Steven E. Nissen

Intravascular ultrasound assessment of lumen size and wall morphology in normal subjects and patients with coronary artery disease.

BackgroundNecropsy studies demonstrate that coronary artery disease (CAD) is frequently complex and eccentric. However, angiography provides only a silhouette of the vessel lumen. Intravascular ultrasound is a new tomographic imaging method for evaluation of coronary dimensions and wall morphology. Few data exist regarding intravascular ultrasound in patients with CAD, and no data exist for subjects with normal coronaries. Methods and ResultsWe used a multielement 5.5F, 20-MHz ultrasound catheter to examine eight normal subjects and 43 patients with CAD. We assessed the safety of coronary ultrasound and the effect of vessel eccentricity on comparison of minimum luminal diameter by angiography and ultrasound. Normal and atherosclerotic wall morphology and stenosis severity were also evaluated by intravascular ultrasound. The only untoward effect was transient coronary spasm in five patients. At 33 sites in normal subjects, the lumen was nearly circular, yielding a close correlation between angiographic and ultrasonic minimum diameter (r = 0.92). At 90 sites in patients with CAD, ultrasound demonstrated a concentric cross section; correlation was also close (r = 0.93). However, at 72 eccentric sites, correlation was not as close (r = 0.77). For 41 stenoses, correlation between angiography and ultrasound for area reduction was moderate (r = 0.63). In normal subjects, wall morphology revealed a thin (0.30 mm or less) intimal leading edge and subadjacent sonolucent zone (0.20 mm or less). Patients with CAD exhibited increased thickness and echogenicity of the leading edge, thickened sonolucent zones, and/or attenuation of ultrasound transmission. ConclusionsThese data establish that intravascular ultrasound is feasible and safe and yields luminal measurements that correlate generally with angiography. Differences between angiographic and ultrasonic measures of lumen size in eccentric vessels probably reflect the dissimilar perspectives of tomographic and silhouette imaging techniques. Intravascular ultrasound provides detailed images of normal and abnormal wall morphology not previously possible in vivo.

Application of a new phased-array ultrasound imaging catheter in the assessment of vascular dimensions. In vivo comparison to cineangiography.

Tomographic imaging techniques such as ultrasound can provide important information in the evaluation of vascular anatomy. Recent technical advances have permitted fabrication of a small (1.83 mm), phased-array, intravascular ultrasonic imaging catheter capable of continuous real-time, cross-sectional imaging of blood vessels. We used this imaging catheter to compare intraluminal ultrasound with cineangiography in the measurement of vascular dimensions in animals and to assess the intraobserver and interobserver variability of the technique. Segmental deformation of vessel anatomy was produced by stenoses created with a tissue ligature or by balloon dilation. The mean value for measurements of vessel diameter was 5.6 mm by cineangiography and 5.7 mm by intravascular ultrasound. The correlation between cineangiography and ultrasound was close (r = 0.98). Mean cross-sectional area by angiography was 28.8 mm2 and 29.6 mm2 (r = 0.96) by ultrasound. Percent diameter reduction produced by the stenoses averaged 48.4% by cineangiography and 40.1% by ultrasound, and the two methods correlated closely (r = 0.89). Correlation between cineangiography and ultrasound for vessel diameter and area before balloon dilation was closer (r = 0.92 and 0.88) than after balloon dilation (r = 0.86 and 0.81). This difference reflected an increase in measured vessel eccentricity following balloon dilation. These data demonstrate that intravascular ultrasound is an accurate and reproducible method for measurement of vascular diameter and cross-sectional area in vivo. Intravascular ultrasound is capable of accurately identifying and quantifying segmental deformation of vascular dimensions produced by either stenoses or balloon dilation.

Value and limitations of computer analysis of digital subtraction angiography in the assessment of coronary flow reserve.

Conventional coronary angiography has significant limitations in quantifying the severity and functional significance of coronary stenoses. However, coronary reactive hyperemia is an excellent physiologic indicator of coronary reserve. Digital subtraction angiography offers the potential to analyze coronary blood flow dynamics quantitatively. Therefore we assessed the accuracy of digital angiographic methods to detect and quantify reductions in coronary flow reserve secondary to stenoses of varying magnitude in an experimental canine preparation. Studies were performed in nine anesthetized open-chest dogs with an electromagnetic flow (EMF) probe and two pneumatic occluders positioned on the left circumflex coronary artery. One occluder served to induce reactive hyperemia by temporary total occlusion, while the other served to produce variable gradations of stenosis. Digital angiography was performed after the subselective injection of contrast under basal conditions and during reactive hyperemia. Time-intensity curves were obtained from digital angiograms for both a coronary and a myocardial region of interest. Measurements included area under the curve, time to peak contrast, and contrast disappearance rate. An index of coronary reserve was computed as the ratio of hyperemic to basal measurements for each of these methods. Coronary blood flow ranged from 6.5 to 142 ml/min, with hyperemic to basal EMF flow ratios of 0.80 to 4.2:1. The index derived from contrast decay rate showed a poor correlation with EMF (r = .34). The correlation between measurements of time to peak myocardial contrast and coronary blood flow was r = .68 (y = 0.16 x + 0.97). The area under the time-intensity curve from a coronary region of interest showed a close correlation with coronary blood flow (y = 0.91 x + 0.1, r = .86). Thus estimates of coronary reserve by computer analysis of digital subtraction angiograms can yield information regarding the physiologic consequences of coronary stenoses.

Mechanism of acute myocardial infarction in patients with prior coronary artery bypass grafting and therapeutic implications

Although acute myocardial infarction (AMI) is usually due to thrombotic occlusion when involving a native coronary artery, the mechanism responsible for AMI in patients with previous coronary artery bypass grafting (CABG) is not well understood. Since knowledge of pathophysiology of AMI may alter subsequent management, angiograms obtained between 1 hour and 7 days of AMI (median 1 day) were reviewed in 50 patients greater than 1 year after CABG. The culprit vessel was identified by the presence of residual stenosis and/or thrombus in the vessel supplying the infarct zone or by reviewing previous angiograms. The infarct vessel was identified as a vein graft in 38 (76%) patients, the native vessel in 8 patients (16%) and could not be accurately determined in 4 patients (8%). Among the 38 vein grafts suspected as the infarct vessel, unequivocal angiographic evidence of residual thrombus (filling defect/persistent staining) was present in 31 (82%) and was greater than 2 cm in length in 15 patients. Successful reperfusion occurred in only 2 of 8 (25%) grafts after intravenous thrombolytic therapy. Intragraft thrombolysis with or without additional angioplasty was successful at restoring flow in 8 of 10 (80%) grafts. Data indicate that in patients who have undergone previous CABG, AMI is usually caused by thrombotic occlusion of a saphenous vein graft and that conventional intravenous thrombolytic therapy may be inadequate to restore flow. The large mass of thrombus and absent flow in the graft may require subselective drug infusion, a higher thrombolytic dose or a mechanical means of recanalization.

A prospective, randomized trial comparing combination half-dose tissue-type plasminogen activator and streptokinase with full-dose tissue-type plasminogen activator. Kentucky Acute Myocardial Infarction Trial (KAMIT) Group.

BACKGROUNDnThe potential benefits of combination thrombolytic agents in the treatment of myocardial infarction remain uncertain. In a small pilot study, we demonstrated that combining half-dose tissue-type plasminogen activator (t-PA) with streptokinase (SK) achieved a high rate of infarct vessel patency and a low rate of reocclusion at half the cost of full-dose t-PA.nnnMETHODS AND RESULTSnWe designed a prospective trial in which 216 patients were randomized within 6 hours of myocardial infarction to receive either the combination of half-dose (50 mg) t-PA with streptokinase (1.5 MU) during 1 hour or to the conventional dose of t-PA (100 mg) during 3 hours. Acute patency was determined by angiography at 90 minutes, and angioplasty was reserved for failed thrombolysis. Heparin and aspirin regimens were maintained until follow-up catheterization at day 7. Acute patency was significantly greater after t-PA/SK (79%) than with t-PA alone (64%, p less than 0.05). After angioplasty for failed thrombolysis, acute patency increased to 96% in both groups. Marked depletion of serum fibrinogen levels occurred after t-PA/SK compared with t-PA alone at 4 hours (37 +/- 36 versus 199 +/- 66 mg/dl, p less than 0.0001) and persisted 24 hours after therapy (153 +/- 66 versus 252 +/- 75 mg/dl, p less than 0.0001). Reocclusion (3% versus 10%, p = 0.06), reinfarction (0% versus 4%, p less than 0.05), and need for emergency bypass surgery (1% versus 6%, p = 0.05) tended to be less in the t-PA/SK group. Greater myocardial salvage was apparent in the t-PA/SK group as assessed by infarct zone function at day 7 (-1.9 SD/chord versus -2.3 SD/chord after t-PA alone, p less than 0.05). In-hospital mortality (6% versus 4%) and serious bleeding (12% versus 11%) were similar between the two groups.nnnCONCLUSIONSnThese results suggest that a less expensive regimen of half-dose t-PA with SK yields superior 90-minute patency and left ventricular function and a trend toward reduced reocclusion compared with the conventional dose of t-PA.

Application of intravascular ultrasound for detection and quantitation of coronary atherosclerosis.

Although angiography is widely utilized to assess the extent and severity of coronary artery disease (CAD), arteriography yields only a silhouette of the vessel lumen. Coronary intravascular ultrasound supplements angiography by providing a tomographic perspective of lumen geometry and vessel wall structure. Intracoronary ultrasound can now be performedin vivo utilizing small, flexible probes capable of negotiating tortuous vessles. We have performed coronary ultrasound in more than 100 patients, including a group of normal subjects, with no serious complications. Measurements of coronary lumen dimensions by angiography and ultrasound correlated closely for normal vessels (r=0.92) and for concentrically narrowed atherosclerotic vessels (r=0.90). However, the correlation between angiography and ultrasound was only fair for eccentrically narrowed arteries (r=0.79) and was poor following angioplasty (r=0.30). Coronary artery wall motion was measured by intravascular ultrasound and demonstrated significant differences between normal arteries (18% lumen area change) and atherosclerotic vessels (11% change). Coronary ultrasound demonstrated important differences in the structure of normal and altherosclerotic vessel walls. Arteries in normal subjects exhibited a thin intimal leading-edge echo (mean 0.20 mm) and subadjacent sonolucent zone (mean 0.12 mm). Atherosclerotic vessels typically demonstrated increased thickness of both structures and often exhibited dense fibrocalcific plaques that shadowed underlying anatomy. These ultrasound abnormalities were often present at angiographically normal sites. Several limitations of coronary intravascular ultrasound were apparent, including echo ‘dropout’, distortions produced by non-coaxial imaging, and inability to image small or severely narrowed vessels. Coronary intravascular ultrasound holds great promise for the detection and quantification of CAD in the clinical setting.

A new thrombolytic regimen for acute myocardial infarction using combination half dose tissue-type plasminogen activator with full dose streptokinase: A pilot study

Because a previous study utilizing a combination of recombinant tissue-type plasminogen activator (rt-PA) and urokinase demonstrated reduced reocclusion rates compared with rates obtained with rt-PA alone, this study was conducted to determine whether the combination of rt-PA and streptokinase might achieve similar results at reduced cost. Forty patients with acute myocardial infarction were treated with a 1 h infusion of rt-PA (50 mg) and streptokinase (1.5 million U) administered within 6 h (mean 3.6 +/- 1.2) of symptom onset. Emergency coronary arteriography revealed patency of the infarct-related artery in 30 (75%) of 40 patients. With the addition of coronary angioplasty in those who had unsuccessful thrombolytic reperfusion, the early patency rate was increased to 98%. In-hospital mortality rate (2.5%) and the incidence of significant bleeding requiring transfusion (15%) were low. Angiographically documented reocclusion of the infarct vessel occurred in 3 (8%) of 37 patients by day 7. Regional wall motion of the infarct zone improved by 0.9 +/- 0.9 SD/chord (p less than 0.0005), and ejection fraction increased 3.6 +/- 8% units (p less than 0.05) between immediate and day 7 studies. In contrast to the price of full dose rt-PA (

Influence of operator- and patient-dependent variables on the suitability of automated quantitative coronary arteriography for routine clinical use

2,300) or rt-PA with urokinase (

Use of exercise doppler echocardiography to evaluate cardiac drugs: Effects of propranolol and verapamil on aortic blood flow velocity and acceleration

3,500), the cost of this regimen was

Relationship of contractile state to ejection performance in patients with chronic aortic valve disease.

1,230. This pilot study demonstrates that at half the cost, a combination of half dose rt-PA with full dose streptokinase offers high infarct vessel patency, recovery of ventricular function, a low rate of reocclusion and few bleeding complications.(ABSTRACT TRUNCATED AT 250 WORDS)