John McB. Hodgson

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

OBJECTIVESnThe 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.nnnBACKGROUNDnAnimal 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.nnnMETHODSnTwenty-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.nnnRESULTSnAlthough 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.nnnCONCLUSIONSnPatients 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.

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

OBJECTIVESnThis 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.nnnBACKGROUNDnIntracoronary 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.nnnMETHODSnIn 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).nnnRESULTSnMorphologic 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).nnnCONCLUSIONSnMorphologic 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.

Intracoronary ultrasound—defined plaque composition: Computer-aided plaque characterization and correlation with histologic samples obtained during directional coronary atherectomy

The ability to classify lesion composition accurately may be important for selecting or guiding interventional therapy and for understanding the pathophysiologic basis of individual lesions. To assess the usefulness of ultrasound in classifying lesions, intracoronary ultrasound images were obtained from 44 atherosclerotic lesions in patients before directional atherectomy. Lesions were classified by visual analysis and by computer-assisted gray-level statistics. Atherectomy samples were evaluated histologically for elastosis and calcium and quantitatively by morphometric analysis for various tissue components. The computer-assisted quantitative classification agreed well with the findings on visual analysis. Visual and computer-assisted quantitative ultrasound images were found to have distinctive histologic features. Lesions with predominantly echogenic plaque had a larger fraction of dense fibrous, elastic, or calcified tissue. Lesions with predominantly echolucent soft plaque had a greater fraction of loose fibrous, smooth-muscle, thrombotic, or necrotic elements. Thus intracoronary ultrasound allows accurate classification of lesion composition in patients.

Correlation of intracoronary ultrasound plaque characteristics in atherosclerotic coronary artery disease patients with clinical variables

It was examined whether intracoronary ultrasound-defined plaque morphology of symptom-producing, severely stenosed, atherosclerotic coronary artery lesions is related to patient-related clinical variables. Data regarding anginal pattern (stable vs unstable), age, sex, history of smoking, diabetes, hypertension, hypercholesterolemia and lesion location were recorded in 146 hemodynamically stable patients referred for clinically indicated balloon angioplasty or directional atherectomy. Intracoronary ultrasound images of the lesions were obtained before and after the intervention. Lesions were classified as soft (homogeneous echoes less dense than adventitia) or hard (bright echoes with or without acoustic shadowing). Eighty-three lesions (57%) were classified as soft and 63 (43%) as hard. Univariate analysis showed anginal pattern, age, vessel location and history of smoking to be significantly related to plaque morphology. Multivariate analysis revealed only anginal pattern, age and vessel location to be independent predictors of plaque morphology. The frequency of echogenic hard plaque was significantly higher in patients aged > 60 years (56 vs 30%; p = 0.001), those with stable angina (69 vs 35%; p = 0.002), and lesions located in the distal arterial segments (68 vs 31%; p < 0.001) than in younger ones, those with unstable angina, and lesions in proximal segments, respectively. Based on previous studies, echogenic hard plaques are likely to be predominantly fibrous or calcific, or both, whereas low-echogenicity soft plaques are likely to be fibrocellular, lipid rich or thrombotic, or a combination. This difference in plaque morphology is probably due to differences in the predominant mechanism of plaque formation (i.e., slow growth vs rupture/thrombosis).(ABSTRACT TRUNCATED AT 250 WORDS)

Measurement by intracoronary ultrasound of in vivo arterial distensibility within atherosclerotic lesions

Arterial distensibility is diminished by atherosclerosis. This process has not been well studied in the coronary arteries. The purpose of this study was to assess changes in coronary arterial distensibility in 4 groups of patients. Group I (n = 20) consisted of patients with normal vessels, group II (n = 40) with diseased undilated vessels, group III (n = 15) after successful percutaneous transluminal coronary angioplasty (PTCA), and Group IV (n = 20) after successful directional coronary atherectomy (DCA). Intracoronary ultrasound imaging was used to assess distensibility, plaque morphology and atherosclerotic burden (expressed as the percentage of total vessel cross-sectional area occupied by plaque: percent plaque area). Distensibility was defined as percent change in lumen area in a cardiac cycle. Group I (normal vessels) had a distensibility = 14 +/- 5%, which was significantly greater than that seen in group II (distensibility = 4 +/- 2%, p < 0.001). In undilated vessels, distensibility was related to the degree of atherosclerotic burden (r = 0.75). This relation was curvilinear with a marked decrease in distensibility when percent plaque area exceeded 30%. Distensibility in group III (after PTCA) was higher than in group II (10 +/- 3 vs 4 +/- 2%, p < 0.001) despite a larger plaque burden (percent plaque area of 56 +/- 12 vs 46 +/- 11%, p < 0.005). The distensibility in group IV (after DCA) was also higher than in group II (8 +/- 4 vs 4 +/- 2%, p < 0.001) despite a similar residual percent plaque area (49 +/- 13 vs 46 +/- 11%, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

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 patients 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.

Comparison of tissue disruption caused by excimer and midinfrared lasers in clinical simulation

Laser coronary angioplasty is a useful therapy for selected complex coronary lesions. Laser-induced acoustic trauma is postulated to be a cause of dissection and acute vessel occlusion. Controversy exists regarding the relative degree of photoacoustic effects of midinfrared and excimer lasers in clinical practice. To date, these systems have not been compared at clinical energy doses and with clinical pulsing strategies. Therefore, we studied the photoacoustic effects of both midinfrared and excimer lasing at clinically accepted doses. Human atherosclerotic iliofemoral artery segments were obtained at autopsy (n = 36) and placed lumen side up in a saline bath. Clinical laser catheters were advanced over an 0.018 guide wire, perpendicular to the tissue. A 10-g down force was applied to the catheter for full-thickness lasing. Pulsing strategies were, for midinfrared laser: 5 pulses, 1-sec pause, 5 pulses, 1-sec pause, 5 pulses, withdraw; for excimer: 5 sec of pulses, wait 10 sec, 5 sec of pulses. Several clinically acceptable energy levels were used; for excimer: 25 mJ/mm2, 40 mJ/mm2, 60 mJ/mm2; for midinfrared: 3 W (400 mJ/mm2), 3.5 W (467 mJ/mm2). Photoacoustic effect was assessed histologically by determining the number of lateral cleavage planes (dissections) arising from the lased crater border and extending into the surrounding tissue. In normal tissue, midinfrared lasing produced less acoustic damage than excimer lasing (2.79 +/- 0.78 vs. 5.27 +/- 0.75 cleavage planes, mean +/- SD, P < 0.05, data for lowest energy for each system). The same was true in noncalcified atheroma (2.48 +/- 0.71 vs. 6.43 +/- 1.09, P < 0.05) and calcified atheroma (2.47 +/- 1.21 vs. 6.27 +/- 1.13, P < 0.05). This effect was similar at all energy levels, with a trend for more damage at higher energies in both systems. This study demonstrates that midinfrared lasing causes less acoustic damage than excimer lasing when using clinical catheters, energy levels, and pulsing strategies. This effect is independent of tissue-type but tends to be dose-related. These findings may explain, in part, the differences in dissection rates seen clinically.

In vivo estimation of elastic properties of arteries with intracoronary ultrasound

In this study we estimate elastic properties Of epicardial arteries before and after coronary intervention using intracoronary ultrasound (XCUS). We developed a method for incorporating the blood pressure signal from the coronary ostium into the ultrasound image. Data were collected in six pa t ien ts dur ing coronary intervention. T h e pressure elastic modulus, incremental elastic moduIus, distensibility and circumferential s t r a in a r e quantified at the stenotic site before and after intervention. We find improvement in mechanical properties of the coronary arteries after intervention. We conclude that estimation o f elastic properties of coronary arteries will be useful in comparing different types of interventions. Changes in elastic properties may also provide useful information in the study of regression or restenosis of atherosclerotic disease.

1000–35 Differential Sizing for Balloon Angloplasty: Preliminary Results Using a New “Focal” Balloon with an Expanding Central Section

The majority of lesions treated by conventional balloon angioplasty (PTCA) are focal and less than 10xa0mm in length. We sought to develop a balloon which could deliver dilating force to the stenosis in a “focal” manner and potentially decrease the chances of proximal and distal vessel dissection due to overexpansion. The CAT balloon (CVD, Irvine, CA) uses variably compliant material to maintain the proximal and distal 5xa0mm ends of the balloon at a constant diameter while allowing the central 10xa0mm “focal” segment to expand above nominal diameter at higher pressures. The additional central diameter achievable is approximately 0.7xa0mm at 16 atm. A prototype 2.5xa0mm (nominal) balloon was used in 30 lesions (23 pts). Success was achieved in all but 1 case (no balloon would cross). In 3 cases, predilation with axa0lxa02.0xa0mm balloon was required. In two lesions a larger balloon was subsequently used. Quantitative analysis was available for 15 lesions. Diameter stenosis was reduced from 65xa0±xa015% to 23xa0±xa014%. There was one type A dissection and no complications. Initial inflation pressures averaged 6.0xa0±xa01.4 atm and final pressures 11.3xa0±xa02.7 atm. QCA measured balloon diameters over a range of pressures from 3 to 16 atm showed progressive relative enlargement of the center section with increased pressures (r xa0=xa00.52). At pressuresxa0lxa010 atm the balloon center was 0.11xa0mm (5.6%) larger than the ends while at pressuresxa0≥xa010 atm, the center was 0.44xa0mm (20.8%) larger (range 0.06 to 0.96xa0mm). Conclusion In this pilot series, the CAT focal balloon with a central expanding section was effectively used to dilate coronary lesions without complications and with a high success rate. A randomized trial is planned to determine if this design has advantages over standard balloon catheters.