Ulrich Solzbach

Vitamin C Improves Endothelial Dysfunction of Epicardial Coronary Arteries in Hypertensive Patients

BACKGROUND There is evidence for increased formation of free radicals in patients with hypertension, raising the possibility that NO is inactivated by free radicals, which impairs coronary endothelial function. Therefore, we tested the hypothesis that the antioxidant vitamin C could improve abnormal endothelial function of coronary arteries in patients with hypertension. METHODS AND RESULTS In 22 hypertensive patients without relevant coronary artery stenoses, endothelium-dependent vascular responses of the left anterior descending coronary artery (LAD) to acetylcholine (0.01, 0.1, and 1.0 micromol/L) were determined before and immediately after intravenous infusion of 3 g vitamin C (17 patients) or placebo (5 patients). In a subgroup of 10 patients, papaverine-induced flow-dependent vasodilation (FDD) was measured before and after vitamin C (5 patients) or placebo (5 patients) infusion. Segmental responses of the coronary artery luminal area were analyzed with quantitative coronary angiography. Before vitamin C infusion, the mean changes of LAD luminal areas at increasing doses of acetylcholine were -6.1+/-2.2%, -15.2+/-4.9%, and -33.9+/-8.1% (negative numbers symbolize vasoconstriction) and during FDD, 5.4+/-1.0%. The vasoconstrictor response during acetylcholine was reduced and FDD was augmented by vitamin C. After vitamin C infusion, LAD luminal areas changed by -3.2+/-2.3%, -5.8+/-3.6%, and -10.2+/-5.6% (P<.05, acetylcholine) and 17.8+/-2.8% (P<.05, FDD). Doppler flow velocity (during baseline, acetylcholine, and FDD) was not significantly affected by vitamin C. CONCLUSIONS Vitamin C improves the endothelium-dependent vasomotor capacity of coronary arteries in patients with hypertension and patent coronary arteries. These findings suggest that increased oxidative stress contributes to endothelial dysfunction in hypertensive patients.

Prognostic Value of Abnormal Vasoreactivity of Epicardial Coronary Arteries to Sympathetic Stimulation in Patients With Normal Coronary Angiograms

Objective—We aimed to evaluate prospectively whether patients with normal coronary angiogram but abnormal epicardial vasoreactivity to cold pressor test (CPT) are at increased risk for cardiovascular events. Methods and Results—Vasoreactivity in response to CPT and dilation of epicardial arteries to intracoronary application of nitroglycerin were assessed quantitatively (percent change of luminal area, &Dgr;LA%) in 130 patients with normal coronary angiograms. Cardiovascular events (cardiovascular death, acute coronary syndrome, myocardial infarction, percutaneous transluminal coronary angioplasty, coronary bypass grafting, ischemic stroke, or peripheral revascularization) were assessed as clinical outcome parameters over a mean follow-up period of 45±9 months. Based on their vascular responses to CPT, patients were assigned into the following 3 groups: group 1, patients with normal vasodilator response (&Dgr;LA >0%; n=37); group 2, patients with moderate vasoconstrictor response (&Dgr;LA between 0% and −15%; n=42); and group 3, patients with severe vasoconstrictor response (&Dgr;LA ≤−15%; n=51). Although patients from groups 2 and 3 had significantly increased vasoconstrictor response to CPT (group 2, &Dgr;LA −6±3% and group 3, &Dgr;LA −24±6% versus group 1, &Dgr;LA 11±9%;P ≤0.0001), they showed normal endothelial-independent epicardial vasodilation to intracoronary application of nitroglycerin similar to patients from group 1 (&Dgr;LA 39±16% and 34±14% versus 41±14%;P =NS, respectively). During follow-up, none of the patients from group 1 developed cardiac events. However, 7 cardiovascular events occurred in group 2 and 30 occurred in group 3 in 4 and 22 patients, respectively (P ≤0.0001, univariate by log-rank test). After adjustment for known risk factors for coronary artery disease, impaired epicardial coronary vasoreactivity to CPT remained significantly associated with the risk of developing cardiovascular events (P =0.040, multivariate by Cox regression model). Conclusions—In patients with normal coronary angiogram, abnormal vasoreactivity of epicardial coronary arteries in response to sympathetic stimulation is associated with the risk of developing cardiovascular events.

Coronary Vasoregulation in Patients With Various Risk Factors in Response to Cold Pressor Testing Contrasting Myocardial Blood Flow Responses to Short- and Long-Term Vitamin C Administration

OBJECTIVES We sought to determine whether abnormal myocardial blood flow (MBF) responses to the cold pressor test (CPT) in patients with various risk factors may involve different mechanisms that could lead to varying responses of short- and long-term administration of antioxidants. BACKGROUND There is a growing body of evidence that increased vascular production of reactive oxygen species markedly reduces the bioavailability of endothelium-derived nitric oxide, leading to impaired vasodilator function. It is unknown whether increased oxidative stress is the prevalent mechanism underlying endothelial dysfunction in patients with different coronary risk factors. METHODS Fifty patients with normal coronary angiograms were studied. The MBF responses to CPT was determined by means of positron emission tomography before and after intravenous infusion of 3 g vitamin C or saline (placebo), as well as after 3 months and 2 years of 2 g vitamin C or placebo supplementation daily. RESULTS In hypertensive patients, the change in MBF (DeltaMBF) was not modified significantly by short-term vitamin C administration challenges (0.20 +/- 0.20 ml/g/min; p = NS) but was significantly increased after three months and two years of treatment with vitamin C versus baseline (0.58 +/- 0.27 and 0.63 +/- 0.17 vs. 0.14 +/- 0.18 ml/g/min; both p < or = 0.001). In smokers, DeltaMBF in response to CPT was significantly increased after short-term vitamin C infusion and long-term vitamin C treatment (0.52 +/- 0.10, 0.54 +/- 0.13, 0.50 +/- 0.07 vs. -0.08 +/- 0.10 ml/g/min; all p < or = 0.001). In hypercholesterolemic patients, no improvement in DeltaMBF during CPT was observed after short- and long-term vitamin C treatment (0.05 +/- 0.14, 0.08 +/- 0.18, 0.02 +/- 0.19 vs. 0.08 +/- 0.16 ml/g/min; p = NS). The CPT-induced DeltaMBF in hypertensive patients and smokers after follow-up was significant as compared with placebo and control subjects (p < or = 0.001). CONCLUSIONS The present study revealed marked heterogeneous responses in MBF changes to short- and long-term vitamin C treatment in patients with various risk factors, which highlights the quite complex nature underlying abnormal coronary vasomotion.

Fusion imaging: Combined visualization of 3D reconstructed coronary artery tree and 3D myocardial scintigraphic image in coronary artery disease

Background: In patients with coronary artery disease, coronary angiography is performed for assessment of epicardial coronary artery stenoses. In addition, myocardial scintigraphy is commonly used to evaluate regional myocardial perfusion. These two-dimensional (2D) imaging modalities are typically reviewed through a subjective, visual observation by a physician. Even though on the analysis of 2D display scintigraphic myocardial perfusion segments are arbitrarily assigned to three major coronary artery systems, the standard myocardial distribution territories of the coronary tree correspond only in 50–60% of patients. On the other hand, the mental integration of both 2D images of coronary angiography and myocardial scintigraphy does not allow an accurate assignment of particular myocardial perfusion regions to the corresponding vessels. To achieve an objective assignment of each vessel segment of the coronary artery tree to the corresponding myocardial regions, we have developed a 3D ‘fusion image’ technique and applied it to patients with coronary artery disease. The morphological data (coronary angiography) and perfusion data (myocardial scintigraphy) are displayed in a 3D format, and these two 3D data sets are merged into one 3D image. Results: Seventy-eight patients with coronary artery disease were studied with this new 3D fusion technique. Of 162 significant coronary lesions, 120 (74%) showed good coincidence with regional myocardial perfusion abnormality on 3D fusion image. No regional myocardial perfusion abnormality was found in 44 (26%) lesions. Furthermore, the 3D fusion image revealed 24 ischemic myocardial regions that could not be related to angiographically significant coronary artery lesions. Conclusion: The results of this study demonstrate that our newly developed 3D fusion technique is useful for an accurate assignment of coronary vessel segments to the corresponding myocardial perfusion regions, and suggest that it may be helpful to improve the interpretative and decision-making process in the treatment of patients with coronary artery disease.

Regional myocardial perfusion defects during exercise, as assessed by three dimensional integration of morphology and function, in relation to abnormal endothelium dependent vasoreactivity of the coronary microcirculation

Objective: To test the hypothesis that scintigraphic regional myocardial perfusion defects during exercise in patients with normal coronary angiography may be related to abnormal endothelium dependent vasoreactivity of the corresponding myocardial territory in response to cold pressor testing. Methods: 38 patients were classified into two groups according to the presence or absence of exercise induced scintigraphic myocardial perfusion defects. A cold pressor test was done in all patients during routine coronary angiography, followed by dynamic positron emission tomography to establish coronary blood flow mediated vasoreactivity of the epicardial coronary artery and the myocardial territories supplied by the left anterior descending, left circumflex, and right coronary arteries. Results: 28 patients had regional myocardial perfusion defects while 10 had normal scintigraphic imaging. The three dimensional scintigraphic fusion image revealed 49 regional myocardial perfusion defects with a mean (SD) reversibility of the original stress defect of 20 (3)%. In patients with exercise induced regional myocardial perfusion defects, the responses of epicardial luminal area and regional myocardial blood flow (RMBF) to cold pressor testing were reduced compared with patients with normal perfusion imaging (epicardial luminal area: 5.2 (1.2) to 4.2 (0.86) mm2v 4.7 (0.5) to 5.8 (0.5) mm2; RMBF: 0.75 (0.16) to 0.78 (0.20) ml/g/min v 0.75 (0.15) to 1.38 (0.26) ml/g/min; p ≤ 0.03, respectively). In patients with regional abnormal scintigraphic perfusion, the corresponding RMBF response to cold pressor testing was more severely impaired than the mean myocardial blood flow in the remaining two vascular territories, but the difference was not significant (0.75 (0.16) to 0.78 (0.20) ml/g/min v 0.75 (0.10) to 0.87 (0.12) ml/g/min; NS). The endothelium independent increase in RMBF induced by glyceryl trinitrate did not differ between patients with exercise induced myocardial perfusion defects and those with normal perfusion images (0.75 (0.16) to 0.94 (0.09) ml/g/min v 0.75 (0.15) to 0.94 (0.09) ml/g/min; NS). There was a highly significant correlation between the endothelium dependent responses of RMBF to cold pressor testing and the severity of exercise induced scintigraphic regional myocardial perfusion defects (r = 0.95, p = 0.001). Conclusions: Exercise induced scintigraphic regional myocardial perfusion defects in patients with angina but normal coronary angiography may be related to abnormal endothelium dependent vasoreactivity of the corresponding myocardial territory.

Effect of stenotic geometry on flow behaviour across stenotic models

In the study the influence of the geometry of stenoses on poststenotic flow characteristics such as faminar flow, separation, flow instabilities and local turbulences were assessed. Stenoses were represented by 12 rigid-walled models. The different geometric characteristics were length, percentage lumen area reduction, exit angle and eccentric location of the residual lumen. The flow characteristics were investigated by visualising the flow pattern with a birefringent solution and by measuring the flow and the pressure drop along the stenoses. All data were obtained under steady flow conditions for Reynolds numbers varying from approximately 1 to 500. In stenoses with short and concentric shapes local turbulence develops at Reynolds numbers well below the corresponding Reynolds numbers obtained in stenoses with the same percent lumen area reduction but with a long and eccentric shape. The results indicate that the photoelastic technique is a suitable method of obtaining a picture of the overall flow field downstream of a constriction.

3D Assessment of myocardial perfusion parameter combined with 3D reconstructed coronary artery tree from digital coronary angiograms

In patients with coronary artery disease coronary angiography plays an important role in the clinical decision-making process. However, it has been recognized that no simple relation exists between the visually or quantitatively evaluated severity of coronary artery stenoses and its effects on regional myocardial perfusion. This paper describes for the first time the development and application of a 3D technique that visualizes and quantifies regional myocardial perfusion parameters from biplane coronary angiograms by using the impulse response analysis technique. The 3D reconstructed coronary tree is automatically superimposed on the 3D perfusion image to generate and visualize an ‘integrated’ 3D image. The preliminary results in patients with critical coronary artery stenoses indicate that our combined 3D fusion image provides flow information from the major coronary arteries. This 3D fusion image may provide useful information in the management of patients with coronary artery disease.

Effect of Ascorbic Acid on Endothelial Dysfunction of Epicardial Coronary Arteries in Chronic Smokers Assessed by Cold Pressor Testing

Background: In chronic smokers there is evidence for increased formation of oxygen-derived free radicals within the vessel wall impairing endothelial function. It has been suggested that the inactivation of endothelium-derived nitric oxide by oxygen free radicals contributes to endothelial dysfunction. Hence, we tested the hypothesis that in chronic smokers the antioxidant ascorbic acid could improve abnormal endothelial function of epicardial coronary arteries. Methods and Results: Thirty-one patients (mean age 57 ± 9 years) referred for routine diagnostic catheterization for evaluation of chest pain and without angiographically significant coronary artery stenoses were randomly assigned to one of the study groups to assess vasomotor response of epicardial coronary arteries due to cold pressor testing (CPT) before and after intravenous infusion of 3 g of ascorbic acid or 100 ml × 0.9% saline infusion. In 6 controls (mean age 55 ± 3 years) CPT led to a similar increase in luminal area before and after ascorbic acid administration (26.5 ± 15.0 vs. 28.4 ± 17.7%, p = NS). In 15 chronic smokers (mean age 55 ± 9 years), CPT induced a decrease in the luminal area of –18.5 ± 6.3%. This flow-dependent vasoconstriction was significantly reversed to 7.7 ± 6.2% (p ≤ 0.03) vasodilation after intravenous ascorbic acid administration. In 10 chronic smokers (mean age 57 ± 11 years) saline infusion (placebo) did not have a significant effect on CPT-induced vasoconstriction (–12.7 ± 5.1 vs. –13.1 ± 5.1%, p = NS). The CPT-induced increase in luminal area in chronic smokers after ascorbic acid infusion was significant compared to controls and placebo (each p ≤ 0.05). Our assessment of endothelium-independent responses to nitroglycerin revealed no significant differences between the single study groups (p = NS). Conclusion: In chronic smokers acute intravenous administration of ascorbic acid significantly improves CPT-induced coronary endothelium-dependent dysfunction. According to the current understanding, this effect is due to improved cellular redox imbalance and prevention of nitric oxide inactivation in the endothelium and subendothelial space.

Computed Triple Orthogonal Projections for Optimal Radiological Imaging with Biplane Isocentric Multidirectional X-ray Systems

One of the major objectives in angiocardiography is the visualization of anatomical details with projections perpendicular to the long axis of the anatomical structure. In addition, ‘one of the most basic rules in radiology . . . is the need for at least two views of the object with the projections being perpendicular to each other’ [1]. Thus, most useful informations can be derived from a radiological study if the concept of ‘triple orthogonality’ is applied: two projections perpendicular to the long axis of the anatomical object and perpendicular to each other.

Use, efficacy and safety of prasugrel in patients with ST segment elevation myocardial infarction scheduled for primary percutaneous coronary intervention in clinical practice. Results of the prospective ATACS-registry

BACKGROUND Prasugrel compared to clopidogrel has been shown to improve outcome in patients with ST elevation myocardial infarction (STEMI) in the TRITON-TIMI 38 trial. Little is known about the use, efficacy and safety of prasugrel in patients with STEMI in clinical practice. METHODS We conducted a prospective registry including patients with STEMI scheduled for primary percutaneous coronary intervention (PCI). Between October 2009 and February 2013 a total of 3291 patients with STEMI receiving a loading dose of either clopidogrel or prasugrel were included in this analysis. RESULTS Prasugrel was predominantly used in patients <75 years, body weight >60 kg and those without prior stroke. In-hospital mortality was numerically lower in the prasugrel group (1.7% vs. 4.4%), as well as non-fatal reinfarction (0.2% vs. 0.5%), non-fatal stroke (0.1% vs. 0.3%) and major cardiac and cerebrovascular events (MACCE) (2.1% vs. 5.2%), while there was no difference in major bleeding complications (0.8% vs. 0.9%). In the multivariate analysis the MACCE-rate tended to be lower in prasugrel treated patients (odds ratio 0.71, 95% confidence intervals 0.42-1.08) but bleeding-rates tended to be higher. CONCLUSIONS In this real life experience in patients with STEMI scheduled for primary PCI, prasugrel was almost exclusively used in the label-recommended patient population and tended to be more effective but associated with more bleedings compared to clopidogrel. These results support the findings in the STEMI population in the randomized TRITON-TIMI 38 study.