment of total occlusions with laser angioplasty can be applied providing that a guidewire traverses the entire length of the occlusion prior to device activation. In many patients with total occlusions, a guidewire is unable to penetrate the target stenosis. This communication presents a new technique termed "wireless" laser recanalization. This approach entails recanalization of a total occlusion with a laser catheter without a leading guidewire.

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This study was conducted to evaluate the feasibility, safety, and acute results of percutaneous excimer laser coronary angioplasty (ELCA) in acute coronary syndromes. Fifty-nine patients were treated with ELCA (308 nm), including 33 patients with unstable angina pectoris (UAP) (35 vessels with 39 lesions) and 26 patients with acute myocardial infarction (AMI) (26 vessels with 29 lesions). In each patient the target lesion had a complex morphology. Overall, 71% of the patients had contraindications for pharmacologic thrombolytic agents or glycoprotein IIb/IIIa receptor antagonists. All patients received adjunct balloon dilation followed by stent implantation in 88% of patients with AMI versus 76% of patients with UAP (p = NS). Quantitative angiography was performed at an independent core laboratory; 86% laser success and 100% procedural success was achieved in the AMI group versus 87% laser success and 97% procedural success in the UAP group (p = NS). In the AMI group, the minimal luminal diameter increased from 0.77 +/- 0.56 to 1.44 +/- 0.47 mm after lasing to a final 2.65 +/- 0.47 mm versus 0.77 +/- 0.38 to 1.35 +/- 0.4 mm after lasing to 2.66 +/- 0.5 mm final in the UAP group. A prelaser percent stenosis of 76 +/- 17% for the AMI group versus 70 +/- 16% for the UAP group (p = NS) was decreased after lasing to 52 +/- 16% for the AMI group versus 51 +/- 14% for the UAP group (p = NS) and to a final stenosis of 15 +/- 17% for the AMI group versus 12 +/- 15% for the UAP group (p = NS). A 96% laser-induced reduction of thrombus burden area was achieved in the AMI group versus 97% in the UAP group (p = NS). Preprocedure Thrombolysis In Myocardial Infarction flow of 1.3 +/- 0.9 in the AMI group versus 2.3 +/- 1.2 for the UAP group (p = 0.01) increased to a final flow of 3.0 +/- 0 for the AMI group versus 3.0 +/- 0 for the UAP group (p = NS). There were no deaths, cerebrovascular accident, emergency bypass surgery, acute closure, major perforation or major dissection, distal embolization, or bleeding complications in either group. One patient with AMI had localized perforation (caused by guidewire) without sequelae and 1 patient with UAP had an abnormal increase in creatine kinase levels. All 59 patients survived the laser procedure, improved clinically, and were discharged. Thus, early experience in patients with acute coronary syndromes suggest that percutaneous ELCA is feasible and safe.

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BACKGROUND AND OBJECTIVE: Aggressive development of allograft coronary artery disease is a major cause of death in heart transplant recipients. Percutaneous balloon angioplasty is considered suboptimal for complex lesions in native coronary vessels and heart transplant recipients, alike. Excimer laser energy (308-nm wavelength) can successfully remove and vaporize atherosclerotic plaques in native coronary vessels; however, its application in heart transplant recipients has not been studied clinically yet. STUDY DESIGN/MATERIALS AND METHODS: Six heart transplant recipients underwent percutaneous excimer laser (CVX-300, Spectranetics, Colorado Springs, CO) coronary angioplasty for treatment of a total of 10 discrete, obstructive coronary artery lesions. By using concentric or eccentric multifiber laser catheters, energy parameters were set at a fluence of 45 mJ/mm(2) or 60 mJ/mm(2) with a frequency of 25 Hz and 40 Hz, respectively, with a pulse duration of 135 ns and output of 200 mJ/pulse. The "saline flush" and "pulse and retreat" lasing techniques were used. In each case, adjunct balloon angioplasty was performed; in five lesions, an intracoronary stent was implanted. Angiographic evaluation was performed by visual assessment. RESULTS: Each procedure was successful as defined by laser recanalization of the target lesion (reduction of target lesion stenosis in more than 20%) and subsequent adequate final luminal patency (reduction of target lesion stenosis to less than 50%) and absence of any major in-cardiac catheterization complication (such as perforation, acute closure, dissection, emergency coronary artery bypass surgery), or in-hospital complications (such as death, myocardial infarction, cardiac enzyme elevation, major bleeding), or need for surgical revascularization. A 92 +/- 5% preprocedural percent diameter stenosis was reduced by laser to 35 +/- 16% and by adjunct balloon angioplasty in all lesions and stenting in five lesions, to final residual stenosis of 2 +/- 6%. Angiographic follow-up between 2 and 6 months after the procedure demonstrated a target lesion restenosis rate of 22%. CONCLUSION: Percutaneous excimer laser is safe and efficacious in the treatment of focal obstructive lesions caused by allograft coronary artery disease. These data represent an early clinical experience; thus, the long-term outcome of this revascularization method in recipients of heart transplantation will have to be determined by a large scale prospective, randomized, multicenter clinical study.

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Transluminal extraction catheter (TEC) is a percutaneous device that performs simultaneous thrombus aspiration and plaque excision. Clinical indications for its application are acute myocardial infarction, unstable angina, and stable angina caused by atherosclerotic, thrombotic lesions located within native coronary arteries and degenerated saphenous vein grafts. The device is useful in management of ischemic patients with contraindications to either pharmacologic thrombolytics or platelet GPIIb/IIIa receptor inhibitors, and can also effectively be used in combination with these agents. A successful TEC procedure requires careful patient selection, strict adherence to recommended indications, optimal equipment selection, familiarity with mechanical components of the device, full understanding of safe and efficacious techniques for deployment and activation, as well as recognition of unique associated angiographic manifestations such as the "empty-pouch phenomenon." As with other debulking devices, the incidence of restenosis post-TEC appears to be directly related to acute luminal gain at the time of procedure and therefore requires the need for adjunct stenting. This communication describes and illustrates various clinical, technical, and angiographic aspects of TEC procedure in patients with acute ischemic-thrombotic coronary syndromes. Cathet. Cardiovasc. Intervent. 48:406-420, 1999.

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Accelerated allograft vasculopathy significantly limits the survival of heart transplant recipients. The prevalence of allograft coronary artery disease is as high as 18% by 1 year and 50% by 5 years following heart transplant. Heart failure and sudden cardiac death are the two most common clinical presentations. In heart transplant recipients with severe, discrete focal allograft vascular disease, percutaneous balloon angioplasty is a viable palliative option. However, its application is limited by a significant restenosis rate and progression of allograft disease in nontreated segments. Diffuse disease with tapering of vessels may be approached by debulking devices. Emerging revascularization modalities for focal stenoses and some of the diffuse tapering vessels include coronary stents, rotational atherectomy, various wavelength lasers, and, to a lesser extent, directional atherectomy. Conceivably, stents will reduce restenosis rates related to focal, discrete plaques; yet it is unknown whether they will be efficacious in short- and long-term treatment of diffusely diseased segments affected by allograft disease. Accurate assessment of clinical outcomes and long-term evaluation is imperative prior to acceptance of these devices as fundamental interventional tools for treatment of allograft coronary artery disease.

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A patient with dual left anterior descending (R. interventricularis anterior of the left coronary artery) coronary artery is presented. A normally arising left anterior descending was hypoplastic, and an anomalous left anterior descending, which arose from the right sinus aorticus had a normal caliber. The anomalous left anterior descending artery traversed between the aorta and the pulmonary artery supplying most of the anterior myocardial wall of the left ventricle. This rare coronary anomaly can potentially have implications on percutaneous coronary interventions or on surgical revascularization procedures.

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BACKGROUND AND PURPOSE: The management of symptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM) has traditionally consisted of beta blockers and calcium channel blockers. Surgical treatment has been employed for operable patients who became refractory to medical therapy. However, associated complications, mortality rate, and recurrence of functional limitations have shifted the focus toward alternative therapy modalities. Recently, permanent dual-chamber (DDD) pacemaker has been introduced as an alternative treatment option. PATIENTS AND METHODS: This study comprises clinical, angiographic, echocardiographic, and electrophysiologic data obtained at a single center on 10 symptomatic patients with HOCM who received a DDD pacemaker after medical therapy failed to relieve symptoms. Presenting symptoms were exertional dyspnea and chest pain (60%), syncope (20%), and presyncope (20%). These symptoms were documented for 8.9+/-7.1 years before pacemaker implantation. All patients were in New York Heart Association functional class III or IV before pacemaker therapy. RESULTS: Placement of a permanent DDD pacemaker decreased the left ventricular outflow tract gradient from 83+/-44 mm Hg (range: 35-180 mm Hg) to 47.1+/-25.3 mm Hg (range: 10-75 mm Hg) in these patients. Within 1 to 30 months, follow-up found that the functional status of eight out of the 10 patients had improved to New York Heart Association class 0 or I. CONCLUSION: In selected patients with symptomatic HOCM who fail to respond to medical therapy, DDD pacemaker may offer a nonsurgical alternative treatment option. Large-scale multicenter, prospective, randomized trials are needed to establish the role of this modality in the treatment of hypertrophic obstructive cardiomyopathy.

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The solid-state, pulsed-wave, holmium:YAG laser operates within strong water absorption peaks at the mid-infrared optical wavelength. This laser has been shown to be capable of inducing a mechanical, photoacoustic dissolution of fibrin, a major constituent of thrombi. It is not known whether this laser's energy combined with pharmacologic therapy can enhance the rate of fibrinolysis. The aims of this study were (1) to test the hypothesis that mid-infrared laser emission can enhance tissue-type plasminogen-activator (t-PA) mediated fibrinolysis and (2) to test the combined effect of these two methods of fibrinolysis on fibrin clots varying in age.Three in vitro experimental protocols were used. (1) Fibrin clots were treated with 116 000 IU t-PA for 1, 6 and 12 h, respectively, and then exposed to mid-infrared laser energy (solid-state, pulsed-wave, holmium:YAG, 2.1 µm wavelength 250 ms pulse length, 5 Hz repetition rate, 500 mJ/pulse (33 J/cm(2))). (2) Fibrin gels layered with t-PA were exposed to either 25, 50, 75 or 100 J laser energy. t-PA was then allowed to interact with the lased gels for an additional 4 h. (3) The effects of varying clot age (1, 4 or 8 h) on laser (75 J) augmentation of t-PA induced fibrinolysis were tested. Each experimental protocol had control gels and following each experimental manoeuvre, 20 µl of the plasmin inhibitor ε-amino-n caproic acid was added and fibrin degradation products (FDPs), an indicator of fibrinolysis, were measured by latex agglutination.In fibrin clots exposed to t-PA for 6 h, the addition of laser energy significantly increased FDPs released (t-PA alone 40±0 µg/ml, laser plus t-PA 160±0 µg/ml, p<0.001). For gels exposed to t-PA for 12 h, addition of laser energy resulted in complete dissolution of the clot (FDPs with t-PA alone 160±0 µg/ml vs. laser plus t-PA>300 µg/ml, p=0.001). The rise in FDPs was significantly greater with 75 J of laser energy compared to 25 J (160±0 µg/ml vs. 80±0 µg/ml, p=0.0001), however, energy levels greater than 75 J did not further increase the amount of FDPs indicating a plateau phenomenon in dose-response relationship. t-PA had a decreased fibrinolytic effect on 4 and 8 h-old clots (FDPs of 60±20 µg/ml and 30±10 µg/ml, respectively). Laser energy reversed this trend and enhanced fibrinolysis in both 4 and 8 h-old clots. In 4 h-old clots, laser plus t-PA resulted in FDP release of 160±0 µg/ml compared to 60±20 µg/ml for t-PA alone (p=0.007). In 8 h-old clots, FDP release with laser plus t-PA was 160±0 µg/ml compared to 30±10 µg/ml with t-PA alone (p=0.0004).It was concluded that in vitro application of mid-infrared laser energy significantly enhances fibrinolysis in fibrin clots initially treated by t-PA. The in vitro interaction between mid-infrared laser and t-PA is energy dependent, however, at energy levels exceeding 75 J there is a plateau phenomenon in dose-response relationship. This wavelength photoacoustic energy also augments the decreased response of ageing clots to t-PA.

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BACKGROUND: Severe allograft coronary artery disease is a significant cause of death in heart transplant recipients. Percutaneous revascularization has thus far been attempted with balloon angioplasty and, to a lesser extent, with directional atherectomy. The new, investigational, solid-state pulsed-wave mid-infrared laser (holmium:YAG) can vaporize and remove atheromatous and thrombotic plaques. This mechanism of plaque ablation may be useful for allograft coronary artery disease associated with focal stenoses deemed unsuitable for standard balloon angioplasty, especially thrombus-containing lesions. METHODS: Five adult heart transplant recipients with severe focal stenoses related to allograft coronary artery disease underwent six laser angioplasty procedures. Laser catheters (2.1 microm, 250 to 600 mJ, 5 Hz) varying from 1.2 mm to 2.0 mm delivered 45 +/- 7.4 pulses (mean +/- SD). Five laser procedures were completed with adjunct balloon angioplasty and one with directional atherectomy. RESULTS: Laser success (defined as stenosis reduction > 20%, no cardiac catheterization laboratory or in-hospital major complication) was achieved in six of seven lesions (85%), and the overall (laser and adjunct balloon) procedural success rate was 100%. No major complications occurred. Laser-assisted angioplasty reduced mean stenosis from 90% +/- 3% to 9% +/- 11%. All five patients recovered and were discharged. Angiographic follow-up demonstrated a 50% restenosis rate. CONCLUSIONS: In selected heart transplant recipients laser-assisted angioplasty can provide safe and successful acute revascularization. Focal lesions considered "nonideal" for balloon angioplasty and, in particular, thrombotic lesions can benefit from application of this device; however, long-term reduction of restenosis rates is not expected from this modality.

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