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Whether bleeding and myocardial infarction (MI) improve the performance of risk prediction models for mortality in patients with acute coronary syndromes (ACS) treated with percutaneous coronary intervention (PCI) remains unknown.This study included 3377 patients with ACS who underwent PCI in the setting of the ISAR-REACT 5 trial. Patients with bleeding, MI or those dying at 1 year after PCI were characterized in terms of baseline characteristics, risk estimates and C-statistic of the risk prediction models for these outcomes.Major bleeding (Bleeding Academic Research Consortium types 3-5), MI and mortality occurred in 195 patients (5.8%), 143 patients (4.3%) and 143 patients (4.3%), respectively. After adjustment, bleeding [hazard ratio = 5.08; 95% confidence interval (CI), 3.03-8.53; P 0.001] and MI [hazard ratio = 5.90; 95% CI, (3.00-11.65); P 0.001) remained independently associated with the risk for 1-year mortality. The C-statistic (with 95% CI) of the model for bleeding, MI and mortality was, 0.755 (0.722-0.786), 0.752 (0.717-0.789) and 0.868 (0.837-0.896), respectively. The inclusion of bleeding [C-statistic: 0.892 (0.867-0.913); delta C-statistic 0.024 (-0.014 to 0.065); P = 0.200] or MI [C-statistic: 0.878 (0.851-0.903); delta C-statistic 0.011 (-0.030 to 0.053); P = 0.635] in the risk prediction models for mortality alongside baseline demographical and clinical variables did not improve prediction for mortality.In patients with ACS treated with PCI, mortality is the most accurately predicted outcome. Bleeding and MI did not improve risk discrimination for mortality when added in the risk prediction models for mortality suggesting that these outcomes do not provide incremental prognostic information on top of baseline demographical and clinical data.

Supplemental material, sj-pdf-1-vmj-10.1177_1358863X20967091 for Outcomes of endovascular treatment for infrapopliteal peripheral artery disease based on the updated TASC II classification by Arne M Müller, Veronika Räpple, Christian Bradaric, Tobias Koppara, Victoria Kehl, Massimiliano Fusaro, Salvatore Cassese, Ilka Ott, Adnan Kastrati, Karl-Ludwig Laugwitz and Tareq Ibrahim in Vascular Medicine

Supplemental material, sj-pdf-1-vmj-10.1177_1358863X20967091 for Outcomes of endovascular treatment for infrapopliteal peripheral artery disease based on the updated TASC II classification by Arne M Müller, Veronika Räpple, Christian Bradaric, Tobias Koppara, Victoria Kehl, Massimiliano Fusaro, Salvatore Cassese, Ilka Ott, Adnan Kastrati, Karl-Ludwig Laugwitz and Tareq Ibrahim in Vascular Medicine

Background: Characterization of tissue integrity and inflammatory processes after acute myocardial infarction (AMI) using non-invasive imaging is predictive of patient outcome. Quantitative cardiovascular magnetic resonance (CMR) techniques such as native T1 and extracellular volume (ECV) mapping as well as 18F-FDG positron emission tomography (PET) imaging targeting inflammatory cell populations are gaining acceptance, but are often applied without assessing their quantitative potential. Using simultaneously acquired PET/CMR data from patients early after AMI, this study quantitatively compares these three imaging markers and investigates links to blood markers of myocardial injury and systemic inflammatory activity.Methods: A total of 25 patients without microvascular obstruction were retrospectively recruited. All imaging was simultaneously performed 5 ± 1 days after revascularization following AMI on an integrated 3T PET/MRI scanner. Native and post-contrast T1 data were acquired using a modified Look-Locker inversion recovery (MOLLI) sequence, ECV maps were calculated using individually sampled hematocrit. 18F-FDG PET was executed after 1 day of dietary preparation, 12 h of fasting, and administration of heparin. ECV, 18F-FDG and native T1 data were compared mutually as well as to peak counts of peripheral blood markers (creatine kinase, creatine kinase-MB, troponin, leukocytes, monocytes) and infarct size.Results: High intra-patient correlations of relative ECV, 18F-FDG PET and native T1 signal increases were observed in combination with no inter-patient correlation of maximum absolute values at the infarct center, suggesting well-colocalized but physiologically diverse processes begetting the respective image signals. Comparison of maximum image signals to markers of myocardial damage and systemic inflammation yielded highly significant correlations of ECV to peak creatine kinase-MB and overall infarct size as well as between native T1 and peak monocyte counts.Conclusions: Absolute native T1 values at the infarct core early after AMI can be linked to the systemic inflammatory response independent of infarct size. Absolute ECV at the infarct core is related to both infarct size and blood markers of myocardial damage.

Supplemental material, 10.1177_1358863X19883945_Supplementary_table for Significant prevalence of peripheral artery disease in patients with disturbed wound healing following elective foot and ankle surgery: Results from the ABI-PRIORY (ABI as a PRedictor of Impaired wound healing after ORthopedic surgerY) trial by Arne M Müller, Andreas Toepfer, Norbert Harrasser, Bernhard Haller, Markus Walther, Rüdiger von Eisenhart-Rothe, Karla Gemperlein, Katharina Bergmann, Christian Bradaric, Karl-Ludwig Laugwitz, Tareq Ibrahim and Ralf J Dirschinger in Vascular Medicine

Background Paclitaxel‐eluting balloon (PEB) angioplasty has superior efficacy compared with conventional balloon angioplasty (BA) for de novo lesions of superficial femoral artery (SFA). Studies investigating the angiographic and clinical performance of PEB angioplasty versus BA for in‐stent restenosis of SFA are limited. We performed a randomized trial to investigate angiographic and clinical performance of PEB versus BA for in‐stent restenosis of SFA. Methods and Results Patients with symptomatic in‐stent restenosis of SFA were randomly assigned to either PEB or BA at 2 centers in Munich, Germany. The primary end point was the percentage diameter stenosis at 6‐ to 8‐month follow‐up angiography. Secondary end points were the rate of binary restenosis at follow‐up angiography and target lesion revascularization, target vessel thrombosis, ipsilateral amputation, bypass surgery of the affected limb, and all‐cause mortality at 24‐month follow‐up. Seventy patients were assigned to PEB (n=36) or BA (n=34). Mean lesion length was 139±67 mm, and roughly one third of lesions were completely occluded at the time of the index procedure. At control angiography, the percentage diameter stenosis (44±33% versus 65±33%, P=0.01) and binary restenosis were significantly reduced with PEB versus BA (30% versus 59%, P=0.03). At 24‐month follow‐up, PEB was associated with a significant reduction of target lesion revascularization in comparison to BA (19% versus 50%, P=0.007). There was no difference with respect to other outcomes of interest. Conclusions In patients with in‐stent restenosis of SFA, a percutaneous therapy with PEB compared with BA has superior angiographic performance at 6 to 8 months and improved clinical efficacy up to 24‐month follow‐up. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01083394.

ObjectivesThis study sought to compare the risk of stent thrombosis among patients treated with bare-metal stents (BMS), first-generation drug-eluting stents (G1-DES), and second-generation drug-eluting stents (G2-DES) for a period of 3 years.BackgroundIn patients undergoing coronary stenting, there is a scarcity of long-term follow-up data on cohorts large enough to compare rates of stent thrombosis across the stent generations.MethodsA total of 18,334 patients undergoing successful coronary stent implantation from 1998 to 2011 at 2 centers in Munich, Germany, were included in this study. Patients were stratified into 3 groups according to treatment with BMS, G1-DES, and G2-DES.ResultsThe cumulative incidence of definite stent thrombosis at 3 years was 1.5% with BMS, 2.2% with G1-DES, and 1.0% with G2-DES. On multivariate analysis, G1-DES compared with BMS showed a significantly higher risk of stent thrombosis (odds ratio [OR]: 2.05; 95% confidence interval [CI]: 1.47 to 2.86; p < 0.001). G2-DES were associated with a similar risk of stent thrombosis compared with BMS (OR: 0.82; 95% CI: 0.56 to 1.19; p = 0.30). Beyond 1 year, the risk of stent thrombosis was significantly increased with G1-DES compared with BMS (OR: 4.72; 95% CI: 2.01 to 11.1; p < 0.001), but not with G2-DES compared with BMS (OR: 1.01; 95% CI: 0.32 to 3.25; p = 0.98).ConclusionsIn a large cohort of unselected patients undergoing coronary stenting, compared with BMS, there was a significant excess risk of stent thrombosis at 3 years with G1-DES, driven by an increased risk of stent thrombosis events beyond 1 year. G2-DES were associated with a similar risk of stent thrombosis compared with BMS.

Background: Improved outcomes in patients with diabetes mellitus undergoing percutaneous coronary intervention remain an unmet clinical need. We assessed the long-term efficacy and safety of novel polymer-free sirolimus- and probucol-eluting stent in diabetic patients enrolled in intracoronary stenting and angiographic results: test efficacy of sirolimus- and probucol-eluting versus zotarolimus-eluting stents 5 trial.Methods: In a pre-specified subgroup analysis, outcomes of diabetic patients treated with a sirolimus- and probucol-eluting stent or a second-generation zotarolimus-eluting stent were compared. The primary endpoint was a device-oriented composite outcome comprising cardiac death, target vessel-related myocardial infarction (MI), or target lesion revascularization (TLR) at 5-year follow-up. Event-free survival was assessed using the Kaplan–Meier method. Hazard ratios (HR) and 95 % confidence intervals (CI) were estimated from univariate Cox proportional hazards models.Results: A total of 870 patients with diabetes mellitus were treated with either a sirolimus- and probucol-eluting stent (n = 575) or a second-generation zotarolimus-eluting stent (n = 295). At 5 years, the rate of device-oriented composite endpoint was comparable between the sirolimus- and probucol-eluting stent and the second-generation zotarolimus-eluting stent (32.9 versus 33.4 %, HR 0.88, 95 % CI 0.76–1.26). No significant differences were observed between the sirolimus- and probucol-eluting stent and the second-generation zotarolimus-eluting stent groups in the incidence of cardiac death (15.6 versus 16.7 % HR 0.92, 95 % CI 0.63–1.32), target-vessel MI (4.6 versus 6.6 %, HR 0.73, 95 % CI 0.40–1.34), and TLR (18.6 versus 18.8 %, HR 1.00, 95 % CI, 0.72–1.41). The rate of definite or probable stent thrombosis was low and similar in both groups (2.5 versus 2.6 %, HR 1.02, 95 % CI, 0.41–2.52).Conclusions: In patients with diabetes the long-term efficacy and safety of a polymer-free sirolimus- and probucol-eluting stent were comparable to a second-generation durable polymer zotarolimus-eluting stent. Trial registration ClinicalTrials.gov NCT00598533. Registered 10 January 2008

Primary percutaneous coronary intervention (PCI) is the preferred reperfusion strategy for patients with ST-segment elevation myocardial infarction (STEMI). Effective and safe adjunct antithrombotic therapy is a major determinant for short- and long-term outcomes after primary PCI. Two separate studies have shown significant benefits vs conventional therapy for 2 recently approved drugs. In the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial, bivalirudin after pretreatment with clopidogrel resulted in improved net clinical outcome compared with heparin plus glycoprotein IIb/IIIa inhibitors. However, during the first 24 hours after PCI, there was an increase in stent thrombosis rates with bivalirudin. In the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis In Myocardial Infarction (TRITON-TIMI) 38 trial, prasugrel was superior to clopidogrel in patients with acute coronary syndrome with and without ST-segment elevation. The synergic actions of prasugrel and bivalirudin may maximize the benefit of antithrombotic therapy for STEMI patients undergoing primary PCI. However, no specifically designed studies have so far compared the combination of prasugrel plus bivalirudin with that of clopidogrel plus unfractionated heparin in these patients. The Bavarian Reperfusion Alternatives Evaluation (BRAVE) 4 study is a randomized, open-label, multicenter trial aimed to test the hypothesis that a strategy based on prasugrel plus bivalirudin is superior to a strategy based on clopidogrel plus unfractionated heparin in terms of net clinical outcome in STEMI patients with planned primary PCI.

ObjectivesThe aim of this research was to evaluate kinetics and extent of myocardial contrast enhancement (CE) in comparison with single-photon emission computed tomography (SPECT) early after acute myocardial infarction (AMI).BackgroundQuantification of infarct size serves as a surrogate end point in evaluating new therapies of AMI. Contrast-enhanced magnetic resonance imaging (CeMRI) of the myocardium is a promising new method for identification of irreversible tissue injury.MethodsA total of 33 patients were examined by CeMRI and SPECT 7 ± 2 days after AMI and successful coronary intervention. After gadolinium-diethylenetraimine pentaacetic acid injection (0.2 mmol/kg), continuous short-axis slices of the left ventricle (LV) were acquired every 7 min up to 42 min using different inversion times (TI). Myocardial CE at each imaging time point was quantified and compared with corresponding SPECT perfusion defect.ResultsAll patients showed myocardial CE in the infarct region. A constant TI for CeMRI resulted in a decrease of signal intensity and extent of CE on late acquisitions. With TI adjustment, infarct image intensity peaked at 21 min with a contrast of 478% of remote myocardium and remained at this level up to 42 min after contrast injection (437%); CE extent was stable over time and agreed well with SPECT within an average difference of 3% of the LV myocardium, yielding the best correlation at 28 min (r = 0.86).ConclusionsIn patients after AMI and successful reperfusion, CE is stable over time and matches well with SPECT perfusion defect; CeMRI under standardized conditions can accurately assess myocardial infarct size in vivo and may be attractive for serving as a surrogate end point early after AMI.

BACKGROUND: Patients receiving oral anticoagulation (OAC) who undergo drug-eluting stent (DES) implantation require additional dual antiplatelet therapy with aspirin and clopidogrel. Such triple therapy confers an elevated bleeding risk, and its optimal duration is not known.OBJECTIVES: The goal of this study was to evaluate whether shortening the duration of clopidogrel therapy from 6 months to 6 weeks after DES implantation was associated with a superior net clinical outcome in patients receiving concomitant aspirin and OAC.METHODS: In this randomized, open-label trial, we enrolled patients receiving OAC who underwent DES implantation at 3 European centers between September 2008 and December 2013. A total of 614 patients receiving concomitant aspirin and OAC were randomized to either 6-week clopidogrel therapy (n = 307) or 6-month clopidogrel therapy (n = 307). The primary endpoint was a composite of death, myocardial infarction (MI), definite stent thrombosis, stroke, or Thrombolysis In Myocardial Infarction (TIMI) major bleeding at 9 months.RESULTS: The primary endpoint occurred in 30 patients (9.8%) in the 6-week group compared with 27 patients (8.8%) in the 6-month group (hazard ratio [HR]: 1.14; 95% CI: 0.68 to 1.91; p = 0.63). There were no significant differences for the secondary combined ischemic endpoint of cardiac death, MI, definite stent thrombosis, and ischemic stroke (12 [4.0%] vs. 13 [4.3%]; HR: 0.93; 95% CI: 0.43 to 2.05; p = 0.87) or the secondary bleeding endpoint of TIMI major bleeding (16 [5.3%] vs. 12 [4.0%]; HR: 1.35; 95% CI: 0.64 to 2.84; p = 0.44).CONCLUSIONS: Six weeks of triple therapy was not superior to 6 months with respect to net clinical outcomes. These results suggest that physicians should weigh the trade-off between ischemic and bleeding risk when choosing the shorter or longer duration of triple therapy. (Triple Therapy in Patients on Oral Anticoagulation After Drug Eluting Stent Implantation [ISAR-TRIPLE]; NCT00776633).

ObjectivesThis study sought to compare cardiac magnetic resonance (CMR) and single-photon emission computed tomography (SPECT) for assessment of area at risk, scar size, and salvage area after coronary reperfusion in acute myocardial infarction.BackgroundMyocardial salvage is an important surrogate endpoint assessing the success of coronary reperfusion in acute myocardial infarction. SPECT, the established modality for assessment of myocardial salvage, requires radiopharmaceutical injection before revascularization and 2 examinations. The combination of T2 and late enhancement imaging in CMR can assess myocardial salvage in 1 examination, but up to now, data comparing both modalities are very limited.MethodsWe analyzed 207 patients who were treated by primary revascularization in acute myocardial infarction and who underwent both SPECT and CMR for assessment of myocardial salvage. In CMR, T2-weighted turbo spin echo sequences for area at risk and contrast-enhanced inversion recovery gradient echo sequences were performed.ResultsImage quality was insufficient in 27 patients (13%). In the remaining 180 patients, mean area at risk was 29.4 ± 18.7% of the left ventricle (LV), and infarct size was 14.7 ± 16.9% LV, resulting in a mean salvage area of 14.9 ± 15.1% LV in SPECT, whereas in CMR, mean area at risk was 28.0 ± 14.5% LV, and infarct size was 16.0 ± 13.5% LV, resulting in a mean salvage area of 11.9 ± 12.3%. Results of both modalities correlated well for area at risk (r = 0.80), scar size (r = 0.87), and salvage area (r = 0.66, all p < 0.0001).ConclusionsAssessment of the salvage area by CMR using T2 and late enhancement imaging correlates well with the established modality of SPECT. CMR therefore may be an alternative to paired SPECT imaging for myocardial salvage assessment, but the contraindications of the modality and limitations in the established T2 imaging sequences currently cause a considerable rate of data loss.

Background Improved outcomes in patients with diabetes mellitus undergoing percutaneous coronary intervention remain an unmet clinical need. We assessed the long-term efficacy and safety of novel polymer-free sirolimus- and probucol-eluting stent in diabetic patients enrolled in intracoronary stenting and angiographic results: test efficacy of sirolimus- and probucol-eluting versus zotarolimus-eluting stents 5 trial. Methods In a pre-specified subgroup analysis, outcomes of diabetic patients treated with a sirolimus- and probucol-eluting stent or a second-generation zotarolimus-eluting stent were compared. The primary endpoint was a device-oriented composite outcome comprising cardiac death, target vessel-related myocardial infarction (MI), or target lesion revascularization (TLR) at 5-year follow-up. Event-free survival was assessed using the Kaplan–Meier method. Hazard ratios (HR) and 95 % confidence intervals (CI) were estimated from univariate Cox proportional hazards models. Results A total of 870 patients with diabetes mellitus were treated with either a sirolimus- and probucol-eluting stent (n = 575) or a second-generation zotarolimus-eluting stent (n = 295). At 5 years, the rate of device-oriented composite endpoint was comparable between the sirolimus- and probucol-eluting stent and the second-generation zotarolimus-eluting stent (32.9 versus 33.4 %, HR 0.88, 95 % CI 0.76–1.26). No significant differences were observed between the sirolimus- and probucol-eluting stent and the second-generation zotarolimus-eluting stent groups in the incidence of cardiac death (15.6 versus 16.7 % HR 0.92, 95 % CI 0.63–1.32), target-vessel MI (4.6 versus 6.6 %, HR 0.73, 95 % CI 0.40–1.34), and TLR (18.6 versus 18.8 %, HR 1.00, 95 % CI, 0.72–1.41). The rate of definite or probable stent thrombosis was low and similar in both groups (2.5 versus 2.6 %, HR 1.02, 95 % CI, 0.41–2.52). Conclusions In patients with diabetes the long-term efficacy and safety of a polymer-free sirolimus- and probucol-eluting stent were comparable to a second-generation durable polymer zotarolimus-eluting stent. Trial registration ClinicalTrials.gov NCT00598533. Registered 10 January 2008

Weltweit leben etwa zwölf Millionen Patienten mit einem angeborenen Herzfehler. Diese sind sowohl mit Folgeerscheinung nach Interventionen/Operationen als auch mit Alterserscheinungen konfrontiert. Arrhythmien, Thromboembolien und Schlaganfälle sind Probleme, die einer Blutverdünnung bedürfen. In dieser retrospektiven monozentrischen klinischen Studie wurden 215 Patienten hingehend der Verträglichkeit einer Therapie mit DOAK untersucht. Es konnte gezeigt werden, dass die Therapie sicher ist. Worldwide, about 12 million patients have congenital heart disease. They face aftereffects of interventional or operational treatment as well as acquired comorbidities. Arrhythmias, thromboembolic events, and strokes are problems that require anticoagulation. 215 patients under a therapy with DOACs were retrospectively identified. Treatment was safe in ACHD patients.

Ziel der Arbeit war die Beurteilung der myokardialen Kontrastmittel-(KM)-Anreicherung nach akutem Myokardinfarkt (AMI). Siebzehn Patienten mit AMI und erfolgreicher Reperfusion wurden in der kontrastunterstützten Magnetresonanztomographie (k–MRT) 1, 7, 35 und 180 Tage nach dem akuten Ereignis untersucht. Die Größe der KM-Anreicherung verringerte sich signifikant von 18,3 %LV [8,4; 27,0] am Tag 1 auf 12,9 %LV [4,6; 19,8] am Tag 7 (p

Die Ablation bei paroxysmalem Vorhofflimmern ist Therapiestandard. Trotz Ablation kommt es zu Rezidiven der Arrhythmie. Ziel der Dissertation ist es, den Erfolg der Ablation bei Patienten mit oder ohne pathologischen Apnoe-Hypopnoe-Index (AHI) zu vergleichen. Der AHI wurde mit einem einfachen Screening-Gerät ermittelt. In den Untersuchungen nach 3 Monaten zeigt sich ein signifikanter Zusammenhang zwischen einem AHI (>15/h) und einem Rezidiv, nach 12 Monaten ein schwach signifikanter Zusammenhang. Der AHI (>15/h) erwies sich als unabhängiger Prädiktor für ein Rezidiv. Ablation in paroxysmal atrial fibrillation is standard therapy. Despite the ablation, the arrhythmia recurs. The aim of the dissertation is to compare the success of ablation in patients with or without a pathological apnea-hypopnea index (AHI). The AHI was determined with a simple screening device. The studies after 3 months showed a significant connection between an AHI (> 15 / h) and a recurrence, after 12 months a weakly significant connection. The AHI (> 15 / h) proved to be an independent predictor of recurrence.

This retrospective, longitudinal study aimed to investigate the effectiveness of the main treatment options in terms of changes in functional health in adolescents and adults with congenital heart disease (CHD). Generally, active treatment was associated with better health-related quality of life (HRQoL) over time. Patients reported better physical HRQoL after surgery and catheter intervention, although this effect was not detectable in the objectively measured exercise capacity. Hence, parallel assessment of HRQoL and exercise capacity is essential in the evaluation of adolescents and adults with CHD. Das Ziel dieser retrospektiven, longitudinalen Studie war es, die Effektivität der wichtigsten Therapieoptionen bezüglich Veränderungen von funktionalen Gesundheitsvariablen in Jugendlichen und Erwachsenen mit angeborenen Herzfehlern (AHF) zu untersuchen. Im Allgemeinen war eine aktive Therapie mit besserer gesundheitsbezogener Lebensqualität verbunden. Patienten gaben eine bessere physische Lebensqualität nach einer Operation und Herzkatheterintervention an, obwohl dieser Effekt nicht in einer Verbesserung der Leistungsfähigkeit nachweisbar war. Daher ist die parallele Erfassung von Lebensqualität und Leistungsfähigkeit für die Evaluation von Jugendlichen und Erwachsenen mit AHF erforderlich.

Die Studie beleuchtet Langzeittherapieeffekte einer „single dose“ RTX-Therapie zur Remissionsinduktion/ Erhaltungstherapie bei AAV (GPA, MPA). Eine Limitation ist der gesteigerte Einsatz supportiver Immunsuppression, sodass die Therapie für die Praxis als tendenziell unterlegen eingestuft wird. Da das „single dose“-Regime imstande ist, selbst bei Patient*innen mit höchstem Rezidivrisikoprofil eine Aktivitätskontrolle zu erreichen, erscheint der individualisierte Einsatz allerdings gerechtfertigt. The study sheds light on possible long-term therapeutic effects of a “single dose” RTX therapy for remission induction and maintenance therapy in AAV (GPA, MPA). One limitation is the increased use of supportive immunosuppression, so that the therapy tends to be classified as inferior in practice. But the “single dose” regime is able to achieve activity control even in patients with the highest risk of relapse, so that its individualized use appears justified

Myokardschäden nach nicht-herzchirurgischen Operationen, definiert durch den postoperativen Anstieg von hoch-sensitivem Troponin T (hsTnT), sind mit kardiovaskulären Komplikationen und erhöhter Mortalität assoziiert. Bei 1010 Hochrisikopatienten werden zwei unterschiedliche Verläufe des hsTnT auf ihren prognostischen Wert für kardiale und nicht-kardiale Komplikationen nach elektiven nicht-herzchirurgischen Operationen untersucht. Diese wurden definiert anhand der Clavien-Dindo Klassifikation in den neun Domänen des Postoperative Morbidity Survey. Myocardial injury after non-cardiac surgery, defined by a postoperative elevation of high-sensitive Troponin T (hsTnT), is associated with cardiovascular events and mortality. The aim of this study was to investigate in 1010 high risk patients, if different cut-offs and courses of hsTnT can differentiate the risk of cardiac or non-cardiac complications after elective non-cardiac surgery. They were defined by a Clavien-Dindo classification in the nine domains of the Postoperative Morbidity Survey.

Der Myokardinfarkt löst eine komplexe Entzündungsreaktion mit zahlreichen Variablen und Mechanismen aus, die vereinfachend in zwei Phasen abläuft. Hierbei scheint eine optimale Balance der beiden Phasen entscheidend für eine gute Heilung zu sein. Mittels Positronen-Emissions-Tomographie (18F-FDG-PET) ist eine prognostische Aussage und auf dieser Basis eine Risikostratifizierung möglich, die in Zukunft eine zielgerichtete Therapie wie etwa mit immunmodulatorischen Medikamenten ermöglichen kann. Myocardial infarction initiates a complex inflammatory response being influenced by several mechanisms and variables, that can be divided roughly into two phases, whereby these two phases should be balanced ideally to enable appropriate healing after myocardial infarction. Positron emission tomography (18F-FDG-PET) allows prognostic prediction and thus risk stratification as a basis for therapeutic interventions in future. Possible therapeutic approaches are for example immunomodulatory drugs.

Welchen Einfluss das Alter einer Restenose nach Koronarintervention mit Implantation eines drug-eluting stent auf das klinische Outcome und den Therapieerfolg der Restenosebehandlung mittels drug-eluting balloon (DEB) hat, ist nicht bekannt. Ziel dieser retrospektiven Analyse der ISAR-DESIRE 3 und 4 Studien ist es zu untersuchen, ob das Alter einer ISR (frühes Auftreten ≤365 Tage vs. spätes Auftreten >365 Tage) einen Einfluss auf das klinische Outcome zwölf Monate nach der Therapie mit DEB hat. Whether the age of in-stent restenosis (ISR) impacts clinical outcomes and efficacy after percutaneous coronary interventions with drug-eluting balloon (DEB) is still unknown. The aim of this retrospective analysis of ISAR-DESIRE 3 and 4 trials was to investigate, if the timing of ISR (early ISR ≤365 days vs. late ISR >365 days) impacts on clinical outcomes twelve months after DEB angioplasty.

This study evaluated the performance of hybrid fluorodeoxyglucose positron emission tomography/magnetic resonance (FDG PET/MR) imaging in myocardial viability assessment in patients with chronic total occlusions (CTO) of coronary arteries, and in the prediction of regional wall motion recovery after revascularisation of CTO lesions, in comparison to PET and MR alone. FDG PET/MR imaging showed a fair accuracy in predicting wall motion improvement after CTO revascularisation, being superior to MR and PET alone. Bei Patienten mit chronischen totalen Verschlüssen der Koronararterien, erlaubt die kombinierte FDG PET/MRT Bildgebung eine bessere Straatifizierung hinsichtlich einer linksventrikulären Funktionsverbesserung nach Revaskularisation im Vergleich zu PET oder MRT allein. Die durch die beiden Modalitäten zusätzlich erbrachten Informationen können dabei helfen kleine Areale von vitalem Myokard zu identifizieren, die nach einer Revaskularisation die Kontraktilität steigern können.

Bei der transkraniellen Dopplersonographie und der retinalen Gefäßanalyse handelt es sich um zwei neue, vielversprechende Diagnoseinstrumente der Alzheimer-Erkrankung. Um ihr Potential zu evaluieren, wurden gesunde Kontrollprobanden (HC), Alzheimer-Patienten im Stadium der Demenz (ADD) sowie Patienten mit leichter kognitiver Einschränkung (MCI) und Subgruppen (MCI-nonAD, MCI-AD) untersucht. Bei ADD und MCI zeigten sich erhöhte Werte für PI und RI sowie eine vergrößerte und verzögerte retinale arterioläre Gefäßreaktion. Im Vergleich zu etablierten Biomarkern sind beide Methoden einfach durchzuführen, nicht-invasiv und flächendeckend verfügbar sowie kostengünstig. The transcranial Doppler ultrasound (TCD) and the retinal vessel analysis are two new and promising methods to diagnose Alzheimer’s Disease. Evaluating their potential for diagnosis, healthy controls (HC), Alzheimer patients suffering from dementia (ADD) and patients with mild cognitive impairment (MCI) as well as subgroups (MCI-nonAD, MCI-AD) were examined. We measured increased results for PI and RI and an increased and delayed retinal arterial vessel response for ADD and MCI. In comparison to established biomarkers, these methods are easy-to-administer, non-invasive, affordable and widely available.

Das Ziel dieser Arbeit ist der Vergleich der diagnostischen Genauigkeit der dynamischen CT-Perfusionsuntersuchung (CTP) mit dem Transluminal Attenuation Gradient (TAG), der aus der CT-Angiographie abgeleitet wird, zur Beurteilung der hämodynamischen Relevanz von Koronarstenosen. Als Referenzmethode dient die invasive Koronarangiographie mit der Messung der fraktionellen Flussreserve (FFR) bei mittelgradigen Stenosen, die als Goldstandard in der Diagnostik der koronaren Herzerkrankung gilt. The Purpose of this research is to compare the diagnostic accuracy to detect hemodynamically significant coronary artery stenoses of the dynamic computed tomography perfusion imaging to the transluminal attenuation gradient derived from coronary computed tomography angiography. Invasive coronary angiography with assessment oft the fractional flow reserve served as the reference standard.

In dieser Studie wurde retrospektiv der Effekt von kontinuierlich verabreichtem Marcumar im Vergleich zu kontinuierlich verabreichten NOAKs (Apixaban, Dabigatran und Rivaroxaban) auf die peripher vaskuläre Komplikationsrate bezüglich Pseudoaneurysmen, Ateriovenöse Fisteln und Blutungen untersucht. Die kontinuierliche Therapie mit NOAKs scheint mindestens gleich sicher zu sein wie die Therapie mit Marcumar. Bei Dabigatran traten sogar signifikant weniger Major Blutungen auf (p = 0,01). Retrospectively the effect of continuously administered Marcumar compared to continuously administered NOACs (Apixaban, Dabigatran and Rivaroxaban) on the peripheral vascular complication rates for pseudoaneurysms, ateriovenous fistulas and bleeding after radiofrequency ablation was investigated in this study. Uninterrupted therapy with NOACs appears to be at least as safe as uninterrupted therapy with Marcumar. In the group of Dabigatran there was significantly less major bleeding (p=0,01).

Kidney transplanted patients frequently suffer high blood pressure values. These high values are major risk factors to graft failure and cardiovascular morbidity. These risks should be averted by renal denervation – a catheter based ablation procedure. This technique intends to interrupt conduction pathways of the central nervous system, which are responsible for elevated blood pressure values. Subject of the randomized study was to examine the feasibility and efficacy of renal sympathetic denervation compared to only medication therapy. After 6 months, we determined a significant reduction in office blood pressure and a decrease in nighttime values in 24h blood pressure recordings. Erhöhte Blutdruckwerte sind ein häufiges Problem für nierentansplantierte Patienten. Aufgrund dieser erhöhten Werte besteht ein bedeutendes Risiko für ein vorzeitiges Transplantatversagen und kardiovaskuläre Morbidität. Bei der Therapie mittels renaler Denervation handelt es sich um ein kathetergestützes Ablationsverfahren. Ziel dieser Methode ist die Durchtrennung von Leitungsbahnen, welche zu einer Fehlregulation des Blutdrucks führen können. Gegenstand der randomisierten Studie war die Untersuchung der Durchführbarkeit und Wirksamkeit dieses Verfahrens, verglichen mit einer alleinigen medikamentösen Therapie. Nach 6 Monaten zeigten sich eine signifikante Reduktion der Office Blutdruckwerte und ein Rückgang der nächtlichen Werte in der 24h Blutdruckmessung.

Die derzeit etablierte Methode zur Bestimmung des Anteils an gerettetem Myokard nach stattgehabtem Herzinfarkt ist die SPECT. Ziel dieser Arbeit war es das gefährdete Myokard, die endgültige Infarktnarbe und das gerettete Myokard durch kontrastmittelgestützte T1-gewichtete MRT im Vergleich zum SPECT zu ermitteln. Insgesamt ist die hier verwendete MRT-Analysemethode ein vielversprechendes Verfahren um die Bestimmung des gefährdeten Myokards mittels einer T1-gewichteten KM-MRT-Untersuchung näherungsweise im Vergleich zum SPECT zu bestimmen. The gold-standard to identify the salvaged myocardium after myocardial infarction is SPECT. The intention of this project was to identify the area at risk, the final infarct size and the salvaged myocardium with contrast-enhanced T1-MRI in comparison to SPECT.The used MRI-analysis-method is a promising tool to identify the area at risk with one T1-contrast-enhanced-MRI approximately to SPECT.

Ambulante Herzsportgruppentherapie ist ein in Deutschland seit Jahrzehnten etabliertes Konzept zur langfristigen Sicherung des kardialen Rehabilitationserfolges. Die Datenlage hinsichtlich der tatsächlichen Effektivität derartiger Gruppen im Langzeitverlauf ist dagegen äußerst gering. Ziel dieser Arbeit war es daher, langjährige Herzgruppenteilnehmer hinsichtlich der Entwicklung der körperlichen Belastbarkeit und des kardiovaskulären Risikoprofils zu untersuchen. For decades, outpatient heart group therapy has been a well-established concept for long-term maintenance of cardiac rehabilitation outcomes in Germany. In contrast, data on the effectiveness of such groups is extremely scarce. The aim of this thesis was to evaluate the long-term effects of participation in heart groups on exercise capacity and cardiovascular risk profile in a large cohort of cardiac patientis.

In dieser Arbeit wird mittels retrospektiver, monozentrischer Kohortenstudie die Sicherheit und Wirksamkeit einer endovaskulären Therapie von Stenosen der Arteria carotis interna durch Stent-geschützte Angioplastie an symptomatischen und asymptomatischen Patienten untersucht. In der statistischen Auswertung der prozeduralen Ergebnisse sowie mittelfristigen klinischen Verläufe von insgesamt 497 Eingriffen an 460 Patienten konnte gezeigt werden, dass diese Behandlung sowohl mit geringem Auftreten von Komplikationen als auch mit guten Verlaufsergebnissen aus klinischer Sicht durchgeführt werden kann. In this study, safety and efficacy of endovascular therapy for stenosis of the internal carotid artery by stent-protected angioplasty in symptomatic and asymptomatic patients is examined by a retrospective single-center cohort analysis. Statistical evaluation of procedural results and mid-term clinical outcomes of 497 interventions in 460 patients was able to show that treatment can be provided in association with a low number of complications as well as good results from the clinical point of view.

In der monozentrischen Studie wurde die endovaskuläre Therapie einer symptomatischen extrakraniellen Vertebralisstenose mit Drug-eluting Stents (DES) und Bare-metal Stents (BMS) untersucht. Analysiert wurden alle Eingriffe am Klinikum RdI und DHZM zwischen 1997 - 2012. Zudem wurde der Einsatz beider Stent-Typen durch eine Metaanalyse bereits veröffentlichter Studien verglichen. Das Verfahren stellt eine sichere und effektive Therapieoption dar. Der Gebrauch von ballondilatierbaren und v. a. DES ist den selbstexpandierbaren Stents überlegen. Der Einsatz von DES ist im Gegensatz zu BMS mit einer signifikant niedrigeren Rate an Restenosen und erneuten Symptomen verbunden. This single-center study investigates the endovascular therapy of an extracranial vertebral artery stenosis with drug-eluting stents (DES) and bare-metal stents (BMS). All procedures at the Klinikum RdI and the DHZM between 1997 – 2012 were analysed. Furthermore the use of both stent types was compared by meta-analysis of already published studies. The procedure is safe and effective. The use of balloon-expandable stents and especially DES is superior to self-expandable stents. The application of DES significantly reduces the rate of restenosis and recurrence of symptoms compared to BMS.

In der vorliegenden Arbeit soll der Einfluss von CNP auf das physiologische und pathophysiologische Expressionsmuster von humanen Monozyten, sowie THP-1 Zellen untersucht werden. Es wurde die Basisexpression von CNP, NPR2, NPR3, TNF-a, IL-1b, IL-6, CD14 und CD68 in THP-1 Zellen gemessen und mit der von humanen Monozyten (PBMC) verglichen. Zudem wurden beide Zellarten sowohl mit LPS als auch mit oxLDL stimuliert und die Änderungen der Expressionsstärken der oben genannten Gene analysiert. in THP-1 Zellen gemessen und mit der von humanen Monozyten (PBMC) verglichen. Zudem wurden beide Zellarten sowohl mit LPS als auch mit oxLDL stimuliert und die Änderungen der Expressionsstärken der oben genannten Gene analysiert. The aim of this study was to investigate the influence of cnp on the physiological and pathophysioligical genomic expression of human monocytes and THP-1 cells. The baseline expression of CNP, NPR2, NPR3, TNF-a, IL-1b, IL-6, CD14 and CD68 was measured and compared to the genomic expression of human monovytes (PBMC). Both cell lines were also stimulated with LPS and oxLDL to investigate changes in the genomic expression.

Die Stentthrombose ist die schwerste Komplikation nach koronarer Stentimplantation. Ziel dieser Arbeit ist die Inzidenz und Prädiktoren der Stentthrombose zu untersuchen. Die Stentthromboserate bei 18 334 Patienten betrug 1.3%. Die Prädiktoren der Stentthrombose waren: Diabetes mellitus, akuter ST-Hebungs-Myokardinfarkt, komplexe Morphologie der behandelten Läsionen, In-Stent-Restenose und eine verbleibende Stenose nach der Stentimplantation. Im Vergleich zu Bare-metal Stents zeigten Drug-eluting Stents der 1. Generation ein erhöhtes Risiko der Stentthrombose, was nicht der Fall war bei Drug-eluting Stents der 2. Generation. Stent thrombosis is a severe complication of coronary stent implantation. The aim of this study was to determine the incidence and predictors of stent thrombosis. The incidence of stent thrombosis among 18 334 patients was 1.3%. Diabetes mellitus, clinical presentation with ST segment elevation myocardial infarction, complex lesion morphology, in-stent restenosis and residual stenosis after stent implantation were predictive factors for stent thrombosis. In comparison with bare metal stents the risk of stent thrombosis was significantly increased with first generation drug eluting stents, which was not the case with second generation drug eluting stents.

Der Faktor melanoma inhibitory activity 3 (MIA3) steht im Zusammenhang mit der Tumorsuppression und der Atherosklerose. Genomweite Studien haben auf eine mögliche Relevanz einzelner Variationen im MIA3-Gen für Krankheiten der Koronararterien hingewiesen. Diese Arbeit leistete einen wesentlich Beitrag zu einer systematischen Untersuchung der Variationen in der MIA3-Region und ihre Resultate zeigten eine Assoziation des Einzelnukleotidpolymorphismus rs17465637 (C>A) sowie zweier Haplotypen, die beide das Risikoallel (C-Allel) des rs17465637 tragen, mit dem Myokardinfarkt. Diese Befunde liefern einen klaren Beleg für die kardiovaskuläre Bedeutung des MIA3-Gens. The factor melanoma inhibitory activity 3 (MIA3) has been linked with tumour suppression and atherosclerosis. Genome-wide scans have pointed to a possible role of isolated variations in the MIA3 gene in diseases of coronary arteries. This work made an essential contribution to a systematic survey of variation in the MIA3 region and its results showed association of the single nucleotide polymorphism rs17465637 (C>A) and two haplotypes, both of which carry the risk allele (C allele) of rs17465637, with myocardial infarction. These findings offer clear evidence for a cardiovascular impact of the MIA3 gene.

Dies ist eine retrospektive Studie von 220 Patienten mit akutem Myokardinfarkt, die nach sechs Tagen eine kardiale Magnetresonanztomographie erhielten. Die Analyse der Elektrokardiogramme (EKG) ergab, dass Unterschiede in der Sensitivität der geläufigen EKG-Definitionen bei der Erkennung des akuten Myokardinfarkts bestehen. Zusätzliche linksdorsale und rechtspräkordiale EKG-Ableitungen erhöhten nicht die Gesamtsensitivität zum Nachweis eines Infarktes. Die Sensitivität der rechtspräkordialen Ableitungen zum Nachweis von rechtsventrikulären Infarkten war gering. Bei den meisten Patienten mit STEMI lag ein transmuraler Infarkt vor, aber auch bei der Hälfte der Patienten mit NSTEMI fand sich in der Magnetresonanztomographie das Bild eines transmuralen Infarktes. This is a retrospective study of 220 patients with acute myocardial infarction who underwent cardiac magnetic resonance imaging after six days. The analysis of the electrocardiogram (ECG) showed differences in the sensitivity of the standard ECG definitions in the detection of acute myocardial infarction. Additional extended posterior and right precordial leads did not improve the overall sensitivity for the detection of infarction. The sensitivity of right precordial leads for the detection of right ventricular infarction was low. Most patients with STEMI had a transmural infarction but also half of the patients with NSTMI showed a transmural infarction in the magnetic resonance imaging.

Sphingosin und Sphingosin-1-Phosphat (S1P) sind wichtige Signalmoleküle in verschiedenen zellulären Prozessen. Thrombozyten spielen eine entscheidende Rolle im Sphingolipid-Metabolismus. Sie tragen zur Entstehung von S1P bei und sind der Hauptort der Phosphorylierung des S1P-Rezeptoragonisten FTY 720. In den durchgeführten Experimenten konnte gezeigt werden, dass die Funktion humaner und muriner Thrombozyten durch Stimulation von S1P-Rezeptoren entscheidend beeinflusst und deren Aggregation gehemmt wird. Der Effekt wird im Wesentlichen vermittelt durch die S1P1- und S1P3- Rezeptoren. Die erhobenen Daten erweitern unser bisheriges Verständnis zur Regulation der Thrombozytenfunktion. Sphingosine and sphingosine-1-phosphate (S1P) are important signalling molecules in various cellular processes. Thrombocytes play an essential role in the sphingolipid metabolism. They contribute to the S1P supply in the body and are the main source of FTY 720-phosphate. The experiments indicate that stimulation of S1P receptors affects the function of human and murine thrombocytes and inhibits platelet aggregation. This effect seems to be mediated by S1P1 and S1P3 receptors. The compiled data contribute to our understanding of the regulation of thrombocyte function.

In dieser Arbeit konnte gezeigt werden, dass die kontrastverstärkte Magnetresonanztomographie (k-MRT) die Erkennung einer Herzbeteiligung im Rahmen des HES in verschiedenen Erkrankungsstadien ermöglicht. Das charakteristische Muster der Kontrastmittelanreicherung bei eosinophiler Schädigung ist auf das Endokard begrenzt und findet sich in den apikalen Regionen beider Ventrikel mit unterschiedlich starker Ausdehnung hin zu den basalen Myokardabschnitten. In der Akutphase der Erkrankung findet sich häufig eine Obstruktion des distalen Cavums, was durch eine kontrastmittelaufnehmende Verdickung des regionalen Endokards oder durch Thrombusformationen bedingt ist. Die k-MRT kann die zugrundeliegenden Pathologien, wie die Entzündungsreaktion in der Akutphase bzw. die Fibrose in der chronischen Phase der Löffler-Endokarditis, direkt darstellen und liefert somit wichtige Informationen für den Nachweis einer kardialen Beteiligung. Das Kontrastmittelmuster ist pathognomonisch für diese Erkrankung und unterscheidet sich deutlich von anderen Entitäten, die mit Anreicherung von Kontrastmittel in der k-MRT einhergehen. This study showed that in patients with Hypereosinophilic Syndrome, contrast-enhanced Cardiovascular Magnetic Resonance Imaging (CE-CMR) provides detection of cardiac involvement at different stages of the disease. Late gadolinium enhancement (LGE) was typically restricted to the endocardium and located circumferentially within the right and left ventricular apex. Extension of LGE towards the basal parts of the heart varied among patients, while the outflow tracts were commonly spared. Furthermore, a partial apical obstruction either by thrombus formation or thickened enhanced endocardium was present in those patients with a short history of symptom onset. CE-CMR has the ability to visulize directly the underlying pathologies of myocardial damage such as inflammation in the early stage respectively fibrosis in the chronic stage of Loeffler's endocarditis and generates information for the evidence of cardiac involvement. The pattern of LGE is pathognomic of this disease and the findings clearly differ from the distribution of LGE in other cardiac entities.

Ziel dieser Studie war es herauszufinden, ob das Allel O1 des ABO-Systems Schutz gegenüber einem Myokardinfarkt bietet. Hierzu wurden 793 konsekutive, angiographisch untersuchte Patienten mit akutem oder vorausgegangenem Myokardinfarkt (MI) in die Studie eingeschlossen. Als Kontrollgruppe dienten 340 angiographisch untersuchte Patienten ohne Erkrankung der Koronararterien oder Anzeichen eines Myokardinfarkts.Bei O1-Allel-Trägern war das MI Risikos um 39 % (Odds Ratio 0,61 [95% Konfidenzintervall, 0,41-0,91]) reduziert. Ein multivariates Model, das eine Kodominanz voraussetzt, zeigte, dass ein Anstieg der Anzahl von O1 Allelen mit einer Abnahme des MI Risikos assoziiert ist. Zudem konnte in einer gesonderten Kontrollgruppe (n=164) gezeigt werden, dass der Plasmaspiegel des von Willebrand-Faktors mit der Anzahl der O1 Allele (P=0,00003) in einer Beziehung steht. An association between ABO blood group and myocardial infarction (MI) has been described.We conducted this genetic study to test whether the ABO O1 allele is associated with a reduced risk of Ml. Cases consisted of 793 consecutive, angiographically examined patients with either acute or prior Ml. As controls served 340 angiographically examined patients with neither coronary artery disease nor signs of Ml.O1 allele carriage was associated with a 39% reduction in the risk of Ml unadjusted odds ratio, 0.61; 95% confidence interval, 0.41-0.91). The significant association was maintained after adjustment for other cardiovascular risk factors.