Assessing coronary stenosis. Quantitative coronary angiography versus visual estimation from cine-film or pharmacological stress perfusion images

Visual judgment of stenosis severity from cine-film or single-photon emission computed tomographic dipyridamole perfusion images was compared to assessment of stenosis severity as measured with digital quantitative coronary angiography. Thirty patients with angiographically verified single-vessel disease underwent dipyridamole thallium stress testing within 90 days of angiography. RESULTS: A percent diameter stenosis of > or = 50%, a percent area stenosis of > or = 75%, and a stenotic flow reserve of < 3.75 measured by quantitative coronary angiography (CMS, version 1.1, Medis Inc.) corresponded to haemodynamically significant stenosis as evaluated by visual estimates from cine-film or perfusion images. Quantitative coronary angiography percent diameter stenosis (51.2% +/- 12.6%) correlated closely (r = 0.74) but underestimated significantly visual assessment of stenosis severity from cine-film (69.3% +/- 21.2%; P = 0.0001). However, quantitative coronary angiography percent area stenosis (74.7% +/- 11.7%) more closely reflected visual estimates from cine-film (P = 0.19). Quantitative coronary angiography stenotic flow reserve showed the highest positive and negative predictive value regarding visual estimates from cine-film (88%, 86%) or perfusion images (88%, 64%) followed by percent diameter stenosis (86%, 75% 86%, 56%) and percent area stenosis (87%, 80%, 87%, 60%), respectively. CONCLUSION: Evaluation of coronary lesions by quantitative coronary angiography corresponds closely with visual estimates from cine-film and haemodynamic significance as evaluated by dipyridamole perfusion images.     

Improvement of exercise capacity by sarpogrelate as a result of augmented collateral circulation in patients with effort angina

OBJECTIVES: The purpose of this study was to evaluate whether a serotonin blocker, sarpogrelate, improves exercise capacity as a result of vasodilation of coronary collateral channels in patients with effort angina. BACKGROUND: Serotonin has been reported to decrease coronary collateral blood flow by collateral vasoconstriction in a canine model, suggesting that platelet activation in feeding coronary arteries of the collateral network has the potential to cause collateral vasoconstriction. METHODS: The subjects consisted of 22 patients with effort angina and reproducible ischemic threshold (group A, 11 patients with thrombolysis in myocardial infarction (TIMI) grade 2 or 3 flow of the ischemia-related coronary artery and Rentrop's collateral index 0 or 1; group B, 11 patients with TIMI grade 0 or 1 flow and Rentrop's collateral index 2 or 3). We repeated the symptom-limited treadmill exercise test using the Balke-Ware protocol and exercise tetrofosmin myocardial perfusion scintigraphy with and without pretreatment with 200 mg orally administered sarpogrelate. Each exercise test was performed at 9:00 a.m. on different days. The order of tests with and without sarpogrelate was randomized. RESULTS: In group A, sarpogrelate increased neither exercise time at 0.1 mV ST depression nor double product at 0.1 mV ST depression. In contrast, in group B sarpogrelate increased the exercise duration at 0.1 mV ST depression from 181+/-112 (SD) to 248+/-131 s (p < 0.05) and also increased the double product at 0.1 mV ST depression by 21% (p < 0.01). The severity score using myocardial perfusion scintigraphy at the same workload was significantly (p < 0.01) decreased by 37% in group B, but not in group A (11%), due to the sarpogrelate treatment. CONCLUSIONS: Sarpogrelate augments flow reserve of the collateral circulation and improves exercise capacity in anginal patients with well-developed collaterals. These findings indicate that a serotonin blocker, sarpogrelate, is useful not only as an antiplatelet drugs, but as an antianginal drug.     

Transcutaneous ultrasound augments lysis of arterial thrombi in vivo

BACKGROUND: External ultrasound has a synergistic effect on thrombus disruption with thrombolytic agents in vitro. We hypothesized that transcutaneous ultrasound could augment thrombolysis in vivo. METHOD AND RESULTS: Thrombus formation was induced electrically in 48 pairs of iliofemoral arteries of 24 rabbits; arterial occlusions were documented angiographically. In 17 of 24 rabbits, 25000 units/kg streptokinase was then administered intravenously. The pairs of iliofemoral arteries were randomized to receive ultrasound treatment or no ultrasound treatment. Low-frequency (26 kHz) ultrasound (continuous wave, 18 W/cm2) was applied transcutaneously over the area of occlusion. In 7 of 24 rabbits, 14 thrombotically occluded iliofemoral arteries were exposed to ultrasound alone without streptokinase. The results were evaluated through the use of angiography (TIMI grade flow) and histopathology. After 30 +/- 10 minutes of activated sonication combined with intravenous streptokinase, 10 of 17 iliofemoral arteries (59%) treated with transcutaneous ultrasound were widely patent angiographically, with TIMI grade 3 flow. Histologically, the patent arteries had only minimal focal moral thrombus. The angiographic patency rate was significantly lower in the control groups: 1 of 17 arteries (6%) treated with streptokinase alone (P = .0012) and 1 of 14 arteries (7%) treated with ultrasound alone (P = .0036). CONCLUSIONS: In vivo transcutaneous ultrasound significantly augments lysis of thrombi with streptokinase in rabbit iliofemoral arteries.     

Angioplasty guidewire velocity: a new simple method to calculate absolute coronary blood velocity and flow

The Thrombolysis In Myocardial Infarction (TIMI) frame count is a relative index of coronary flow that measures time by counting the number of frames required for dye to travel from the ostium to a standardized coronary landmark in a cineangiogram filmed at a known speed (frames/s). We describe a new method to measure distance along arteries so that absolute velocity (length divided by time) and absolute flow (area x velocity) may be calculated in patients undergoing percutaneous transluminal coronary angiography (PTCA). After PTCA, the guidewire tip is placed at the coronary landmark and a Kelly clamp is placed on the guidewire where it exits the Y-adapter. The guidewire tip is then withdrawn to the catheter tip and a second Kelly clamp is placed on the wire where it exits the Y-adapter. The distance between the 2 Kelly clamps outside the body is the distance between the catheter tip and the anatomic landmark inside the body. Velocity (cm/s) may be calculated as this distance (cm) divided by TIMI frame count (frames) x film frame speed (frames/s). Flow (ml/s) may be calculated by multiplying this velocity (cm/s) and the mean cross-sectional lumen area (cm2) along the length of the artery to the TIMI landmark. In 30 patients, velocity increased from 13.9 +/- 8.5 cm/s before to 22.8 +/- 9.3 cm/s after PTCA (p <0.001). Despite TIMI grade 3 flow both before and after PTCA in 18 patients, velocity actually increased 38%, from 17.0 +/- 5.4 to 23.5 +/- 9.0 cm/s (p = 0.01). For all 30 patients, flow doubled from 0.6 +/- 0.4 ml/s before to 1.2 +/- 0.6 ml/s after PTCA (p <0.001). In the 18 patients with TIMI grade 3 flow both before and after PTCA, flow increased 86%, from 0.7 +/- 0.3 to 1.3 +/- 0.6 ml/s (p = 0.001). Distance along coronary arteries (length) can be simply measured using a PTCA guidewire. This length may be combined with the TIMI frame count to calculate measures of absolute velocity and flow that are sensitive to changes in perfusion. TIMI grade 3 flow is composed of a range of velocities and flows.     

The relationship between the electrocardiographic pattern with TIMI flow class and ejection fraction in patients with a first acute anterior wall myocardial infarction

AIMS: The aim of this study was to assess the value of the electrocardiogram in predicting the patency of the left anterior descending artery and left ventricular ejection fraction in patients with a first acute anterior wall myocardial infarction at discharge from the coronary care unit. METHOD: We included 116 consecutive patients with an acute anterior myocardial infarction who had undergone coronary angiography and left ventriculography before discharge from the coronary care unit (7th to 10th day). The ST segment, either elevated or isoelectric (< 1 mm), and the T wave (positive or negative) in precordial leads V2-V4 were analysed and compared to the TIMI flow from each patient. RESULTS: Out of 69 patients with negative T waves, 38 (55%) had TIMI flow 3 compared with 20 (29%) and 11 (16%) with TIMI flow 2 and 0-1, respectively; and out of 47 patients with positive T waves seven (15%) had TIMI flow 3, 17 (36%) TIMI flow 2 and 23 (49%) TIMI flow 0-1 (P < 0.001). Out of 63 patients with an isoelectric ST segment, 35 (55%) had TIMI flow 3, 18 (29%) TIMI flow 2 and 10 (16%) TIMI flow 0-1, and out of 53 with ST segment elevation, 10 (19%) had TIMI flow 3, 19 (36%) TIMI flow 2 and 24 (45%) TIMI flow 0-1 (P < 0.001). When both parameters were analysed together, we found that in 46 patients with both isoelectric ST segments and negative T waves, 30 (65%) had TIMI flow 3 compared with two of 30 (7%) patients with ST segment elevation and positive T waves (P < 0.001). Patients with isoelectric ST segments had a better degree of left ventricular ejection fraction (57.8 +/- 14.1%) than patients with ST segment elevation (41.7 +/- 13%) (P < 0.001). Patients with positive and negative T waves had a similar left ventricular ejection fraction (49 +/- 18.1% vs 51 +/- 14%). CONCLUSION: We concluded that patients with a first acute anterior myocardial infarction and an electrocardiogram pattern of an isoelectric ST segment and a negative T wave have a higher incidence of a patent left anterior descending coronary artery than similar patients with ST segment elevation and a positive T wave. An isoelectric ST segment is also related to better left ventricular function.     

Relationship between the flow pattern and vasomotor reactivity in the ophthalmic artery, siphon and vessels within the circle of Willis in the unilateral internal carotid artery occlusion

The aim was to study a relationship between the flow pattern in the ophthalmic artery (OA), the siphon and vessels within the circle of Willis. 27 patients, 22 males and 5 females, mean age 63 +/- 15 years (SD) with unilateral occlusion of the internal carotid artery (ICA) were examined by 3-dimensional Transcranial Doppler scanner. Flow signals from the OA, the siphon and intracranial vessels were registered before and after i.v. injection of 1 g acetazolamide. Pathological flow pattern was found in 18 patients in the OA on the occluded side consisting of 12 retrograde and 6 isoelectric flow directions. After acetazolamide injection retrograde systolic velocities (SV) increased significantly (p < 0.01), but anterograde velocities remained unchanged as did 3 isoelectric flow patterns, 2 turned to retrograde and one to anterograde flow direction. In the siphon lower resting anterograde mean velocities (MV) were found on both sides (p < 0.05) compared to normal subjects. Six patients had the same retrograde flow as in the OA. After acetazolamide MV in the siphon increased (p < 0.01) only on the nonoccluded side. Baseline retrograde ophthalmic SV and MV in the siphon correlated (p < 0.01 and p < 0.05 respectively) with MV in the middle cerebral artery (MCA) according to linear regression analysis (r = 0.78 and 0.59 respectively). All patients, having impaired vasomotor reactivity (VMR) < or = 11% in the anterior cerebral artery (ACA) on the occluded side, had pathological flow pattern in the OA. Patients with greatest difference (delta) between MV in the ACA on the nonoccluded and occluded side had a tendency to anterograde flow (r = 0.56, p < 0.05). Pulsative index (PI) in the ACA on the occluded side was lowest in the category with retrograde flow in the OA (0.67 +/- 0.14) and differed (p < 0.05) from normals and from the category with isoelectric and anterograde flow. Correlation of retrograde flow direction in the OA and baseline MV in the MCA and low PI in the ACA on the occluded side indicates a supplying ophthalmic collateral to the anterior brain circulation. Impaired VMR in the ACA on the occluded side in connection with pathological flow pattern in the OA may reflect an exhaustion of the ACA as a supplying vessel.     

TRP trapped in fly signaling web

BACKGROUND: Recent reports indicate that myocarditis can be associated with acute myocardial ischemia and even myocardial infarction in patients with normal arteriograms. We therefore tested the hypothesis that patients with biopsy-proven myocarditis have endothelial dysfunction despite angiographically smooth epicardial coronary arteries. METHODS AND RESULTS: Graded concentrations of the endothelium-dependent vasodilator acetylcholine (10(-6) to 10(-4) mol/L) and for comparison, the non-endothelium-dependent vasodilator nitroglycerin (0.3 mg intracoronary), were infused into the left coronary arteries of 18 patients (mean age 47+/-9 years, 8 women and 10 men) with biopsy-proven myocarditis but without angiographically demonstrable coronary artery disease. Vascular responses were analyzed by quantitative coronary angiography. Three patients had an intact vasodilator response to acetylcholine concentrations of up to 10(-4) mol/L in all segments of the left coronary artery, with a mean dilatation of +9.9%+/-2%. In contrast, paradoxical constriction by acetylcholine occurred in 9 patients, who showed a mean change in coronary artery diameter of - 11%+/-3%. Six patients had no significant change in any segments in response to acetylcholine (-2.5%+/-4%). There was a significant inverse correlation between the number of T-lymphocytes in the myocardium and the response of the epicardial coronary arteries to acetylcholine (Pearson correlation coefficient -0.49, P=.03). CONCLUSIONS: It can be assumed that the process of myocarditis is associated with impairment of endothelium-dependent vasodilation in response to acetylcholine in most patients. Vasoconstriction in the presence of acetylcholine in myocarditis is likely to reflect an abnormality of endothelial function. Endothelial dysfunction of coronary arteries may explain the occurrence of myocardial ischemia in patients with myocarditis.     

Differential expression patterns of GABA transporters (GAT1-3) in the rat olfactory bulb

OBJECTIVES: This report used intravascular ultrasound and quantitative coronary angiography to explore the relation between lesion-associated calcium and risk factors, clinical presentation and angiographic severity of coronary artery stenoses. BACKGROUND: Coronary artery calcium is a marker for significant coronary atherosclerosis. Noninvasive procedures are being proposed as screening tests for coronary artery disease. Intravascular ultrasound identification of tissue calcium has been validated in vitro. METHODS: Independent chart review, preintervention intravascular ultrasound imaging and coronary angiography were used to study primary native vessel lesions in 1,442 patients. Target lesions and reference segments were evaluated according to previously published quantitative and qualitative methods. Results are presented as mean value +/- SD. RESULTS: Overall, 1,043 lesions contained target lesion calcium (72%); the arc of target lesion calcium was 110 +/- 109 degrees. Lesions with an ultrasound plaque burden > 0.75 or an angiographic diameter stenosis > 0.25 had a prevalence of calcium of at least 65%, with a mean arc > 100 degrees. Intermediate lesions had as much target lesion calcium as did angiographically severe lesions. Using multivariate linear regression analysis, patient age, stable (vs. unstable) angina and the intravascular ultrasound lesion site and reference segment plaque burden (but not the angiographic diameter stenosis) were the independent predictors of the arc of target lesion calcium (all p < 0.0001). CONCLUSIONS: Intravascular ultrasound analysis shows that coronary calcification correlates with plaque burden but not with degree of lumen compromise. Thus, the noninvasive detection of coronary calcium is predictive of future cardiac events, presumably because coronary calcification is a marker for overall atherosclerotic plaque burden. Coronary calcium increases with increasing patient age and is less common in unstable lesion subsets.     

The effect of hemodilution with stroma-free hemoglobin and dextran on collateral perfusion of ischemic myocardium in the dog

The effect of hemodilution with stroma-free hemoglobin (SFH) solution was assessed on the collateral perfusion of acutely ischemic myocardium in anesthetized dogs. A similar protocol was used in three groups: one hour following occlusion of the LAD coronary artery, a rapid exchange-transfusion was performed and the changes were followed for the subsequent two hours. Group I was hemodiluted with SFH, in Group II whole blood was reinfused, and Group III was hemodiluted with dextran 70. Following the exchange-transfusions, blood flow to the ischemic zone (15 +/- 3 micrometer microspheres) increased in all groups, but only marginally so in Group II (23 +/- 17%). The greatest increments were seen in the SFH-hemodiluted group (Group I) in which endocardial flow increased by 83 +/- 29% (p less than .05) and epicardial flow increased by 45 +/- 21%; these resulted in the greatest improvements in oxygen delivery. Significant increments in blood flow were seen in Group III, as well, but oxygen delivery was less adequate. Group I also exhibited the lowest output of CPK from the heart and was the only one in which indices of left ventricular performance (dP/dt and EDP) were returned to the pre-occlusion level. these findings suggest the possibility that reduction of blood viscosity by dilution with SFH improves collateral perfusion of the ischemic myocardium.     

Can we provide reperfusion therapy to all unselected patients admitted with acute myocardial infarction?

OBJECTIVES: This study sought to assess the maximal rate of acute Thrombolysis in Myocardial Infarction (TIMI) grade 3 patency that can be achieved in unselected patients. BACKGROUND: Early and complete (TIMI grade 3 flow) reperfusion is an important therapeutic goal during acute myocardial infarction. However, thrombolysis, although widely used, is often contraindicated or ineffective. The selective use of primary and rescue percutaneous transluminal coronary angioplasty (PTCA) may increase the number of patients receiving reperfusion therapy. METHODS: A cohort of 500 consecutive unselected patients with acute myocardial infarction were prospectively treated using a patency-oriented scheme: Thrombolysis-eligible patients received thrombolysis (n = 257) and underwent 90-min angiography to detect persistent occlusion for treatment with rescue PTCA. Emergency PTCA (n = 193) was attempted in patients with contraindications to thrombolysis, cardiogenic shock or uncertain diagnosis and in a subset of patients admitted under "ideal conditions." A small group of patients (n = 38) underwent acute angiography without PTCA. Conventional medical therapy was used in 12 patients with contraindications to both thrombolysis and PTCA. RESULTS: Ninety-eight percent of patients received reperfusion therapy (thrombolysis, PTCA or acute angiography), and angiographically proven early TIMI grade 3 patency was achieved in 78%. Among patients with TIMI grade 3 patency, thrombolysis alone was the strategy used in 37%, emergency PTCA in 40% and rescue PTCA after failed thrombolysis in 15%; spontaneous patency occurred in 8%. CONCLUSIONS: Reperfusion therapy can be provided to nearly every patient (98%) with acute myocardial infarction. Rescue and direct PTCA provided effective early reperfusion to patients in whom thrombolysis failed or was excluded.     

Synergistic effects of some pairs of antioxidants and related agents on mouse leukaemia L5178Y cell growth in-vitro

Intravenous injections or infusions of perfluorocarbon-exposed sonicated dextrose albumin microbubbles were given 2.4 +/- 1.6 days following acute myocardial infarction to 45 consecutive patients. Patients were divided into 3 groups: patients with Thrombolysis In Myocardial Infarction (TIMI) grade 3 angiographic flow but persistent myocardial contrast defects by echocardiography (no reflow), patients with TIMI 3 flow and myocardial contrast enhancement (reflow), and patients with TIMI grade 0 to 2 flow in the infarct vessel. Thirty-five patients had TIMI 3 flow at the time of contrast study. Of these, 25 had evidence of reflow with intravenous contrast, whereas 10 (29%) still had contrast defects. At follow-up, end-systolic volume index decreased significantly in patients who exhibited reflow (21 +/- 8 ml/m2 at baseline to 18 +/- 8 ml/m2 at follow-up; p = 0.04), whereas those with no reflow had a significant increase (26 +/- 9 ml/m2 at baseline to 32 +/- 9 ml/m2 at follow-up; p = 0.006). A persistent contrast defect in the infarct zone demonstrated with intravenous ultrasound contrast following restoration of TIMI grade 3 flow in the infarct vessel identified patients likely to have deterioration in both regional and global systolic function.     

Redistribution of collateral blood flow from necrotic to surviving myocardium following coronary occlusion in the dog

Early changes in collateral blood flow after acute coronary occlusion may be critical for survival of ischemic myocardium. We used 15-mum radioactive microspheres to study myocardial blood flow in thoracotomized dogs 10 minutes and 24 hours after occlusion of the left anterior descending coronary artery (LAD). The ischemic area was delineated by dye injected into the distal artery, and indentification of potentially ischemic samples was confirmed by a newly developed technique in which microspheres were excluded from the normally perfused LAD. Layers were separated into necrotic or normal as defined by gross inspection and confirmed by histological examination and creatine phosphokinase assay. Infarction always involved endocardial layers and extended toward the epicardium. Average myocardial blood flow in 48 necrotic samples from 16 dogs either remained low (less than 0.05 ml/min g-1) or declined, falling from 0.11 +/-0.02(SE) at 10 minutes to 0.05 +/-0.01 ml/min g-1 at 24 hours (P less than 0.001). In contrast, in the 32 normal-appearing samples which were ischemic at 10 minutes, flow increased from 0.24 +/-0.03 to 0.39 +/-0.04 ml/min g-1 (P less than 0.001). Flow in control myocardium was 1.43 +/-0.12 and 1.04 +/-0.07 ml/min g-1, respectively. Peripheral mean coronary arterial pressure increased from 26 +/- 3 to 35 +/- 3 mm Hg, largely because of enlargement of collateral vessels; collateral conductance calculated from retrograde flow in 14 dogs increased from 0.023 +/- 0.005 after occlusion to 0.051 +/- 0.009 ml/min mm Hg-1 24 hours later (P less than 0.001). Thus, coronary collateral blood flow is redistributed from necrotic endocardial layers to surviving epicardial ones. In combination with a developing collateral supply this process may be essential for sparing myocardium after coronary occlusion.     

Coronary collateral circulation behaviour and myocardial viability in chronic total occlusion treated with coronary angioplasty

AIMS: We explored the role of microcirculation integrity following the chronic occlusion of an infarct-related artery to assess the behaviour of collateral circulation during and after reperfusion by coronary angioplasty METHODS AND RESULTS: Eighteen patients with a proximally occluded left anterior descending artery and firm evidence of intercoronary collateral circulation were studied with selective coronary angiography and selective intracoronary myocardial contrast echocardiography, before coronary angioplasty, and at 5 and 15 min and 12 h later. Myocardial enhancement during myocardial contrast echocardiography was evaluated with a semiquantitative score (0-3), which was correlated to basal and 6 months' regional left ventricular wall motion results. 16/18 procedures were successfully performed; four patients with an inadequate acoustic window were excluded. Restenosis was evident at the 6 months' follow-up in two patients. Basal myocardial contrast echocardiography indicated that 81/192 segments from the left anterior descending coronary artery and 90/192 from the right coronary artery were perfused; no perfusion was observed in 21 segments either before or after coronary angioplasty. After coronary angioplasty, the angiographic intercoronary collateral circulation immediately disappeared, and myocardial contrast echocardiography revealed that there was a progressive reduction of segments perfused by the right coronary artery and an increase in segments perfused by the left anterior descending coronary artery. Regional left ventricular wall motion analysis demonstrated that there was abnormal motion in 51/192 segments. There was no improvement in segments with score 0 and abnormal motion after 6 months (100% sensitivity), but 16/17 segments with score 3 did show an improvement (98% specificity). The predictive value of intermediate scores (1-2) in detecting long-term improvement, was only 43%. CONCLUSION: These data show that the adaptive mechanism observed in the behaviour of epicardial and microvascular circulation after reperfusion of a chronic occluded infarct-related artery can vary. In addition, this study clearly shows that microvascular integrity detected by myocardial contrast echocardiography can provide myocardial viability.     

Trypsin-like enzymes during fertilization in the shrimp Rhynchocinetes typus

OBJECTIVE: To determine factors affecting postoperative pulmonary circulation in patients with major systemic-to-pulmonary collateral arteries. METHODS: A total of 48 patients underwent biventricular repair subsequent to unifocalization at ages in the range 1-34 years. The preparative procedures consisted of ligation of the collateral arteries in 6, plasty to the pulmonary arteries using no artificial materials in 12 and extensive reconstruction using heterologous pericardial tubes in 30. The number of the pulmonary vascular segments unifocalized was 9-18 (16 +/- 3). The amount of flow draining via residual minute systemic-to-pulmonary collaterals measured at the time of repair was 4-58% (24 +/- 16%) of the total perfusion by the cardiopulmonary bypass machine. RESULTS: This value was 40 +/- 16% in 5 patients dying in the short term after repair. The number of segments was nine or ten after unifocalization in 2 of these. Another 4 patients died in the longer term, 3 of these with CATCH 22 syndrome dying because of pulmonary hypertension. Postoperative catheterization demonstrated mean pulmonary arterial pressures in the range 8-40 (21 +/- 9) mmHg and pulmonary resistance in the range 1.7-10 (5.0 +/- 2.1) units/m2. Pulmonary resistance was correlated statistically to age at repair (r = 0.77), the number of pulmonary vascular segments (r = -0.41) and to percent collateral flow (r = 0.48). The use of a heterologous pericardial tube for unifocalization was also related probably to higher pulmonary resistance. CONCLUSION: It is essential to accomplish effective unifocalizations followed by earlier definitive repair so as to establish better pulmonary circulation.     

Role of angiographically identifiable thrombus on long-term luminal renarrowing after coronary angioplasty: a quantitative angiographic analysis

BACKGROUND: Experimental studies suggest that mural thrombus may be involved in postangioplasty restenosis. The aim of our study was to examine the role of angiographically identifiable thrombus in the clinical situation. METHODS AND RESULTS: The study population comprised 2950 patients (3583 lesions). The presence of angiographically identifiable thrombus either before or after the procedure was defined as the presence of a generalized haziness or filling defect within the arterial lumen. Restenosis was assessed by both a categorical (> 50% diameter stenosis at follow-up) and a continuous approach (absolute and relative losses). The study population included 160 lesions with and 3423 lesions without angiographically identifiable thrombus. The categorical restenosis rate was significantly higher in lesions containing angiographically identifiable thrombus: 43.1% versus 34.4%, P < .01; relative risk, 1,449; CI, 1.051 to 1.997. The absolute and relative losses were also higher in lesions containing angiographically identifiable thrombus (absolute loss, 0.43 +/- 0.66 versus 0.32 +/- 0.52; relative loss, 0.16 +/- 0.26 versus 0.13 +/- 0.21; both P < .05). The higher restenosis in these lesions was due primarily to an increased incidence of occlusion at follow-up angiography in this group: 13.8% versus 5.7%, P < .001. When lesions that went on to occlude by the time of follow-up angiography were excluded from the analysis, the restenosis rate between the two groups was similar by both the categorical (34.1% versus 30.4%, P=NS; relative risk, 1.183; CI, 0.824 to 1.696) and continuous (absolute loss, 0.23 +/- 0.46 versus 0.24 +/- 0.42, P=NS; relative loss, 0.09 +/- 0.17 versus 0.09 +/- 0.16, P=NS) approaches. CONCLUSIONS: Our results indicate that the presence of angiographically identifiable thrombus at the time of the angioplasty is associated with higher restenosis. The mechanism by which this occurs is through vessel occlusion at follow-up angiography. Measures aimed at improving outcome in this group of patients should be focused in this direction.     

Electrophysiologic characteristics and anatomical complexities of accessory atrioventricular pathways with successful ablation of anterograde and retrograde conduction at different sites

INTRODUCTION: Catheter ablation may eliminate anterograde and retrograde accessory pathway conduction at closely adjacent but anatomically discrete sites. However, the mechanisms of this discrepancy, the electrophysiologic and anatomical characteristics, and information about systematic study from a large patient population are not available. The purpose of this study was to investigate the electrophysiologic characteristics and anatomical complexities of the accessory pathway in which anterograde and retrograde conduction was successfully ablated at different sites. METHODS AND RESULTS: Thirty-eight (10.9%) patients (19 men and 19 women; mean age 37 +/- 2.4 years) fulfilling the criteria of having separate ablation sites for anterograde and retrograde conduction were designated as group I, and the other 310 patients (215 men and 95 women; mean age 47 +/- 0.6 years) were designated as group II. The patients with right-sided free-wall pathways had the highest incidence (18.6%) of separate ablation sites. The anatomical distance between anterograde and retrograde directions (left anterior oblique view, 13 +/- 0.6 vs 8 +/- 0.9 mm, P < 0.01; right anterior oblique view, 17 +/- 0.6 vs 5 +/- 0.7 mm, P < 0.01), and incidence of conduction impairment in one direction after successful ablation of another direction (15% vs 78%, P < 0.05) differed significantly between left and right free-wall pathways. The mean distances obtained from left (7 +/- 0.4 vs 14 +/- 0.4 mm, P < 0.05) and right (7 +/- 1.1 vs 15 +/- 0.9 mm, P < 0.05) anterior oblique views were shorter in patients who had impairment of conduction properties than those in patients without impaired conduction after successful ablation of one direction. CONCLUSIONS: This study showed that anatomical and functional dissociation of the accessory pathway into anterograde and retrograde components was possible. Further study on the relation between electrophysiologic and pathologic characteristics would be helpful to confirm these findings.     

Sixty-minute alteplase protocol: a new accelerated recombinant tissue-type plasminogen activator regimen for thrombolysis in acute myocardial infarction

OBJECTIVES: Our aim was to design and evaluate a new and easily administered recombinant tissue-type plasminogen activator (rt-PA) regimen for thrombolysis in acute myocardial infarction (AMI) based on established pharmacokinetic data that improve the reperfusion success rate. BACKGROUND: Rapid restoration of Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow is a primary predictor of mortality after thrombolysis in AMI. However, TIMI grade 3 patency rates 90 min into thrombolysis of only 50% to 60% indicate an obvious need for improved thrombolytic regimens. METHODS: Pharmacokinetic simulations were performed to design a new rt-PA regimen. We aimed for a plateau tissue-type plasminogen activator (t-PA) plasma level similar to that of the first plateau of the Neuhaus regimen. These aims were achieved with a 20-mg rt-PA intravenous (i.v.) bolus followed by an 80-mg i.v. infusion over 60 min (regimen A). This regimen was tested in a consecutive comparative trial in 80 patients versus 2.25 10(6) IU of streptokinase/60 min (B), and 70 mg (C) or 100 mg (D) of rt-PA over 90 min. Subsequently, a confirmation trial of regimen A in 254 consecutive patients was performed with angiographic assessment by independent investigators of patency at 90 min. RESULTS: The comparative phase of the trial yielded, respectively, TIMI grade 3 and total patency (TIMI grades 2 and 3) of 80% and 85% (regimen A), 35% and 50% (B), 50% and 55% (C) and 60% and 70% (D). In the confirmation phase of the trial, regimen A yielded 81.1% TIMI grade 3 and 87.0% total patency. At follow-up angiography 7 (4.1%) of 169 vessels had reoccluded. In-hospital mortality rate was 1.2%. Nadir levels of fibrinogen, plasminogen and alpha2-antiplasmin were 3.6 +/- 0.8 mg/ml, 60 +/- 21% and 42 +/- 16%, respectively (mean +/- SD). Fifty-seven patients (22.4%) suffered from bleeding; 3.5% needed blood transfusions. CONCLUSIONS: The 60-min alteplase thrombolysis in AMI protocol achieved a TIMI grade 3 patency rate of 81.1% at 90 min with no indication of an increased bleeding hazard; it was associated with a 1.2% overall mortality rate. These results are substantially better than those reported from all currently utilized regimens. Head to head comparison with established thrombolytic regimens in a large-scale randomized trial is warranted.     

Effect of platelet activation on coronary collateral blood flow

BACKGROUND: The platelet products thromboxane A2 and serotonin have been shown to cause constriction of well-developed coronary collateral vessels. This study was performed to determine whether intravascular platelet activation produced with platelet activating factor (PAF) can cause a decrease in coronary collateral blood flow. METHODS and RESULTS: Collateral vessel growth was induced by embolization of a hollow stainless steel plug into the left anterior descending coronary artery (LAD) of adult dogs. The animals were returned to the laboratory 3 to 6 weeks later for surgical instrumentation and measurement of collateral blood flow. Collateral flow was assessed by measuring retrograde blood flow from the cannulated collateral-dependent artery. PAF (10 nmol) was injected into the left main coronary artery to allow products of platelet activation to reach collateral vessels arising from the left coronary system. PAF caused a vasoconstrictor response, which became maximal 3 minutes after injection and resulted in a 40.3+/-7.4% decrease in retrograde blood flow (32.1+/-2.1 to 19.6+/-3.2 mL/min; P<0.05). By 15 minutes after the PAF injection, both retrograde blood flow and transcollateral resistance had returned to normal. After pretreatment with the thromboxane A2 receptor antagonist SQ30, 741, the vasoconstrictor response to PAF was abolished and, in contrast to the decrease in retrograde blood flow from PAF alone, a weak vasodilator effect was unmasked. CONCLUSIONS: PAF caused a decrease in coronary collateral blood flow. This vasoconstrictor response required the participation of thromboxane A2.     

Assessment of myocardial viability with 99mTc-sestamibi tomography before coronary bypass graft surgery: correlation with histopathology and postoperative improvement in cardiac function

BACKGROUND: Assessment of myocardial viability by 99mTc-sestamibi remains controversial. Accordingly, we investigated the use of sestamibi as a marker of myocardial viability, defined by histopathology, and for predicting improvement of myocardial function after coronary artery bypass graft surgery (CABG). METHODS AND RESULTS: 99mTc-sestamibi perfusion tomography and radionuclide angiography were performed within 2 days before CABG in 21 patients with > or = 75% stenosis of the left anterior descending coronary artery and resting anterior wall dyssynergy. During CABG, transmural myocardial biopsies were obtained from the dyssynergic anterior wall and from normal myocardial segments to determine the extent of viable myocardium by histopathology. Improvement of regional left ventricular function was evaluated by radionuclide angiography at 6 to 8 weeks after CABG. There was a good correlation (r=.85, P<.001) between the quantified sestamibi activity and the extent of viable myocardium determined morphometrically. Among 21 biopsied dyssynergic myocardial segments, 11 improved their function after CABG and 10 failed to improve. Biopsied segments with improved postoperative function had significantly higher sestamibi activity (81+/-5% versus 49+/-16%, P<.0001) and significantly lower extent of interstitial fibrosis (7+/-4% versus 31+/-21%, P=.0002) than segments that failed to improve. A 55% threshold of 99mTc-sestamibi activity had positive and negative predictive values of 79% and 100%, respectively, for recovery of function after CABG in the biopsied segments. CONCLUSIONS: Myocardial 99mTc-sestamibi activity correlates well with the extent of viable myocardium and predicts improvement in regional function after CABG. This lends support to the use of sestamibi as a myocardial viability agent.