Coronary artery plaque morphology in stable angina and subsets of unstable angina: an in vivo intracoronary ultrasound study.

Little information is available regarding the in vivo composition of angina producing culprit atherosclerotic lesions in various anginal syndromes. In this study we used intracoronary ultrasound to determine the composition of culprit lesions in various subsets of anginal syndromes and correlated this composition with the patient's clinical presentation. One hundred and forty six patients referred for angioplasty or atherectomy were classified as having either chronic stable angina (angina which was clinically unchanged for > 2 months), crescendo angina (an accelerating pattern of frequent or prolonged anginal episodes), severe rest angina (abrupt onset of prolonged angina) or post-infarction angina (angina within 2 weeks of acute myocardial infarction). Intracoronary ultrasound imaging of the culprit lesion was performed before intervention. Lesions were classified as soft, mixed fibrous without calcium, mixed fibrous with calcium or calcified. Analysis of the ultrasound images revealed that the majority of culprit lesions were soft in severe rest (71%) and post-infarction angina (73%) whereas, the majority of culprit lesions were mixed fibrous or calcified in chronic stable (69%) and crescendo (53%) angina (X2 = 22.73, p = 0.007). In addition, the frequency of intralesional calcium in chronic stable or crescendo angina was significantly higher than that in severe rest or stable angina. We conclude that the composition of culprit lesions in various anginal subsets are different. The lesion morphology in crescendo angina frequently resembles that in chronic stable angina; while those in severe rest and post-infarction angina are frequently similar. These findings may have implications for medical or interventional treatment of patients with angina.

Evidence that selective endothelial dysfunction may occur in the absence of angiographic or ultrasound atherosclerosis in patients with risk factors for atherosclerosis.

OBJECTIVES: The purpose of this study was to test the hypothesis that endothelial dysfunction occurs in humans before the development of structural coronary atherosclerosis when risk factors for this disease are present. BACKGROUND: Animal studies have demonstrated that known risk factors for coronary atherosclerosis (hyperlipidemia, hypertension, diabetes) result in impaired endothelium-dependent vascular reactivity before the development of structural atherosclerosis. Previous studies in patients have been unable to distinguish early structural atherosclerotic disease from dysfunctional endothelium. METHODS: Twenty-six patients with angiographically normal coronary arteries were studied at cardiac catheterization. The epicardial arteries were imaged using high resolution intravascular ultrasound to detect early structural changes and to determine changes in lumen size during pharmacologic provocation. A selective intracoronary Doppler velocity catheter was subsequently used to determine coronary blood flow velocity changes in response to the same pharmacologic provocation. Group I (9 patients) had no risk factors for atherosclerosis. Group II (17 patients) had one or more risk factors present. RESULTS: Although both Groups I and II had a normal microvascular vasodilator response to adenosine or papaverine infusion (estimated coronary flow increase 396 +/- 200% vs. 326 +/- 161% [mean +/- SD], respectively, p = 0.103), only Group I patients had an intact response to acetylcholine infusion (378 +/- 203% vs. 75 +/- 93% in Group II, p = 0.001). Group II patients had an abnormal epicardial artery cross-sectional area vasoconstriction response to acetylcholine infusion (-16.6 +/- 12.4% [13 patients] vs. 1.3 +/- 11.5% in Group I, p = 0.0007). An additional four Group II patients had severe spasm during acetylcholine infusion. Epicardial vasodilator response to nitroglycerin infusion, however, was preserved in Group II (14.6 +/- 4.3% vs. 9.6 +/- 3.5% in Group I, p = 0.212). All Group I patients had normal vessels by intravascular ultrasound. Of the 17 patients in Group II, 7 had minimal disease on ultrasound (intimal thickening or small eccentric plaque) in the study vessel. These patients did not respond differently from the 10 Group II patients without demonstrable disease on ultrasound. CONCLUSIONS: Patients with risk factors for coronary artery disease, normal coronary angiograms and no measurable disease by intracoronary ultrasound exhibit selective endothelial dysfunction at both the epicardial and microvascular levels. These findings may have implications for the treatment of "preclinical" coronary atherosclerosis.

Mechanisms of angiographically successful directional coronary atherectomy: evaluation by intracoronary ultrasound and comparison with transluminal coronary angioplasty.

To assess the mechanisms of luminal improvement, 40 patients undergoing directional coronary atherectomy and a matched control group of 25 patients undergoing angioplasty were evaluated with intracoronary ultrasound imaging before and after intervention. Despite similar sized vessels, a similar angiographic severity of diameter stenosis (75 +/- 12% for the angioplasty group vs 69 +/- 15% for the atherectomy group, p = NS), and a similar plaque burden (percent plaque area) before intervention (84 +/- 5% in the angioplasty group vs 85 +/- 13% in the atherectomy group, p = NS), the residual plaque area after intervention was significantly smaller in the atherectomy group (54 +/- 14%) compared with the angioplasty group (65 +/- 13%, p = 0.002). Despite excellent angiographic results, significant residual plaque was noted after either successful intervention. Based on the absolute changes in lumen area, plaque area, and vessel area, improvement in the lumen area in the atherectomy group occurred as a result of plaque "compression" (48%), plaque removal (37%), and vessel expansion (15%). In the angioplasty group, plaque "compression" accounted for 94% of the improvement in lumen area, whereas vessel expansion contributed 6%. Thus "compression" of plaque remains the major mechanism of luminal improvement during atherectomy.

Construction of cDNA libraries from cultures of Armillaria mellea.

1. Conditions were established for growth of mycelial cultures of Armillaria mellea such that the production of its lysine-specific proteinase was maximized. Proteinase synthesis was confirmed by immunoprecipitation. 2. Mycelia grown under these same conditions were used as a source of RNA and this RNA was translatable in a wheat germ translation system to produce proteins with M(r) in the range < 10,000- > 90,000. 3. Double-stranded cDNA was prepared and was inserted into the EcoR1 site of lambda gt10 and lambda gt11 using an adaptor ligation strategy. Packaging of these materials yielded large cDNA libraries. The form lambda gt10 contained 2.9 x 10(6) pfu/ml with 70% recombinants whereas that from lambda gt11 contained 2.2 x 10(6) pfu/ml with 60% recombinants.

Intracoronary ultrasound imaging: correlation of plaque morphology with angiography, clinical syndrome and procedural results in patients undergoing coronary angioplasty.

OBJECTIVES: This study was designed to establish the relation between ultrasound-derived atheroma morphology and the clinical, procedural and angiographic features of patients presenting for coronary angioplasty. BACKGROUND: Intracoronary ultrasound imaging provides accurate dimensional information regarding arterial lumen and wall structures. Atheroma composition may also be assessed by ultrasound; however, only limited studies have been performed in patients. METHODS: In 65 patients a diagnostic ultrasound imaging catheter or a combination imaging-angioplasty balloon catheter was used during coronary angioplasty to image both the lesion and the vessel segment just proximal to it (reference segment). Ultrasound images were analyzed for lumen, total vessel and plaque areas and were classified into five morphologic subtypes (soft, fibrous, calcific, mixed plaque and concentric subintimal thickening). These data were compared with angiographic morphologic features, procedural results and clinical angina pattern (stable vs. unstable). RESULTS: Morphologic analysis of the ultrasound images obtained from the lesion correlated well with the clinical angina syndrome. Compared with patients with stable angina, patients with unstable angina had more soft lesions (74% vs. 41%), fewer calcified and mixed plaques (fibrotic, soft or calcific components in one or more combinations [25% vs. 59%]) and fewer intralesional calcium deposits (16% vs. 45%) (all p < 0.01). There was no correlation between ultrasound and angiographic lesion morphologic characteristics for either the reference segment or the lesion. Ultrasound demonstrated greater sensitivity than angiography for identifying unstable lesions (74% vs. 40%). Dimensional analysis demonstrated a large plaque burden in the reference segments (45 +/- 15% of total vessel area). Postangioplasty plaque burden was also high (62 +/- 9%). There was a significant, but only fair correlation between lumen area determined by angiography and ultrasound for both the reference segment (r = 0.70, p < 0.001) and the postangioplasty lesion (r = 0.63, p < 0.05). CONCLUSIONS: Morphologic plaque classification by ultrasound is closely correlated to clinical angina but has little relation to established angiographic morphologic characteristics. Intracoronary ultrasound imaging during angioplasty identifies a large residual plaque burden in both the reference segment and the lesion. In the future, determination of plaque composition by intracoronary ultrasound may be important in selecting or modifying interventional therapeutic options.

Subnormal parasympathetic activity after cardiac transplantation.

Heart period variability (standard deviation of 120 consecutive RR or PP intervals) was used to assess baseline parasympathetic activity in 18 patients with congestive heart failure before and after orthotopic cardiac transplantation, and was compared to that of 16 age-matched control subjects. Mean heart period variability (+/- standard error of the mean) was significantly greater (p less than 0.05) in control subjects (58 +/- 5 ms) than in the patients at any time before or after transplantation. Heart period variability of innervated recipient atria did not change significantly early (1 to 4 weeks) after transplantation (16 +/- 2 to 24 +/- 5 ms; p = 0.11), but increased significantly between weeks 15 and 37 after transplantation (30 +/- 5 ms, p less than 0.002 versus before transplantation). A stepwise regression model (R2 = 0.35; p = 0.01) showed that heart period variability was directly related to time after transplantation and inversely related to systolic arterial pressure after transplantation and degree of rejection. Heart period variability of the denervated donor atria did not change from early to late periods after transplantation, suggesting that vagal reinnervation of the donor heart had not occurred. These data indicate that baseline parasympathetic activity does not increase significantly during the first month after transplantation but increases significantly between months 3 and 6.