Erbel, Raimund

Background: Cardiovascular risk factors have an impact on coronary atherosclerosis evolution. However, there is only limited information about the relationship between risk and atherosclerotic plaque as measured invasively by Intravascular Ultrasound Radiofrequency (IVUS-RF) analysis. The Aim of this study was to assess the impact of cardiovascular risk factors not only on overall coronary plaque volume but on coronary plaque composition. Methods: 990 patients from 42 centers were enrolled in the prospective, multicenter, non randomized, global VH-IVUS registry. Coronary lesions were measured by conventional and IVUS-VH parameters using 20MHz Intravascular Ultrasound catheter. The four IVUS-VH plaque components (Dense Calcium-DC, Necrotic Core-NC, Fibrous tissue-F, Fibro Fatty-FF) were analyzed in every recorded frame. The results were expressed as mean cross-sectional areas, and percentage of total plaque volume. Risk factor assessment included correlation with family history of myocardial infarction, past or current smoking, diabetes mellitus, hypertension, and laboratory measurements. Results: Patients with diabetes have an increased relative amount of NC (6.47±0.28% vs. 5.86±0.14%, p=0.037) and DC (4.58±0.27% vs. 3.90±0.14%, p=0.017), Patients with hypertension have an increased relative amount of FF, DC (4.35±0.16% vs. 3.57±0.17%, p=0.02) and NC (6.24±0.17% vs. 5.60±0.19%, p=0.01). Compared with patients with LDL cholesterol 160 mg/dl had higher plaque volume (342.1±26.2mm 3 vs. 318.6±10.7mm 3 ). Linear Regression Analysis showed a correlation between the level of HDL and F (r=−0.149, p<0.01), FF (r=−0 –106, p< 0.01), and NC (r=−0.90, p<0.05). The level of LDL correlated with F (r = 0.110, p < 0.01). Patients with prior MI have an increased percentage of F (30.03±0.59 % vs. 28.20±0.37 %, p<0.009). Smoking had no relevant effect on plaque composition. Conclusion: IVUS-RF analysis detects marked differences in coronary plaque depending on the risk factor profile with particular focus on lipid levels. Patients with greater amounts of necrotic core were associated with hypertension, myocardial infarction, and low HDL. This may have implications for prognosis and systemic treatment of patients with coronary artery disease.

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 ≥1.03 mm 2 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.

Background An atrial septal aneurysm (ASA) is a well-recognized abnormality of uncertain clinical relevance. We reevaluated the clinical significance of ASA in a large series of patients. The aims of the study were to define morphological characteristics of ASA by transesophageal echocardiography (TEE), to define the incidence of ASA-associated abnormalities, and to investigate whether certain morphological characteristics of ASA are different in patients with and without previous events compatible with cardiogenic embolism. Methods and Results Patients with ASA were enrolled from 11 centers between May 1989 and October 1993. All patients had to undergo transthoracic and transesophageal echocardiography within 24 hours of each other; ASA was defined as a protrusion of the aneurysm >10 mm beyond the plane of the atrial septum as measured by TEE. Patients with mitral stenosis or prosthesis or after cardiothoracic surgery involving the atrial septum were excluded. Based on these criteria, 195 patients 54.6±16.0 years old (mean±SD) were included in this study. Whereas TEE could visualize the region of the atrial septum and therefore diagnose ASA in all patients, ASA defined by TEE was missed by transthoracic echocardiography in 92 patients (47%). As judged from TEE, ASA involved the entire septum in 100 patients (51%) and was limited to the fossa ovalis in 95 (49%). ASA was an isolated structural defect in 62 patients (32%). In 106 patients (54%), ASA was associated with interatrial shunting (atrial septal defect, n=38; patent foramen ovale, n=65; sinus venosus defect, n=3). In only 2 patients (1%), thrombi attached to the region of the ASA were noted. Prior clinical events compatible with cardiogenic embolism were associated with 87 patients (44%) with ASA; in 21 patients (24%) with prior presumed cardiogenic embolism, no other potential cardiac sources of embolism were present. Length of ASA, extent of bulging, and incidence of spontaneous oscillations were similar in patients with and without previous cardiogenic embolism; however, associated abnormalities such as atrial shunts were significantly more frequent in patients with possible embolism. Conclusions As shown previously, TEE is superior to the transthoracic approach in the diagnosis of ASA. The most common abnormalities associated with ASA are interatrial shunts, in particular patent foramen ovale. In this retrospective study, patients with ASA (especially with shunts) showed a high frequency of previous clinical events compatible with cardiogenic embolism; in a significant subgroup of patients, ASA appears to be the only source of embolism, as judged by TEE. Our data are consistent with the view that ASA is a risk factor for cardiogenic embolism, but thrombi attached to ASA as detected by TEE are apparently rare.

Background —Residual reduction of relative coronary flow velocity reserve (rCVR) after successful coronary intervention has been related to microvascular impairment. However, the incidence of cardiac enzyme elevation as a surrogate marker of an underlying embolic myocardial injury in these cases has not been studied. Methods and Results —A series of 55 consecutive patients with successful coronary stenting, periprocedural intracoronary Doppler analysis, and determination of creatine kinase (CK; upper limit of normal [ULN] for women 70 IU/L, for men 80 IU/L) and cardiac troponin T (cTnT; bedside test, threshold 0.1 ng/mL) before and 6, 12, and 24 hours after intervention were studied. Postprocedural rCVR was the only intracoronary Doppler parameter that independently correlated with cTnT ( r =−0.498, P <0.001) and CK outcome ( r =−0.406, P =0.002). Receiver operating characteristic analysis identified a postprocedural rCVR of 0.78 as the best discriminating value, with a sensitivity of 83.3% and 69.2% and a specificity of 79.1% and 76.2% for detection of cTnT and CK elevation, respectively. Stratified according to this cutoff value, the incidence of cTnT elevation was 52.6% in patients with (n=19) and 5.6% in patients without (n=36) a postprocedural rCVR <0.78 ( P <0.001), associated with a CK elevation >1 times the ULN in 36.8% and 5.6% ( P =0.005) of patients, respectively. Conclusions —Cardiac marker elevation can frequently be found after coronary procedures that are associated with a persistent reduction of rCVR, indicating procedural embolization of atherothrombotic debris with microvascular impairment and myocardial injury as a potential underlying mechanism.

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.