Gerald M. Lawrie

Patterns of atherosclerosis and their surgical significance.

The records of 13,827 patients admitted on one or more occasions to The Methodist Hospital in Houston on the service of the senior author for the treatment of arterial atherosclerotic occlusive disease from 1948 to 1983 were analyzed. The data derived from this analysis are believed to support the concept that atherosclerotic occlusive disease tends to assume characteristic patterns that may be classified, by predominant site or distribution of the disease, into five major categories: (I) the coronary arterial bed, (II) the major branches of the aortic arch, (III) the visceral arterial branches of the abdominal aorta, (IV) the terminal abdominal aorta and its major branches, and (V) a combination of two or more of these categories occurring simultaneously. Category IV had the highest proportion of patients (about two-fifths), Category I the second highest (almost one-third), and Category III had the lowest percentage (3%). Atherosclerotic occlusive disease in all categories tends to be well localized and usually occurs in the proximal or midproximal portions of the arterial bed. Such lesions are amenable to effective surgical treatment directed toward restoration of normal circulation. Less commonly, however, the occlusive disease in all categories occurs predominantly in the distal portions of the arterial bed, and such lesions are usually not amenable to effective surgical treatment. Patients in Categories I and III were significantly younger than those in the other categories and, although males predominated in all categories, Categories II and III contained significantly more female patients than did the other categories. In general, however, female patients behaved like male patients in virtually all aspects of the study. The rates of progression of the disease may be classified into: rapid (0 to 36 months), moderate (37 to 120 months), and slow (more than 120 months). The rapid and moderate rates of progression occurred most frequently in Categories II and IV, and the moderate and slow rates occurred most frequently in Category I. The possibility for development of recurrence or progression of disease in the same category and in a new category was significantly greater in younger patients. The patients sex had no significant influence in this regard. Among the various categories, patients in Category IV had the highest incidence of development of disease in a new category, and Category I had the lowest incidence. Patients originally in Category II had a somewhat greater tendency to development of disease in Category IV, and patients originally in Category IV, for development of disease in Category II.(ABSTRACT TRUNCATED AT 400 WORDS)

Quantitation and localization of apolipoproteins [a] and B in coronary artery bypass vein grafts resected at re-operation.

Lp[a] is a lipoprotein whose plasma concentration is highly correlated with cardiovascular disease. Its protein moiety, apoLp[a], consists of two large polypeptides, apo[a] and apo B. The possible contribution of Lp[a] to atherosclerosis in saphenous vein aortocoronary bypass grafts was studied in a population of patients undergoing coronary re-bypass surgery. The vein graft tissue levels of apoLp[a] were compared with graft duration, gross and light microscopic pathology, as well as plasma levels of apoLp[a]. The localization pattern of apo[a] and apo B in vein graft tissue was determined. In addition, the plasma levels of cholesterol, triglycerides, apoproteins (apo) A-I, A-II, and E were measured. In a representative subpopulation of 17 patients with a mean age of 63 years from whom grafts with a mean duration of 112 months were resected, the mean total plasma cholesterol level was 221 mg/dl, the mean high density lipoprotein cholesterol level was 31 mg/dl, and the mean plasma triglyceride level was 228 mg/dl. In normal saphenous veins, the level of apoLp[a] was below measurable limits (less than 2 ng/mg), and the level of apo B was very low (3.3 ng/mg). In resected grafts, the mean tissue level of apoLp[a] was 32 ng/mg, and that of apo B was 70 ng/mg, demonstrating the net accumulation of these apoproteins in veins from the time of their grafting into the arterial bed. The apoLp[a]/apo B ratio was determined in 77 tissue segments from 59 grafts (28 patients) and was found to be 0.313. This tissue ratio was significantly higher (p = 0.02) than the plasma apoLp[a]/apo B ratio from these patients, which was 0.132. Immunostaining showed co-localization of apo[a] and apo B in the neointima of grafts. The most abundant pathologic features observed in resected grafts were proliferated intima (43/52), thrombus (28/52), and atherosclerotic core regions (21/52). The level of tissue apo B correlated well with the abundance of core regions (r = 0.501), whereas the level of tissue apoLp[a] did not correlate as well with this feature (r = 0.233). Although apo[a] and apo B are almost absent from normal saphenous vein, these apoproteins (and presumably the lipoproteins Lp[a] and low density lipoprotein) accumulate in bypass vein grafts. The data support the view that these lipoproteins play a significant role in vein graft atherosclerosis.

Improved results of carotid endarterectomy in patients with symptomatic coronary disease: an analysis of 1,546 consecutive carotid operations.

The significant risk of fatal myocardial infarction after carotid endarterectomy in patients with coronary disease long has been recognized. In 1,546 consecutive carotid endarterectomies performed in 1,238 patients over the last 10 years, angina pectoris was present in 17% (212/1,238) of patients; a further 32% (396/1,238) of patients were asymptomatic, but had a history of myocardial infarction. The perioperative mortality (30 day) in the 1306 consecutive endarterectomies in 1,026 patients without symptomatic coronary artery disease was 1.5% (15/1,026 patients). Of the 212 patients with symptoms, 85 carotid endarterectomies were performed in 77 patients without prior coronary bypass operation with an operative mortality of 18.2% (14/77 patients). The remaining 135 patients had 155 carotid endarterectomies but were treated by either prior coronary artery bypass (84 patients) or simultaneous carotid endarterectomy and coronary artery bypass (51 patients) with an operative mortality of 3% (4/135 patients). The greatly unproved survival in those patients with symptomatic coronary disease who had a coronary artery bypass prior to or at the same time as carotid endarterectomy, and the absence of permanent neurological deficit in the 51 of these 135 patients who had simultaneous carotid endarterectomy and coronary artery bypass suggests that significantly improved survival can be achieved after carotid endarterectomy in these high risk patients by the use of simultaneous coronary artery bypass surgery.

Aortocoronary bypass saphenous vein graft atherosclerosis. Anatomic study of 99 vein grafts from normal and hyperlipoproteinemic patients up to 75 months postoperatively

Abstract In this anatomic study of 99 saphenous vein grafts recovered at autopsy from 55 patients who survived aortocoronary bypass for 0 to 75 months, a comparison was made between patients with normal and elevated lipid levels in regard to the severity of vein graft intimai proliferation and the prevalence of true atherosclerosis. Although progression of intimai proliferation with time occurred in both patient groups, a greater proportion of hyperlipemic patients had high grade luminal narrowing of vein grafts as the interval after aortocoronary bypass increased. True atherosclerosis did not develop before 12 months in any of the 59 vein grafts from the 27 normolipemic and 5 hyperlipemic patients who survived aortocoronary bypass, but it occurred in 3 of 26 vein grafts (11.5 percent) from normolipemic and 11 of 14 vein grafts (78.6 percent) from hyperlipemic patients who survived 13 to 75 months after aortocoronary bypass. The observation that microscopic changes of atherosclerosis may occur in saphenous vein grafts in some patients without hyperlipemia also emphasizes the importance of effective control not only of blood lipids but also of the other recognized risk factors for atherosclerosis.

Identification of Hibernating Myocardium With Quantitative Intravenous Myocardial Contrast Echocardiography Comparison With Dobutamine Echocardiography and Thallium-201 Scintigraphy

Background—There are currently no data on the accuracy of intravenous myocardial contrast echocardiography (MCE) in detecting myocardial hibernation in man and its comparative accuracy to dobutamine echocardiography (DE) or thallium 201 (Tl201) scintigraphy. Methods and Results—Twenty patients with coronary artery disease and ventricular dysfunction underwent MCE 1 to 5 days before bypass surgery and repeat echocardiography at 3 to 4 months. Patients also underwent DE (n=18) and rest-redistribution Tl201 tomography (n=16) before revascularization. MCE was performed using continuous Optison infusion (12 to 16 cc/h) with intermittent pulse inversion harmonics and incremental triggering (1:1 to 1:8). Myocardial contrast intensity (MCI) replenishment curves were constructed to derive quantitative MCE indices of blood velocity and flow. Recovery of function occurred in 38% of dysfunctional segments. MCE parameters of perfusion in hibernating myocardium were similar to segments with normal function and higher than dysfunctional myocardium without recovery of function (P <0.001). The best MCE parameter for predicting functional recovery was Peak MCI×&bgr;, an index of myocardial blood flow (area under the curve, 0.83). MCE parameters were higher in segments with contractile reserve and Tl201 uptake ≥60% (P <0.05) and identified viable segments without contractile reserve by DE. The sensitivity of Peak MCI×&bgr; >1.5 dB/s for recovery of function was 90% and was similar to Tl201 scintigraphy (92%) and any contractile reserve (80%); specificity was higher than for Tl201 and DE (63%, 45%, and 54%, respectively;P <0.05). Conclusions—MCE with intravenous contrast identifies myocardial hibernation in humans. Prediction of viable myocardium with MCE is best using quantification of myocardial blood flow and provides improved accuracy compared with DE and Tl201 scintigraphy.

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.

The influence of residual disease after coronary bypass on the 5-year survival rate of 1274 men with coronary artery disease.

To determine the independent influence of the extent and site of residual disease on late survival, we analyzed the fate of 1448 consecutive patients who had coronary artery bypass surgery during 1968-1974. There were 1274 males, mean age 53.4 ± 8 years (range 24-75 years). Females were excluded from further analysis. Two hundred twenty-six patients (17.7%) had one-vessel disease, 492 (38.6%) had two-vessel disease, 408 (32.0%) had three-vessel disease and 148 (11.6%) had left main stenosis. Survival was determined at a follow-up of at least 5 years. Survival data were analyzed by Kaplan-Meier survival curves for the patients with two- and three-vessel disease according to the extent of residual disease. For patients with two-vessel disease and good ventricular function, survival was similar at 5 years, 89.1 % and 87.7% for no and one residual lesion; for those with two-vessel disease and poor ventricular function, 5-year survival was 84.5% and 52.6% for no and one residual lesion; for those with three-vessel disease and good ventricular function, it was 92.0 %, 83.4%, and 75.0% for no, one and two residual lesions, respectively. With poor ventricular function, the corresponding results were 83.1%, 72.5% and 23.1%. The Cox multivariate analysis technique was used to analyze the influence of age at operation, number of vessels diseased preoperatively, preoperative left ventricular function, period of surgery, and the number and site of residual lesions after operation. Residual disease, age at operation and left ventricular function were the most important variables affecting survival of patients with two- and three-vessel disease. Residual lesions of the left anterior descending or circumflex coronary arteries were the most important predictors of survival; residual lesions of the right coronary artery exerted a lesser influence. The results of this study suggest that the greatest benefit in terms of improved survival may come from the first two to three grafts placed.

Microvascular Structural Correlates of Myocardial Contrast Echocardiography in Patients With Coronary Artery Disease and Left Ventricular Dysfunction Implications for the Assessment of Myocardial Hibernation

Background—Myocardial contrast echocardiography (MCE) has been used to evaluate myocardial viability. There are no data, however, on the pathological determinants of myocardial perfusion by MCE in humans and the implications of such determinants. Methods and Results—MCE was performed in 20 patients with coronary artery disease and ventricular dysfunction within 24 hours before myocardial biopsy at surgery using a continuous Optison infusion (12 to 16 cc/h), with intermittent pulse inversion harmonics and incremental triggering. Peak myocardial contrast intensity (MCI) and the rate of increase in MCI (&bgr;) were quantitated. Thirty-six transmural myocardial biopsies (2 per patient) were obtained by transesophageal echocardiography. Total microvascular (<100 &mgr;m) density, capillary density and area, arteriolar and venular density, and percent collagen content were quantitated with immunohistochemistry. Peak MCI correlated with microvascular density (r =0.59, P <0.001) and capillary area (r =0.64, P <0.001) and inversely correlated with percent collagen content (r =−0.45, P =<0.01). The best relation was observed when the ratio of peak MCI in the 2 biopsied segments in each patient was compared with the ratio of microvascular density and capillary area (r =0.84 and 0.87, respectively;P <0.001). A significant overlap in microvascular density was seen between segments with and without recovery of function. The new MCE indices of blood velocity (&bgr;) and flow (peak MCI×&bgr;) better identified recovery of function compared with microvascular density and the sole use of peak MCI. Conclusions—Microvascular integrity is a significant determinant of maximal MCI in humans. MCE indices of blood velocity and flow are important parameters that predict recovery of function after revascularization.

Surgical ablation of ventricular tachycardia: improved results with a map-directed regional approach.

To determine whether a regional approach to surgery for ventricular tachycardia would improve on the results of previously reported methods of endocardial resection, an analysis was performed of our surgical experience over a 5 year period. Of 46 consecutive patients operated on for recurrent sustained ventricular tachycardia or ventricular fibrillation, 39 patients with ischemic heart disease underwent subendocardial resection and/or cryoablation. The mean age of the patients was 61 +/- 8 (SD) years, the mean left ventricular ejection fraction was 32 +/- 11%, and the mean number of ineffective antiarrhythmic drugs was 3.8 +/- 1.2 per patient. In 35 of 39 patients in whom mapping data were obtainable, 56 (86%) tachycardias had earliest sites of activation in the left ventricle and nine (14%) had earliest sites in the right ventricle. Ten patients had 14 tachycardias (21%) mapped to areas outside visible dense scar. Of these 35 patients, 10 underwent localized subendocardial resection and 25 underwent a regional procedure in which all areas activated before the surface QRS during ventricular tachycardia were excised and/or cryoablated. In the operative survivors of electrophysiologically guided surgery, three of eight (38%) patients with the localized and one of 24 (4%) patients who underwent the regional procedure had recurrence of ventricular tachycardia during a follow-up period of 1 to 59 (mean 22 +/- 17) months (p = .04). The favorable outcome of regional surgery was not influenced by the presence of multiple morphologies in 54%, disparate sites of origin in 29%, or inferior wall foci in 46% of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitation and Localization of Matrix Metalloproteinases and Their Inhibitors in Human Carotid Endarterectomy Tissues

Background—Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) play a central role in arterial wall remodeling, affecting stability of fibrous caps covering atherosclerotic plaques. The objective of this study was to determine the spatial distribution of TIMP mass and MMP mass and activity of carotid endarterectomy (CEA) tissues and relate it to the distribution of atherosclerotic lesions. Methods and Results—Fresh CEA tissues were imaged by multicontrast MRI to generate 3D reconstructions. Tissue segments were cut transversely from the common, bifurcation, internal, and external regions. Segments were subjected to total protein extractions and analyzed by ELISA for MMP-2 and -9 and TIMP-1 and -2 mass and by zymography for gelatinase activity. Segments at or near the bifurcation with highly calcified lesions contained higher MMP levels and activity than segments distant from the bifurcation; highly fibrotic or necrotic plaque contained lower MMP levels and activity and higher TIMP levels. Fatty streak, fibroatheroma with hemorrhage and calcification, and fully occluded lesions were enriched in MMP-2, MMP-9, and TIMP-1 and TIMP-2, respectively. Conclusion—The spatial distribution of MMPs and TIMPs in carotid atherosclerotic lesions is highly heterogeneous, reflecting lesion location, size, and composition. This study provides the first semi-quantitative maps of differential distribution of MMPs and TIMPs over atherosclerotic plaques.