Robert E. Dinsmore

A Definition of Advanced Types of Atherosclerotic Lesions and a Histological Classification of Atherosclerosis A Report From the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association

This report is the continuation of two earlier reports that defined human arterial intima and precursors of advanced atherosclerotic lesions in humans. This report describes the characteristic components and pathogenic mechanisms of the various advanced atherosclerotic lesions. These, with the earlier definitions of precursor lesions, led to the histological classification of human atherosclerotic lesions found in the second part of this report. The Committee on Vascular Lesions also attempted to correlate the appearance of lesions noted in clinical imaging studies with histological lesion types and corresponding clinical syndromes. In the histological classification, lesions are designated by Roman numerals, which indicate the usual sequence of lesion progression. The initial (type 1) lesion contains enough atherogenic lipoprotein to elicit an increase in macrophages and formation of scattered macrophage foam cells. As in subsequent lesion types, the changes are more marked in locations of arteries with adaptive intimal thickening. (Adaptive thickenings, which are present at constant locations in everyone from birth, do not obstruct the lumen and represent adaptations to local mechanical forces). Type II lesions consist primarily of layers of macrophage foam cells and lipid-laden smooth muscle cells and include lesions grossly designated as fatty streaks. Type III is the intermediate stage between type II and type IV (atheroma, a lesion that is potentially symptom-producing). In addition to the lipid-laden cells of type II, type III lesions contain scattered collections of extracellular lipid droplets and particles that disrupt the coherence of some intimal smooth muscle cells. This extracellular lipid is the immediate precursor of the larger, confluent, and more disruptive core of extracellular lipid that characterizes type IV lesions. Beginning around the fourth decade of life, lesions that usually have a lipid core may also contain thick layers of fibrous connective tissue (type V lesion) and/or fissure, hematoma, and thrombus (type VI lesion). Some type V lesions are largely calcified (type Vb), and some consist mainly of fibrous connective tissue and little or no accumulated lipid or calcium (type Vc).

Interobserver variability in coronary angiography.

Four experienced coronary angiographers (two radiologists and two cardiologists) independently assessed the location and degree of coronary artery stenosis, and the location and degree of left ventricular wall motion abnormalities in 20 coronary angiograms. Marked interobserver variability was noted in quantifying percent coronary artery stenosis and degree of left ventricular wall motion abnormalities. For example, in only 13/20 (65%) of the coronary angiograms did all observers agree about the significance of a stenosis (defined as greater than 50% in diameter luminal narrowing) in the proximal or mid left anterior descending coronary artery. In 3/20 (15%) angiograms there was disagreement by at least one observer about the significance of lesions noted in the main left coronary artery.The ventricle was divided into five segments and the degree of wall motion abnormality graded into six categories of increasing severity from normal to dyskinesis. There was a 42% mean disagreement among all four observers where a disagreement between observers was defined as any difference in grading wall motion abnormalities.Interobserver variability reveals a significant limitation of coronary angiography.

Heart failure in outpatients: a randomized trial of digoxin versus placebo.

The view that digitalis clinically benefits patients with heart failure and sinus rhythm lacks support from a well-controlled study. Using a randomized, double-blind, crossover protocol, we compared the effects of oral digoxin and placebo on the clinical courses of 25 outpatients without atrial fibrillation. According to a clinicoradiographic scoring system, the severity of heart failure was reduced by digoxin in 14 patients; in nine of these 14, improvement was confirmed by repeated trials (five patients) or right-heart catheterization (four patients). The other 11 patients had no detectable improvement from digoxin. Patients who responded to digoxin had more chronic and more severe heart failure, greater left ventricular dilation and ejection-fraction depression, and a third heart sound. Multivariate analysis showed that the third heart sound was the strongest correlate of the response to digoxin (P less than 0.0001). These data suggest that long-term digoxin therapy is clinically beneficial in patients with heart failure unaccompanied by atrial fibrillation whose failure persists despite diuretic treatment and who have a third heart sound.

Dissecting Aneurysm of the Aorta: Aortographic Features Affecting Prognosis

Thirty-one consecutive patients with medically treated dissecting aneurysm of the aorta were divided into two groups based on the aortographic findings. Ten showed no opacification of the false channel; 21 did show opacification, indicating an open communication with the aortic lumen. The long-term survival rates of the two groups were 90% and 43%, respectively. Implications of these findings are discussed.

Aberrant Coronary Artery Origin From the Aorta Diagnosis and Clinical Significance

Twenty-one patients with anomalous coronary artery origin from the aorta are discussed, and the cases reported in the literature are reviewed. The left anterior descending (LAD) and left circumflex (Cx) arteries arose aberrantly from the right sinus of Valsalva of the aorta (RSV) in six patients. In four of these patients the connecting branch from the anomalous origin passed anterior to the aorta and the right ventricular in-fundibulum (RVinf), and in two patients, this branch passed between the aorta and RVinf. In 11 patients only the Cx was aberrant, and arose either from the RSV directly or from the right coronary artery (RCA), and passed posterior to the aorta and RVinf. In four patients the RCA arose aberrantly — in three from the left sinus of Valsalva of the aorta passing anteriorly, and in one from the left Cx passing posteriorly.Aberrant coronary artery origin from the aorta had clinical consequences only when the branch connecting the LAD and Cx to the RSV passed between the aorta and RVinf. Both our findings and those reported in the literature associate this variant with exertional sudden death in young persons. Anomalous coronary patterns can be delineated readily by selective coronary cineangiography, and as illustrated, the right anterior oblique projection can readily distinguish those prone to sudden death from the clinically insignificant variants. The former can be corrected with coronary artery bypass surgery.

Right ventricular infarction: Clinical diagnosis and differentiation from cardiac tamponade and pericardial constriction

Twelve patients with a clinical diagnosis of right ventricular infarction are described. All had acute inferior wall myocardial infarction associated with the bedside findings of jugular venous distension, clear lungs on auscultation, and arterial hypotension. Hemodynamically, there was elevation of right-sided filling pressures not explained by normal or minimally elevated pulmonary wedge pressures. Four patients had an incorrect diagnosis of acute cardiac tamponade. However, a review of the data showed that the hemodynamic features of right ventricular infarction more closely resemble those of pericardial constriction, a point that may be helpful in distinguishing right ventricular infarction from cardiac tamponade. Invasive and noninvasive techniques that exclude the presence of pericardial fluid and suggest enlargement and abnormal contractility of the right ventricle were helpful in establishing the diagnosis of right ventricular infarction in several patients.

Transient defects of resting thallium scans in patients with coronary artery disease.

Defects on resting thallium-201 (201T1) scans in patients who do not have evidence of acute myocardial ischemia have been thought to represent myocardial scar. Our study of 20 patients with stable but severe coronary artery disease (CAD), including nine with ECG evidence of myocardial scar, was undertaken to reexamine the significance of such defects. Imaging was performed in two views, beginning within 10 minutes after Tl administration and repeated over a 2-4-hour period. Images in each of the two projections were divided into three zones, for a total of 120 zones in 20 patients. An initial defect was present in 43 zones in 15 patients, while five patients demonstrated totally normal studies. On later scans 18 defects persisted while 25 filled in. Twelve of 18 persistent defects were associated with ECG evidence of infarction, compared with only six of 25 transient defects (p>0.01). Correlation with angiographic left ventricular wall motion was possible for 12 of 18 persistent defects and 18 of 25 transient defects. Six of 12 persistent defects, compared with only one of 18 transient defects, were associated with akinesia/dyskinesia (p>0.01). In addition, 17 of 18 transient defects were associated with either normal left ventricular wall motion (12 defects) or hypokinesia (five defects). Finally, 23 of 25 transient defects, compared with only 41 of 77 normal zones, were associated with severe CAD (p>0.001).Thus, in resting patients with stable CAD: 1) serial imaging reveals that many initial defects fill in over time; 2) initial resting defects on TI scans may not indicate myocardial scar; and 3) transient defects are usually associated with severe CAD, but normal or only mildly abnormal left ventricular wall motion.

Proximal Jet Size by Doppler Color Flow Mapping Predicts Severityof Mitral Regurgitation: Clinical Studies

Background Recent studies have shown that many instrument and physiological factors limit the ability of color Doppler total jet area within the receiving chamber to predict the severity of valvular regurgitation. In contrast, the proximal or initial dimensions of the jet as it emerges from the orifice have been shown to increase directly with orifice size and to correlate well with the severity of aortic insufficiency. Only limited data, however, are available regarding the value of proximal jet size in mitral regurgitation, and it has not been examined in short-axis or transthoracic views. The purpose of the present study, therefore, was to evaluate the relation between proximal jet size and other measures of the severity of mitral regurgitation. Methods and Results In 49 patients, the anteroposterior height of the proximal jet as it emerges from the mitral valve was measured in the parasternal long-axis view; proximal jet width and area were measured in the short-axis view at the same level. Results we...

Restoration of Coronary Flow in Myocardial Infarction by Intravenous Chimeric 7E3 Antibody Without Exogenous Plasminogen Activators Observations in Animals and Humans

BACKGROUND Coronary thrombus is composed of platelets and fibrin, and during thrombolytic treatment, reflow may be slowed by platelet deposition. It may be possible to initiate coronary reflow without exogenous plasminogen activators by blocking platelet aggregation while fibrin generation is impeded with heparin. METHODS AND RESULTS In 14 dogs, left anterior descending coronary artery thrombosis was produced by endothelial trauma and thrombin instillation in the presence of stenosis distally. Reflow was monitored by flow probe during treatment with (1) heparin, (2) heparin and aspirin, and (3) heparin, aspirin, and intravenous 7E3. Eighty percent of dogs treated with the third combination showed stable reflow (> or = 25% of prestenotic flow) in 50 +/- 9 minutes. In addition, 13 patients were studied during intravenous administration of c7E3 10 minutes before primary angioplasty for acute myocardial infarction and Thrombolysis In Myocardial Infarction (TIMI) grade 0 or 1 flow. Pretreatment included heparin and oral aspirin. Flow increased during a 10-minute period by at least one TIMI grade in 11 (85%) of 13 and reached TIMI grade 2 or 3 in 7 (54%) of 13 patients. Average TIMI grade flow increased from 0.31 +/- 0.5 to 1.54 +/- 0.8 (P < .001). Thrombus length 10 minutes after c7E3 was 5.1 +/- 3.5 mm. All but 1 patient then underwent angioplasty. There were no complications. CONCLUSIONS Coronary reflow can be initiated by intravenous 7E3 administration in the presence of heparin and aspirin. In human patients, this flow can be observed in 10 minutes without exogenous thrombolytic agents.

Observer variance in the qualitative evaluation of left ventricular wall motion and the quantitation of left ventricular ejection fraction using rest and exercise multigated blood pool imaging.

Multigated blood-pool imaging (MBPI) at rest and with exercise has been widely used for the evaluation of left ventricular regional wall motion and ejection fraction. Because the precision of these tests depends on interobserver and intraobserver variations in interpretation, we performed the following study. Fifty-nine patients had MBPI at rest and during peak supine bicycle exercise and left ventriculography (LV gram) at rest during cardiac catheterization. Forty-nine patients had significant coronary artery disease and 10 did not. Rest MBPI, exercise MBPI and LV gram regional wall motion were graded by three independent observers. For scoring purposes the left ventricular wall was subdivided into anterolateral, apical, inferior, septal, apical-inferior and posterior walls. Wall motion for both the tracer and contrast studies was scored subjectively on a five-point scale: 3 = normal, 2 = mild hypokinesis, 1 = moderate-to-severe hypokinesis, 0 = akinesis, −1 = dyskinesis. Ejection fraction was determined by two independent observers six times for both rest and exercise MBPI using a counts technique that allowed frame-by-frame variations in the regions of interest. Ejection fraction was determined by two independent observers three times for the LV gram using an area-length method. Results were analyzed by a two-way analysis of variance and expressed as ± 2 SD. Using the five-point scoring system, the estimated interobserver variance for regional wall motion scores ranged from 0.60 to ± 1.02 grade for the rest MBPI, ± 0.94 to ± 1.46 grade for the exercise MBPI, and ± 0.66 to ± 0.98 grade for the LV gram, depending on the wall analyzed. The estimated interobserver variance for regional wall motion scores ranged from ± 0.56 to ± 1.08 grade for a change between rest and exercise MBPls, depending on the wall analyzed. Interobserver variance for the rest MBPI was greater than that for the LV gram for only the septal wall (p < 0.01).Intraobserver and interobserver variance for ejection fraction determinations were 5.8% and ± 6.0%, respectively, for the rest MBPI, ± 9.2% and ± 9.6% for the exercise MBPI and ± 11.0% and ± 11.4% for a change in ejection fraction between rest and exercise MBPIs. When a single observer determined the ejection fraction twice for both the rest and the exercise MBPI, and then compared the averaged rest with the averaged exercise ejection fraction, the intraobserver variance was reduced to ± 4.6%. Intraobserver and interobserver variance for the LV gram ejection fraction were ± 6.0% and ± 11.6%. Although intraobserver variance for the rest MBPI and LV gram ejection fraction were not significantly different, interobserver variance for the rest MBPI ejection fraction was significantly less than that for the LV gram (p < 0.005).Interobserver variance for rest MBPI regional wall motion, and interobserver and intraobserver variance for rest MBPI ejection fraction are comparable to those for the LV gram, except for the septal wall. The results offer objective criteria by which exercise-induced changes in left ventricular regional wall motion and ejection fraction can be interpreted. To minimize the error due to observer variance, exercise-induced changes in ejection fraction should be determined by comparing averaged ejection fractions derived from at least two determinations for both the rest and the exercise MBPI.