Integrated microscopy techniques for comprehensive pathology evaluation of an implantable left atrial pressure sensor.

The safety and efficacy of an implantable left atrial pressure (LAP) monitoring system is being evaluated in a clinical trial setting. Because the number of available specimens from the clinical trial for histopathology analysis is limited, it is beneficial to maximize the usage of each available specimen by relying on integrated microscopy techniques. The aim of this study is to demonstrate how a comprehensive pathology analysis of a single specimen may be reliably achieved using integrated microscopy techniques. Integrated microscopy techniques consisting of high-resolution gross digital photography followed by micro-computed tomography (micro-CT) scanning, low-vacuum scanning electron microscopy (LVSEM), and microground histology with special stains were applied to the same specimen. Integrated microscopy techniques were applied to eight human specimens. Micro-CT evaluation was beneficial for pinpointing the location and position of the device within the tissue, and for identifying any areas of interest or structural flaws that required additional examination. Usage of LVSEM was reliable in analyzing surface topography and cell type without destroying the integrity of the specimen. Following LVSEM, the specimen remained suitable for embedding in plastic and sectioning for light microscopy, using the positional data gathered from the micro-CT to intersect areas of interest in the slide. Finally, hematoxylin and eosin (H&E) and methylene blue staining was deployed on the slides with high-resolution results. The integration of multiple techniques on a single specimen maximized the usage of the limited number of available specimens from the clinical trial setting. Additionally, this integrated microscopic evaluation approach was found to have the added benefit of providing greater assurance of the derived conclusions because it was possible to cross-validate the results from multiple tests on the same specimen.

Synergistic interactions of physiologic increments of glucagon, epinephrine, and cortisol in the dog: a model for stress-induced hyperglycemia.

To evaluate the role of anti-insulin hormone actions and interactions in the pathogenesis of stress-induced hyperglycemia, the counterregulatory hormones, glucagon, epinephrine, and cortisol were infused alone as well as in double and triple combinations into normal conscious dogs in doses that were designed to simulate changes observed in severe stress. Infusion of glucagon, epinephrine, or cortisol alone produced only mild or insignificant elevations in plasma glucose concentration. In contrast, the rise in plasma glucose produced by combined infusion of any two counterregulatory hormones was 50-215% greater (P < 0.005-0.001) than the sum of the respective individual infusions. Furthermore, when all three hormones were infused simultaneously, the increment in plasma glucose concentration (144+/-2 mg/dl) was two- to fourfold greater than the sum of the responses to the individual hormone infusions or the sum of any combination of double plus single hormone infusion (P < 0.001). Infusion of glucagon or epinephrine alone resulted in a transient rise in glucose production (as measured by [3-(3)H]glucose). While glucagon infusion was accompanied by a rise in glucose clearance, with epinephrine there was a sustained, 20% fall in glucose clearance. When epinephrine was infused together with glucagon, the rise in glucose production was additive, albeit transient. However, the inhibitory effect of epinephrine on glucose clearance predominated, thereby accounting for the exaggerated glycemic response to combined infusion of glucagon and epinephrine. Although infusion of cortisol alone had no effect on glucose production, the addition of cortisol markedly accentuated hyperglycemia produced by glucagon and(or) epinephrine primarily by sustaining the increases in glucose production produced by these hormones. The combined hormonal infusions had no effect on beta-hydroxybutyrate concentration. It is concluded that (a) physiologic increments in glucagon, epinephrine, and cortisol interact synergistically in the normal dog so as to rapidly produce marked fasting hyperglycemia; (b) in this interaction, epinephrine enhances glucagon-stimulated glucose output and interferes with glucose uptake while cortisol sustains elevations in glucose production produced by epinephrine and glucagon; and (c) these data indicate that changes in glucose metabolism in circumstances in which several counterregulatory hormones are elevated (e.g., "stress hyperglycemia") are a consequence of synergistic interactions among these hormones.

Elevated troponin I level on admission is associated with adverse outcome of primary angioplasty in acute myocardial infarction.

BACKGROUND: In patients with acute myocardial infarction (AMI) undergoing thrombolytic therapy, an elevated troponin level on admission is associated with a lower reperfusion rate and a complicated clinical course. Whether an elevated troponin level on admission similarly predicts an adverse outcome in patients undergoing primary angioplasty is currently unknown and was investigated in the present study. METHODS AND RESULTS: Cardiac troponin I (cTnI) was determined on admission in 110 consecutive patients with AMI associated with ST-segment elevation or left bundle branch block who underwent primary angioplasty. Fifty-four patients (49%) had an elevated cTnI (>/=0.4 ng/mL) on admission. In patients with elevated cTnI, primary angioplasty was less likely to achieve TIMI 3 flow (as classified by the Thrombolysis in Myocardial Infarction trial) in univariate (76% versus 96%, P:=0.03) or in multivariate (odds ratio 0.1, 95% CI 0.02 to 0.54) analysis. Patients with elevated cTnI were more likely to develop congestive heart failure (23% versus 9%, P:<0.05) and death, heart failure, or shock (30% versus 9%, P:=0.006). Elevated cTnI remained a significant predictor of the composite end point after controlling for other clinical data that were available early in the course, including time to presentation and angiographic results (relative risk 5.2, 95% CI 1.03 to 26.3). During a follow-up of 426+/-50 days, elevated admission cTnI was a predictor of cardiac mortality (11% versus 0%, P:=0.012), adverse cardiac events (cardiac mortality or nonfatal reinfarction; 19% versus 5.4%, P:=0.04), and adverse cardiac events plus target vessel revascularization (32% versus 14%, P:=0.054). CONCLUSIONS: In patients with ST-segment elevation AMI, an elevated cTnI on admission is associated with an increased risk of primary angioplasty failure and a more complicated clinical course.

Effects of beta(-)-emitting (188)Re balloon in stented porcine coronary arteries: an angiographic, intravascular ultrasound, and histomorphometric study.

BACKGROUND: Restenosis within stents may be prevented by ionizing radiation from an intravascular source. METHODS AND RESULTS: A liquid beta(-) radiation ((188)Re) balloon was evaluated in a randomized and blinded porcine coronary model of stent restenosis. Group A pigs (n=17) received 0,16, 22, or 29 Gy at 0.5-mm depth, followed by stenting. Restenosis was quantified by angiography, ultrasound, and histomorphometry at 30 days. Group B (n=7) was stented first and then treated with 0 or 29 Gy with follow-up at 60 days. There was a measurable effect at 16 Gy, which improved with increasing doses. At 29 Gy, the histological stenotic area was reduced by 67% (22% versus 66% in controls, P<0.001). Radiation after stenting was equally effective; the stenotic area was reduced (21% versus 65%, P<0.001). At 16 Gy, the vessel just distal to the stent was significantly smaller than control vessels because of intimal thickening (P=0.003). Radiated vessels had distinctive histology consisting of neointimal fibrin and reduced smooth muscle cells and matrix (P<0.0001). CONCLUSIONS: (188)Re balloon brachytherapy in porcine coronary arteries results in dose-dependent and injury-independent inhibition of stent restenosis for up to 60 days. Restenosis at the borders of the irradiated zone is a potential limitation and may be related to underdosing. Brachytherapy with the (188)Re balloon appears to be safe and feasible for clinical studies.

Stent implantation of saphenous vein graft aorto-ostial lesions in patients with unstable ischemic syndromes: immediate angiographic results and long-term clinical outcome.

OBJECTIVES: This study examined the immediate angiographic and long-term clinical results of stenting saphenous vein graft aorto-ostial stenosis at a single center. BACKGROUND: Data on the feasibility, safety and short- and long-term clinical results of stent implantation in aorto-ostial lesions in patients with unstable angina are limited. METHODS: Palmaz or Palmaz-Schatz stents were deployed in 29 patients (mean [+/- SD] age 70 +/- 10 years) with complex (B2 or C) vein graft aorto-ostial lesion morphology. All patients had angina at rest; 23 (79%) had a previous myocardial infarction; and 13 (45%) had two previous bypass operations (mean graft age 9 +/- 5 years). Mean left ventricular ejection fraction was 42 +/- 13%. RESULTS: Thirty-two stents were deployed in 25 new and 4 restenotic aorto-ostial lesions. Ten additional stents were implanted in five patients for eight lesions other than at ostial locations. Stent implantation was successful in all patients. There was no death, Q wave myocardial infarction, bypass surgery or stent thrombosis in the first 30 days. Stenting improved minimal lumen diameter from 0.7 +/- 0.5 mm (95% confidence interval [CI] 0.5 to 0.8) to 3.3 +/- 0.5 mm (CI 3.2 to 3.5) and percent diameter stenosis from 80 +/- 13% (CI 75% to 85%) to 1 +/- 12% (CI -3% to 6%) (p < 0.001 for both variables). Immediate loss from recoil was 0.2 +/- 0.2 mm (CI 0.2 to 0.3), corresponding to a percent recoil of 7 +/- 5% (CI 5% to 9%). Clinical follow-up in all patients at a mean of 11 +/- 8 months revealed that 27 patients (94%) were free of death or myocardial infarction. Bypass surgery and balloon angioplasty were required in one (3%) and two (6%) patients, respectively. In 21 (88%) of the remaining 24 patients, symptoms were lessened by two or more symptom classes. CONCLUSIONS: Palmaz or Palmaz-Schatz stent implantation for saphenous vein graft aorto-ostial stenosis has a high likelihood of immediate success and is associated with a large immediate gain in lumen diameter. Thirty-day and long-term adverse event rates are low. These data suggest that stenting saphenous vein graft aorto-ostial lesions is an acceptable therapeutic option in selected elderly patients with unstable angina and large-diameter vessels.

Implantation and recovery of temporary metallic stents in canine coronary arteries.

OBJECTIVES: The purpose of this study was to test the feasibility of implanting and retrieving a heat-activated recoverable temporary stent and to determine its effect on the angiographic, gross and histologic appearance of a normal coronary artery wall. BACKGROUND: Permanent coronary stenting is associated with a significant incidence of thrombosis, bleeding and vascular complications. These may be avoided by temporarily stenting for a period of hours to several days. METHODS: Seventy-eight stents constructed from the shape-memory nickel-titanium alloy nitinol were deployed by balloon expansion in the coronary arteries of 28 dogs and left in place for up to 6 months. Thirty minutes to 1 week after implantation, 70 stents were recovered by flushing the coronary arteries with 3 to 5 ml of 75 degrees C lactated Ringer solution, with collapse of the stent over a recovery catheter and subsequent withdrawal. RESULTS: All stents were successfully recovered and removed percutaneously. Mean vessel diameter after stenting was 12 +/- 6% (p < 0.05) greater than baseline diameter. Mean vessel diameter after stent removal remained enlarged (6 +/- 3%, p < 0.05). No angiographic or gross evidence of thrombosis, dissection, embolization, migration or spasm was associated with implantation or recovery. Microscopic examination revealed minor intimal injury in 40 segments (51%). Microscopic focal medial necrosis was associated with mural platelet-fibrin thrombus in 23 stented segments (29%) and media was interrupted in 7 (9%). CONCLUSIONS: This study demonstrates the feasibility of a new method of temporary stenting that uses the thermoelastic properties of nitinol to permit reliable recovery of the stent in normal canine coronary arteries.

Contribution of inadequate compensatory enlargement to development of human coronary artery stenosis: an in vivo intravascular ultrasound study.

OBJECTIVES: This intravascular ultrasound study sought to examine to what extent native coronary artery stenosis is accompanied by vessel wall thickening or inadequate compensatory enlargement (relative vessel constriction), or both. BACKGROUND: In human femoral arteries, inadequate compensatory enlargement is reported to be a paradoxic mechanism for the development of severe arterial lumen narrowing. However, it is unclear in human coronary arteries whether inadequate compensatory enlargement contributes to the development of critical arterial stenosis. METHODS: Thirty-five primary coronary artery lesions from 30 patients (19 men, 11 women; mean [+/- SD] age 65 +/- 13 years) were imaged by intravascular ultrasound. The vessel cross-sectional area and lumen area were measured, and the wall area (vessel cross-sectional area minus lumen area) was calculated at the lesion site and at the proximal and distal reference sites. We defined compensatory enlargement to be present when the vessel cross-sectional area at the lesion site was larger than that at the proximal reference site, inadequate compensatory enlargement when the vessel cross-sectional area at the lesion site was smaller than that at the distal reference site and intermediate remodeling when the vessel cross-sectional area at the lesion site was intermediate between the two reference sites. RESULTS: Compensatory enlargement was observed in 19 (54%) of 35 lesions, inadequate compensatory enlargement in 9 (26%) of 35 and intermediate remodeling in 7 (20%) of 35. In the inadequate compensatory enlargement group, reduction of the vessel cross-sectional area contributed to 39% of lumen reduction. CONCLUSIONS: Compensatory enlargement commonly (54%) occurs at stenotic coronary lesions. However inadequate compensatory enlargement results in a substantial amount (39%) of the lumen area reduction in 26% of primary coronary artery lesions.

Long-term follow-up of a high risk cohort after stent implantation in saphenous vein grafts.

OBJECTIVES: We sought to provide short- and long-term clinical outcomes of a high risk cohort treated with stents in saphenous vein grafts (SVGs). BACKGROUND: Data on the long-term outcome of SVG stenting in high risk patients are limited. METHODS: Johnson & Johnson stents were implanted in the SVGs of 186 patients (302 stents, 244 lesions). Ninety percent of patients presented with myocardial infarction (MI) or unstable angina (mean +/- SD ejection fraction [EF] 44 +/- 11%, patient age 71 +/- 9 years, graft age 9.4 +/- 5 years). Using a risk score classification, 155 patients (83%) were defined as high risk for repeat surgical repair or angioplasty. RESULTS: The procedural success rate was 97.3%, with 2.7% major complications (death, Q wave MI, coronary artery bypass graft surgery [CABG]). Clinical follow-up was obtained in 177 patients (mean 19.1 +/- 13.5 months, range 7 to 59). Event rates were 10% for death; 9% for MI; 11% for repeat CABG; and 15% for repeat angioplasty (total events 45%). Kaplan-Meier estimated survival and event-free survival at 4 years were 0.79 +/- 0.06 and 0.29 +/- 0.07, respectively. Predictors of death were congestive heart failure (p < 0.01) and EF <44% (p < 0.05). Predictors of combined events of death, MI and CABG were low EF (p < 0.01) and high SVG age (>10 years, p < 0.01). There were 66 revascularization procedures (35% of patients), 24% of which were in nontarget lesions. Fifty-three percent of the cardiac events occurred during the first year of follow-up. Of the 160 survivors, 36% were free of angina, 49% were in Canadian Cardiovascular Society functional class I or II, and 15% were in class III or IV. Sixty-nine percent of patients were in class I or II according to the Specific Activity Scale, and 31% of patients were in class III or IV. CONCLUSIONS: Balloon-expandable stent implantation in the SVGs of high risk patients is associated with a low early complication rate. Expected survival rates are good, as are the anginal and functional classifications, but there is a high rate of recurrent events and need for repeat revascularization. Vein graft stenting is an acceptable palliative option in many high risk patients.

Computer analysis of Doppler color flow mapping images for quantitative assessment of in vitro fluid jets.

To determine the ability of Doppler color flow mapping to accurately and reproducibly assess the flow volume and kinetic energy of in vitro fluid jets, a Doppler color flow mapping system was interfaced with an image processing computer. An aliasing correction algorithm was used to extend the upper limit of measurable velocity to 184 cm/s. Images were analyzed for jet area (equal to the total number of image pixels) and jet energy (equal to the sum of all pixel velocities squared), both integrated over all frames of the injection and in single maximal frames. The Doppler flow mapping area and energy measurements were compared with known flow volume and delivered kinetic energy, and the effects of four experimental variables (orifice area, gain setting, chamber compliance and chamber size) were evaluated. Jet area correlated nonlinearly with flow volume and was markedly affected by each of these experimental variables, increasing by 40 to 150% from the smallest to the largest orifice size, 15 to 94% with the highest versus the lowest gain setting, 1 to 54% with greater chamber compliance and 7 to 70% in the large versus the small chamber. In contrast, jet energy correlated linearly with delivered kinetic energy up to 350,000 ergs, at which point velocities started to exceed the extended velocity range and second wrap aliasing occurred. The relation was not affected by orifice area, gain or compliance, and was only minimally affected by chamber size.(ABSTRACT TRUNCATED AT 250 WORDS)

Synchronized coronary venous retroperfusion for support and salvage of ischemic myocardium during elective and failed angioplasty.

To determine the safety and efficacy of synchronized coronary venous retroperfusion during brief periods of ischemia, 30 patients undergoing angioplasty of the left anterior descending coronary artery were studied. Each patient underwent a minimum of two angioplasty balloon inflations. Alternate dilations were supported with retroperfusion; the unsupported inflations served as the control inflations. Synchronized retroperfusion was performed by pumping autologous femoral artery blood by means of an electrocardiogram-triggered retroperfusion pump into the great cardiac vein through a triple lumen 8.5F balloon-tipped retroperfusion catheter inserted percutaneously from the right internal jugular vein. Clinical symptoms, hemodynamics and two-dimensional echocardiographic wall motion abnormalities were analyzed. Retroperfusion was associated with a lower angina severity score (0.8 +/- 1 vs. 1.2 +/- 1) and delay in onset of angina (53 +/- 31 vs. 37 +/- 14 s; p less than 0.05) compared with the control inflations. The magnitude of ST segment change was 0.11 +/- 0.14 mV with retroperfusion and 0.16 +/- 0.17 mV without treatment (p less than 0.05). The severity of left ventricular wall motion abnormality was also significantly (p less than 0.01) reduced with retroperfusion compared with control (0.7 +/- 1.4 [hypokinesia] vs. -0.3 +/- 1.6 [dyskinesia]). There were no significant changes in hemodynamics, except in mean coronary venous pressure, which increased from 8 +/- 3 mm Hg at baseline to 13 +/- 6 mm Hg with retroperfusion. Four patients required prolonged retroperfusion for treatment of angioplasty-induced complications. The mean retroperfusion duration in these patients was 4 +/- 2 h (range 2 to 7). In the three patients who underwent emergency bypass surgery, the coronary sinus was directly visualized during surgery and found to be without significant injury. There were no major complications. Minor adverse effects were transient atrial fibrillation (n = 2), jugular venous catheter insertion site hematomas (n = 4) and atrial wall staining (n = 1), all of which subsided spontaneously. Thus, retroperfusion significantly reduced and delayed the onset of coronary angioplasty-induced myocardial ischemia and provided effective supportive therapy for failed and complicated angioplasty.

Percutaneous excimer laser coronary angioplasty: results in the first consecutive 3,000 patients. The ELCA Investigators.

OBJECTIVES: We report the comprehensive results of the first consecutive 3,000 patients treated in an excimer laser coronary angioplasty registry. BACKGROUND: Excimer laser coronary angioplasty involves the use of a pulsed, 308-nm ultraviolet laser transmitted by optical fibers to reduce coronary stenoses. Preliminary reports have described safety and efficacy profiles in small numbers of patients. METHODS: Patients were enrolled in a prospective, nonrandomized manner. The catheters used were 1.3, 1.6, 2.0, 2.2 and 2.4 mm in diameter, at energy densities up to 70 mJ/mm2. Procedures were performed by standard angioplasty technique with conventional guide catheters. RESULTS: Seventy-five percent of patients were male, 68% were in Canadian Cardiovascular Society functional class III or IV and the cohort included 3,592 lesions. Procedural success (final stenosis < or = 50% without in-hospital Q wave myocardial infarction, coronary artery bypass surgery or death) was 90% and did not differ between the first 2,000 and the last 1,000 patients treated. There was no significant difference in success or complication rates with respect to lesion length, nor were there differences between selected complex and simple lesions. Complications included in-hospital bypass surgery (3.8%), Q wave myocardial infarction (2.1%) and death (0.5%). Coronary artery perforation occurred in 1.2% of patients (1% of lesions) but significantly decreased to 0.4% in the last 1,000 patients (0.3% of lesions). Angiographic dissection occurred in 13% of lesions, transient occlusion in 3.4% and sustained occlusion in 3.1%. Comprehensive lesion morphologic data collected in the latter portion of the study showed the procedure predominantly limited to American College of Cardiology-American Heart Association type B2 and C lesions, with no significant difference in short-term outcome between groups. CONCLUSIONS: Excimer laser angioplasty can be safely and effectively applied, even in a variety of complex lesions not well suited for percutaneous transluminal coronary angioplasty. These types may include aorto-ostial, long lesions, total occlusions crossable with a wire, diffuse disease and vein grafts. Most recent data show a trend for the selection of predominantly complex lesions and a reduction in the incidence of perforation. This procedure may broaden the therapeutic window for the interventional treatment of selected complex coronary artery disease.

Fibrinolytic therapy of St. Jude valve thrombosis under guidance of digital cinefluoroscopy.

Fibrinolytic therapy is an alternative to urgent reoperation for patients with St. Jude prosthetic valve thrombosis, but requires an accurate method for repeated assessment of prosthetic function. Since the St. Jude valve is not well visualized by conventional cinefluoroscopy, digital subtraction techniques were developed that improved visualization of the value and allowed assessment of leaflet separation and velocity. A 74 year old woman with prosthetic valve thrombosis 5 years after St. Jude aortic valve placement had an opening angle of 58 degrees (normal range 10 to 13; n = 8) with a maximal opening velocity of 1.37 degrees/ms (normal range 2.46 to 2.93). The closing angle was 125 degrees (normal range 120 to 127) with a maximal closing velocity of 1.38 degrees/ms (normal range 2.24 to 3.60). The patient received 250,000 U of streptokinase intravenously, then 100,000 U/h for 72 hours. Improvement in auscultatory findings occurred at 12 hours; repeat digital cinefluoroscopy showed an opening angle of 20 degrees with a maximal velocity of 2.77 degrees/ms, and a closing angle of 126 degrees with a maximal velocity of 1.91 degrees/ms. Digital cinefluoroscopy 4 weeks after discharge on warfarin and dipyridamole therapy was unchanged. There have been no thromboembolic complications after 6 months of follow-up. Thus, digital cinefluoroscopy is a new noninvasive technique that permits accurate measurement of normal and abnormal St. Jude leaflet function. Intravenous streptokinase dissolution of prosthetic valve thrombosis under digital cinefluoroscopic guidance may be an acceptable alternative to emergency reoperation. The frequency and significance of residual subclinical leaflet dysfunction after fibrinolytic therapy and the indications for elective reoperation require further evaluation.

Effect of early systemic thrombolytic therapy on left ventricular mural thrombus formation in acute anterior myocardial infarction.

To determine the effects of intravenous thrombolytic therapy on the development of left ventricular (LV) thrombi after anterior acute myocardial infarction (MI), 22 consecutive patients were prospectively studied with radionuclide ventriculography and serial 2-dimensional echocardiography: 12 patients who presented within 3 hours after MI received intravenous streptokinase (STK) followed by intravenous heparin as thrombolytic treatment and 10 patients who were seen later than 3 hours after the onset of symptoms served as controls. The LV ejection fraction was less than 0.40 in 3 of 12 patients who received STK and in 7 of 10 who did not (control subjects) (p less than 0.05). Apical dyssynergy was observed in all 12 patients treated with STK and in 9 of 10 control subjects. LV thrombi were presented within 36 hours of MI in 5 control subjects. Thrombi were detected by 2-dimensional echocardiography in 7 of 10 control subjects and in 1 of 12 patients who received intravenous STK (p less than 0.005). Early thrombolytic therapy with intravenous STK and heparin appears to significantly reduce the frequency of LV thrombus formation despite persistence of apical dyssynergy.

Lack of sustained clinical improvement in an elderly population after percutaneous aortic valvuloplasty.

The hemodynamic and clinical results following 25 percutaneous aortic valvuloplasty (PAV) procedures on 24 patients are reported. The mean aortic gradient decreased from 66 +/- 23 to 40 +/- 15 mm Hg (p less than 0.001) and the mean valve area increased from 0.5 +/- 0.17 to 0.7 +/- 0.26 cm2 (p less than 0.001). Although the aortic gradient determined by both Doppler and direct measurement correlated well before PAV, the Doppler gradients determined 24 +/- 48 hours after the procedure were significantly higher than the directly measured gradients at the time of PAV. Ninety-two percent of patients were New York Heart Association class III or IV before PAV. Of the remaining 12 patients, 6 (50%) were classified as class II, 2 (17%) were class III, and 4 were (33%) class IV. Necropsy examination of the patient who died shortly after valvuloplasty revealed localized hematoma and tear in the anterior mitral valve leaflet. Smaller initial valve areas yielded smaller valve areas after PAV. Patients with greater valve areas following PAV showed greater functional improvement. Only 7 patients (29%) had at least 1 functional class improvement at the final follow-up. PAV can be performed relatively safely in elderly, moribund patients, although sustained improvement of functional status is not common. In this population, PAV should be limited to patients severely symptomatic in whom surgery is not an acceptable option.

Usefulness of a prototype directional catheter for excimer laser coronary angioplasty in narrowings unfavorable for conventional excimer or balloon angioplasty.

We report clinical and angiographic results in 53 patients with 57 significant coronary or saphenous vein graft narrowings treated with directional excimer laser angioplasty. The target vessels were the left main (1%), anterior descending (32%), circumflex (19%), right coronary artery (39%), and vein grafts (9%). Lesions were morphologic class B1 (18%), B2 (79%), or C (3%), with 40 de novo and 17 restenotic lesions. Adjunctive balloon angioplasty was used in 53 lesions (93%). Mean pre- and postprocedural minimal lumen diameters were 0.6 +/- 0.3 and 1.9 +/- 0.7 mm (p < 0.001), corresponding to a mean diameter stenosis of 72 +/- 20% and 27 +/- 16%. Procedural success rate was 91%. Cumulative risk of death, Q-wave myocardial infarction, or emergency bypass operation was 9% (5 patients). Of patients who had a successful laser procedure, 28 (60%) with 30 lesions underwent angiographic follow-up at 6 +/- 3 months after the procedure. Restenosis rates (> 50% diameter restenosis or acute gain loss) were 37% and 23%, respectively. Four patients underwent bypass, 3 angioplasty, and 1 patient died from cancer. This study demonstrates the feasibility of directional application of laser energy to selected unfavorable narrowings for conventional excimer laser or balloon angioplasty. Further evaluation of this device using the now standard saline infusion technique is necessary to establish its ultimate role as a primary interventional device.

Quantitative severity of stress thallium-201 myocardial perfusion single-photon emission computed tomography defects in one-vessel coronary artery disease.

The relation between the quantitative myocardial perfusion defect severity of exercise thallium-201 single-photon emission computed tomography (SPECT) and the quantitative degree of coronary stenosis was examined in 18 patients with 1-vessel disease (> or = 50% diameter stenosis), and abnormal thallium-201 SPECT. A total of 26 vessels were analyzed. Thallium-201 SPECT quantitative defect severity score was derived by summing the number of pixels in a coronary territory in which counts fell below the normal mean and multiplied by the number of SDs by which they fell below the normal mean. The thallium-201 defect severity score was significantly (p < 0.001) related to the maximal percent luminal diameter narrowing (r = 0.93), percent area narrowing (r = 0.89), absolute stenotic area (r = 0.79), and absolute stenotic diameter (r = 0.81). As expected, the strongest relation between thallium-201 defect severity and quantitative angiographic indexes was in the low and high ranges of coronary stenosis, with more variability and lower correlation coefficients (percent diameter: r = 0.75, p < 0.02, percent area stenosis: r = 0.63, p < 0.05) in the middle ranges (50 to 80% diameter stenosis). This observation is likely to be due to the complex flow characteristics across stenotic lesions. The findings suggest that in a select population, thallium-201 defect severity is potentially useful for noninvasive characterization of the functional severity of coronary artery stenosis and may complement coronary angiography in predicting functionally significant stenosis.

Digital quantification eliminates intraobserver and interobserver variability in the evaluation of coronary artery stenosis.

A leading problem with subjective interpretation of coronary angiography is high intraobserver and interobserver variability. Four experienced angiographers independently determined percent diameter narrowing of 36 stenoses using 3 methods: by subjective analysis of single-frame cine film images (film), by subjective analysis of digitized nonenhanced single-frame images (digital), and by using a semiautomated digital caliper quantification system (Corona). The reproducibility of interpretations was assessed by comparison of estimated intraclass correlation coefficients. Digital and Corona readings correlated well with subjective interpretation of film (r greater than 0.85 for both). In contrast to Corona, the angiographers systematically overestimated the magnitude of stenoses in the intermediate (50 to 75%) range. Corona markedly improved intraobserver (p less than 0.005) and interobserver (p less than 0.001) reproducibility. Corona less frequently misclassified individual observations than did film when categories of less than 50%, 50 to 75% and more than 75% diameter stenosis were used (3.7% vs 31.5%, p less than 0.001). Our results suggest that digitization of a coronary angiogram in a 512 X 512 matrix has no significant adverse effects on the perception and quantification of stenosis by angiographers. Additionally, automatic measurement of coronary stenosis has 2 major advantages: It is accurate compared with a group of experienced angiographers and for the practical purpose of clinical decision-making, it eliminates intraobserver and interobserver variability.

Usefulness of intracoronary brachytherapy for in-stent restenosis with a 188Re liquid-filled balloon.

The objective of this randomized pilot trial with 21 patients was to evaluate the effectiveness of a rhenium-188 liquid-filled balloon system to prevent recurrent restenosis after percutaneous transluminal coronary angioplasty for in-stent restenosis. A significant benefit from brachytherapy was seen at 6-month repeat angiography, as well as during the clinical follow-up of 12 months.

Percutaneous excimer laser coronary angioplasty.

To determine the efficacy of percutaneous excimer laser coronary angioplasty as an adjunct or alternative to conventional balloon angioplasty, 55 patients were studied in a multicenter trial. These patients underwent the procedure using a modification of conventional balloon angioplasty technique. A first-generation, 1.6-mm diameter catheter constructed of 12 individual silica fibers concentrically arranged around a guidewire lumen was used. Catheter tip energy density varied from 35 to 50 mJ/mm2. The mean number of pulses delivered at 20 Hz was 1,272 +/- 1,345. Acute success was defined as a greater than or equal to 20% increase in stenotic diameter and a lumen of greater than or equal to 1 mm in diameter after laser treatment. Acute success was achieved in 46 of 55 (84%) patients. Adjunctive balloon angioplasty was performed on 41 patients (75%). The percent diameter stenosis as determined by quantitative angiography decreased from a baseline of 83 +/- 14 to 49 +/- 11% after laser treatment and to 38 +/- 12% in patients undergoing adjunctive balloon angioplasty. The mean minimal stenotic diameter increased from a baseline of 0.5 +/- 0.4 to 1.6 +/- 0.5 mm after laser treatment and to 2.1 +/- 0.5 mm after balloon angioplasty. There were no deaths and no vascular perforations. One patient (1.8%) required emergency coronary bypass surgery. These data suggest that excimer laser energy delivered percutaneously by specially constructed catheters can safely ablate atheroma and reduce coronary stenoses.

Epinephrine and the regulation of glucose metabolism: effect of diabetes and hormonal interactions.

Elevations of plasma epinephrine comparable to those observed in physiologic stress, cause a sustained 20--35 mg/dl elevation of plasma glucose in normal humans. This hyperglycemic action is due to a transient increase in hepatic glucose output as well as a reduction in the rate of glucose disposal which accounts for the persistence of hyperglycemia. The latter results from epinephrine-induced suppression of endogenous insulin secretion and, more importantly from a direct inhibitory effect on insulin-stimulated glucose utilization. In diabetes, the hyperglycemic effect of epinephrine is markedly accentuated. The enhanced rise in plasma glucose is due to an alternation in response of the liver to epinephrine. Despite infusion of insulin, epinephrine produces a sustained rather than transient elevation in hepatic glucose output in diabetic subjects. In contrast, the inhibitory effect of epinephrine on glucose utilization is unchanged by the diabetic state. In normal subjects, the hyperglycemic action of epinephrine is enhanced by simultaneous elevations of glucagon and cortisol. The former increases the magnitude, but not the duration, of the rise in hepatic glucose output induced by epinephrine. The latter, converts epinephrine's hepatic action from a transient to a sustained response. Our data thus suggest that marked hyperglycemia in normal subjects requires the concomitant elevation of multiple anti-insulin hormones, whereas such changes may occur in diabetes if any member of this group of hormones is increased. These findings may account for long-standing clinical observation that stress adversely affects blood glucose regulation to a much greater extent in diabetics as compared to normal subjects.