Search

Supplementary Figures 1 and 2 from Immunologic and Clinical Responses after Vaccinations with Peptide-Pulsed Dendritic Cells in Metastatic Renal Cancer Patients

A phase I trial was conducted to evaluate the feasibility, safety, and efficacy of a dendritic cell–based vaccination in patients with metastatic renal cell carcinoma (RCC). Autologous mature dendritic cells derived from peripheral blood monocytes were pulsed with the HLA-A2-binding MUC1 peptides (M1.1 and M1.2). For the activation of CD4+ T-helper lymphocytes, dendritic cells were further incubated with the PAN-DR-binding peptide PADRE. Dendritic cell vaccinations were done s.c. every 2 weeks for four times and repeated monthly until tumor progression. After five dendritic cell injections, patients additionally received three injections weekly of low-dose interleukin-2 (1 million IE/m2). The induction of vaccine-induced T-cell responses was monitored using enzyme-linked immunospot and Cr release assays. Twenty patients were included. The treatment was well tolerated with no severe side effects. In six patients, regression of the metastatic sites was induced after vaccinations with three patients achieving an objective response (one complete response, two partial responses, two mixed responses, and one stable disease). Additional four patients were stable during the treatment for up to 14 months. MUC1 peptide–specific T-cell responses in vivo were detected in the peripheral blood mononuclear cells of the six patients with objective responses. Interestingly, in patients responding to the treatment, T-cell responses to antigens not used for vaccinations, such as adipophilin, telomerase, or oncofetal antigen, could be detected, indicating that epitope spreading might occur. This study shows that MUC1 peptide–pulsed dendritic cells can induce clinical and immunologic responses in patients with metastatic RCC. (Cancer Res 2006; 66(11): 5910-8)

Background Ventricular tachycardia can be triggered by myocardial ischaemia. These often fatal events are nearly always accompanied by a significant circulatory depression. However, the exact mechanical alterations and mechanisms of adaption during such arrhythmia episodes are still unknown. Case summary We report on a 71-year-old male patient with a distinct cardiovascular risk profile, recurrent incidences of dizziness and palpitations. A Holter electrocardiogram was performed showing multiple episodes of ventricular tachycardia. He was immediately transferred to our hospital for further monitoring and diagnostics. During echocardiography, one of these episodes could be recorded with a four-dimensional (4D) probe in triplane acquisition mode and strain analysis was done. Afterwards, a heart catheter examination was performed. A one-vessel coronary heart disease was diagnosed and treated with three drug-eluting stents. The burden of non-sustained ventricular tachycardia (nsVT) significantly reduced post-procedure. During the follow-up, new episodes of nsVT occurred after 6 weeks, which were treated by electrophysiological examinations. Discussion Modern 4D echocardiography machines offer the possibility to visualize the entire heart simultaneously. Thus ventricular arrhythmias can be evaluated using off-line strain analysis. This technology allows new real-time insights into the human heart showing compensatory mechanisms to overcome stressful episodes, such as ventricular tachycardia.

Health-related quality of life (HRQoL) is impaired in patients with stable angina but patients often present with other forms of chest pain. The aim of this study was to compare the pre-diagnostic HRQoL in patients with suspected coronary artery disease (CAD) according to angina type, gender, and presence of obstructive CAD.From the pilot study for the European DISCHARGE trial, we analysed data from 24 sites including 1263 patients (45.9% women, 61.1 ± 11.3 years) who were clinically referred for invasive coronary angiography (ICA; 617 patients) or coronary computed tomography angiography (CTA; 646 patients). Prior to the procedures, patients completed HRQoL questionnaires: the Short Form (SF)-12v2, the EuroQoL (EQ-5D-3 L) and the Hospital Anxiety and Depression Scale.Fifty-five percent of ICA and 35% of CTA patients had typical angina, 23 and 33% had atypical angina, 18 and 28% had non-anginal chest discomfort and 5 and 5% had other chest discomfort, respectively. Patients with typical angina had the poorest physical functioning compared to the other angina groups (SF-12 physical component score; 41.2 ± 8.8, 43.3 ± 9.1, 46.2 ± 9.0, 46.4 ± 11.4, respectively, all age and gender-adjusted p 0.01), and highest anxiety levels (8.3 ± 4.1, 7.5 ± 4.1, 6.5 ± 4.0, 4.7 ± 4.5, respectively, all adjusted p 0.01). On all other measures, patients with typical or atypical angina had lower HRQoL compared to the two other groups (all adjusted p 0.05). HRQoL did not differ between patients with and without obstructive CAD while women had worse HRQoL compared with men, irrespective of age and angina type.Prior to a diagnostic procedure for stable chest pain, HRQoL is associated with chest pain characteristics, but not with obstructive CAD, and is significantly lower in women.Clinicaltrials.gov, NCT02400229.

To evaluate diagnostic impact of clinical use of coronary computed tomography angiography (CCTA) in patients with suspected stable coronary artery disease (CAD) and its consequences in daily practice for patient management, depending on stress test results in daily practice. Between 2009 and 2014 of a total population of 1352 patients of the German Cardiac Computed Tomography (CT) Registry who had previously undergone stress tests, CCTA visualizations were carried out on the coronary arteries with suspected stable CAD. Patients were divided into three groups according to stress test results: Group 1 with inconclusive (n = 178, 13.2%), Group 2 with ischemia in stress test (n = 372, 27.5%) and Group 3 without ischemia in stress test (n = 802, 59.3%). The test of preference was the stress electrocardiogram (ECG), which was performed more frequently in patients without ischemia in stress test as compared to those with ischemia (96.3% vs. 93.0%, p = 0.015). The incidence of detected obstructive CAD was lower in patients with suggested ischemia in stress test as compared to patients with inconclusive results (14.1% vs. 21.1%, p = 0.037). There was no difference in the incidence of an obstructive CAD in patients with and without ischemia in stress test (14.1% vs. 15.8%, p = 0.440). CCTA is a reliable, non-invasive option for ruling-out obstructive CAD irrespective of the stress test result.

Background: Health-related quality of life (HRQoL) is impaired in patients with stable angina but patients often present with other forms of chest pain. The aim of this study was to compare the pre-diagnostic HRQoL in patients with suspected coronary artery disease (CAD) according to angina type, gender, and presence of obstructive CAD.Methods: From the pilot study for the European DISCHARGE trial, we analysed data from 24 sites including 1263 patients (45.9% women, 61.1 ± 11.3 years) who were clinically referred for invasive coronary angiography (ICA; 617 patients) or coronary computed tomography angiography (CTA; 646 patients). Prior to the procedures, patients completed HRQoL questionnaires: the Short Form (SF)-12v2, the EuroQoL (EQ-5D-3 L) and the Hospital Anxiety and Depression Scale.Results: Fifty-five percent of ICA and 35% of CTA patients had typical angina, 23 and 33% had atypical angina, 18 and 28% had non-anginal chest discomfort and 5 and 5% had other chest discomfort, respectively. Patients with typical angina had the poorest physical functioning compared to the other angina groups (SF-12 physical component score; 41.2 ± 8.8, 43.3 ± 9.1, 46.2 ± 9.0, 46.4 ± 11.4, respectively, all age and gender-adjusted p p p Conclusions: Prior to a diagnostic procedure for stable chest pain, HRQoL is associated with chest pain characteristics, but not with obstructive CAD, and is significantly lower in women.Trial registration: Clinicaltrials.gov, NCT02400229.

No abstract available

Background: In ST-segment elevation myocardial infarction (STEMI) patients treated with percutaneous coronary intervention, direct transport from the scene to the catheterisation laboratory bypassing the emergency department has been shown to shorten times to reperfusion. The aim of this study was to investigate the effects of emergency department bypass on mortality in both haemodynamically stable and unstable STEMI patients. Methods: The analysis is based on a large cohort of STEMI patients prospectively included in the German multicentre Feedback Intervention and Treatment Times in ST-Elevation Myocardial Infarction (FITT-STEMI) trial. Results: Out of 13,219 STEMI patients who were brought directly from the scene by emergency medical service transportation and were treated with percutaneous coronary intervention, the majority were transported directly to the catheterisation laboratory bypassing the emergency department ( n=6740, 51% with emergency department bypass). These patients had a significantly lower in-hospital mortality than their counterparts with no emergency department bypass (6.2% vs. 10.0%, PConclusion: In STEMI patients, emergency department bypass is associated with a significant reduction in mortality, which is most pronounced in patients presenting with cardiogenic shock. Our data encourage treatment protocols for emergency department bypass to improve the survival of both haemodynamically stable patients and, in particular, unstable patients. Clinical Trial Registration: NCT00794001 ClinicalTrials.gov: NCT00794001

Coronary computed tomography angiography (CTA) is increasingly used as a test to rule out coronary artery disease (CAD) in patients with a low to intermediate pre-test probability of the disease. We used the database of the German CT registry, collected between 2009 and 2014 in a broad patient population, to analyze contemporary radiation dose associated with coronary CTA in clinical practice. The prospective observational registry included a total of 7061 patients ≥18 years, referred to 12 participating centers for a clinically indicated cardiac CT examination. All centers were cardiology units well experienced in CTA and used multi-slice CT scanners with at least 64 rows. Coronary CTA was performed in a subset of 5001 patients, 59.6 ± 11.8 years, body mass index (BMI) 26.9 ± 4.5 kg/m2, 38% females. Three time periods with approximately equal numbers of patients were created (01/09–03/10, 04/10–03/11, 04/11–07/14). The dose–length product of all examinations and derived effective dose in mSv (conversion factor k = 0.014) as well as the influence of patient characteristics on dose were compared for the three time periods. BMI and proportion of female patients remained stable over time, and mean heart rate decreased from 60.3 ± 9.0 to 58.5 ± 9.3 bpm from the first to the last time period (p

In patients with heart failure (HF) and reduced ejection fraction (EF), non-invasive cardiac imaging provides diagnostic, prognostic, and therapeutic information and assists decision-making. The aim of this consensus paper is to provide an overview of the clinical applications of non-invasive cardiac imaging in the management of HF patients with systolic dysfunction, mostly focusing on impact on clinical decision-making ( Figure 1 ). Figure 1 Use of cardiac imaging for the management of patients with chronic systolic heart failure. HF, heart failure; BNP, brain natriuretic peptide; CMR, cardiac magnetic resonance; EF, ejection fraction; CAD, coronary artery disease; CCTA, cardiac computed tomographic angiography; SPECT, single photon emission computed tomography; PET, positron emission tomography; ICD, implantable cardioverter defibrillator; CRT, cardiac resynchronization therapy; OMT, optimal medical therapy. *might precede stress imaging in patients with angina. In patients with suspected HF, an electrocardiogram, chest X-ray, and brain natriuretic peptide (BNP or NT-proBNP) assay should be performed before non-invasive cardiac imaging,1 but in particular clinical situations with high likelihood of the disease, i.e. symptoms of HF in patients with previous myocardial infarction, cardiac imaging might be directly performed without previous BNP assay. Left ventricular (LV) systolic dysfunction, conventionally identified when EF at rest is 60 mm or 32 mm/m2 with LV volume >97 mL/m2) and end-systolic diameter and …

BACKGROUND AND OBJECTIVE A positive correlation between the presence of coronary artery disease (CAD) and peripheral endothelial dysfunction (ED) of the brachial artery has been shown in several studies. Aim of the present study was to evaluate whether the non-invasive determination of ED could also be used as a screening test in patients suspected of having CAD. PATIENTS AND METHODS 122 patients were included. 112 had an exercise-ECG before hospital admission. Preceding coronary angiography, FMD% was measured by high-resolution ultrasound (13 Mhz). Longitudinal scans of the brachial artery were done at rest, during reactive hyperemia and after the sublingual administration of nitroglycerin. RESULTS In 101 of the 122 patients the presence of CAD was diagnosed by angiography, whereas 21 patients had normal coronary arteries. The extent of the vasodilation (FMD%) was found to be largely independent of the resting vessel diameters (FMD%/vessel diameter at rest: r = -0.32767 p = 0.0002). FMD% was significantly higher in patient without CAD than in the CAD group (7.01 +/- 3.5% vs. 3.73 +/- 4.11%, p < 0.001). Comparison of sensitivity and specificity to predict the presence of CAD between FMD% [sensitivity 71.3%, specificity 81%] and exercise-ECG [sensitivity 82.4%, specificity 57.1%] gave similar results. No correlation was found between the degree of the impairment of FMD% and the severely of CAD. CONCLUSION The determination of peripheral ED was found to be a sensitive and specific measure for predicting the presence of CAD in our cohort. Since this approach is non-invasive, non-radioactive and cost-effective it warrants further evaluation of its role as an additional screening test in patients clinically suspected of having CAD.

In the past 2 years mechanical multidetector-row CT (MDCT) systems with simultaneous acquisition of four slices and half-second scanner rotation have become widely available. Data acquisition with these scanners allows for considerably faster coverage of the heart volume compared with single-slice scanning. This increased scan speed can be used for retrospective gating together with 1-mm collimated slice widths and allows coverage of the entire cardiac volume in one breath hold. Initial results from studies in correlation with intracoronary ultrasound suggest that MDTC technology not only offers the possibility to visualize intracoronary stenoses non-invasively but also to differentiate plaque morphology. This is especially the case with the next generation of 16-row multidetector CT. An increased number of simultaneously acquired slices and sub-millimeter collimation for cardiac applications allows true isotropic scanning with high temporal resolution. Contrast-enhanced MDTC is a promising non-invasive technique for the detection, visualization, and characterization of stenotic artery disease. It could act as a gate keeper prior to cardiac catherization and finally replace conventional diagnostic modalities.

Die klinische Wirksamkeit von GP IIb/IIIa Antagonisten wurde bei prainterventioneller prophylaktischer Applikation in grosen klinischen Studien nachgewiesen. Ziel dieser prospektiven Studie war es, die Wirksamkeit von Abciximab bei der Anwendung in „bail-out” Situationen zu untersuchen.¶ Methoden: Insgesamt wurden bei 104 (5,5%) der 1903 Patienten, welche im Beobachtungszeitraum in unserem Zentrum dilatiert wurden, akute oder drohende Gefasverschlusse beobachtet. In dieser Situation wurde Abciximab in einer Dosierung von 0,25mg/kg als Bolus, gefolgt von einer Infusion von 10μg/min uber 12 Stunden appliziert. Kurz nach der Gabe des Bolus wurde eine erneute PTCA durchgefuhrt. Am Ende der Intervention wurde die Schleuse belassen und nach 24 Std. eine Kontrollangiographie durchgefuhrt.¶ Ergebnisse: Bei 100 der 104 Patienten konnte ein ausreichender (TIMI III) Fluss wiederhergestellt werden. Bei 4 Patienten war die zusatzliche Implantation eines Stents notwendig. Eine Kontrollangiographie am Folgetag zeigte in allen bis auf 2 Falle offene Gefase mit gutem antegraden Fluss (TIMI III). Bei 4 Patienten trat nach der Intervention ein subakuter Gefasverschluss auf. Drei von ihnen verstarben trotz einer sofort durchgefuhrten Notfall-ACVB OP. Das 12 Monats Follow-up beinhaltet den klinischen Status sowie eine Kontrollangiographie des Zielgefases. Wahrend des Nachbeobachtungszeitraums kam es bei 15 Patienten zu einem klinischen Ereignis (2 MI, 8 ACVB, 5 Re-PTCA).¶ Schlussfolgerung: Die Ergebnisse dieser prospektiven Studie zeigen die hohe Wirksamkeit von Abciximab in „bail-out” Situationen wahrend oder direkt nach der PTCA. Weitere Studien sollten dieses Konzept mit dem der prophylaktischen Behandlung vergleichen.

Background: The low molecular weight heparin Reviparin reduces smooth muscle cell proliferation in cell culture experiments. Clinical studies with systemic application of the substance did not show a reduction of the incidence of restenosis following balloon angioplasty. Local delivery, by achieving higher local concentrations of the drug, may have the potential to decrease smooth muscle cell proliferation in the treated arterial segment. Objectives: The aim of this study was to investigate the effects of local delivery of reviparin following stent implantation in the pig coronary artery. Methods: A coronary stent was implanted in the LAD of 34 pigs. In the treatment group 5 ml reviparin was injected with the Infusasleeve catheter at a proximal pressure of 80 psi. After 28 days the animals were sacrificed. Quantitative morphometric analysis comprised the intimal area, medial area and the lumen. The extent of vessel injury and the intimal thickness were assessed separately for each stent strut region. The correlation of injury and neointimal thickness was analysed using linear regression. Results: There was no relevant difference in the extent of vessel injury (1.9 ± 0.7 vs. 1.6 ± 0.6), the neointimal areas (2.4 ± 0.9 vs. 2.4 ± 1.0 mm2) and the resulting stenosis (46 ± 18 vs. 47 ± 17%). The medial area was larger in the animals treated with local delivery (2.2 ± 0.4 vs. 1.6 ± 0.4 mm2; p < 0,01). The correlation of injury and neointimal thickness was comparable in both groups. In two animals the passage of the stent area with the delivery system resulted in stent dislocation and fatal subacute thrombosis. Conclusion: In this animal model, local delivery of reviparin with the Infusasleeve catheter did not result in a reduction of neointimal proliferation following stent implantation. Local delivery after stent implantation carries the risk of stent dislocation as a result of the passage with the delivery system.

Paclitaxel, a potent anti-tumor agent, shifts the cytoskeleton equilibrium towards assembly of altered and extraordinarily stable microtubules. These cellular modifications lead to reduced proliferation, migration, and signal transduction. It is highly lipophilic, which promotes a rapid cellular uptake, and has a long-lasting effect in the cell due to the structural alteration of the cytoskeleton. This makes paclitaxel a promising candidate for local drug delivery intended to address the proliferative and migratory processes involved in restenosis. In this article, results of our in vitro and in vivo studies with paclitaxel are presented. Cell culture experiments with monocultures of human arterial smooth muscle cells as well as co-cultures with human endothelial cells showed that paclitaxel leads to an almost complete growth inhibition within a dose range of 1.0-10.0 mumol/l, even after a short (20 min) single dose application. The comparison of an active, semi-active, and passive delivery system (porous balloon, microporous balloon, and double balloon) favored the double balloon for the following in vivo experiments. Tubulin staining and electron microscopy enabled visualization of paclitaxel-induced vessel wall alterations. In the rabbit model, locally delivered paclitaxel resulted in reduced neointima formation and enlargement in vessel size; in the pig model, however, after stenting, this inhibition was not significant. Both reduced proliferation and enlargement in vessel size contribute to a preservation of vessel shape and are likely to be caused by a structural alteration of the cytoskeleton, which is also supported by vascular contraction force experiments.

Hintergrund: Die Qualitatskontrolle gewinnt in der interventionellen Kardiologie zunehmend an Bedeutung. Da aber die Nachbetreuung von Patienten, die mit einer perkutanen transluminalen Koronarangioplastie (PTCA) behandelt wurden, meist durch die jeweiligen Hausarzte durchgefuhrt wird, gehen dem kardiologischen Zentrum wichtige Informationen hinsichtlich des klinischen Langzeitverlaufs verloren. Ziel dieser retrospektiven Studie war daher, den klinischen Status dieser Patienten vier Jahre nach der Behandlung mit einer PTCA an unserer Institution zu untersuchen. Patienten und Methode: Einschluskriterium war die Behandlung mit einer PTCA im Zeitraum vom 1.7.1989 bis 30.6.1991 (549 Patienten). Zur Erhebung der Langzeitergebnisse (45±7 Monate nach PTCA) wurde den Patienten ein Fragebogen zugesandt. Vier Erhebungszeitpunkte wurden definiert: vor PTCA (T1), direkt nach PTCA (T2), drei Monate nach PTCA (T3) und zum Erhebungszeitpunkt (T4). Ergebnisse: Fragebogen von 500/549 (91,1%) Patienten kamen zur Auswertung. 115 (23%) Patienten musten sich einer Reintervention unterziehen (PTCA: 69 Patienten [13,8%], aortokoronare Venen-Bypass-(ACVB-)Operation: 46 Patienten [9,2%]). Zu T4 hatten 11,2% Patienten starkere Angina-pectoris-Beschwerden. 35 Patienten (7%) waren im Erhebungszeitraum verstorben. 219 Patienten (52%) nahmen an einer Anschlusheilbehandlung teil. Zu T4 waren diese Patienten nicht haufiger beschwerdefrei als Patienten ohne Anschlusheilbehandlung (60,7% vs. 66,4%, p = 0,29). Der Anteil der nach Intervention neu berenteten Patienten (n = 114 [22,8%] war in der Gruppe mit Anschlusheilbehandlung hoher (68 Patienten [13,6%] mit Anschlusheilbehandlung vs. 46 Patienten [9,2%] ohne Anschlusheilbehandlung, p = 0,0036). Positiven Einflus hatte die Teilnahme an einer Anschlusheilbehandlung auf Anderungen des Lebensstils und der Esgewohnheiten. Schlusfolgerung: Diese retrospektive Befragung erwies sich als sinnvoll (Antwortrate 91,1%), um Daten zur Qualitatskontrolle zu erheben. Wichtige Informationen sowohl hinsichtlich der Qualitat der Koronarinterventionen (niedrige Reinterventionsrate) als auch hinsichtlich des klinischen Langzeitverlaufs (niedriger Anteil von Patienten mit schwerer Symptomatik nach vier Jahren) konnten hierdurch gewonnen werden.

For selected indications, coronary computed tomographic (CT) angiography is an established clinical technology for evaluation in patients suspected of having or known to have coronary artery disease. In coronary CT angiography, image quality is highly dependent on heart rate, with heart rate reduction to less than 60 beats per minute being important for both image quality and radiation dose reduction, especially when single-source CT scanners are used. β-Blockers are the first-line option for short-term reduction of heart rate prior to coronary CT angiography. In recent years, multiple β-blocker administration protocols with oral and/or intravenous application have been proposed. This review article provides an overview of the indications, efficacy, and safety of β-blockade protocols prior to coronary CT angiography with respect to different scanner techniques. Moreover, implications for radiation exposure and left ventricular function analysis are discussed.

A phase I trial was conducted to evaluate the feasibility, safety, and efficacy of a dendritic cell–based vaccination in patients with metastatic renal cell carcinoma (RCC). Autologous mature dendritic cells derived from peripheral blood monocytes were pulsed with the HLA-A2-binding MUC1 peptides (M1.1 and M1.2). For the activation of CD4+ T-helper lymphocytes, dendritic cells were further incubated with the PAN-DR-binding peptide PADRE. Dendritic cell vaccinations were done s.c. every 2 weeks for four times and repeated monthly until tumor progression. After five dendritic cell injections, patients additionally received three injections weekly of low-dose interleukin-2 (1 million IE/m2). The induction of vaccine-induced T-cell responses was monitored using enzyme-linked immunospot and Cr release assays. Twenty patients were included. The treatment was well tolerated with no severe side effects. In six patients, regression of the metastatic sites was induced after vaccinations with three patients achieving an objective response (one complete response, two partial responses, two mixed responses, and one stable disease). Additional four patients were stable during the treatment for up to 14 months. MUC1 peptide–specific T-cell responses in vivo were detected in the peripheral blood mononuclear cells of the six patients with objective responses. Interestingly, in patients responding to the treatment, T-cell responses to antigens not used for vaccinations, such as adipophilin, telomerase, or oncofetal antigen, could be detected, indicating that epitope spreading might occur. This study shows that MUC1 peptide–pulsed dendritic cells can induce clinical and immunologic responses in patients with metastatic RCC. (Cancer Res 2006; 66(11): 5910-8)

□ Eigner Fall Ein 32jahriger adiposer Patient wurde wegen heftigster Oberbauchschmerzen notfallmasig in unsere Klinik stationar aufgenommen. Routineuntersuchungen fuhrten zunachst zu keiner Diagnose. Der Patient entwickelte im weiteren Verlauf hohes Fieber, verbunden mit einer Polydipsie und Polyurie. Serologisch wurde eine akute Hantaan-Virus-Infektion nachgewiesen. Laborchemisch zeigte sich eine partielle Hypophysenvorder- und-hinterlappeninsuffizient mit einem vollstandigen Ausfall von ACTH, ausgelost durch zwei primar intrakraniell gelegene Germinome.

The objective of this study was to evaluate the accuracy of electrocardiography (ECG)-gated 16-slice multidetector-row computed tomography (MDCT) in detection of stenosis of bypass grafts and native coronary arteries in patients who have undergone coronary artery bypass grafting (CABG). ECG-gated contrast-enhanced MDCT using 12 x 0.75-mm collimation was performed in 20 patients with recurrent angina 4.75 years after undergoing CABG. A total of 50 grafts, 16 arterial and 34 venous, were examined. All graft and coronary segments were evaluated for stenosis in comparison with conventional coronary angiography (CCA). Among the 80 arterial graft segments, 62 could be assessed (77.5%). Sensitivity, specificity, and positive and negative predictive values for stenosis were 96.2%, 97.2%, 96.2%, and 97.2%, respectively. In a total of 180 venous graft segments, 167 could be assessed. Sensitivity, specificity, and positive and negative predictive values for stenosis were 98.5%, 93.9%, 91.8%, and 98.9%, respectively. MDCT could assess 179 of 260 native coronary artery segments (68.8%). Sensitivity, specificity, and positive and negative predictive values for stenosis were 92.1%, 76.9%, 87.5%, and 84.7%, respectively. Sixteen-slice MDCT provides excellent image quality and diagnostic accuracy in detection of graft and coronary artery lesions in patients with suspected graft dysfunction.

The first computed tomography (CT) systems, introduced in 1972, produced image slices which represent the distribution of the object’s X-ray attenuation in the image plane. Since then the progress to third generation fan beam geometry and continuous spiral scanning has changed CT from a sequential single-slice imaging technology to a continuous-volume imaging modality. The introduction of spiral acquisition in 1991 was a first breakthrough for CT in vascular diagnosis with contrast-enhanced CT angiography (CTA) examinations. A second major leap in CT technology came with the advent of multislice acquisition in 1998. This technology allows for almost isotropic three-dimensional (3D) spatial resolution, short examination times, and coverage of large volumes for CT angiographic imaging of the abdominal, cerebral, and peripheral vessels. Furthermore, very short image acquisition times due to increased gantry rotation speed in combination with ECG synchronization allow for diagnosis of the heart, the cardiovascular vessels, and the coronary arteries.

Coronary artery disease (CAD) is the leading killer in Europe and the United States. CAD accounted for almost 600,000 deaths in Europe in 1998. Although many patients initially present with symptoms, about half of all patients have no symptoms before their sudden death. Thus, a screening test for CAD might help stratify coronary risk in asymptomatic adults. Since its introduction in 1983, electron beam computed tomography scanning (EBCT) has been proposed as a means of coronary calcium assessment for screening. However, direct visualization of the epicardial coronary arteries is necessary to establish the presence and focal severity of lumen disease. Selective coronary angiography is the only clinical method to accurately visualize and quantify coronary artery anatomy in vivo. This. method provides exceptional spatial resolution and a general road map of the coronary system. More than one million diagnostic catheterizations are performed in the United States each year. Selective coronary angiography is expensive and requires at least a brief hospital stay and a period of observation for several hours after the procedure. A convenient noninvasive and safe means to perform coronary angiography clearly would be of clinical benefit. Promising results have been reported for EBCT with a decent sensitivity and specificity in the detection of coronary artery stenoses [12, 16]. A major caveat of this method is, however, the high incidence of motion artifacts, leading to uninterpretable images [1, 4]. This limitation might now be overcome by the emergence of superfast multislice CT (MSCT) technology with spiral scanning at high temporal (125 ms) and superior spatial (10 1p/cm) resolution [11].

Background: The microtubule stabilizing compound paclitaxel has proved to have potent antiproliferative effects on smooth muscle cells both in vitro and in vivo. It induces cellular modifications that result in reduced proliferation, migration and signal transduction by shifting the cellular microtubule equilibrium towards assembly. We therefore reasoned that a visualization of the altered cytoskeleton could enable an evaluation of the drug effects following local drug delivery. Methods and results: 3 catheters – the porous balloon, the microporous balloon and the double balloon catheter – were chosen for this study representing the spectrum from passive to active, pressure-driven delivery. After the induction of a defined plaque in the right carotid arteries of 40 New Zealand rabbits by electrical stimulation, 32 animals underwent balloon dilatation and 8 animals served as pre-interventional control group with electrostimulation only. In 24 animals (n = 8 in each group) subsequent local paclitaxel delivery (10 μmol/L) was performed. 8 animals served as control with angioplasty only. Vessels were excised 1 week following intervention. Immunohistochemistry with antibodies against bromodeoxyuridine, alpha-actin, macrophages, von Willebrand factor and α-tubulin was performed. Cytoskeletal changes were analyzed by electron microscopy. Tubulin staining and electron microscopy revealed changes with distinct staining patterns for the different catheters. Specific catheter-induced injuries could be identified for the porous and double balloon catheter. Intimal proliferation, percentage of macrophages and extent of injury favor the double balloon catheter for local paclitaxel delivery. Conclusions: The alterations of the cytoskeleton induced by paclitaxel allowed for the detection of drug action by staining of tubulin and electron microscopy. This enables an evaluation of transfer, distribution and drug effects directly in the vasculature without marker substances. The double balloon catheter appears to be best suited for local paclitaxel therapy.

Injection parameters for local drug delivery are frequently determined by studies with marker substances. However, the pharmacologic properties of the actual drug may influence delivery efficiency and lead to different results. Aim of this study was to assess the delivery capacities of two device-drug combinations in order to verify this approach for further in vivo studies. Tritiated (3H) preparations (5 ml) of the hydrophylic low-molecular-weight heparin reviparin and the lipophilic taxane paclitaxel were injected into the left anterior descending artery of freshly explanted porcine hearts with the Infusasleeve II catheter system. A balloon support pressure of 6 atm and infusion pressures of 40, 60, 80, or 100 psi were used. In three additional groups, reviparin was injected following stent implantation and paclitaxel was injected prior to or following stent implantation. Arteries along with surrounding myocardium were harvested. The artery was carefully dissected, and artery and myocardium were separately homogenized, and activity was measured. Of the totally delivered activity, 0.09% ± 0.03% (40 psi) to 0.17% ± 0.13% (100 psi) of reviparin and 2.03% ± 0.67% (60 psi) to 2.68% ± 1.57% (100 psi) of paclitaxel were found in the vessel wall. The results for different injection pressures were not significantly different for either drug. The percentage activity delivered to the vessel wall was substantially larger in the paclitaxel group as compared to reviparin delivery (P < 0.01 at 60, 80, and 100 psi). The mean concentration of reviparin in the artery was 20 to 33 times higher than in the myocardium. For paclitaxel the factors were 110 to 243. Stent implantation prior to or following local delivery did not result in a different delivery efficiency. The results demonstrate that the characteristics of the delivered drug contribute largely to the delivery efficiency. Using identical injection parameters, drug concentrations in the arterial wall were significantly higher for the lipophilic paclitaxel as compared to the hydrophilic reviparin. Stenting of the artery did not influence delivery efficiency. Cathet. Cardiovasc. Intervent. 47:102–106, 1999. © 1999 Wiley-Liss, Inc.

The present case report describes a 37-year-old man who presented to the emergency room with symptoms of a myocardial infarction but no high-grade stenosis on conventional catheter angiography. Consecutive multi-detector row computed tomography of the coronary arteries showed an intimal flap along a fibrous plaque formation in the left anterior descending artery. This finding was found to represent a plaque rupture, and the lesion was treated with an 18 mm stent. Multidetector row computed tomography helped to correctly position the stent by identifying the exact location of the rupture along the long plaque formation.

Can we simplify the measurement of cardiovascular calcification in patients on hemodialysis?

High reproducibility is a key requirement for coronary calcium scoring in follow-up examinations. We investigated the inter-examination reproducibility of calcium scoring with retrospectively ECG-gated multisection spiral CT (MSCT). Fifty patients were examined twice with MSCT. Slices were reconstructed with retrospective ECG gating in the diastolic phase with 3-mm slice width and up to 125-ms temporal resolution. We calculated the Agatston score, calcium volume with and without isotropic interpolation, and calcium mass, and derived the mean and median variability. We investigated the change of variability with use of 3-mm non-overlapping and overlapping increments (2, 1.5, 1 mm). Use of overlapping increment results in considerably reduced interscan variability. We observed a minimum mean variability of 12% and a minimum median variability of 9% for the Agatston score. For volume and mass quantification we obtained a minimum mean variability of 7.5% and a minimum median variability of 5%. Multisection spiral CT enables coronary calcium quantification with high reproducibility in follow-up examinations mainly founded on image data with reduced partial-volume errors due to overlapping increment.

OBJECTIVE The aim of this study was to evaluate the potential of paclitaxel to prevent restenosis in vivo. BACKGROUND Paclitaxel (Taxol) is a microtubule-stabilizing compound with potent antitumor activity. It influences the cytoskeleton equilibrium by increasing the assembly of altered microtubules, thereby inducing cellular modifications that result in reduced proliferation, migration and signal transduction. METHODS Before the in vivo study, delivery efficiency was determined with radiolabeled paclitaxel in porcine hearts. After induction of a defined plaque in the right carotid arteries of 76 New Zealand rabbits by electrical stimulation, 27 animals underwent balloon dilation and subsequent local paclitaxel delivery (10 ml, 10 μmol/liter) with a double-balloon catheter. Twenty-nine animals served as control with angioplasty only, 10 animals underwent local delivery of vehicle only (0.9% NaCl solution) and 10 animals were solely electrostimulated. Vessels were excised one, four, and eight weeks after intervention. RESULTS The extent of stenosis in paclitaxel-treated animals was significantly reduced compared with balloon-dilated control animals (p = 0.0012, one, four and eight weeks after intervention: 14.6%, 24.6% and 20.5%, vs. 24.9%, 33.8% and 43.1%, respectively). Marked vessel enlargement compared with balloon-dilated control animals could be observed (p = 0.0001, total vessel area after one, four and eight weeks: paclitaxel group: 1.983, 1.700 and 1.602 mm2, control: 1.071, 1.338 and 1.206 mm2, respectively). Tubulin staining and electron microscopy revealed changes in microtubule assembly, which were limited to the intimal area. Vasocontractile function after paclitaxel treatment showed major impairment. CONCLUSIONS Local delivery of paclitaxel resulted in reduced neointimal stenosis and enlargement in vessel size. Both these effects contribute to a preservation of vessel shape and are likely to be caused by a structural alteration of the cytoskeleton.

To methodically evaluate the reproducibility and accuracy of coronary arterial calcification measurements by using spiral multi-detector row and electron-beam computed tomography (CT) with a beating heart phantom.A phantom was built to mimic a beating heart with coronary arteries and calcified plaques. The simulated vessels moved in a pattern similar to that of a beating heart. The phantom operated at a variety of pulse rates (0-140 beats per minute). The phantom was repeatedly scanned in various positions by using various protocols with electron-beam and multi-detector row CT scanners to assess interexamination variability. Statistical analysis was performed to determine significant differences in interexamination variability for various acquisition protocols.Electrocardiographically (EKG) gated volume coverage with spiral multi-detector row CT (2.5-mm collimation) and overlapping image reconstruction (1-mm increment) was found to significantly improve the reliability of coronary arterial calcium quantification, especially for small plaques (P.05). Mean interexamination variability was reduced from 35% +/- 6 (SD) (Agatston score, standard electron-beam CT) to 4% +/- 2 (P.05) (volumetric score, spiral EKG-gated multi-detector row CT).By coupling retrospective gating with nearly isotropic volumetric imaging data, spiral multi-detector row CT provides better input data for quantification of coronary arterial calcium volume. Multi-detector row CT allows precise and repeated measurement of coronary arterial calcification, with low interexamination variability.