Dietrich Baumgart

Comparison of Electron Beam Computed Tomography With Intracoronary Ultrasound and Coronary Angiography for Detection of Coronary Atherosclerosis

OBJECTIVES This analysis compared the results of electron beam computed tomography (EBCT) with those of coronary angiography and intracoronary ultrasound (ICUS) for the in vivo detection of coronary atherosclerotic plaques. BACKGROUND EBCT is a new imaging modality for identification of coronary calcifications. Coronary angiography depicts advanced changes in coronary morphology, whereas ICUS is an established diagnostic tool that detects the early stages of coronary artery disease. METHODS In 57 patients (54 +/- 9 years old), 267 coronary segments were analyzed with EBCT (3-mm slices, acquisition time 100 ms, threshold definition of coronary calcification at 130 Hounsfield units in an area > or = 1 mm2, Agatston calcium score), coronary angiography and ICUS. The analysis was based on the number and extent of coronary calcifications on EBCT, coronary lumen reduction on coronary angiography and plaque formation with and without ultrasound signs of calcifications on ICUS. RESULTS Compared with coronary angiography, EBCT yielded a sensitivity of 66%, a specificity of 78%, a positive predictive value of 39% and a negative predictive value of 91%. Compared with ICUS, EBCT yielded an overall sensitivity of 66%, a specificity of 88% and an overall accuracy of 81%. For plaques with and without ultrasound signs of calcifications, the sensitivity of EBCT was 97% and 47%, specificity 80% and 75% and overall accuracy 82% and 69%, respectively. CONCLUSIONS This in vivo correlation between ICUS and EBCT demonstrates that EBCT is a noninvasive method that helps to visualize the atherosclerotic process by localization and quantification of coronary artery calcifications. EBCT detects calcified plaques with high accuracy. Plaques without ultrasound signs of calcifications can be detected by EBCT but with lower sensitivity but equivalent specificity.

Endoluminal Beta-Radiation Therapy for the Prevention of Coronary Restenosis after Balloon Angioplasty

BACKGROUND: Beta radiation is effective in reducing vascular neointimal proliferation in animals after injury caused by balloon angioplasty. However, the lowest dose that can prevent restenosis after coronary angioplasty has yet to be determined. METHODS: After successful balloon angioplasty of a previously untreated coronary stenosis, 181 patients were randomly assigned to receive 9, 12, 15, or 18 Gy of radiation delivered by a centered yttrium-90 source. Adjunctive stenting was required in 28 percent of the patients. The primary end point was the minimal luminal diameter six months after treatment, as a function of the delivered dose of radiation. RESULTS: At the time of follow-up coronary angiography, the mean minimal luminal diameter was 1.67 mm in the 9-Gy group, 1.76 mm in the 12-Gy group, 1.83 mm in the 15-Gy group, and 1.97 mm in the 18-Gy group (P=0.06 for the comparison of 9 Gy with 18 Gy), resulting in restenosis rates of 29 percent, 21 percent, 16 percent, and 15 percent, respectively (P=0.14 for the comparison of 9 Gy with 18 Gy). At that time, 86 percent of the patients had had no serious cardiac events. In 130 patients treated with balloon angioplasty alone, restenosis rates were 28 percent, 17 percent, 16 percent, and 4 percent, respectively (P=0.02 for the comparison of 9 Gy with 18 Gy). Among these patients, there was a dose-dependent enlargement of the lumen in 28 percent, 50 percent, 45 percent, and 74 percent of patients, respectively (P<0.001 for the comparison of 9 Gy with 18 Gy). The rate of repeated revascularization was 18 percent with 9 Gy and 6 percent with 18 Gy (P=0.26). CONCLUSIONS: Intracoronary beta radiation therapy produces a significant dose-dependent decrease in the rate of restenosis after angioplasty. An 18-Gy dose not only prevents the renarrowing of the lumen typically observed after successful balloon angioplasty, but actually induces luminal enlargement.

Plaque Distribution and Vascular Remodeling of Ruptured and Nonruptured Coronary Plaques in the Same Vessel: An Intravascular Ultrasound Study In Vivo

OBJECTIVES This study was designed to identify potential differences between the intravascular ultrasound (IVUS) characteristics of spontaneously ruptured and nonruptured coronary plaques. BACKGROUND The identification of vulnerable plaques in vivo may allow targeted prevention of acute coronary events and more effective evaluation of novel therapeutic approaches. METHODS Intravascular ultrasound was used to identify 29 ruptured plaques in arteries containing another nonruptured plaque in an adjacent segment. Intravascular ultrasound characteristics of these plaques were compared with plaques of computer-matched controls without evidence of plaque rupture. Plaque distribution was assessed by measuring the eccentricity of lumen location (inside the total vessel). Lumen cross-sectional area narrowing was calculated as [1 - (target/reference lumen area)] x 100%. A remodeling index was calculated as lesion/reference arterial area (>1.05 = compensatory enlargement, <0.95 = shrinkage). RESULTS Among the three groups of plaques, there was no significant difference in quantitative angiographic parameters, IVUS reference dimensions and IVUS lumen cross-sectional area narrowing. There was a difference in plaque distribution; lumen location by IVUS was significantly more eccentric in ruptured than in nonruptured (p = 0.002) and control plaques (p < 0.0001). The arc of disease-free vessel wall was larger in ruptured than in control plaques (p < 0.0001). The remodeling pattern of ruptured and nonruptured plaques differed significantly from that of the control plaques (p = 0.0001 and 0.003); compensatory enlargement was found in 66%, 48%, and 17%, whereas shrinkage was found in 7%, 10% and 48%, respectively. CONCLUSIONS Intravascular ultrasound assessment of plaque distribution and vascular remodeling may help to classify plaques with the highest probability of spontaneous rupture.

α-Adrenergic Coronary Vasoconstriction and Myocardial Ischemia in Humans

The use of quantitative coronary angiography, combined with Doppler and PET, has recently been directed at the study of alpha-adrenergic coronary vasomotion in humans. Confirming prior animal experiments, there is no evidence of alpha-adrenergic coronary constrictor tone at rest. Again confirming prior experiments, responses to alpha-adrenoceptor activation are augmented in the presence of coronary endothelial dysfunction and atherosclerosis, involving both alpha(1)- and alpha(2)-adrenoceptors in epicardial conduit arteries and microvessels. Such augmented alpha-adrenergic coronary constriction is observed during exercise and coronary interventions, and it is powerful enough to induce myocardial ischemia and limit myocardial function. Recent studies indicate a genetic determination of alpha(2)-adrenergic coronary constriction.

Coronary Artery Calcium in Acute Coronary Syndromes A Comparative Study of Electron-Beam Computed Tomography, Coronary Angiography, and Intracoronary Ultrasound in Survivors of Acute Myocardial Infarction and Unstable Angina

BACKGROUND Quantification of coronary artery calcified plaques by electron-beam CT (EBCT) may predict cardiovascular events. However, whereas advanced coronary atherosclerotic plaques can be identified, mildly stenotic lipid-rich (soft) plaques may be difficult to detect. The value of EBCT in a subgroup of patients has therefore been questioned. To investigate this, we evaluated patients with acute coronary syndromes by EBCT and compared the results with coronary angiography and, in patients with an indeterminate angiogram, intracoronary ultrasound (ICUS). METHODS AND RESULTS EBCT was performed in 118 consecutive patients (57+/-11 years of age) with previous myocardial infarction (n=101) or unstable angina (n=17). A standard protocol requiring a CT density >130 Hounsfield units in an area > or =1.03 mm2 was used for the definition of coronary artery calcium. We found that 110 patients had moderate to severe coronary artery disease by coronary angiography, and 8 had either mildly stenotic plaques at a single site (4 patients, confirmed by ICUS) or nonatherosclerotic causes of the unstable coronary syndrome (4 patients). One hundred and five of the 110 patients (96%) with moderate to severe angiographic disease but only 1 of the 8 other patients (13%) had a positive EBCT. Patients with acute coronary syndromes and negative EBCTs were significantly younger than patients with positive EBCTs (46+/-12 versus 58+/-10 years, P<.001), and a higher percentage was actively smoking (100% of the smokers versus 46%, P<.05). CONCLUSIONS The vast majority of patients with acute coronary syndromes and at least moderate angiographic disease have identifiable coronary calcium by EBCT. Those patients with negative EBCTs have minimal or no atherosclerotic plaque formation. They are younger and tend to be active cigarette smokers.

Preprocedural statin medication reduces the extent of periprocedural non-Q-wave myocardial infarction.

Background—Stenting-related myocardial injury has been recognized as a frequent and prognostically important event, the extent of which depends on microcirculatory impairment in association with platelet aggregation, inflammation, and increased oxidative stress. Recent studies underscored the non–lipid-lowering effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) with antithrombotic, antiinflammatory, and antioxidative aspects. Thus, we tested the hypothesis that preprocedural statin therapy is associated with a reduction in the extent of stenting-related myocardial injury. Methods and Results—We stratified 296 consecutive patients who were undergoing stenting of a de novo stenosis according to the preprocedural status of statin therapy (229 statin-treated and 67 control patients). Incidence of periprocedural myocardial injury was assessed by analysis of creatine kinase (CK; upper limit of normal [ULN] 70 IU/L for women, 80 IU/L for men) and cardiac troponin T (cTnT; bedside test; threshold 0.1 ng/mL) before and 6, 12, and 24 hours after the intervention. Relative to control patients, the incidence of CK elevation >3× ULN was more than 90% lower in statin-treated patients (0.4% versus 6.0%, P =0.01). Statin therapy was the only factor independently associated with a lower risk of CK elevation >3× ULN (OR: 0.08, 95% CI: 0.01 to 0.75;P =0.03). The overall incidences of CK and cardiac troponin T elevation were slightly lower in statin-treated than in control patients (14.4% versus 20.9%, P =0.3, and 17.9% versus 22.4%, P =0.5, respectively). Conclusions—Preprocedural statin therapy is associated with a reduction in the incidence of larger-sized, stenting-related myocardial infarctions. Prospective, randomized trials are warranted to further assess this cardioprotective effect of statins in coronary intervention.

Relation Between Progression and Regression of Atherosclerotic Left Main Coronary Artery Disease and Serum Cholesterol Levels as Assessed With Serial Long-Term (≧=">12 Months) Follow-Up Intravascular Ultrasound

Background—The relation between serum lipids and risk of coronary events has been established, but there are no data demonstrating directly the relation between serum low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol versus serial changes in coronary plaque dimensions. Methods and Results—We performed standard analyses of serial intravascular ultrasound (IVUS) studies of 60 left main coronary arteries obtained 18.3±9.4 months apart to evaluate progression and regression of mild atherosclerotic plaques in relation to serum cholesterol levels. Overall, there was (1) a positive linear relation between LDL cholesterol and the annual changes in plaque plus media (P&M) cross-sectional area (CSA) (r =0.41, P <0.0001) with (2) an LDL value of 75 mg/dL as the cutoff when regression analysis predicted on average no annual P&M CSA increase; (3) an inverse relation between HDL cholesterol and annual changes in P&M CSA (r =−0.30, P <0.02); (4) an inverse relation between LDL cholesterol and annual changes in lumen CSA (r =−0.32, P <0.01); and (5) no relation between LDL and HDL cholesterol and the annual changes in total arterial CSA (remodeling). Despite similar baseline IVUS characteristics, patients with an LDL cholesterol level ≥120 mg/dL showed more annual P&M CSA progression and lumen reduction than patients with lower LDL cholesterol. Conclusions—There is a positive linear relation between LDL cholesterol and annual changes in plaque size, with an LDL value of 75 mg/dL predicting, on average, no plaque progression. HDL cholesterol shows an inverse relation with annual changes in plaque size.

Screening of ruptured plaques in patients with coronary artery disease by intravascular ultrasound

AIM To visualise the characteristics of ruptured plaques by intravascular ultrasound (IVUS) and to correlate plaque characteristics with clinical symptoms to establish a quantitative index of plaque vulnerability. METHODS 144 consecutive patients with angina were examined using IVUS. Ruptured plaques, characterised by a plaque cavity and a tear on the thin fibrous cap, were identified in 31 patients (group A), of whom 23 (74%) presented with unstable angina. Plaque rupture was confirmed by injecting contrast medium filling the plaque cavity during IVUS examination. Of the patients without plaque rupture (group B, n = 108), only 19 (18%) had unstable angina. RESULTS No significant differences were found between groups A and B in relation to plaque and vessel area (p > 0.05). Mean (SD) per cent stenosis in group A was less than in group B, at 56.2 (16.5)% v67.9 (13.4)%; p < 0.001. Area of the emptied plaque cavity in group A (4.1 (3.2) mm2) was larger than the echolucent zone in group B (1.32 (0.79) mm2) (p < 0.001). The plaque cavity to plaque ratio in group A (38.5 (17.1)%) was larger than the echolucent area to plaque ratio in group B (11.2 (8.9)%) (p < 0.001). The thickness of the fibrous cap in group A was less than in group B, at 0.47 (0.20) mm v 0.96 (0.94) mm; p < 0.001. CONCLUSIONS Plaques seem to be prone to rupture when the echolucent area is larger than 4.1 (3.2) mm2, when the echolucent area to plaque ratio is greater than 38.5 (17.1)%, and when the fibrous cap is thinner than 0.7 mm. IVUS can identify plaque rupture and vulnerable plaques. This may influence patient management and treatment.

G Protein β3 Subunit 825T Allele and Enhanced Coronary Vasoconstriction on α2-Adrenoceptor Activation

Abstract—Recently, α2-adrenoceptor activation was shown to play an important role in the vasoconstriction of normal coronary arteries, whereas in the presence of atherosclerosis, the activation of both α1- and α2-adrenoceptors reduces coronary blood flow in humans. α2-Adrenoceptors activate pertussis toxin (PTX)-sensitive G proteins, whereas α1-adrenoceptors couple to PTX-insensitive G proteins. Thus, the 825T allele of the β3 subunit of heterotrimeric G proteins, associated with enhanced PTX-sensitive G protein signaling, was expected to determine the α2-adrenoceptor–, but not the α1-adrenoceptor–, mediated reduction in coronary blood flow (CBF). Genotyping was performed on 48 individuals. Twelve of the 48 received the α1-adrenoceptor agonist methoxamine (MTX; 5 mg IC), and 12 received the α2-adrenoceptor agonist BHT 933 (BHT; 5 mg IC). Twenty-four additional individuals received both MTX and BHT during the same investigational procedure. CBF was calculated on the basis of coronary angiography and intrac...

Improved Assessment of Coronary Stenosis Severity Using the Relative Flow Velocity Reserve

BACKGROUND Myocardial fractional flow reserve (FFR) is based on pressure measurements. We have now sought to establish a Doppler-based concept of relative flow velocity reserve (RFVR) for the functional assessment of stenosis severity in epicardial coronary arteries. A clear threshold value to discriminate the functional severity of a coronary stenosis does not exist for coronary flow velocity reserve (CVR) based on intracoronary Doppler measurements. In contrast, the concept of FFR, which is based on intracoronary pressure measurements, has been extensively validated. An FFR value below 0.75 reliably indicates a significant stenosis. METHODS AND RESULTS RFVR is calculated as the ratio between distal CVR in the stenosed target vessel and distal CVR in a nonstenotic reference vessel. In 21 patients, RFVR was determined in 24 target vessels by use of intracoronary adenosine and correlated to the FFR, determined as the ratio of mean poststenotic to aortic pressures, in the target vessel. Stenosis severity was classified according to quantitative coronary angiography analysis. Reference diameter was 3.0+/-0.4 mm (mean+/-SD), and area stenosis was 74+/-15% (range, 40% to 95%). CVRs in the target and reference vessels were 2.1+/-0.5 and 2.6+/-0.7, respectively. FFR ranged from 0.49 to 0.99 (mean, 0.81+/-0.15) and RFVR from 0.53 to 1.0 (mean, 0.82+/-0.13). Poststenotic CVR did not correlate with either percent area stenosis (r=0.27, P=NS) or FFR (r=0.33, P=NS). In contrast, FFR as well as RFVR showed a curvilinear relation to percent area stenosis (r=0.89, P<0.0001 and r=0.79, P<0.0001, respectively). There was a close linear correlation between FFR and RFVR (r=0.91, P<0.0001). CONCLUSIONS RFVR correlates closely to FFR and to percent area stenosis, whereas the correlation of CVR with FFR and percent area stenosis is rather poor. RFVR is a promising new concept for assessment of coronary stenosis severity and clinical decision making based on Doppler measurements.