The German CPU registry: Comparison of smokers and nonsmokers.

BACKGROUND: Chest pain is a major reason for admission to an internal emergency department, and smoking is a well-known risk factor for coronary artery disease (CAD) and acute coronary syndrome (ACS). The aim of this analysis is to illustrate the differences between smokers and nonsmokers presenting to German chest pain units (CPU) in regard to patient characteristics, CAD manifestation, treatment strategy, and prognosis. METHODS: From December 2008 to March 2014, 13,902 patients who had a complete 3­month follow-up were enrolled in the German CPU registry. The analysis comprised 5796 patients with ACS and documented smoking status. RESULTS: Of all the patients in the CPU registry, 35.2% were smokers. Compared with nonsmokers, they were 13.5 years younger (58.2 vs. 71.7 years, p < 0.001), predominantly men (77.1% vs. 65.2%, p < 0.001), and were more frequently diagnosed with single-vessel disease (32.1% vs. 25.2%) as well as ST-elevation myocardial infarction (STEMI; 23.8% vs. 15.5%, p < 0.001). Although the Global Registry of Acute Coronary Events (GRACE) Risk Score for hospital mortality was lower in the group of smokers (106.1 vs. 123.3, p < 0.001), we did not observe any differences in CPU death (0.4% vs. 0.4%, p = 0.69) and CPU major adverse cardiac event (MACE) rates (3.8% vs 2.9%, p = 0.073) between the groups. In the 3­month follow-up, we documented higher mortality rates in the nonsmoker group (1.9% vs. 2.9%, p = 0.035) in correlation with the GRACE Risk Score (80.3 vs. 105.2, p < 0.001). MACE rates were similar during the follow-up (3.1% vs. 4.1%, p = 0.065). CONCLUSION: Observations from the German CPU registry demonstrate that smoking is a strong predictor of acute CAD manifestation early in life, especially STEMI. In spite of a lower GRACE Risk Score and fewer comorbidities, smokers had a rate of hospital mortality similar to the older group of nonsmokers.

Coronary CT angiography (CCTA) using third-generation dual-source CT for ruling out in-stent restenosis.

AIMS: Late in-stent restenosis (ISR) has become increasingly important, in particular due to neo-atherosclerosis. CCTA is a highly sensitive method for detecting coronary plaques. Its diagnostic accuracy regarding ISR is controversial. Stent artifacts can impede image quality, but recent developments in CT-technology may help to overcome some of these problems and allow for improved diagnostic accuracy. METHODS: Consecutive patients after previous coronary revascularization who had stable symptoms or signs of possible disease progression were examined using a third-generation dual-source CT scanner. After the scan, patients were followed for clinical events (MACE) over a mean of 399 days. Patients with high-grade stenoses were referred for invasive coronary angiography (ICA), unclear findings were further evaluated either by ICA or functional testing. RESULTS: Overall, 226 patients were included. A total of 457 stents were evaluated (2.0 ± 1.4 per patient). Mean stent diameter was 2.9 ± 0.45 mm. In 61%, a high-pitch protocol was employed. Mean dose-length product (DLP) of CCTA was 159.2 mGy cm, corresponding to 2.2 mSv using a conversion factor of k = 0.014. Mean amount of contrast agent was 58.3 ± 12.5 ml. In 145 patients (64%), CCTA was negative. In this group, one MACE occurred (acute coronary syndrome) during follow-up in a patient who had also undergone unremarkable ICA. In 23 patients (10%), CCTA detected 28 ISR which were confirmed and treated by ICA (true positive). In 27 patients (12%), ISR was suspected by CCTA but excluded by ICA (false positive), 30 patients (13%) had unclear findings and normal non-invasive tests. No MACE occurred during follow-up in these patients. One patient was misclassified in CCTA as having intermediate and not high-grade ISR who underwent revascularization within 3 months. Eleven patients (5%) were lost to follow-up. During follow-up, eight patients had myocardial infarctions due to five ISRs and three de novo lesions. No patient died. In cases with unclear or false-positive findings, the amount of stents was significantly higher, stents were smaller and patients had a higher BMI. CONCLUSION: In almost two-thirds of symptomatic patients with previous coronary stent implantation, ISR could be ruled out by CCTA. 10% of patients had definite ISR. The rate of false-negative findings was low (< 1%), whereas the rate of false positive or inconclusive findings was 25%, leading to invasive rule-out of ISR by ICA in 12%. CCTA appears valuable as a tool for safely excluding ISR. It might help to avoid invasive diagnostic procedures. Further analyses are warranted, in particular regarding the influence of stent dimensions and the total amount of stents in a patient.

Admission heart rate in relation to presentation and prognosis in patients with acute myocardial infarction. Treatment regimens in German chest pain units.

BACKGROUND: Higher heart rates on admission have been associated with poor outcomes in patients with an acute coronary syndrome in previous cohorts. Whether such a linear relationship still exists in contemporary high-level care is unclear. METHODS: Prospectively collected data from patients presenting with myocardial infarction (MI) in centers participating in the Chest Pain Unit (CPU) Registry between December 2008 and July 2014 were analyzed. Patients were classified according to their initial heart rate (I: < 50; II: 50-69; III: 70-89; IV: ≥ 90 bpm). A total of 6,168 patients out of 30,339 patients presenting to 38 centers were included in the study. RESULTS: Patients in group IV had more comorbidities, while patients in group I more often had a history of MI. Patients in the lowest heart rate group presented significantly earlier to the hospital (4 h 31 min vs. 7 h 37 min; p < 0.05) and had the highest rate of interventions. The overall survival after 3 months was significantly worse in group IV after adjusting for baseline variables. In the subgroup analysis, heart rate was a prognostic factor in the non-ST-segment elevation MI group but not in the ST-segment elevation MI group. The correlation between heart rate and major adverse cardiac events followed a J-shaped curve with worst outcomes in the lowest and highest heart rate groups. CONCLUSION: Patients admitted to a dedicated CPU with the diagnosis of MI and a heart rate > 90 bpm experience reduced survival at 3 months despite optimal treatment. Patients with bradycardia also seem to be at increased risk for cardiovascular events despite much earlier presentation and treatment.

Endoscopic closure of esophageal intrathoracic leaks: stent versus endoscopic vacuum-assisted closure, a retrospective analysis.

BACKGROUND AND STUDY AIM: Placement of covered self-expanding metal or plastic stents (SEMS or SEPS) is an established method for managing intrathoracic leaks. Recently, endoscopic vacuum-assisted closure (EVAC) has been described as a new effective treatment option. Our aim was to compare stent placement with EVAC for nonsurgical closure of intrathoracic anastomotic leaks. PATIENTS AND METHODS: In a retrospective analysis we were able to identify 39 patients who were treated with SEMS or SEPS and 32 patients who were treated with EVAC for intrathoracic leakage. In addition to successful fistula closure, we analyzed hospital mortality, number of endoscopic interventions, incidence of stenoses, and duration of hospitalization. RESULTS: In a multivariate analysis, successful wound closure was independently associated with EVAC therapy (hazard ratio 2.997, 95 % confidence interval [95 %CI] 1.568 - 5.729; P = 0.001). The overall closure rate was significantly higher in the EVAC group (84.4 %) compared with the SEMS/SEPS group (53.8 %). No difference was found for hospitalization and hospital mortality. We found significantly more strictures in the stent group (28.2 % vs. 9.4 % with EVAC, P < 0,05). CONCLUSIONS: EVAC is an effective endoscopic treatment option for intrathoracic leaks and showed higher effectiveness than stent placement in our cohort.

[Secondary sclerosing cholangitis following liver transplantation: a rare cause for graft failure]. / Sekundär sklerosierende Cholangitis nach Lebertransplantation: Eine seltene Ursache für ein Transplantatversagen.

We report on a 25-year-old female patient who presented with recurrent cholestasis following liver transplantation due to primary sclerosing cholangitis. Abdominal ultrasound and computed tomography showed intrahepatic bile duct dilatation and stenosis of the common hepatic artery with flow acceleration and decreased resistance index. The patient developed a severe secondary sclerosing cholangitis (SSC) with biliary casts - despite interventional stent placement of the common hepatic artery - thus requiring retransplantation. After prolonged intensive care unit treatment the patient was discharged in a good general condition. This case report describes SSC as a rare cause for graft failure. In unclear cholestasis after liver transplantation SSC has to be considered as the underlying cause.

Secondary sclerosing cholangitis in critically ill patients: model of end-stage liver disease score and renal function predict outcome.

Secondary sclerosing cholangitis in critically ill patients (SSC - CIP) is an underdiagnosed emerging disease. The aim of this study was to characterize clinical features and prognostic factors for mortality in SSC - CIP. This retrospective study included 54 patients who were diagnosed via endoscopic retrograde cholangiopancreatography (ERCP) after cardiothoracic surgery (n = 21), sepsis (n = 13), polytrauma (n = 11), and others (n = 9). In total, 33 patients who either died (n = 27) or needed liver transplantation (n = 6) were compared with surviving patients (n = 21). The model for end-stage liver disease (MELD) score and need for renal replacement therapy were independent risk factors for mortality. Compared with ERCP, accuracy was 30% for ultrasound and 36 % for liver biopsies. As a result of microbiological bile analysis, 28 % of patients required a change in antibiotic treatment. SSC - CIP is frequently a fatal disease. ERCP should be considered in selected patients to establish the diagnosis and hence provide useful clinical information.

BRCA1/2 testing: uptake, phenocopies, and strategies to improve detection rates in initially negative families.

In families with clustering of breast and ovarian cancer, molecular testing of the major susceptibility genes BRCA1/2 helps to identify patients with disease mutations and healthy persons at high risk who can participate in targeted intervention programs. We investigated 5559 families from the German Consortium for Hereditary Breast and Ovarian Cancer included between 1997 and 2008 and treated under clinical routine conditions. In each family an index patient/person had been screened for deleterious mutations in BRCA1/2. Healthy relatives agreed to predictive testing in 888 of 1520 BRCA1/2 mutation-positive families (58%). Of 2646 eligible unaffected first-degree relatives 1143 decided to be tested (43%). In 325 families with BRCA1/2-positive index patients one related BC/OC patient was tested and 39 (12.0%; 95% confidence interval: 8.7-16.0%) discrepant cases found. A second related individual was screened in 163 of 3388 (4.9%) families with BRCA1/2-negative index patient and in eight families a BRCA1/2 mutation was found. In BRCA1/2 mutation-positive families, BC/OC patients lacking the familial mutation have to be expected at a rather high rate. In families with BRCA1/2-negative index patient we recommend a second screening if another patient with a high probability of carrying a BRCA1/2 mutation is available.

[Hemoptysis as the first sign of ruptured thoracic aorta]. / Hämoptyse als erstes Anzeichen einer thorakalen Aortenruptur.

Acute aortic rupture is associated with a high mortality. The leading symptoms are chest pain, dyspnea and hemodynamic instability as well as hemoptysis. In the current case report a patient with known coronary artery disease and prior coronary artery bypass surgery presented with hemoptysis. He was initially treated for a presumed gastroenterological disorder. The chest X-ray delineated a structure suggestive of aortic rupture and this diagnosis was confirmed by computed tomography. Emergency treatment was performed by implantation of an endovascular stent prosthesis. This procedure is currently regarded the standard treatment of rupture of the descending thoracic aorta. We conclude our case report with a discussion of epidemiology, symptoms, pathogenesis and therapy of this clinically dramatic disease.

In-vitro evaluation of coronary stents and 64-detector-row computed tomography using a newly developed model of coronary artery stenosis.

BACKGROUND: Stent implantation is the predominant therapy for non-surgical myocardial revascularization in patients with coronary artery disease. However, despite substantial advances in multidetector computed tomography (MDCT) coronary imaging, a reliable detection of coronary in-stent restenosis is currently not possible. PURPOSE: To examine the ability of 64-detector-row CT to detect and to grade in-stent stenosis in coronary stents using a newly developed ex-vivo vessel phantom with a realistic CT density pattern, artificial stenosis, and a thorax phantom. MATERIAL AND METHODS: Four different stents (Liberté and Lunar ROX, Boston Scientific; Driver, Medtronic; Multi-Link Vision, Guidant) were examined. The stents were placed on a polymer tube with a diameter of 2.5, 3.0, 3.5, or 4.0 mm. Different degrees of stenosis (0%, 30%, 50%, 70-80%) were created inside the tube. For quantitative analysis, attenuation values were measured in the non-stenotic vessel outside the stent, in the non-stenotic vessel inside the stent, and in the stenotic area inside the stent. The grade of stenosis was visually assessed by two observers. RESULTS: All stents led to artificial reduction of attenuation, the least degree of which was found in the Liberté stent (11.3+/-10.2 HU) and the Multi-Link Vision stent (17.6+/-17.9 HU; P = 0.25). Overall, the non-stenotic vessel was correctly diagnosed in 55.5%, the low-grade stenosis in 58.3%, the intermediate stenosis in 63.8%, and the high-grade stenosis in 80.5%. In the 3.0-, 3.5-, and 4.0-mm vessels, in none of the cases was a non-stenotic or low-grade stenotic vessel misdiagnosed as intermediate or high-grade stenosis. The average deviation from the real grade of stenosis was 0.40 for the Liberté stent, 0.46 for the Lunar ROX stent, 0.45 for the Driver stent, and 0.58 for the Multi-Link Vision stent. CONCLUSION: Our ex-vivo data show that non-stenotic stents and low-grade in-stent stenosis can be reliably differentiated from intermediate and high-grade in-stent stenosis in vessels with a diameter of 3 to 4 mm. With regard to artifacts and the grading of stenoses, the Liberté stent was best suited for CT coronary angiography.

The role of parvalbumin and calbindin D28k in experimental scrapie.

AIMS: Prion diseases are generally characterized by pronounced neuronal loss. In particular, a subpopulation of inhibitory neurones, characterized by the expression of the calcium-binding protein parvalbumin (PV), is selectively destroyed early in the course of human and experimental prion diseases. By contrast, nerve cells expressing calbindin D28 k (CB), another calcium-binding protein, as well as PV/CB coexpressing Purkinje cells, are well preserved. METHODS: To evaluate, if PV and CB may directly contribute to neuronal vulnerability or resistance against nerve cell death, respectively, we inoculated PV- and CB-deficient mice, and corresponding controls, with 139A scrapie and compared them with regard to incubation times and histological lesion profiles. RESULTS: While survival times were slightly but significantly diminished in CB-/-, but not PV-/- mice, scrapie lesion profiles did not differ between knockout mice and controls. There was a highly significant and selective loss of isolectin B(4)-decorated perineuronal nets (which specifically demarcate the extracellular matrix surrounding the 'PV-expressing' subpopulation of cortical interneurones) in scrapie inoculated PV+/+, as well as PV-/- mice. Purkinje cell numbers were not different in CB+/+ and CB-/- mice. CONCLUSIONS: Our results suggest that PV expression is a surrogate marker for neurones highly vulnerable in prion diseases, but that the death of these neurones is unrelated to PV expression and thus based on a still unknown pathomechanism. Further studies including the inoculation of mice ectopically (over)expressing CB are necessary to determine whether the shortened survival of CB-/- mice is indeed due to a neuroprotective effect of this molecule.

In vitro evaluation of coronary stents and in-stent stenosis using a dynamic cardiac phantom and a 64-detector row CT scanner.

INTRODUCTION: The aim of the study was to examine the ability of a 64-slice MDCT to detect in-stent stenoses in an ex vivo model of coronary stents. METHODS: Five different stents (Liberté, Boston Scientific; Driver, Medtronic; Multi-Link Vision, Guidant; Taxus Express, Boston Scientific; Cypher, Cordis) were examined using a dynamic cardiac phantom. The stents were pulled over a vessel model that consists of a polymer tube with diameters of 3.0, 3.5, and 4.0 mm and four different degrees of stenoses (0%; 30%; 50%; 70-80%). This model was moved with a rate of 60 bpm to mimic cardiac motion. To assess the degree of artificial signal reduction (artificial reduction of attenuation (ARA)) by the different stents, attenuation values were measured in the vessel outside the stent, and in the non-stenotic vessel inside the stent. Furthermore the grade of stenosis was assessed by two clinical observers. RESULTS: Highest ARA was found for the Cypher Stent (35 HU), whereas the Liberté Stent presented the lowest ARA (16 HU). Depending on the stent and the vessel diameter, up to 87.5% of the stenoses were correctly diagnosed. In the 3.0 and 3.5 mm vessels, a nonstenotic or low-grade stenotic vessel was diagnosed as intermediate or high-grade stenosis in 22.5%, whereas in the 4.0 mm vessels, this kind of overestimation did not occur. A 50% stenosis was diagnosed as a 30% stenosis in 30%. On the other hand, high-grade stenoses were underestimated in only 10%. On a four-point scale, the average deviation from the real grade of stenosis was 0.21 for the Liberté stent, 0.54 for the Taxus Express stent, 0.29 for Driver stent, 0.62 for the Multi-Link Vision stent, and 0.37 for the Cypher stent. CONCLUSIONS: In a dynamic cardiac phantom model, high grade stenoses in vessels with a diameter of 4 mm could be reliably detected irrespective of the stent type used in this study. Vice versa, high grade stenoses (> or = 50%) could only be ruled out with certainty in vessels with a diameter of 4 mm. In smaller vessels, the ability to correctly diagnose high-grade stenoses was dependent on the type of stent and the imaging artifacts associated with it.

Noninvasive coronary angiography using 64-detector-row computed tomography in patients with a low to moderate pretest probability of significant coronary artery disease.

PURPOSE: To evaluate the value of 64-detector-row computed tomography for ruling out high-grade coronary stenoses in patients with a low to moderate pretest probability of significant coronary artery disease. MATERIAL AND METHODS: The study included 61 patients with a suspicion of coronary artery disease on the basis of atypical angina or ambiguous findings in noninvasive stress testing and a class II indication for invasive coronary angiography (ICA). All patients were examined by 64-detector-row computed tomography angiography (CTA) and ICA. On a coronary segmental level, the presence of significant (> or = 50% diameter) stenoses was examined. RESULTS: In a total of 915 segments, CTA detected 62 significant stenoses. Thirty-four significant stenoses were confirmed by ICA, whereas 28 stenoses could not be confirmed by ICA. Twenty-two of them showed wall irregularities on ICA, and six were angiographically normal. Accordingly, on a coronary segmental basis, 28 false-positive and 0 false-negative findings resulted in a sensitivity of 100%, a specificity of 96.8%, a positive predictive value of 54.8%, and a negative predictive value of 100%. The diagnostic accuracy was 96.9%. CONCLUSION: Sixty-four-detector-row computed tomography reliably detects significant coronary stenoses in patients with suspected coronary artery disease and appears to be helpful in the selection of patients who need to undergo ICA. Calcified and non-calcified plaques are detected. Grading of stenoses in areas with calcification is difficult. Frequently, stenosis severity is overestimated by 64-detector-row computed tomography.

Assessment of left ventricular function and mass in patients undergoing computed tomography (CT) coronary angiography using 64-detector-row CT: comparison to magnetic resonance imaging.

PURPOSE: To quantify left ventricular function and mass derived from retrospectively ECG-gated 64-detector-row computed tomography coronary angiography data sets in comparison to cine magnetic resonance (MR) imaging as the reference standard. We hypothesized that the administration of beta-blockers prior to multidetector computed tomography (MDCT) coronary angiography has a significant impact on left ventricular functional parameters. MATERIAL AND METHODS: Multiplanar reformations in the short-axis orientation were calculated from axial contrast-enhanced CT images in 21 patients (16 male, five female; age range 41-75 years, mean 64.3+/-6.8 years) referred for CT coronary angiography. Patients whose heart rates exceeded 60 bpm received 5 mg bisoprolol orally 1 hour before the MDCT examination. In case of insufficient heart-rate reduction, up to four vials (20 mg) of metoprolol were injected intravenously. The end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), ejection fraction (EF), cardiac output (CO), and left ventricular mass (LVM) of the reformatted images were analyzed compared to volumetric measurements based on continuous short-axis steady-state free-precession cine MR sequences (TR 3 ms, TE 1.5 ms, FA 60 degrees ). RESULTS: On average, each patient received 15.5 mg metoprolol (range 0-20 mg) and 3.85 mg bisoprolol (range 0-5 mg). The mean heart rate was 56+/-5 bpm during CT and 73+/-9 bpm during MRI examination. This difference was statistically significant (P<0.05). Mean EDV and ESV measured on MDCT were significantly higher compared to MR (MDCT vs. MR: EDV 164.2+/-52.5 vs. 144.2+/-46.7 ml, ESV 77.3+/-46.6 vs. 63.8+/-47.3 ml; P<0.05). Mean EF and CO derived from MDCT images were significantly lower compared to MR (MDCT vs. MR: EF 55.4+/-11.8 vs. 59.3+/-15.4%, CO 4822+/-779 vs. 5755+/-1267 ml; P<0.05). Mean SV and LVM were not significantly different between both methods (MDCT vs. MR: SV 86.8+/-18.1 vs. 80.3+/-15.6 ml, P = 0.44; LVM 132.4+/-42.5 vs. 138.7+/-39.1 g, P = 0.31). CONCLUSION: Left ventricular volumes assessed by the newest-generation MDCT scanners are significantly higher compared with MRI, whereas ejection fraction and cardiac output are significantly lower in MDCT. This appears to be a result of the frequent application of beta-blockers prior to MDCT examinations.

The pathogenic mechanisms of prion diseases.

Prion diseases are rare fatal neurodegenerative disorders that may either occur sporadically, or be inherited or infectiously acquired in humans. Irrespective of etiology, they can be transmitted to other individuals, this fact being responsible for the public attention prion diseases have received especially since the nineteen nineties, when a new variant of Creutzfeldt-Jakob disease linked to the consumption of prion contaminated beef occurred for the first time in Great Britain. The infectious particle, termed prion, is presumably composed exclusively of a misfolded, partially protease-resistant conformer (PrP(Sc)) of a normal cell surface protein, the cellular prion protein (PrP(C)). The pathogenesis of prion diseases comprises entry, spread, and amplification of infectivity in the body periphery in infectiously acquired forms, as well as mechanisms of neuronal cell death in the central nervous system in all disease subtypes. Most experimental therapeutic approaches are either targeted to PrP(C) or PrP(Sc), or to the process of conversion from PrP(C) to PrP(Sc). Neuroprotective strategies aiming at an interruption of central nervous system pathogenesis have also been tested, albeit with only moderate success. In this review, we discuss actual and potential drug targets in the context of the pathogenic mechanisms of prion diseases.

High prevalence of subclinical hypothyroidism in patients with Anderson-Fabry disease.

Anderson-Fabry disease is a rare lysosomal storage disorder. It results from a deficiency of the lysosomal alpha-galactosidase A and leads to progressive accumulation of globotriaosylceramide in the endothelium and tissue cells of various organs. Some of the typical clinical findings such as tiredness, dry skin, myalgia and arthralgia as well as vague gastrointestinal complaints are also symptoms of hypothyroidism. Therefore, we studied the thyroid function in patients with Anderson-Fabry disease. Thyroid function was studied in 11 patients (6 female, 5 male) with Anderson-Fabry disease by measuring thyroid-stimulating hormone (TSH) and free thyroxine serum levels. Nine patients had chronic kidney disease with stage 1 and two with stage 5. Subclinical hypothyroidism (normal serum free thyroxine concentrations along with elevated serum TSH levels) was found in 4 of 11 patients (36.4%). Subclinical hypothyroidism was observed in both male and female patients as well as in patients with stage 1 and stage 5 kidney disease. Subclinical hypothyroidism is a common finding in patients with Anderson-Fabry disease, showing an excess prevalence as compared to the normal population. The high frequency seems to be relevant regarding the potential consequences of a hypothyroid state.

Hormonal profile and fertility in patients with Anderson-Fabry disease.

Anderson-Fabry disease is a glycosphingolipid storage disorder with an X-linked recessive inheritance. The alpha-galactosidase A deficiency leads to a progressive accumulation of globotriaosylceramide in the endothelium and tissue cells of various organs. The kidney, heart and brain are predominantly affected. Reports on endocrine function and fertility rates in patients with Anderson-Fabry disease are sparse. In the present study, we assessed ovarian, testicular and adrenal function in a cohort of patients with Anderson-Fabry disease. Plasma follicle-stimulating hormone, luteinizing hormone, prolactin, estradiol, testosterone, sex hormone-binding globulin, somatotropin, insulin-like growth factor-I and serum cortisol were measured in 13 patients (six female and seven male), currently observed in an outpatient clinic. The profile revealed an undisturbed hormonal function and a normal fertility rate in both male and female Anderson-Fabry patients when compared with the corresponding Austrian population.