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Background: The long-term effects of treatment with sirolimus-eluting stents, as compared with bare-metal stents, have not been established., Methods: We performed an analysis of individual data on 4958 patients enrolled in 14 randomized trials comparing sirolimus-eluting stents with bare-metal stents (mean follow-up interval, 12.1 to 58.9 months). The primary end point was death from any cause. Other outcomes were stent thrombosis, the composite end point of death or myocardial infarction, and the composite of death, myocardial infarction, or reintervention., Results: The overall risk of death (hazard ratio, 1.03; 95% confidence interval [CI], 0.80 to 1.30) and the combined risk of death or myocardial infarction (hazard ratio, 0.97; 95% CI, 0.81 to 1.16) were not significantly different for patients receiving sirolimus-eluting stents versus bare-metal stents. There was a significant reduction in the combined risk of death, myocardial infarction, or reintervention (hazard ratio, 0.43; 95% CI, 0.34 to 0.54) associated with the use of sirolimus-eluting stents. There was no significant difference in the overall risk of stent thrombosis with sirolimus-eluting stents versus bare-metal stents (hazard ratio, 1.09; 95% CI, 0.64 to 1.86). However, there was evidence of a slight increase in the risk of stent thrombosis associated with sirolimus-eluting stents after the first year., Conclusions: The use of sirolimus-eluting stents does not have a significant effect on overall long-term survival and survival free of myocardial infarction, as compared with bare-metal stents. There is a sustained reduction in the need for reintervention after the use of sirolimus-eluting stents. The risk of stent thrombosis is at least as great as that seen with bare-metal stents., (Copyright 2007 Massachusetts Medical Society.)

Objective: The electron-beam computed tomography-(EBCT-)derived calcium score provides a measure of coronary atherosclerotic plaque disease which may allow for more precise risk stratification in symptomatic patients. However, it remains unclear if EBCT can add prognostic information compared with the clinical information derived from risk factor assessment, exercise stress testing, and coronary angiography., Methods and Results: A cohort of 300 consecutive patients with recent (<3 months) onset of symptoms was retrospectively identified who were examined for possible coronary artery disease (CAD) and who all underwent EBCT. Successful follow-up after 3.5 years was obtained in 255 (85%) patients whose mean age at baseline was 58+/-11 years (n = 181 (71%), males). Four clinical categories with increasing evidence of CAD were constructed on the basis of risk factor assessment, exercise stress testing, coronary angiographic anatomy, and coronary revascularization at baseline. During follow-up, major adverse cardiac events (MACE: myocardial infarction, cardiac death, revascularization) were observed in 40 (16%) patients, including myocardial infarction and cardiac death in 5 patients. The 4 clinical categories were highly predictive of MACE, with a relative risk estimate of 28.3 (95% CI, 6.7-119.1) in the upper vs. the reference category. In univariate analysis, the relative risk estimate of MACE associated with a calcium score > or =100 was 12.0 (95% CI, 4.7-30.6). After adjustment for the clinical categories and for age, this estimate decreased in multivariate analysis, but remained predictive at 4.4 (95% CI, 1.5-12.6)., Conclusion: In patients with first-time evaluation of possible CAD, EBCT-derived coronary calcium is suggested to provide for independent and additional information compared with the clinically available information.

Despite advances in the interventional treatment of coronary disease, diabetics still have double the case fatality rate as nondiabetics. The purpose of this analysis from the Radiation in Europe With Novoste (RENO) registry was to assess the clinical and angiographic 6-month outcome of diabetic patients in comparison to nondiabetic patients after localized beta-radiation. A total of 1,098 patients (83.8% with in-stent restenosis) treated with the Novoste Beta-Cath system in Europe were enrolled in the RENO registry. Diabetes was, irrespective of the type of lesion treated, no significant risk factor for major adverse cardiac events or target vessel revascularization. Individuals with diabetes (n = 256) and without diabetes (n = 833) displayed no significant differences concerning clinical or angiographic endpoints. Vascular brachytherapy appears to be the first technique to even out the increased risk of diabetic patients undergoing percutaneous coronary interventions in the routine clinical setting. Thus, intracoronary brachytherapy represents a promising treatment option for diabetic patients., (Copyright 2004 Wiley-Liss, Inc.)

The 825T allele of a polymorphism at GNB3, encoding the G protein beta(3) subunit, is associated with an enhanced coronary blood flow (CBF) reduction in response to alpha(2)-, but not to alpha(1)-adrenoceptor activation. Because the regulation of vascular tone by alpha(2)-adrenoceptors includes direct vasoconstriction as well as vasodilatation by endothelial release of nitric oxide, the eNOS Glu298Asp variant might further contribute to explain the variability of CBF reduction in response to alpha-adrenoceptor activation. Genotyping at the GNB3 and the eNOS gene was performed on 48 individuals receiving either the alpha(1)-adrenoceptor agonist methoxamine (5 mg i.c.) and/or the alpha(2)-adrenoceptor agonist BHT 933 (5 mg i.c.). CBF was calculated from quantitative coronary angiography and intracoronary Doppler flow velocity measurement. To analyse the impact of genotypes and coronary artery disease, a linear regression model was used, including cholesterol levels, heart rate, smoking and mean aortic blood pressure. An initial, univariate analysis suggested an impact of the eNOS Glu298Asp variant on alpha(2)-adrenoceptor-induced coronary constriction (CBF reduction 53.4 ch006.1 TT/TG versus 30.7 ch006.9% GG; P = 0.003). However, multifactorial analysis showed that the GNB3825T allele was associated exclusively with the CBF reduction on alpha(2)-adrenoceptor activation (58.2 +/- 4.4% TT/TC versus 27.9 +/- 4.3% CC; P < 0.0001). Contrary to the initial analysis, the Glu298Asp variant of the eNOS gene provides no additional information on the genetic basis of alpha(2)-adrenoceptor-induced coronary vasoconstriction, which appears exclusively associated to the 825T allele at GNB3. Analysis of modifying genes appears crucial for the understanding of genetic associations.

Background: The development of interventional cardiology (PCI) started already with the introduction of catheterization but was pushed forward by A. Grüntzig with the percutaneous transluminal coronary angioplasty (PTCA) 1977. In the beginning very slow progress could be observed. This changed when Grüntzig changes to Emory university, Atlanta. Already after 10 years alternative techniques were introduced like stent implantation and rotablation, coronary atherectomy, laser angioplasty, ultrasound therapy. During the following years, it became obvious that only for stent implantation (see W. Rutsch et al, Berlin, p.481) and rotablation (see T. Dill et al, Bad Nauheim, p.502) standard indications could be seen in addition to PTCA. Brachytherapy for treatment of in stent restenosis and laserwire recanalisation of occluded vessels were added., New Methods: New protection systems - aspiration or filters - were introduced for increase of PCI safety in venous bypass stenosis (see C. Hamm et al, Bad Nauheim, p.527). The main step forward seems to be the introduction of drug eluting covered stent either with polymer (see E. Grube et al, Siegburg, p.508) or ceramic coating (see H. Wieneke et al, Essen, p.518). Restenosis rates, which were already reduced by bare stent for 20-30%, could be lowered below 10%., Results: In patients with diabetes and main stem stenosis or multi vessel disease, coronary artery bypass surgery is indicated, but in other patients PCI seems to be as good as surgery in relation to mortality and myocardial infarction rates. With drug eluting stents the role of PCI may become even more pronounced, because the revascularization rate could be further reduced (see W. Rutsch, Berlin, p.481)., Conclusion: The future will demonstrate even further main steps for interventions like the percutaneous bypass attempts and the introduction of gen-therapy (A. B. Buchwald, Göttingen, p.533). Meanwhile we can observe a drop of 1-2% mortality in coronary artery disease related to 60% influence of prevention and 40% to advanced PCI therapy. This is still a remarkable successful story in medicine provided by cardiology.

We present the case of 67-year-old man with exertional chest pain. Coronary angiography revealed myocardial bridging of the left anterior descending coronary artery (LAD) with mild systolic vessel compression. An intracoronary Doppler sonographic examination of the LAD showed a fingertip-shaped antegrade flow pattern with a steep acceleration of coronary flow velocity during early diastole, followed by a steep deceleration and then a plateau in the coronary flow velocity during mid and late diastole. An intravascular sonographic examination using a 30-MHz transducer catheter showed eccentric vessel compression during systole and substantial augmentation of vessel compression after an incidental extrasystole. Both intracoronary Doppler sonography and intravascular sonography provided important information that helped us to identify myocardial bridging in this patient., (Copyright 2002 Wiley Periodicals, Inc.)

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: Distal coronary flow velocity reserve (CVR) is significantly improved after a successful balloon angioplasty (PTCA). Furthermore, a postinterventional CVR >2.5 and a percent diameter stenosis (%DS) 0.88 was the best single predictor of MACE, with an incidence of 6.8%, whereas the combination of a CVR(rel)>0.88 and a %DS

Electron-beam CT may assess the progression of coronary atherosclerosis by visualizing changes in calcification. The present investigation analyzes (1) the rate of progression of calcification in symptomatic patients, (2) the topographic pattern, and (3) the influence of baseline plaque burden and risk factors. Progression of calcification during a mean (median) interval of 18 (15) months was measured in 102 symptomatic outpatients (aged 59+/-9 years, 80% male) with calcification. In 4 patient groups with a baseline total score (Agatston criteria) of 1 to 30, >30 to 100, >100 to 400, and >400, the median was 3.1, 26.1, 58.9, and 109.7, respectively, for absolute annual progression of the score (P<0.05) and 57%, 49%, 32%, and 15%, respectively, for relative progression (P<0.05). On the coronary segmental level, changes were largely restricted to typical predilection sites of coronary atherosclerosis. The presence of angiographically defined coronary narrowing influenced absolute, but not relative, progression. Of the risk factors, only low density lipoprotein cholesterol levels showed a trend, although not significant, for predicting progression. These data indicate that baseline plaque burden determines the rate of progression of calcification. This appears to be a coronary systemic process, reflecting the natural history of coronary atherosclerosis.

Intracoronary irradiation is currently the most promising approach to reduce restenosis after percutaneous transluminal coronary angioplasty. Meanwhile numerous data are available concerning efficacy and safety of this novel method. These data confirm the results of preclinical studies that reported a dramatic reduction of neo-intima proliferation and negative remodeling. However, the number of reports on an elevated incidence of late stent thrombosis (> 30 days post intervention) are increasing. It is commonly suggested that the delayed neo-intima formation within vascular stents is responsible for this new phenomenon. We report the case of a 48-year-old man who underwent coronary irradiation therapy after stent placement in a de-novo/restenotic lesion. Despite an explicit recommendation of a combined anti-aggregatory therapy consisting of ticlopidine and acetysalicylic acid for at least 6 months, ticlopidine was withdrawn after 4 weeks. Two weeks later, the patient was readmitted to an external hospital with an acute myocardial infarction and successfully treated with thrombolysis. The angiographic and intravascular control, which was conducted after another two weeks, showed absolutely no neointima formation within the implanted stent. Thus, a late thrombotic occlusion of the implanted stent appears most likely to be the cause underlying the myocardial infarction. This case underlines, together with other existing reports, the importance of a prolonged, combined anti-aggregatory therapy after stent placement and subsequent intracoronary irradiation.

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.

Aims: Exercise stress testing is often used as the initial non-invasive diagnostic test in symptomatic patients with suspected obstructive coronary artery disease. Positive standard ECG criteria are quite specific for obstructive coronary artery disease, but there may be a substantial number of false negative tests, including patients with severe coronary artery disease. Also, exercise stress tests frequently yield equivocal results. Instead of detecting the functional consequences, electron-beam computed tomography visualized atherosclerotic plaque disease directly, but its relationship to functional testing has not been clearly delineated. It was the aim of the current study to examine electron-beam computed tomography for the identification of obstructive coronary artery disease in patients with a normal, abnormal, or equivocal exercise stress test., Methods and Results: Symptomatic patients referred for coronary angiography were prospectively included in a consecutive manner if they had no prior diagnosis of coronary artery disease and an unremarkable resting ECG. All patients underwent both exercise stress test and electron-beam computed tomography on the day before coronary angiography. Standard protocols and ECG criteria to diagnose inducible ischaemia were used for the exercise stress test. The electron-beam computed tomography-derived total calcium score was computed according to standard Agatston criteria. Of the 323 patients (mean age, 55+/-11 years; 77% male), 179 (55%) had obstructive coronary artery disease, defined angiographically as luminal diameter narrowing >/=50%. A normal exercise stress test was documented in 105 patients (32.5%), an abnormal exercise stress test ('diagnostic for ischaemia') in 113 (35%), and an equivocal exercise stress test ('inadequate exercise or non-diagnostic ECG-changes') in 105 (32.5%). Multivariate analysis indicated that exercise stress test and electron-beam computed tomography yielded independent information for predicting obstructive coronary artery disease. Sensitivity, specificity and overall accuracy of the exercise stress test were 71%, 75% and 73%, respectively, if equivocal tests were not included, and 50%, 84% and 65% if they were included. Irrespective of the cutpoint regarded as 'positive', the overall accuracy of the electron-beam computed tomography-derived calcium score remained approximately 80% in patients with a normal, abnormal or equivocal exercise stress test. In patients with an equivocal and - to a lesser degree - with a normal exercise stress test, electron-beam computed tomography was able to significantly improve classification regarding obstructive coronary artery disease. Electron-beam computed tomography added no incremental predictive value in patients with an abnormal exercise stress test., Conclusion: In patients who are judged to have an intermediate post-test probability of disease after exercise stress test, electron-beam computed tomography scanning may be a meaningful strategy for further stratification regarding the likelihood of obstructive coronary artery disease., (Copyright 2000 The European Society of Cardiology.)

Background: With the introduction of Doppler-tipped guide wires, intracoronary Doppler flow measurement has been increasingly accepted as an additional diagnostic approach in the catheterization laboratory. However, the safety of intracoronary Doppler flow measurement has not been well-investigated. The purpose of our study was to evaluate the safety of intracoronary Doppler flow measurement using the Doppler FloWire (Cardiometrics, Mountain View, Calif)., Methods and Results: A total of 906 patients were examined by intracoronary Doppler with a 0.014-inch or an 0.018-inch Doppler FloWire. For coronary flow reserve measurement, intracoronary injection of adenosine or papaverine was used. Of the patients studied, 77 were cardiac transplant recipients and 829 were patients who had not received a transplant, of whom 617 had undergone diagnostic coronary procedures and 212 had coronary interventions. In 27 (2.98%) of 906 patients adverse cardiac events were observed. Fifteen (1.66%) of 906 patients had severe transient bradycardia develop (asystole or second- to third-degree atrioventricular block) after intracoronary administration of adenosine, 14 of which occurred in the right coronary artery and 1 in the left anterior descending artery. Nine (0.99%) of 906 patients had coronary spasm during the passage of the Doppler wire (5 in the right coronary artery, 4 in the left anterior descending artery). Two (0.22%) of 906 patients had ventricular fibrillation during the procedure. Hypotension with bradycardia and ventricular extrasystole each occurred in 1 (0.11%) of 906 patients. The incidence of complication was significantly higher in transplant recipients than in patients who underwent either diagnostic or interventional procedures (12.99% vs 2.43% vs 0.94%, P <.001). The Doppler measurements in the right coronary artery were associated with a higher incidence of complications, especially bradycardia, compared with the left anterior descending and the left circumflex arteries (right coronary, 5.87% vs left anterior descending, 1.05% vs left circumflex, 0.17%; P <.001). All complications were cured medically., Conclusion: Intracoronary Doppler flow measurement with Doppler wires and intracoronary administration of adenosine is a safe method. However, severe complications such as bradycardia and coronary spasm can occur. Attention should be paid to the examination of the right coronary artery, especially in heart transplant recipients.

Objectives: In order to limit the variability of coronary flow velocity reserve (CFVR), we analyzed which factors independently affect CFVR and established a new parameter integrating these factors., Background: Coronary flow velocity reserve (CFVR) is a frequently used parameter for evaluating the physiological significance of epicardial stenosis and microvascular function. Since CFVR measurements are done in substantially different hemodynamic and clinical situations, interpretation of CFVR requires correction for major influencing factors., Methods: In 141 patients with angina-like symptoms and angiographically unobstructed coronary arteries, intracoronary Doppler measurements were performed in at least two coronary vessels. Coronary flow velocity reserve was calculated as the ratio of hyperemic average peak velocity (hAPV), after intracoronary bolus of adenosine, to baseline average peak velocity (bAPV)., Results: Analysis of covariance revealed that only bAPV (p < 0.0001) and age (p < 0.0001) were independent factors influencing CFVR. Based on a regression model for estimation of predicted CFVR values, individual CFVR values (CFVRind) obtained at different bAPV and age were transformed in corrected CFVR values (CFVRcorr) by relating them to a mean bAPV of 15 cm/s and a mean age of 55 years. The transformation from CFVRind into CFVRcorr for the left anterior descending artery can be done by using the following equation: CFVRcorr = 2.85*CFVR(ind)*10(0.48*log(bAPV)+(0.0025*age)-1.16). When applying this new parameter to conditions assumed to cause microvascular dysfunction, analysis showed that only patients with diabetes showed a significant decrease of traditional CFVR and CFVRcorr, whereas a history of hypertension and current smoking habit had no influence on CFVRcorr., Conclusions: The concept of CFVRcorr standardizes CFVR for bAPV and age as the major physiological determinants. Especially in patients with microvascular dysfunction, this approach may help to discriminate between conditions directly affecting vasodilator reserve and conditions primarily affecting bAPV.

The development and progression of coronary artery disease is the result of exposure to a variety of different risk factors. In larger populations, strong associations exist between risk factors and the development of both angiographic and clinical coronary artery disease. But, this relationship is extremely variable in individual subjects. Coronary calcification is a specific marker of coronary artery disease. Its formation and progression is determined by largely identical risk factors compared with angiographic coronary artery disease. Coronary calcification quantitated by electron beam tomography (EBT) thus enables the non-invasive assessment of whether the risk factor exposure has actually led to the development of coronary atherosclerosis in an individual subject. Whereas other non-invasive tests focus on the physiological consequences of coronary obstruction, EBT represents anatomic disease itself. Because the propensity of plaques to cause coronary obstruction partly depends on the degree of arterial remodelling, large plaques may not necessarily appear as high-grade stenoses angiographically. Indeed, angiography and EBT evaluate two facets of atherosclerotic plaque disease, i.e. luminal obstruction and calcified plaque itself. Coronary calcification is strongly associated with the presence, extent, and severity of angiographic coronary artery disease. A number of studies have shown that it is clearly superior in this respect compared with conventional risk factors. However, because of the indirect relationships between plaque formation and luminal obstruction, EBT does not permit the site-specific prediction of coronary stenoses. Recent investigations have focused on the ability of EBT to represent the extent of anatomic coronary artery disease, which is an important predictor of future cardiac events. The availability of a simple, non-invasive test for the direct visualization of coronary artery disease holds great promise regarding improved definitions of the relationships between risk factors and coronary atherosclerosis as well as regarding the diagnosis of non-obstructive coronary disease, which can nevertheless result in acute events.

Coronary flow velocity reserve (CFVR) measurement using intracoronary Doppler techniques has been increasing accepted for the assessment of physiological significance of epicardial stenosis and the functional changes after coronary interventions. However, large discrepancy exists concerning the acute changes of CFVR immediately after intervention. The purpose of this study was to investigate the prevalence of microvascular dysfunction in patients with significant coronary artery disease. Intracoronary Doppler flow measurements were performed in a total of 212 patients who underwent coronary interventions because of significant epicardial stenosis using 0.014" Doppler flow wire (Cardiometrics, Inc, Mountain View, CA). Intracoronary bolus injection of adenosine (12 micrograms for the right coronary and 18 micrograms for the left coronary arteries) was used to induce hyperemic reaction. CFVR was registered as the ratio of average peak velocity during hyperemia (hAPV) to at baseline (bAPV). Successful coronary interventions either by percutaneous transluminal coronary balloon angioplasty (PTCA) or by stenting could significantly improve the CFVR. In 80 patients with PTCA, the bAPV elevated from 16.6 +/- 2.1 cm/s to 20.6 +/- 13.4 cm/s and hAPV from 30.1 +/- 15.9 cm/s to 45.2 +/- 17.7 cm/s (both p < 0.001) with PTCA and the CFVR increased from 1.94 +/- 0.78 to 2.58 +/- 0.87 correspondingly (p < 0.001). Significant elevation of coronary flow parameters were also found in 132 patients with subsequent stent implantation (bAPV from 15.3 +/- 6.7 cm/s to 18.7 +/- 9.1 cm/s, hAPV from 28.7 +/- 14.4 cm/s to 44.3 +/- 17.7 cm/s and CFVR from 1.90 +/- 0.70 to 2.59 +/- 0.87, all p < 0.001). Reduction of CFVR (< 3.0) after intervention still existed in 46 (61.3%) of 80 patients after PTCA and 88 (66.7%) of 132 patients after stenting. Moreover, CFVR < 3.0 were found in 50 (45.9%) of 109 reference vessels in patients with single vessel disease. Significant improvement of coronary flow velocity and coronary flow velocity reserve could be obtained after successful angioplasty. However, microvascualr dysfunction existed in a large proportion of patients either in normal reference vessels or in target vessels after interventions.

Coating stents with autologous venous grafts has been suggested to prevent problems associated with conventional stenting, but the need for surgical vessel harvest hampered broad application. A novel synthetic coronary stent graft (CSG) overcomes this limitation by a synthetic membrane, fixed between two thin metallic stents. We successfully implanted 21 CSGs in 18 patients for treatment of acute coronary rupture, thrombus-containing lesions, and lesions with plaque rupture or adjacent pseudoaneurysm. Substantial residual angiographic diameter stenoses were seen in seven CSGs (25% +/- 10% vs. 8% +/- 6%; P < 0.01), which were implanted with relatively small balloon catheters (balloon-to-artery ratio 1.00 +/- 0.09 vs. 1.24 +/- 0.18; P = 0.01) and required postdilatation. Overall, the largest balloon catheter applied measured 4.0 +/- 0.7 mm (balloon-to-artery ratio 1.21 +/- 0.20) and the inflation pressure was 16 +/- 3 atm. Final intravascular ultrasound imaging demonstrated adequate and symmetrical expansion of the CSG (> or = 85% +/- 15% of the reference lumen). Elective implantation was associated with two small non-Q-wave myocardial infarctions, resulting from unavoidable occlusions of side branches. Thus, implantation of CSG is feasible and safe. Adequate expansion can be achieved by the use of relatively large low-compliant balloon catheters inflated with high pressure.

Background: Although adrenergic activation plays a major role in the initiation of experimental myocardial ischemia, the significance of alpha-adrenergic coronary constriction in humans has been questioned. The present study assessed the impact of selective alpha-adrenergic receptor activation in patients with normal or atherosclerotic coronary arteries., Methods and Results: In 39 patients, coronary blood flow (CBF, mL/min) was determined from combined angiography and Doppler measurements. In 8 patients with normal coronary arteries (group 1) and 9 with single coronary artery stenosis (group 2), doses of 1, 2.5, 5, and 10 mg IC of the alpha1-agonist methoxamine (M) were injected. Identical doses of the alpha2-agonist BHT933 (B) were injected in 8 patients with normal coronary arteries (group 3) and 8 with single stenosis (group 4). In 6 additional patients with single stenosis (group 5), aortocoronary sinus lactate differences were measured in response to M and B. CBF remained unchanged in group 1. In contrast, CBF was decreased dose-dependently in group 2, with a maximum at 10 mg M (39.0+/-9.4 versus 15.2+/-7.0). In groups 3 and 4, CBF was also decreased dose-dependently, with a maximum at 10 mg B (63.3+/-24.8 versus 49. 1+/-27.9 and 41.5+/-19.0 versus 12.7+/-8.0, respectively). In group 5, there was more net lactate production with B than with M (-0. 34+/-0.11 versus -0.04+/-0.09 mmol/L)., Conclusions: In normal coronary arteries, alpha1-adrenergic activation does not reduce CBF, whereas alpha2-adrenergic activation reduces CBF by microvascular constriction. Both alpha1- and alpha2-adrenergic epicardial and microvascular constriction are augmented by atherosclerosis and can induce myocardial ischemia.

Chest pain following successful percutaneous coronary interventions is a common problem. Although the development of chest pain after coronary interventions may be of benign character, it is disturbing to patients, relatives and hospital staff. Such pain may be indicative of acute coronary artery closure, coronary artery spasm or myocardial infarction, but may also simply reflect local coronary artery trauma. The distinction between these causes of chest pain is crucial in selecting optimal care. Management of these patients may involve repeat coronary angiography and additional intervention. Commonly, repeat coronary angiography following percutaneous transluminal coronary angioplasty (PTCA) in patients with chest pain demonstrates widely patent lesion sites suggesting that the pain was due to coronary artery spasm, coronary arterial wall stretching or was of non-cardiac origin. As reported by the National Heart, Lung and Blood Institute PTCA Registry, 4.6% of patients after angioplasty have coronary occlusions, 4.8% suffer a myocardial infarction, and 4.2% have coronary spasm. The frequency of chest pain after new device coronary interventions (atherectomy and stenting) seems to be even higher. However, only the minority of patients with post-procedural chest pain have indeed an ischemic event. Therefore, the vast majority of patients have recurrent chest pain without any signs of ischemia. There is some evidence that non-ischemic chest pain after coronary interventions is more common after stent implantation as compared to PTCA (41% vs. 12%). This may be due to the continuous stretching of the arterial wall by the stent as the elastic recoil occurring after PTCA is minimized. In conclusion, chest pain after coronary interventional procedures may potentially be hazardous when due to myocardial ischemia. However, especially after coronary stent placement, cardiologists must consider "stretch pain" due to the overdilation and stretching of the artery caused by the stent in the differential diagnosis. Clinically, it is, therefore, important to recognize that in addition to ischemia-related chest pain other types of chest pain do exist with cardiac origin.

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.

Measurements of coronary flow reserve, once used only for research, have gained wide acceptance as an additional diagnostic approach in the decision-making process of diagnostic cardiac catheterization and coronary interventions. Apart from the noninvasive determination of coronary flow reserve, intracoronary Doppler flow wires have facilitated decision making in the catheterization laboratory. Different techniques, unstandardized procedures, and data from uncomparable patient populations have remained a confounding factor. This review examines current concepts of coronary flow reserve as well as methodologic considerations and pitfalls. Applications of coronary flow reserve for periinterventional assessment are evaluated on the background of practical guidance. According to a detailed examination of arterial structure and function, a normal coronary flow reserve exceeds a value of 3.0. Values below 3.0 suggest involvement of microvascular disease caused by functional or structural alterations. The influences of various factors such as age, hemodynamics, hypercholesterolemia, hypertrophy, hypertension, syndrome X, and coronary artery disease are discussed in relation to the effect on coronary flow reserve. From available information, measurements of coronary flow reserve are an adjunct to current interventional technology to optimize individual patient care. Further efforts should be undertaken to incorporate these new methods into our routine clinical decision making.

We compared intracoronary ultrasound (ICUS) and electron-beam computed tomography (EBCT) on a coronary segmental basis in 40 consecutive patients with acute coronary syndromes and no or minimal to moderate angiographic disease (53+/-10 years; 34 men, 6 women). ICUS was used to define plaques, and EBCT was used to quantify coronary calcium (using a threshold of a CT density > 130 Hounsfield units in an area > 1.03 mm2). In a site-by-site analysis, coronary segments were defined as normal if both methods were negative, as containing noncalcified plaques if only ICUS was positive, and as containing calcified plaques if both methods were positive. A total of 222 coronary segments were analyzed (5.6+/-1.9 segments per patient). In 36 patients (90%), a total of 95 segments with plaques were identified, whereas in 4 patients (10%), only normal segments were seen. Of the 95 segments with plaques, 61 (64%) were calcified, and 34 (36%) were noncalcified. There was a linear relationship between the number of segments with calcified and with noncalcified plaques (r = 0.86, p <0.0001), but the mean relative frequency of segments with calcified plaques (55+/-38%) was highly variable. Calcium was found in 15 of 16 patients (93%) with 3 or more segments with plaques, while it was found in only 12 of 20 patients (60%) with one or 2 segments with plaques (p = 0.026). Younger age, higher low-density lipoprotein-cholesterol levels, diabetes, and active smoking predicted a higher relative frequency of segments with noncalcified plaques. Thus, in patients with acute coronary syndromes but no angiographically critical stenoses, there is a linear relationship between segments with calcified plaques versus segments with noncalcified plaques. However, while the mean ratio of these segments is close to 1:1, it is highly variable among individual patients.

Techniques in the field of coronary artery imaging can be divided into two groups: invasive and non-invasive methods. Apart from the conventional coronary artery angiography, invasive methods include intracoronary ultrasound, intracoronary angioscopy, and optical coherence tomography. Non-invasive methods include magnetic resonance tomography, synchrotron-coronary angiography, and electron beam computed tomography. In the late 1980s, intracoronary ultrasound has come into clinical practice. It offers a real-time, cross-sectional image of the coronary artery in high resolution. Coronary arteries enlarge in the presence of atherosclerotic plaque formation in order to compensate for luminal narrowing caused by plaque formation (remodeling). With coronary angiography, the plaque formation cannot be detected until a lumen reduction of about 40-45%. With intravascular ultrasound, the early stages of atherosclerosis can clearly be demonstrated. In combination with the intracoronary Doppler technique, syndrome X can be differentiated. Another important role of intracoronary ultrasound in the diagnosis of coronary artery disease is to guide coronary interventions and to assess the result of coronary interventions especially to evaluate the result of stent implantation. Due to the clinical use of intracoronary ultrasound and the guidance of high pressure stent implantation, the incidence of acute stent thrombosis has decreased to about 1%. Coronary angioscopy portrays the surface of the vessel lumen. It is helpful to identify the mural thrombus especially to differentiate fresh and chronic thrombus formation. Magnetic resonance tomography is able to image the coronary arterial contour of the proximal segment. With today's gating technique, it is possible to portray the whole coronary tree and avoid disturbances resulting from the heart beat and respiration. Electron beam computed tomography is a very promising technique in screening for coronary artery disease. It is a very sensitive method to identify coronary calcification and, thus, to detect atherosclerotic plaque. Studies have shown that the presence of calcification almost invariably indicates the presence of coronary artery disease and that the absence of calcification can nearly rule out significant coronary artery disease. Moreover, a close correlation exists between the amount of calcification and the severity of coronary artery disease. Additionally, in combination with contrast injection, coronary artery perfusion can be evaluated. This is important to assess the conductance of coronary stent and bypass graft.

Percutaneous transluminal coronary balloon angioplasty (PTCA) still is the most frequently applied interventional technique for treatment of coronary artery disease. Plastic deformation of the obstructive plaque with creation of splits, intimal tears and dissections is the main mechanism of PTCA for lumen widening. As a result, acute complications due to flow limiting dissections and acute vessel closure can unpredictably occur resulting in myocardial infarction, urgent bypass surgery and death. Furthermore, long-term success of PTCA is limited by restenosis. In order to overcome these limitations of PTCA, alternative interventional techniques were developed, which instead of deforming the obstructive plaque ablate this tissue. These techniques include high and low speed rotational angioplasty, directional atherectomy, the transluminal extraction catheter, ultrasound angioplasty and laser (Light Amplification by Stimulated Emission of Radiation) angioplasty. 308 nm XeCl excimer laser angioplasty today is the laser technique of choice for clinical application. This pulsed laser requires direct contact to the obstructive plaque. It creates fast (< 200 microseconds) expanding gas bubbles which induce plaque ablation. Main indications for 308 nm XeCl excimer laser angioplasty are diffuse and long coronary lesions and total coronary occlusions. Despite promising initial results this technique showed no better acute and long-term results in comparison to PTCA for the treatment of these types of lesions ("Amsterdam-Rotterdam" Study, "Excimer Rotational Balloon Angioplasty Comparison" Study). As a result, this interventional technique was rarely applied for patient treatment. More recently, the concept of plaque ablation by 308 nm XeCl excimer laser angioplasty was renewed for the treatment of in-stent restenosis. This indication is being investigated in the "Laser Angioplasty of Restenosed Stents" trial. First results document the practicability and safety of this approach. Long-term results are awaited. With ongoing miniaturization, laser guidewires were developed for the recanalization of chronic total occlusions. The randomized multicenter "Total Occlusion Trial with Angioplasty assisted by Laser guidewire "Study documented a success rate of laser wire recanalization in up to 66% in contrast to 47.5% for mechanical wires only. Long-term results are still awaited. Technical and procedural progress including saline flush during laser application, homogeneous light distribution and the concept of smooth laser ablation is pushed foreward to make excimer laser angioplasty safer, more predictable and more effective.

Despite numerous efforts in catheter technology and procedural approaches the problem of restenosis in interventional cardiology persists. Although the implantation of coronary stents has significantly reduced restenosis rates based on the inhibition of elastic recoil, intimal proliferation as the second major mechanism for postinterventional restenosis could not effectively be suppressed. Intimal proliferation is the response to vessel injury following interventional procedure, e.g. balloon angioplasty. It results in the adhesion of mono- and lymphocytes which themselves trigger the colonisation of myofibroblasts. Intracoronary irradiation seeks to prevent this proliferative process as it destroys or irreversibly alters DNA structures of cells at the site of balloon injury. The antiproliferative effect depends on the irradiation dosis, the timing and the cell cycle phase. Mainly beta- and gamma-radiation is used for intracoronary irradiation. Beta-emitters are characterized by a sharp decline of dose rate within millimeters from the actual source. The exposure to surrounding tissue as well the catheter staff can be kept to a minimum. The high intensity of beta-emitters allow a short treatment period of minutes to gain an effective radiation dose to the target. In contrast, gamma-emitters have a low radial dose distribution resulting in high dosage even centimeters away from the source. These emitters require additional shielding in the catheter laboratory and lead to excessive whole body doses. To achieve a sufficient dose in the target tissue, irradiation times of more than 20 minutes are necessary which prolongs the interventional procedure substantially. At present, catheter based systems or radioactive implantable stents are available to deliver the required dose. Catheter based systems seem more flexible in a number of considerations. On the other hand they require a substantial amount of hardware. Beta-emitting stents are implanted via a conventional stent delivery system with small shielding modifications. However, stents emit an inhomogeneous radiation profile due to the mesh-like structure. In addition, not every lesion can be reached by a stent nor does every lesion require a stent solely to deliver radiation. External irradiation is presently not recommended due to its ineffectiveness and the high rate of side effects. In the experimental setting the porcine model comes closest to the clinical situation in man. Animal experiments have demonstrated the effective reduction of intimal proliferation using beta- and gamma-sources in a wide dose range of 3 to 56 Gy. Although the initial and early results are convincing little is know about the long term results. Only few studies have been and are currently performed in patients. Some of these investigations demonstrate a significant reduction of restenosis rate after 6 months. Again, information on long-term results are lacking. It has to be considered that perivascular fibrosis, which may occur with a delay of 5 to 10 years depending on the dosage, could curtail the initial success. Intracoronary irradiation is a promising method for the prevention of restenosis. The dose finding with respect to the dose effect relation, the determination of the therapeutic window and the timing of irradiation have to be further defined in the clinical setting. Nevertheless, intracoronary irradiation remains high on the priority list in fighting restenosis.

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.

X-ray densitometric evaluation of digital subtraction coronary arteriograms allows a qualitative and quantitative detection of contrast medium propagation through the epicardial coronary arteries, the capillary system and the coronary venous system. So-called "time-density-curves" (TDCs) can be generated following Lambert-Beer's law similar to indicator dilution curves by using contrast medium as the indicator. Several time and density parameters can be derived from these TDCs, which are related to local myocardial perfusion. Different animal validation studies have shown the applicability of this concept for in-vivo evaluation of coronary blood flow and myocardial perfusion. Nevertheless, absolute measurement of volumetric coronary blood flow or myocardial perfusion failed. Therefore, relative changes in coronary blood flow or myocardial perfusion in response to pharmacologically induced maximum hyperemia were measured and coronary or myocardial perfusion reserve was calculated as the ratio of hyperemic flow or perfusion divided by baseline values. Despite theoretical attractions for an application during routine cardiac catheterization, this densitometric approach did not get a wide acceptance. Primary reason for this limited use in specialized centers was the time consuming process of densitometric evaluation of the subtraction coronary arteriograms, which require digital cine angiography and necessitates enormous computer hard ware. This main limitation has been overcome since more powerful computer hard ware (processor speed, hard disk space, digitization boards) has become rapidly available during the last years at more moderate pricing and digital techniques today are state of the art in cardiac catheterization laboratories. In addition, soft ware program packages allowed an automatization of the digitization and densitometric evaluation process. These programs include ECG triggered cine image digitization with improved temporal resolution, semiautomatic definition of regions-of-interest including definition of reference regions-of-interest for the detection of background density changes and quality-controlled densitometric parameter analysis. This progress made an application during routine cardiac catheterization feasible. In animal validation studies this improved X-ray densitometric approach for evaluation of local myocardial perfusion was validated versus colour-coded microsphere techniques. The time parameter "rise time", defined as the time from the start of local contrast medium induced density change to its maximum revealed a close correlation (r2 = 0.965) to the results of the microsphere technique over a wide range of perfusion. We have applied this technique before and after coronary interventions such as balloon angioplasty and stenting. Results documented an improvement of poststenotic myocardial perfusion reserve immediately after coronary balloon angioplasty and an additional improvement after adjunct coronary stenting. Only after stenting but usually not after coronary balloon angioplasty alone poststenotic myocardial perfusion reserve gained the intraindividual reference level, measured in a perfusion bed supplied by an epicardial coronary artery without stenoses. These results documented the functional benefit of coronary stenting on poststenotic myocardial perfusion in addition to the well known morphologic benefit with the creation of a larger and more circular conduit.

Interventional cardiology is a rapidly developing field of medicine with annually increasing numbers of coronary interventions. Especially through the development of alternative techniques for coronary angioplasty, new indications have been found and more difficult lesions are tackled. Inevitably, such complex interventions are time-consuming and require high amounts of contrast medium. Newer, mostly nonionic agents have been developed with improved tolerability as well as fewer cardiac and renal side effects due to their nonionic, hydrophilic structure, and their osmolality isotonic to plasma. This study sought to investigate the effects of high-volume nonionic, dimeric contrast medium during coronary interventions with special emphasis on renal and hemodynamic side effects during routine hospital stays. Retrospectively, 25 consecutive patients (age 56 +/- 10 yr) with normal renal and cardiac function receiving > 500 ml of the nonionic dimeric contrast medium iodixanol during complex coronary interventions were analyzed. The analysis was based on serum creatinine levels 1 day before and 2 days after contrast medium administration for the monitoring of renal function. Additionally, heart rate and left ventricular pressures were evaluated before and after left ventricular angiography. Mean serum creatinine rose from 0.9 +/- 0.2 mg/dl to 1.1 +/- 0.2 mg/dl (P < 0.05) after 2 days of coronary intervention. Heart rate, left ventricular systolic pressure, and left ventricular end-diastolic pressure did not change significantly. No major side effects were encountered in the short follow-up period of 2 days. Based on this retrospective analysis, high-volume nonionic, dimeric contrast medium administration in patients without preexisting renal insufficiency is associated with little impairment of renal function, and has only minor hemodynamic and general side effects. Iodixanol 320 mg I/ml is well-tolerated and effective for the use of cardioangiography. Given the limitations of this retrospective analysis, future prospective studies should systematically address the effects of high-volume contrast medium administration in otherwise healthy patients as well as in high-risk patients undergoing coronary interventions.

Unlabelled: The aim of the study was the evaluation of electron beam computed tomography as a non-invasive method to localize coronary stents and to document patency in stented vessel segments., Methods: Twenty-two patients (16m/6f, 58 +/- 7.8 years) with coronary Palmaz-Schatz stents were examined. Contrast enhanced electron beam computed tomography using an Evolution scanner (Siemens) and coronary angiography were carried out within 7 days of each other. Stent localization was performed using the single-slice mode of the electron beam computed tomography scanner. Patency of the coronary target segment was assessed using the multi-slice mode after peripheral venous injection of a 40 ml bolus of contrast medium (Ultravist 370). Qualitative image analysis of a cine loop of 10 consecutive frames and quantitative analysis of densitometric curves in a region of interest distal to the stented vessel segment were performed., Results: All stented vessel segments were identified. In 20 patients (91%), qualitative assessment of contrast enhancement patterns enabled stent patency to be evaluated. In 18 patients (90%), contrast medium was visualized distal to the stent. Quantitative coronary angiography confirmed that the stented vessel segments were not stenosed. Densitometric curves obtained in 16 of these 18 patients yielded contrast enhancement distal to the stented vessel segment of 63 +/- 6% compared to the aorta. In one patient, qualitative and quantitative analysis showed prolonged contrast enhancement of reduced density, which hinted at a stenosis related to the stented vessel segment. Coronary angiography revealed subtotal occlusion of the stented vessel directly distal to the stent. In another patient, no contrast visualization of the vessel distal to the stent was achieved. Coronary angiography revealed complete stent occlusion in this case., Conclusion: Electron beam computed tomography can reliably localize coronary stents and may become a useful tool for providing information on stented vessel segment patency.

Background: Stents provide a scaffold for coronary arteries after angioplasty and inhibit elastic recoil., Methods and Results: In 25 patients with postangioplasty restenosis of the left anterior descending artery, ECG-gated digital subtraction coronary angiograms were recorded at baseline and during hyperemia (12 mg papaverine IC) before and after balloon predilatation (PTCA), after implantation of a Palmaz-Schatz stent, and after 6 months. Densitometric evaluation revealed different time and density parameters to calculate two definitions of myocardial perfusion reserve (MPR1 and MPR2) and maximum flow ratio (MaxFR). Poststenotic MPR1 increased from 1.57 +/- 0.14 to 2.59 +/- 0.86 after PTCA and to 3.10 +/- 0.41 after stenting, with 2.90 +/- 0.65 at follow-up (ANOVA, P < .05), while reference MPR1 remained unchanged at 3.10 +/- 0.40. Poststenotic MPR2 increased from 1.36 +/- 0.28 to 2.50 +/- 1.20 and to 3.40 +/- 0.58, respectively, with 3.20 +/- 0.92 at follow-up (ANOVA, P < .05), while reference MPR2 remained unchanged at 3.40 +/- 0.60. MaxFR was 2.13 +/- 0.53 after PTCA, elasticity 2.83 +/- 0.35 after stenting, and 2.73 +/- 0.58 at follow-up (ANOVA, P < .05). A good correlation was found between minimal stenotic luminal diameter and MPR1 or MPR2 (r = .87 and r = .94) and between luminal gain and MaxFR (r = .75). A negative correlation was measured between recoil and MPR1, MPR2, and MaxFR (r = -.80, r = -.86, and r = -.83). At follow-up, a steeper correlation was found between MPR and minimal stenosis diameter (MPR1: slope, 0.52 versus 0.91; MPR2: slope, 1.48 versus 1.95) and between MaxFR and net lumen gain (slope, 0.78 versus 1.27)., Conclusions: Coronary stent implantation in patients with postangioplasty restenosis normalized poststenotic myocardial perfusion immediately as a result of a larger postprocedural lumen and a more pronounced inhibition of elastic recoil. After 6 months this benefit was sustained despite progressive lumen loss.

Coronary artery disease (CAD) is one of the leading causes of mortality and morbidity in the western industrialized countries. Recent studies demonstrate the feasability of successful primary and secondary prevention. However, the detection of early stages of coronary artery disease is an unresolved issue. Whereas sensitivity and specificity of traditional risk factor assessment and stress tests are limited, the analysis of coronary calcification allows to obtain a direct sign of coronary atherosclerosis. This concept has been applied using fluoroscopy and conventional computed tomography (CT). However, the exact localization and quantification of coronary calcification only became possible with the advent of electron beam CT (EBCT). This new method showed a high prevalence of coronary calcification in the asymptomatic population. With the definition of a standardized "calcium score" the normal age-specific distribution and amount of coronary calcification was investigated. EBCT proved to be more sensitive in the diagnosis of both non-obstructive and obstructive coronary artery disease than risk factor analysis and stress testing, respectively. Obstructive coronary artery disease, however, cannot yet be predicted with high enough accuracy. A close correlation of EBCT coronary calcification was found to a) the total coronary plaque volume defined by histo-pathology, b) intracoronary ultrasound findings, c) the number of coronary risk factors, d) the coronary prognosis. Using EBCT, a reliable non-invasive identification of persons at risk was obtained for the first time. Guidelines for the use of EBCT in the early diagnosis and treatment of coronary artery disease are being developed.

Stents scaffold coronary arteries after angioplastic treatment and inhibit elastic recoil resulting in a larger and more circular focal lumen. In 25 patients with significant stenoses of the left anterior descending coronary artery, presenting no collaterals or myocardial infarction, EKG-gated digital subtraction angiograms were recorded at baseline and during hyperemia induced by intracoronary injection of 12 mg papaverine before and after balloon angioplasty, and after adjunct implantation of a single Palmaz-Schatz stent. Densitometric evaluation revealed the time parameters contrast medium appearance time (MCAT) rise time (RT) and mean transit time (MTT) and maximum intensity (Imax). Myocardial perfusion reserve (MPR1) was calculated as the ratio of baseline MCAT and hyperemic MCAT multiplied by the ratio of hyperemic Imax and baseline Imax while MPR2 was calculated as the ratio of baseline RT and hyperemic RT. Maximum flow ratio (MaxFR) was calculated as the ratio of preprocedural hyperemic MTT and postprocedural hyperemic MTT. Post-stenotic MPR1 increased from 1.36 +/- 0.28 to 2.50 +/- 1.20 and to 3.40 +/- 0.58 (ANOVA p < 0.05), while reference MPR1 remained unchanged with 3.40 +/- 0.60. Post-stenotic MPR2 increased from 1.57 +/- 0.14 to 2.59 +/- 0.86 after balloon angioplasty and to 3.10 +/- 0.41 after stenting (ANOVA p < 0.05), while reference MPR2 remained unchanged with 3.10 +/- 0.40. MaxFR was 2.13 +/- 0.53 after balloon angioplasty and 2.83 +/- 0.35 after stenting (p < 0.05). A good correlation was found between minimal stenosis diameter and MPR1 or MPR2 (MPR1: r = 0.94; MPR2: r = 0.87) and between luminal gain and MaxFR (r = 0.75). A negative correlation was measured between recoil, defined as the difference between inflated balloon diameter and resulting minimal stenosis diameter, and MPR1 and MPR2 and MaxFR (MPR1: r = -0.86; MPR2 r = -0.80; MaxFR r = -0.83). In conclusion, adjunct coronary stent implantation normalized post-stenotic myocardial perfusion immediately in contrast to balloon angioplasty alone resulting from a larger postprocedural lumen and a more pronounced inhibition of elastic recoil.

In this study, we examined whether percutaneous coronary angioplasty (PTCA) of native coronary arteries with high inflation pressure can improve the immediate postinterventional result in comparison to PTCA with nominal inflation pressure. Using quantitative coronary angiography, we analyzed the coronary angiograms of 24 patients who underwent PTCA with nominal inflation pressure (< 10 atm; group 1) and of 20 patients who underwent PTCA with high inflation pressure (> or = 10 atm; group 2). Only balloon catheters with little compliance were used. The following variables were recorded: 1) minimal luminal diameter (MLD), reference diameter and percent diameter stenosis before and after PTCA, 2) average balloon diameter during PTCA, 3) balloon/artery diameter ratio, 4) acute luminal gain (difference between MLD before and after PTCA), 5) nominal elastic recoil (difference between nominal balloon diameter and MLD after PTCA), 6) actual elastic recoil (difference between average balloon diameter during PTCA and MLD after PTCA). Nominal balloon diameter, reference diameter before and after PTCA and the balloon/artery diameter ratio were similar in both groups. Application of high inflation pressure resulted in a greater average balloon diameter. In group 2 (high inflation pressure), average balloon diameter amounted to 94 +/- 12% of nominal balloon diameter, whereas in group 1 (nominal inflation pressure), it reached only 84 +/- 9% of nominal balloon diameter. Actual elastic recoil was not different between the two groups. Nominal elastic recoil, however, was greater in the cohort which received PTCA with nominal inflation pressure (1.13 +/- 0.35 mm vs. 0.83 +/- 0.28 mm; p < 0.02). After use of high inflation pressure, acute postinterventional luminal gain was significantly increased (1.04 +/- 0.25 mm vs. 0.77 +/- 0.34 mm; p < 0.02) and the postinterventional percent diameter stenosis was significantly lower (12 +/- 10% vs. 24 +/- 13%; p < 0.05). Application of high inflation pressure improves the postinterventional result after PTCA because of a greater acute luminal gain. The stenotic coronary artery is expanded to a greater degree, and actual elastic recoil remains unchanged.

The implantation of intracoronary stents is increasingly employed in interventional cardiology. Even with high-resolution x-ray equipment the tiny struts of stainless steel stents can usually not be visualized. Coronary angiography is required to prove stent patency, and correct localization and deployment of the stent can only be assessed with intravascular ultrasound. In this setting a non-invasive diagnostic method would be of great advantage to document patency of the stented vessel segment. Herein we describe two patients with stent implantation in whom contrast-medium-enhanced electron beam tomographic scanning was applied to check for vessel patency. A pathological finding with reduced contrast enhancement could be distinguished from a normal finding, as was confirmed subsequently as a highly obstructed and a patent stented vessel segment by angiography. Thus, for the first time an alternative non-invasive diagnostic method may provide information on patency of stented vessel segments and may be useful for sequential follow-up investigations.

Objective: The extent of coronary calcification demonstrated by electron beam tomography was correlated with the individual cardiac risk profile., Patients and Methods: The possible presence of coronary calcifications was studied by electron beam tomography (EBT) in 650 patients (526 men, 124 women; mean age 54 +/- 10 [28-81] years) with known or suspected coronary heart disease. Depending on the degree of density and the size of the lesion a score was calculated according to an international standard., Results: No calcification was shown to be present in 202 patients (score of 0). A score of more than 0 was calculated in 73.8% of men and 48.4% of women. The average score was 227.8 +/- 24.8 in men, compared with 65.3 +/- 26.5 in women (P < 0.001). There were significantly more calcifications in older patients: Men aged 71-75 years had the highest score, 859.4, while the lowest, 9.6, was in those aged 36 to 40 years. The most important variables for the presence of calcification were age (relative risk per age group: 1.6), male sex (relative risk: 4.3), hypertension (relative risk: 2.4) and nicotine consumption (relative risk: 1.8). The median point score in patients without known risk factors was 1.3, with one known factor it was 7.2, and with three it was 48.0. The vessel segment most affected with calcification was the anterior interventricular branch with an average score of 84., Conclusion: Together with an evaluation of the risk profile EBT provided a better assessment of individual risk than conventional examination.

In this investigation, we studied the feasibility of 3D-reconstruction from 2D cross-sectional intracoronary ultrasound images. A computer-aided, automated 3D-reconstruction was used to generate cylindrical and sagittal format of vessels in vitro (n = 9) and in vivo (n = 48). Ultrasound 2D-images were acquired with a 20 MHz mechanical intracoronary ultrasound catheter (Boston Scientific). A slow pullback (about 1 mm/s) of the catheter was performed during continuous recording of the ultrasound images. The recorded 2D-images were then fed to an image processing computer. Correction and scaling of the axial vessel dimensions was performed by the assessment of the catheter position in the simultaneously recorded biplane fluoroscopy. Digitized data were then processed to 3D-images with use of voxel space modeling. The 3D-views from any plane can be reconstructed. The in-vitro study demonstrated that the reconstructed images were able to correctly portray the pathological changes of the vessel wall in all specimen as proved by pathologic examination. In the in-vivo study, 3D-reconstruction provided not only a spatial visualization of the coronary arterial disorders (such as coronary aneurysm, coronary dissection, spontaneous plaque rupture etc.) but also provides the potential to quantify the mass of lesions. By combining sagittal and cylindrical views, 3D-reconstruction enables longitudinal and orthogonal imaging of the both the vessel lumen and vessel wall, therefore, it has the advantage of cross-sectional viewing as obtained from intracoronary ultrasound and the longitudinal viewing as derived from coronary angiography. These preliminary results of the study indicate that 3D-reconstruction of coronary segments is a promising technique for studying coronary artery disease. Analysis can be based not only on single or multiple cross-sectional images but also on vessel segments facilitating serial studies as for instance studies assessing the progression and regression of atherosclerosis.

Ventricular arrhythmias are primarily responsible for sudden cardiac death early after the onset of acute myocardial ischemia. We designed an experimental model to simultaneously characterize regional myocardial function, myocardial blood flow, and electrophysiological parameters, and to determine predisposing factors for the development of early ventricular arrhythmias (EVA). The left circumflex coronary artery was occluded in six anesthetized (n = 2 piritramide/N2O, n = 4 chloralose/urethane) mongrel dogs. Systolic wall thickening (%WT) in a control zone and in the central ischemic zone was measured with sonomicrometry and regional myocardial blood flow (RMBF) with colored microspheres. Excitability and relative refractory period at the stimulus electrode and conduction times to all other electrodes were determined with a three-dimensional transmural multi(16)-electrode assay using a computer algorithm. In three of six dogs spontaneous EVA occurred 4 to 6 min after coronary occlusion, degenerating to ventricular fibrillation in two of these dogs. The three dogs developing EVA were not distinguished from those not developing EVA, neither by the kind of anesthesia nor by ischemic % WT (-6.6 +/- 3.8 [SD] vs -7.8 +/- 1.6, ns). Also, dogs with and without EVA did not differ significantly in excitability and relative refractory period. In contrast, dogs with EVA were characterized by a greater mass of severely ischemic myocardium, i.e., exhibiting a RMBF reduction to less than 0.1 ml/(min.g) (18 +/- 3 g vs 7 +/- 4 g, p less than 0.05), and by an increase in subendocardial conduction times of greater than 100% above the respective pre-ischemic values (120 +/- 18% vs 66 +/- 9%, p less than 0.05). Dogs with and without EVA were not as clearly distinguished by the increases in subepicardial (81 +/- 22% vs 46 +/- 15%, ns) and transmural (98 +/- 31% vs 67 +/- 14%, ns) conduction times. The development of EVA is associated with a greater mass of severely ischemic myocardium and a greater increase in subendocardial conduction times.

Diabetes is associated with coronary microvasculature abnormalities and impaired coronary flow reserve (CFR). CFR is the ratio of coronary flow under maximal vasodilation to basal flow and is a measure for coronary vasoreactivity. Insulin resistance is the central defect in the development of type 2 diabetes, preceding its onset by 10–20 years. Thus, the relationship between insulin sensitivity and CFR in nondiabetic subjects is particularly interesting. The aim of the study was to investigate this relationship.Cross-sectional study.The study population consisted of 18 nondiabetic subjects without coronary artery stenosis on coronary angiography. We excluded patients with structural heart disease or with conditions affecting CFR or insulin sensitivity such as low density lipoprotein (LDL)-cholesterol≥ 4·14 mmol/l, smoking, hypertension or obesity with a body mass index (BMI)> 28 kg/m2.CFR was 3·1 ± 0·8 (range 1·7–4·8), as assessed by intracoronary Doppler measurements in the left anterior descending coronary arteries after adenosine stimulation. Intravascular ultrasound revealed zero to moderate coronary atherosclerotic changes. Whole-body insulin sensitivity (M-value) was 7·5 ± 2·9 mg/kg/min (range 2·2–12·6), as assessed by the hyperinsulinaemic–euglycaemic clamp test. Subjects with low CFR (< 3·0) had a significantly lowerM-value than subjects with normal CFR (> 3·0) (6·0 ± 2·5vs.9·0 ± 2·5 mg/kg/min,P = 0·021). Univariate linear regression demonstrated a strong correlation between CFR andM-value (r = 0·76,P < 0·001). In multiple regression analysis, the significant association of CFR withM-value was independent of potential confounders (sex, age, BMI, LDL-cholesterol and plaque burden on intravascular ultrasound). Bootstrap analysis corroborated this finding.Whole-body insulin sensitivity relates to coronary vasoreactivity. Across a wide range of both insulin sensitivity and coronary flow reserve from markedly abnormal to normal values, an increase in insulin sensitivity appears to be associated with an increase in coronary flow reserve. Insulin resistance is therefore associated with coronary microvasculature abnormalities in nondiabetics. [ABSTRACT FROM AUTHOR]

A rare case of left coronary artery–pulmonary artery fistula is reported. Transoesophageal echocardiography was capable of precisely demonstrating the origin, the course and the drainage site of the fistula. In contrast, transthoracic echocardiography could visualise a drainage flow in the pulmonary artery only. In conclusion, transoesophageal echocardiography may be helpful in the diagnosis or exclusion of the form of coronary artery fistula. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Purpose of our study was to determine if homocysteine plasma levels are related to the risk of in-stent restenosis after percutaneous coronary stent implantation in de novo lesions. Background: The putative role of homocysteine as a predictive cardiovascular biomarker of coronary artery disease is well established. The impact of homocysteine levels in the development of in-stent restenosis, however, is controversially discussed. Methods: A total of 177 patients with stable angina pectoris undergoing stent implantation in coronary de novo lesions were included. Laboratory determination comprised blood sample evaluation for homocysteine and other conventional risk factors before baseline coronary intervention and prior to six months control catheterization. Binary restenosis, late lumen loss, and late loss index after six months were assessed by quantitative coronary angiography. Endpoints included target lesion and target vessel failure, homocysteine levels as well as major adverse cardiac events. Results: There was a significant correlation between the length of the implanted stent (p <0.006), the percentage of stenosis (p <0.003) and the pre-interventional luminal diameter (p <0.0001) with late loss index. Linear regression analysis demonstrated no significant impact of the initial or six months homocysteine levels on angiographic restenosis, late lumen loss, or late loss index. Conclusions: In contrast to homocysteine levels, luminal diameter, stent length and percentage of stenosis correlated with the appearance of restenosis. Taking our data into consideration, we hypothesise that homocysteine may not serve as a safe and independent biomarker of in-stent restenosis after a six months period following percutaneous coronary stenting. [Copyright &y& Elsevier]

Electron-beam computed tomography (EBCT) allows for accurate noninvasive detection and quantification of coronary calcium that is representative of underlying atherosclerotic disease. The present study quantitatively analyzes the topography and establishes the natural history of coronary calcium in patients with variable degrees of coronary atherosclerosis. EBCT was performed in 330 consecutive patients aged 56 +/- 12 years (70% men) with recent (<3 months) onset of signs or symptoms of coronary artery disease (CAD) or who were evaluated because of a presumed high risk. Total calcium scores, computed by the Agatston method, were positive in 269 patients (82%) (mean age 58 +/- 11 years, 73% men). These patients were classified into 4 groups, with total calcium scores ranging between 1 and 30, >30 and 100, >100 and 400, and >400, respectively. The presence and amount of calcium was additionally assessed in 10 major segments of the coronary arterial tree, including the major coronary arteries. Of the 72 patients with calcium of only 1 of the major coronary arteries, the left anterior descending coronary artery was involved in 39 patients (54%) and the right coronary artery in 18 patients (25%). Left main stem calcium was observed in only 10 of 139 patients (7%) with 1- or 2-vessel calcium and in 17 of 77 patients (23%) with 3-vessel calcium. Calcium was consistent most frequently in the proximal left anterior descending coronary artery, followed by the proximal left circumflex and right coronary artery segments. A significant decrease of frequency and amount of calcium from the proximal to distal segments was observed in the left coronary system but not in the right coronary artery, where the distribution was more even. With increasing total calcium scores, segmental scores in the more distal segments were enhanced, but the increase was most pronounced in the proximal segments and particularly in the proximal left anterior descending coronary artery. EBCT-derived coronary calcium shows an axial distribution that appears comparable to that of atherosclerotic lesions observed in pathologic and angiographic studies, highlighting the potential role of EBCT for studying the natural history of CAD. [ABSTRACT FROM AUTHOR]