Decreased type II/type I TGF-beta receptor ratio in cells derived from human atherosclerotic lesions. Conversion from an antiproliferative to profibrotic response to TGF-beta1.

Atherosclerosis and postangioplasty restenosis may result from abnormal wound healing. The present studies report that normal human smooth muscle cells are growth inhibited by TGF-beta1, a potent wound healing agent, and show little induction of collagen synthesis to TGF-beta1, yet cells grown from human vascular lesions are growth stimulated by TGF-beta1 and markedly increase collagen synthesis. Both cell types increase plasminogen activator inhibitor-1 production, switch actin phenotypes in response to TGF-beta1, and produce similar levels of TGF-beta activity. Membrane cross-linking of 125I-TGF-beta1 indicates that normal human smooth muscle cells express type I, II, and III receptors. The type II receptor is strikingly decreased in lesion cells, with little change in the type I or III receptors. RT-PCR confirmed that the type II TGF-beta1 receptor mRNA is reduced in lesion cells. Transfection of the type II receptor into lesion cells restores the growth inhibitory response to TGF-beta1, implying that signaling remains responsive. Because TGF-beta1 is overexpressed in fibroproliferative vascular lesions, receptor-variant cells would be allowed to grow in a slow, but uncontrolled fashion, while overproducing extracellular matrix components. This TGF-beta1 receptor dysfunction may be relevant for atherosclerosis, restenosis and related fibroproliferative diseases.

Specific inhibition of eIF-5A and collagen hydroxylation by a single agent. Antiproliferative and fibrosuppressive effects on smooth muscle cells from human coronary arteries.

Restenosis occurs in 35% of patients within months after balloon angioplasty, due to a fibroproliferative response to vascular injury. These studies describe a combined fibrosuppressive/antiproliferative strategy on smooth muscle cells cultured from human primary atherosclerotic and restenotic coronary arteries and from normal rat aortas. L-Mimosine suppressed the posttranslational hydroxylation of the precursors for collagen and for eukaryotic initiation factor-5A (eIF-5A) by directly inhibiting the specific protein hydroxylases involved, prolyl 4-hydroxylase (E.C. 1.14.11.2) and deoxyhypusyl hydroxylase (E.C. 1.14.99.29), respectively. Inhibition of deoxyhypusyl hydroxylation correlated with a dose-dependent inhibition of DNA synthesis. Inhibition of prolyl hydroxylation caused a dose-dependent reduction in the secretion of hydroxyproline-containing protein and decreased the formation of procollagen types I and III. The antifibroproliferative action could not be attributed to nonspecific or toxic effects of mimosine, appeared to be selective for the hydroxylation step in the biosynthesis of the procollagens and of eIF-5A, and was reversible upon removal of the compound. The strategy of targeting these two protein hydroxylases has important implications for the pathophysiology of restenosis and for the development of agents to control fibroproliferative diseases.

Genomic instability in the type II TGF-beta1 receptor gene in atherosclerotic and restenotic vascular cells.

Cells proliferating from human atherosclerotic lesions are resistant to the antiproliferative effect of TGF-beta1, a key factor in wound repair. DNA from human atherosclerotic and restenotic lesions was used to test the hypothesis that microsatellite instability leads to specific loss of the Type II receptor for TGF-beta1 (TbetaR-II), causing acquired resistance to TGF-beta1. High fidelity PCR and restriction analysis was adapted to analyze deletions in an A10 microsatellite within TbetaR-II. DNA from lesions, and cells grown from lesions, showed acquired 1 and 2 bp deletions in TbetaR-II, while microsatellites in the hMSH3 and hMSH6 genes, and hypermutable regions of p53 were unaffected. Sequencing confirmed that these deletions occurred principally in the replication error-prone A10 microsatellite region, though nonmicrosatellite mutations were observed. The mutations could be identified within specific patches of the lesion, while the surrounding tissue, or unaffected arteries, exhibited the wild-type genotype. This microsatellite deletion causes frameshift loss of receptor function, and thus, resistance to the antiproliferative and apoptotic effects of TGF-beta1. We propose that microsatellite instability in TbetaR-II disables growth inhibitory pathways, allowing monoclonal selection of a disease-prone cell type within some vascular lesions.

Trends in use of anti-thrombotic agents and outcomes in patients with non-ST-segment elevation myocardial infarction (NSTEMI) managed with an invasive strategy.

OBJECTIVE: To analyze trends in utilization of anti-thrombotic agents (ATA) and in-hospital clinical outcomes in non-ST-elevation myocardial infarction (NSTEMI) patients managed with an invasive strategy from 2007 to 2010. METHODS & RESULTS: Using ACTION Registry(®)-GWTG™ data, we analyzed trends in use of ATA and in-hospital clinical outcomes among 64,199 NSTEMI patients managed invasively between 2007 and 2010. ATA included unfractionated heparin (UFH), low molecular weight heparin (LMWH), glycoprotein IIb/IIIa inhibitors (GPI) and bivalirudin. Although the proportion of NSTEMI patients treated with PCI within 48h of hospital arrival was similar in 2007 and 2010, percentage use of bivalirudin (13.4-27.3%; p<0.01) and UFH increased (60.0-67.5%, p<0.01), and that of GPI (62.3-41.0%; p<0.01) and LMWH (41.5-36.8%; p<0.01) declined. Excess dosing of UFH (75.9-59.3%, p<0.01), LMWH (9.6-5.2%; p<0.01) and GPI (8.9-5.9%, p<0.01) was also significantly lower in 2010 compared with 2007. Though in-hospital mortality rates were similar in 2007 and 2010 (2.3-1.9%, p=0.08), the rates of in-hospital major bleeding (8.7-6.6%, p<0.01) and non-CABG related RBC transfusion (6.3-4.6%, p<0.01) were significantly lower in 2010 compared with 2007. CONCLUSION: Compared with 2007, patients with NSTEMI, who were managed invasively in 2010 received GPI and LMWH less often and bivalirudin and UFH more frequently. There were sizeable reductions in the rates of excess dosing of UFH (though still occurred in 67% of patients), GPI and LMWH. In-hospital major bleeding complications and post-procedural RBC transfusion were lower in 2010 compared with 2007.

Angiogenesis gene therapy: phase I assessment of direct intramyocardial administration of an adenovirus vector expressing VEGF121 cDNA to individuals with clinically significant severe coronary artery disease.

BACKGROUND: Therapeutic angiogenesis, a new experimental strategy for the treatment of vascular insufficiency, uses the administration of mediators known to induce vascular development in embryogenesis to induce neovascularization of ischemic adult tissues. This report summarizes a phase I clinical experience with a gene-therapy strategy that used an E1(-)E3(-) adenovirus (Ad) gene-transfer vector expressing human vascular endothelial growth factor (VEGF) 121 cDNA (Ad(GV)VEGF121.10) to induce therapeutic angiogenesis in the myocardium of individuals with clinically significant coronary artery disease. METHODS AND RESULTS: Ad(GV)VEGF121.10 was administered to 21 individuals by direct myocardial injection into an area of reversible ischemia either as an adjunct to conventional coronary artery bypass grafting (group A, n=15) or as sole therapy via a minithoracotomy (group B, n=6). There was no evidence of systemic or cardiac-related adverse events related to vector administration. In both groups, coronary angiography and stress sestamibi scan assessment of wall motion 30 days after therapy suggested improvement in the area of vector administration. All patients reported improvement in angina class after therapy. In group B, in which gene transfer was the only therapy, treadmill exercise assessment suggested improvement in most individuals. CONCLUSIONS: The data are consistent with the concept that direct myocardial administration of Ad(GV)VEGF121.10 to individuals with clinically significant coronary artery disease appears to be well tolerated, and initiation of phase II evaluation of this therapy is warranted.

Ventricular entrapment of a Swan-Ganz catheter: a technique for nonsurgical removal.

Entrapment of a balloon-tipped flow-directed catheter by atrial sutures during open heart surgery is a rare but serious complication. Several methods have been used to free such catheters with nonsurgical techniques. A case of entrapment in the right ventricle after repair of a ventricular septal defect is presented and a method for percutaneous removal described.

Percutaneous coronary excimer laser-assisted angioplasty: initial multicenter experience in 141 patients.

Initial multicenter clinical experience with percutaneous coronary excimer laser-assisted angioplasty is described for 158 lesions in 141 patients. Using a xenon chloride (308 nm) excimer laser generator and 1.5 to 1.75 mm catheters, excimer laser angioplasty was attempted at 135 ns pulse width, 25 to 40 Hz repetition rate, 2 to 5 s laser delivery time and 30 to 60 mJ/mm2 energy fluence. Laser success (greater than 20% improvement in luminal diameter) was achieved in 138 (87%) of 158 lesions, with a reduction to less than 50% stenosis noted in 77 lesions (49%). Overall, laser-assisted balloon angioplasty success (less than 50% residual stenosis without major complication) was observed in 129 (91%) of 141 patients. Procedural complications (abrupt closure 1.3%, side branch occlusion 1.9%, intimal dissection 6.3%, embolization 1.3%, filling defect 1.3%, perforation 1.9% and spasm 1.3% and major complications (non-Q wave myocardial infarction 4.8%, emergency coronary bypass surgery 3.5% and death 0%) were infrequent and predominantly related to subsequent balloon angioplasty. In the early follow-up period (range 1 to 10 months, mean 7), 111 (79%) of the 141 patients remain asymptomatic, whereas symptoms have recurred in 27 (19%) and 3 patients (2.1%) have died. Thus, percutaneous coronary excimer laser angioplasty appears to be a feasible and safe procedure. Assessment of the impact of this technology on the acute complications of and restenosis rates after angioplasty awaits further follow-up analysis.

Excimer laser-facilitated balloon angioplasty of a nondilatable lesion.

Preliminary clinical experience with excimer laser coronary angioplasty shows that it is a safe and effective means of achieving nonsurgical coronary revascularization in selected patients but specific indications for its use are as yet undefined. In the present report a specific indication is proposed for the use of the excimer laser: to facilitate balloon inflation in a rigid stenosis that fails to dilate despite high balloon inflation pressures.

Percutaneous coronary laser thermal angioplasty.

Percutaneous coronary laser thermal angioplasty was successfully performed before conventional balloon angioplasty in a 55 year old white man with a 90% left anterior descending artery stenotic lesion and angina at rest (Canadian Heart Association class IV). The lesion was reduced to 50% residual stenosis using a 1.7 mm laser-heated metallic capped fiber and two pulses of 8 W of argon laser energy, each delivered for 5 seconds. With subsequent balloon angioplasty, the lesion was further decreased to 10% residual stenosis. The entire procedure was well tolerated without chest pain or burning, vessel perforation or spasm, thrombus formation or embolization of debris. The patient was free of pain at 1 month follow-up. This case demonstrates the feasibility of safely performing percutaneous coronary laser thermal angioplasty. Additional studies are indicated to determine the clinical role and potential benefits of coronary laser thermal angioplasty in relation to the established procedures of bypass surgery and conventional balloon angioplasty.

Experimental angioplasty: circumferential distribution of laser thermal energy with a laser probe.

A new laser probe that converts argon laser energy to heat in a metallic cap on a fiberoptic fiber was compared with a bare argon laser fiberoptic catheter system for the dissolution of atherosclerotic obstructions under fluoroscopic guidance in 24 atherosclerotic rabbits. Twelve animals were randomly assigned to receive treatment with either a bare fiberoptic system or a laser probe coupled to an argon laser. Both fibers had similar outer (0.9 mm) and core (400 mu) diameters. Pulses of 1 watt for 1 second's duration were delivered from the tip of the fiberoptic system, while pulses of 6 watts for 2 seconds' duration were delivered to the laser probe. The results of angiography indicated that widening of luminal stenosis was seen in only 2 of 12 animals treated with the fiberoptic system compared with 8 of 12 animals treated with the laser probe. Perforation of the vessel wall occurred more frequently with the fiberoptic fiber (9 of 12 animals) as compared with the laser probe (1 of 12 animals). Histologic examination of direct laser radiation with the fiberoptic fiber revealed a small localized laser defect along one side of the vessel wall associated with charring, a gradient of thermal injury and considerable thrombus formation. In contrast, those vessels treated with the laser probe showed histologic evidence of thermal injury distributed evenly around the entire luminal circumference. This was associated with minimal charring, a gradient of thermal injury and thinner, flatter thrombus formation. Carbonization of the metallic tip and adherence of atherosclerotic debris with secondary vessel tearing were potential adverse effects of the laser probe.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute biologic response to excimer versus thermal laser angioplasty in experimental atherosclerosis.

Vascular injury and platelet accumulation after balloon angioplasty are two potentially important triggers of the process of restenosis that may be minimized by the use of laser energy to ablate atherosclerotic plaque. The type of laser most suitable to achieve these goals remains unknown. Accordingly, angiographic and histologic studies and quantitative platelet deposition analysis were performed on 27 atherosclerotic rabbit iliac arteries randomized to treatment with excimer laser or thermal laser angioplasty. Excimer laser angioplasty was achieved with 35 to 40 mJ/mm2 of 308 nm xenon chloride irradiation delivered through a 4.5F catheter made of 13 concentrically arranged 200 microns fiber optics, at a repetition rate of 25 to 30 Hz and a pulse duration of 135 ns; thermal laser angioplasty was achieved with a 1.7 mm metal probe heated with 10 W of continuous wave argon laser energy. The baseline and post-laser luminal diameters of excimer laser-treated vessels (0.92 +/- 0.28 and 1.56 +/- 0.48 mm, respectively) were similar to those observed in thermal laser-treated vessels (1.05 +/- 0.44 and 1.61 +/- 0.41 mm, respectively). Perforation occurred in 4 (29%) of 14 thermal laser-treated arteries and in 0 of 13 excimer laser-treated arteries (p = 0.04); spasm was observed in only 1 thermal laser-treated vessel. On the basis of a quantitative histologic grading scheme (damage scores of 0 to 4), greater degrees of injury were measured in thermal versus excimer laser-treated vessels (2.4 +/- 1.0 versus 1.3 +/- 0.4, p = 0.009).(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary excimer laser angioplasty: reduced complications and indium-111 platelet accumulation compared with thermal laser angioplasty.

The relative safety and thrombogenicity of pulsed excimer and thermal laser angioplasty systems were compared in 20 normal coronary artery segments in a total of seven pigs. Using similar over the wire catheter systems and laser delivery periods of 3 to 5 s, thermal laser angioplasty was achieved with a 1.3 mm metal probe heated with 10 W of continuous argon laser energy and excimer laser angioplasty was performed with a 4.5F excimer laser catheter consisting of 13 concentrically arranged 200 microns fiber optics delivering 35 to 40 mJ/mm2 of xenon chloride (308 nm) excimer laser irradiation at a repetition rate of 25 to 30 Hz and a pulse duration of 120 ns. On angiography, the incidence of vessel perforation (1 in 10 versus 3 in 10) and abrupt vessel closure (0 in 10 versus 2 in 10) was less with excimer compared with thermal laser angioplasty. Macroscopically, there was a greater incidence of mural and occlusive thrombus formation after thermal laser than after pulsed excimer laser angioplasty. Histologic examination confirmed that this thrombogenicity was associated with greater charring and coagulation necrosis of the media. Quantitative indium-111-labeled platelet deposition was significantly increased after thermal laser angioplasty (median 87.2 x 10(6)/cm length) compared with excimer-treated (0.4 x 10(6)/cm length) or control (1.2 x 10(6)cm length) segments (p less than 0.001). Thus, excimer laser angioplasty was found to result in fewer complications and, as a consequence, less thrombosis and platelet accumulation than did thermal laser angioplasty.

Analysis of late lumen narrowing after excimer laser-facilitated coronary angioplasty.

OBJECTIVES: The purpose of this study was to analyze the quantitative angiographic factors affecting restenosis after excimer laser-facilitated coronary angioplasty. BACKGROUND: Restenosis after balloon angioplasty, directional atherectomy and coronary stenting has been analyzed using both dichotomous (> or = 50% diameter stenosis) and continuous (late lumen narrowing) end points, leading to the conclusion that achieving a large lumen diameter at the time of the procedure is associated with a lower risk of angiographic restenosis. METHODS: Quantitative angiographic measurements were made before treatment, after laser angioplasty, after adjunctive balloon angioplasty and at 6-month angiographic follow-up in 168 patients with 179 treated lesions. RESULTS: The immediate increase in lumen diameter (total acute gain 1.45 +/- 0.71 mm [mean +/- SD]) was due to the combination of laser treatment (0.79 +/- 0.61 mm) and subsequent adjunctive balloon angioplasty (0.66 +/- 0.55 mm). At follow-up, the minimal lumen diameter had decreased (late loss 0.71 +/- 0.84 mm), yielding an overall restenosis rate of 50% (defined dichotomously by > or = 50% diameter stenosis). Multivariable regression analyses showed that restenosis was related to vessel diameter, as well as minimal lumen diameter, achieved immediately after the procedure. CONCLUSIONS: Although the restenosis rates for the small vessels typically treated with excimer laser angioplasty were high, the lowest restenosis rates were seen in large vessels with the largest postprocedural minimal lumen diameters. The goal of this procedure should be to safely achieve the largest lumen possible with the combination of laser treatment and adjunctive balloon dilation.

Coronary artery perforation during excimer laser coronary angioplasty. The percutaneous Excimer Laser Coronary Angioplasty Registry.

OBJECTIVES: The aim of this study was to analyze the risk of vessel perforation during excimer laser angioplasty. BACKGROUND: Vessel perforation is a serious complication of angioplasty. METHODS: A total of 764 patients had 858 stenoses treated with excimer laser angioplasty. Laser catheters had a diameter of 1.4, 1.7 or 2 mm. Laser energy was delivered in pulses of 135 ns, at a frequency of 25 s-1 and at a fluence of 30 to 60 mJ/mm2. Follow-up angiography was requested for all patients who did not require emergency bypass surgery. RESULTS: In the 764 consecutive patients treated with excimer laser coronary angioplasty, vessel perforation occurred in 23 patients (3%). Nine patients had a major complication resulting directly from vessel perforation (cardiac tamponade, myocardial infarction or need for bypass surgery) and 14 had no clinical complications after successful sealing of the puncture site. No patient with a perforation died. Multivariate analysis showed that bifurcation lesions (odds ratio [OR] = 3.5; p = 0.049), diabetes mellitus (OR = 3.15; p = 0.029) and female gender (OR = 2.86; p = 0.013) were associated with an increased risk of vessel perforation. Lesions > 10 mm in length (OR = 0.45; p = 0.206), calcified stenoses (OR = 0.26; p = 0.088) and saphenous vein graft lesions (OR = 0.50; p = 0.295) were not at increased risk. Vessel perforation was seen in 10 (8.3%) of 120 lesions in which the laser catheter was equivalent in diameter to the target vessel (< or = 0.5 mm smaller in size) but in only 8 (1.5%) of 525 lesions in which the laser catheter was > 1 mm smaller than the target vessel (p = 0.001). CONCLUSIONS: Most lesions thought to be suitable for excimer laser treatment are not at increased risk of perforation. The complication may be avoided by improved patient and laser catheter size selection.

Immediate sealing of arterial puncture sites after cardiac catheterization and coronary angioplasty using a biodegradable collagen plug: results of an international registry.

OBJECTIVES: The aim of this study was to evaluate the safety and efficacy of a biodegradable collagen plug that has been developed to reduce the arterial compression time required to achieve hemostasis at the arterial puncture site after diagnostic and interventional coronary procedures. BACKGROUND: After diagnostic and interventional coronary catheterization procedures, local arterial compression is required to achieve hemostasis and complications may ensue, especially in patients on full anticoagulation. METHODS: Between March 1991 and July 1991, 252 patients admitted for routine coronary angiography or angioplasty to four large hospitals received such a hemostatic device immediately after the procedure. Hemostasis was achieved with collagen in 87% of patients after a mean compression time of 4.8 min. Time to hemostasis was independent of the heparin load. A total of 54 hematomas (21%) was reported; all but 2 resolved without additional treatment. Two patients had a severe hematoma, requiring blood transfusion, and two patients required surgery to repair a pseudoaneurysm. During a follow-up period of 4 weeks no severe late complications were reported. CONCLUSIONS: We conclude that the collagen plug appears to be a safe device to achieve hemostasis at the arterial puncture site, independent of anticoagulation.

A multicenter randomized trial comparing a percutaneous collagen hemostasis device with conventional manual compression after diagnostic angiography and angioplasty.

OBJECTIVES: A new percutaneous collagen hemostasis device was compared with conventional compression techniques after diagnostic catheterization and angioplasty. BACKGROUND: Peripheral vascular complications after diagnostic catheterization or more complex interventional procedures, as well as the discomfort of manual compression and prolonged bed rest, represent significant morbidity for invasive cardiac procedures. METHODS: A prospective, multicenter, randomized trial was designed to compare the hemostasis time in minutes and the incidence of vascular complications in patients receiving a vascular hemostasis device with those undergoing conventional compression techniques. RESULTS: After diagnostic catheterization, hemostasis time was significantly less with the vascular hemostasis device than with conventional manual compression (4.1 +/- 2.8 min [n = 90 patients] vs. 17.6 +/- 9.2 min [n = 75], p < 0.0001). This difference was greater in patients undergoing angioplasty and was unrelated to the anticoagulation status (4.3 +/- 3.7 min [n = 71 not receiving heparin], 7.6 +/- 11.6 min [n = 85 receiving heparin], 33.6 +/- 24.2 min [n = 134 control patients not receiving heparin], p < 0.0001 vs. control patients). The time from the start of the procedure to ambulation was slightly less after diagnostic catheterization in patients treated with the device (13.3 +/- 12.1 h vs. 19.2 +/- 17.8 h, p < 0.05). It was also less in patients who underwent angioplasty when the device was used after discontinuation of anticoagulation (23.0 +/- 11.1 h, without heparin), as compared with control compression techniques (32.7 +/- 18.8 h, p < 0.0001). Time to ambulation was even shorter (16.1 +/- 11.1 h, p < 0.0001) in patients in whom the device was placed immediately after angioplasty while they were still fully anticoagulated with a prolonged activated clotting time (336 +/- 85 s). There were no major complications (surgery or transfusion) after diagnostic catheterization and a low incidence of major complications in patients who underwent angioplasty (0.7% in control patients, 1.4% with the device without heparin, 1.2% with the device and heparin, p = NS). After angioplasty, there was a trend toward fewer hematomas when the device was used in the absence of heparin (4.2% vs. 9.7% in control patients, p = 0.14). CONCLUSIONS: A new vascular hemostasis device can significantly reduce the puncture site hemostasis time and the time to ambulation without significantly increasing the risk of peripheral vascular complications. The role of this technology in reducing complications, length of hospital stay and cost remains to be determined.

Percutaneous coronary excimer laser-assisted balloon angioplasty: initial clinical and quantitative angiographic results in 50 patients.

The initial clinical experience and quantitative angiographic results of percutaneous coronary excimer laser-assisted balloon angioplasty are described for 55 lesions in 50 patients. With use of a xenon chloride (308 nm) excimer laser generator and 1.5 to 1.75 mm catheters, excimer laser angioplasty was attempted at 135 ns pulse width, 25 to 40 Hz repetition rate, 2 to 5 s laser delivery time and 30 to 60 mJ/mm2 energy fluence. Laser success (greater than 20% reduction in absolute percent diameter stenosis) was achieved in 41 (75%) of 55 lesions, with 100% subsequent balloon angioplasty success (less than 50% residual stenosis). By quantitative digital caliper technique, the percent diameter stenosis (mean +/- SE) was reduced from 81 +/- 1% to 50 +/- 3% after excimer laser angioplasty (p less than 0.001) and to 20 +/- 1% after balloon angioplasty (p less than 0.001); minimal luminal diameter increased from 0.56 +/- 0.04 to 1.46 +/- 0.08 mm (p less than 0.001) and 2.03 +/- 0.07 mm (p less than 0.001), respectively. By videodensitometric techniques, the percent area stenosis decreased from 86 +/- 2% to 54 +/- 3% after excimer angioplasty (p less than 0.001) and to 26 +/- 3% after balloon angioplasty (p less than 0.001). There were no perforations, need for emergency bypass surgery or deaths. The overall incidence of abrupt closure (3.6%), dissection (1.8%), embolization (1.8%), filling defect (6%), myocardial infarction (5.5%), side branch occlusion (3.6%) or spasm (3.6%) was infrequent and more related to subsequent balloon angioplasty than to the laser procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiogenic shock complicating acute myocardial infarction--etiologies, management and outcome: a report from the SHOCK Trial Registry. SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK?

OBJECTIVES: This SHOCK Study report seeks to provide an overview of patients with cardiogenic shock (CS) complicating acute myocardial infarction (MI) and the outcome with various treatments. The outcome of patients undergoing revascularization in the SHOCK Trial Registry and SHOCK Trial are compared. BACKGROUND: Cardiogenic shock is the leading cause of death in patients hospitalized for acute MI. The randomized SHOCK Trial reported improved six-month survival with early revascularization. METHODS: Patients with CS complicating acute MI who were not enrolled in the concurrent randomized trial were registered. Patient characteristics were recorded as were procedures and vital status at hospital discharge. RESULTS: Between April 1993 and August 1997, 1,190 patients with CS were registered and 232 were randomized in the SHOCK Trial. Predominant left ventricular failure (78.5%) was most common, with isolated right ventricular shock in 2.8%, severe mitral regurgitation in 6.9%, ventricular septal rupture in 3.9% and tamponade in 1.4%. In-hospital Registry mortality was 60%, with ventricular septal rupture associated with a significantly higher mortality (87.3%) than all other categories (p < 0.01). The risk profile and mortality were lower for Registry patients who were managed with thrombolytic therapy and/or intra-aortic balloon counter-pulsation, coronary angiography, angioplasty and/or coronary artery bypass surgery. After adjusting for these differences, the extent to which survival was improved with early revascularization was similar to that observed in the randomized SHOCK Trial. CONCLUSIONS: In this prospective Registry the etiology of CS was a mechanical complication in 12%. The similarity of the beneficial treatment effect in patients undergoing early revascularization in the SHOCK Trial Registry and SHOCK Trial provides strong support for the generalizability of the SHOCK Trial results.

Acute complications of excimer laser coronary angioplasty: a detailed analysis of multicenter results. Coinvestigators of the U.S. and European Percutaneous Excimer Laser Coronary Angioplasty (PELCA) Registries.

OBJECTIVES: The aim of this study was to document and analyze the incidence and consequences of complications of excimer laser coronary angioplasty. BACKGROUND: Excimer laser coronary angioplasty has been reported to be a safe and feasible alternative or adjunct to conventional balloon angioplasty, but serious and unique complications have been observed. METHODS: Data on 1,595 interventions of excimer laser coronary angioplasty in 1,521 patients were analyzed, using a merged data base from the U.S. and European Percutaneous Excimer Laser Coronary Angioplasty (PELCA) registries. RESULTS: Procedural success was achieved in 89.3% of interventions. Stand-alone laser angioplasty was performed in 17.8% of interventions. Complications included dissection (22.0%), vasospasm (6.1%), filling defects (4.8%), abrupt reclosure (6.1%), embolization (2.3%), perforation (2.4%), arrhythmia (0.7%) and aneurysm formation (0.3%). Major complications were non-Q wave myocardial infarction (2.3%), Q wave myocardial infarction (1.0%), coronary artery bypass grafting (3.1%) and death (0.7%). Logistic regression analysis revealed correlation between dissections and the use of larger catheter size (p = 0.0005), high energy per pulse levels (p = 0.0001 for native vessels), lesion length > 10 mm (p = 0.001) and presence of a side branch (p = 0.01). The incidence of perforations was higher in women (p = 0.004), in treatment of total occlusions (p = 0.02) and in the presence of a side branch (p = 0.03). Fatal complications were correlated with patients with multivessel disease (p < 0.0001), patients with acute myocardial infarction (p = 0.0009) and older patients (> 70 years old, p = 0.004). The incidence of major complications decreased after performance of 50 laser angioplasty procedures at one institution (p = 0.02). CONCLUSIONS: This analysis defines both the learning curve and the profile of complications for excimer laser angioplasty and provides insight into the selection of appropriate patients and proper performance of the procedure.

Impact of thrombolysis, intra-aortic balloon pump counterpulsation, and their combination in cardiogenic shock complicating acute myocardial infarction: a report from the SHOCK Trial Registry. SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK?

OBJECTIVES: We sought to investigate the potential benefit of thrombolytic therapy (TT) and intra-aortic balloon pump counterpulsation (IABP) on in-hospital mortality rates of patients enrolled in a prospective, multi-center Registry of acute myocardial infarction (MI) complicated by cardiogenic shock (CS). BACKGROUND: Retrospective studies suggest that patients suffering from CS due to MI have lower in-hospital mortality rates when IABP support is added to TT. This hypothesis has not heretofore been examined prospectively in a study devoted to CS. METHODS: Of 1,190 patients enrolled at 36 participating centers, 884 patients had CS due to predominant left ventricular (LV) failure. Excluding 26 patients with IABP placed prior to shock onset and 2 patients with incomplete data, 856 patients were evaluated regarding TT and IABP utilization. Treatments, selected by local physicians, fell into four categories: no TT, no IABP (33%; n = 285); IABP only (33%; n = 279); TT only (15%; n = 132); and TT and IABP (19%; n = 160). RESULTS: Patients in CS treated with TT had a lower in-hospital mortality than those who did not receive TT (54% vs. 64%, p = 0.005), and those selected for IABP had a lower in-hospital mortality than those who did not receive IABP (50% vs. 72%, p < 0.0001). Furthermore, there was a significant difference in in-hospital mortality among the four treatment groups: TT + IABP (47%), IABP only (52%), TT only (63%), no TT, no IABP (77%) (p < 0.0001). Patients receiving early IABP (< or = 6 h after thrombolytic therapy, n = 72) had in-hospital mortality similar to those with late IABP (53% vs. 41%, n = 64, respectively, p = 0.172). Revascularization rates differed among the four groups: no TT, no IABP (18%); IABP only (70%); TT only (20%); TT and IABP (68%, p < 0.0001); this influenced in-hospital mortality significantly (39% with revascularization vs. 78% without revascularization, p < 0.0001). CONCLUSIONS: Treatment of patients in cardiogenic shock due to predominant LV failure with TT, IABP and revascularization by PTCA/CABG was associated with lower in-hospital mortality rates than standard medical therapy in this Registry. For hospitals without revascularization capability, a strategy of early TT and IABP followed by immediate transfer for PTCA or CABG may be appropriate. However, selection bias is evident and further investigation is required.