11:30 Uhr
PS64:
T1 and T2 Mapping for Evaluation of Myocardial Involvement in Patients with ANCA-associated Vasculitides
S. Greulich (Stuttgart, DE)
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Autor:innen:
S. Greulich (Stuttgart, DE)
A. Mayr (DE)
D. Kitterer (DE)
J. Latus (DE)
J. Henes (DE)
N. Braun (DE)
P. Kaesemann (DE)
A. Patrascu (DE)
M. Alscher (DE)
U. Sechtem (DE)
H. Mahrholdt (DE)
Background: Myocardial involvement in AAV patients might be silent, presenting with no or nonspecific symptoms, normal ECG, and preserved left-ventricular ejection fraction (LV-EF). Since up to 50% of deaths in these patients may be due to myocardial involvement, a reliable diagnostic tool is warranted. In contrast to LGE-CMR, which has its strengths in detecting focal inflammatory or fibrotic processes, recent mapping techniques are able to detect even subtle, diffuse inflammatory or fibrotic processes. Our study sought to investigate ANCA (antineutrophil cytoplasmic antibody)-associated vasculitides (AAV) patients for myocardial involvement by a cardiovascular magnetic resonance (CMR) protocol, including late gadolinium enhancement (LGE) and mapping sequences.
Methods: Thirty-seven AAV patients were prospectively enrolled and underwent CMR imaging. Twenty healthy volunteers served as controls.
Results: Mean LV-EF was 64%; LGE prevalence of the AAV patients was 43%. AAV patients had higher median native T1 (988 vs. 952 ms, p<0.001), lower post-contrast T1 (488 vs. 524 ms, p=0.03), expanded extracellular volume (ECV) (27.5 vs. 24.5%, p<0.001), and higher T2 (53 vs. 49 ms, p<0.001) compared to controls, with most parameters independent of the LGE status. Native T1 and T2 in AAV patients showed the highest prevalence of abnormally increased values beyond the 95% percentile of controls.
Conclusion: AAV patients demonstrated increased T1, ECV, and T2 values, with native T1 and T2 showing the highest prevalence of values beyond the 95% percentile of normal. Since these findings seem to be independent of LGE, mapping techniques may provide complementary information to LGE-CMR in the assessment of myocardial involvement in patients with AAV.
11:36 Uhr
PS65:
Einfluss von Adipokinen auf die Differenzierung der Spongiosa-abgeleiteten mesenchymalen Stammzellen von Arthrosepatienten
L. Tsiklauri (Bad Nauheim, DE)
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Autor:innen:
L. Tsiklauri (Bad Nauheim, DE)
J. Werner (DE)
K. Frommer (DE)
R. Engel (DE)
S. Rehart (DE)
S. Wenisch (DE)
U. Müller-Ladner (DE)
E. Neumann (DE)
Der altersbedingte Knochenverlust korreliert mit einer erhöhten Fettinfiltration im Knochenmark. Daher findet sich das osteoporotisch veränderte Hartgewebe direkt an der Grenze zu den Adipozyten des Knochenmarks. Das Fettgewebe ist metabolisch hochaktiv. Es sezerniert unter anderem Adipokine (zB Visfatin, Resistin und Leptin), die möglicherweise die Differenzierung im Knochenmark lokalisierten mesenchymalen Stammzellen (MSC) beeinflussen und zum fortschreitenden Knochenverlust an den Knochen-Knochenmark-Grenzflächen in Rahmen der Osteoporose (OP) beitragen können. Daher wurde die Expression der Adipokine im Knochen osteoporotischer und nicht-osteoporotischer Spender mit Arthrose sowie ihre Effekte auf die osteogene und adipogene Differenzierung von MSC untersucht.
Nach der Isolierung von RNA aus Spongiosa humaner Hüftköpfe sowie aus differenzierten MSC wurden Genexpressionsanalysen mittels Real-Time PCR durchgeführt. Die Differenzierung von MSC erfolgte über 21 Tagen mit bzw. ohne Zugabe von Adipokinen (Visfatin, Resistin, Leptin). Die Sekretion von Entzündungsmediatoren wurde mittels ELISA gemessen. Alizarin Red S Färbung diente zum Nachweis von mineralisierter Matrix. Für Spongiosa-Transfer Experimente wurde die Spongiosa unter sterilen Bedingungen aufgereinigt (zellfrei) und die MSC zur Differenzierung in die Spongiosa gegeben.
Das Expressionslevel von Visfatin und Leptin war signifikant im osteoporotischen Knochen (n=14) erhöht, während Resistin deutlich herunterreguliert war. Visfatin führte zu einer signifikanten Erhöhung von IL-6, IL-8 und MCP-1 während der adipogenen sowie osteogenen Differenzierung. Eine verstärkte Mineralisierung durch Visfatin konnte in Rahmen der Osteogenese nachgewiesen werden, wobei die Kollagen Typ 1 Expression durch Visfatin signifikant herabgesetzt war (zB Tag 21: 4,6-fach). Im Gegensatz zu Resistin und Leptin bewirkte Visfatin eine signifikante Reduktion von MMP13 (zB Tag 21: 3,2-fach), MMP2 (zB Tag 21: 2,4-fach), TIMP1 (zB Tag 21: 3,2-fach), TIMP2 (zB Tag 21: 4,3-fach) und RunX2 (zB Tag 21: 5,8-fach) in osteogen differenzierten Zellen. Während der adipogenen Differenzierung führte Visfatin zu einem signifikanten Expressionsanstieg von MMP13 (zB Tag 21: 104±88). Zwar war die Visfatin-induzierte MMP13-Expression während der Adipogenese auf gereinigten autologen Spongiosa-Fragmenten nachweisbar, dieser Effekt fiel aber deutlich geringer aus als unter Standard-Zellkulturbedingungen.
Die Ergebnisse weisen darauf hin, dass Visfatin die Differenzierung der MSC beeinflusst: Visfatin verstärkt die Mineralisierung, reduziert aber die Expression von Kollagen Typ 1. Dies könnte zu einem erhöhten Fragilitätsrisiko führen. Durch die Reduktion der RunX2-Expression verringert Visfatin das osteogene Differenzierungspotential. Die Visfatin-induzierte Dysregulation der MMP- und TIMP-Expression sowie von Entzündungsmediatoren trägt möglicherweise zu einem gestörten Knochenumbau an den Knochen-Knochenmark-Grenzflächen bei der OP bei.
11:42 Uhr
PS66:
A rare cause for alveolar hemorrhage and acute kidney failure
M. Cabrera (DE)
C. Löffler (Mannheim, DE)
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Autor:innen:
M. Cabrera (DE)
C. Löffler (Mannheim, DE)
U. Benck (DE)
B. Krämer (DE)
We present a case of a 42-year-old female with no medical history who was admitted to our department with hemoptysis, fever, rapidly progressive renal failure, lower limb edema and severe hypertension (240/100 mmHg). These symptoms had been occurring progressively within the last 7 days prior to admission. Urinalysis revealed microhematuria and a nephrotic-range proteinuria. Chest radiographs and computed tomography showed bilateral infiltration suggestive of alveolar hemorrhage. The kidneys presented with hyperechogenic parenchyma and were of normal size in renal sonography. Bronchoscopy with bronchoalveolar lavage confirmed alveolar hemorrhage and ruled out an infection.
Steroid pulse therapy, plasmapheresis and cyclophosphamide were started because of a strong suspicion of immune mediated pulmonary renal syndrome as seen in ANCA associated vasculitis or Goodpasture’s syndrome. Due to severe fluid overload and refractory hypertension despite antihypertensive treatment hemodialysis was initiated. Renal biopsy findings showed no evidence of active necrotizing glomerulonephritis or crescent formation, however, a severe lumen constricting arteriosclerosis, severe thrombotic microangiopathy and mild tubular damage. Testing for proteinase 3 and myeloperoxidase specific ANCA (PR3-/MPO-ANCA), antinuclear autoantibodies (ANA), anti-GBM antibodies and anti-phospholipid antibodies were negative. C-reactive protein levels and erythrocyte sedimentation rate were not suggestive of an inflammatory disease.
We therefore considered malignant hypertension to be the underlying diagnosis in this case. Pathophysiologically, hypertensive vascular stress can cause acute endothelial damage leading to alveolar hemorrhage and renal failure. To date, only very few cases are published regarding this rare manifestation (pulmonary alveolar hemorrhage) of malignant hypertension.
Plasmapheresis and immunosuppressive treatment were discontinued immediately. In the further course pulmonary hemorrhage completely dissolved under treatment with antihypertensive agents. The renal function, however, did not recover. Four months after discharge the patient continued to be dialysis dependent, her blood pressure was normal and chest radiographs showed no pathological findings.
Although the clinical characteristics, course and outcome of malignant hypertension are well defined, we present an unusual manifestation with pulmonary alveolar hemorrhage and acute kidney failure mimicking an immune mediated pulmonary renal syndrome. Once the diagnosis of diffuse alveolar hemorrhage is established malignant hypertension should be taken into account as a differential diagnosis in the proper clinical setting.
11:48 Uhr
PS67:
Evaluation of Myocardial Fibrosis in Non-ischemic Dilated Cardiomyopathy and its Prognostic Value
E. Kayvanpour (Heidelberg, DE)
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Autor:innen:
E. Kayvanpour (Heidelberg, DE)
F. Sedaghat-Hamedani (DE)
D. Li (DE)
F. Tugrul (DE)
N. Grabe (DE)
B. Lahrmann (DE)
L. Frankenstein (DE)
C. Stock (DE)
E. Herpel (DE)
S. Buss (DE)
H. Katus (DE)
B. Meder (DE)
Introduction: Myocardial fibrosis and extracellular matrix expansion occur during pathological remodeling of the heart and is associated with worse outcome of affected patients. On a molecular level, novel circulating biomarkers aim to assess cardiac fibrotic remodeling. Imaging tools, such as cardiac MRI implement Gadolinium contrast agent or T1 mapping to detect larger fibrotic formations. More sufficiently, LV endomyocardial biopsies (LV-EMB) are used to assess cardiac fibrosis, to identify the individual causes (e.g. viral replication), and to aid differential diagnosis. In this study we evaluated the prognostic values of the mentioned three methods in a large DCM cohort with a follow up period of up to 10 years.
Methods: We included a total number of 542 patients who had undergone left ventricular EMB (LV-EMB) due to suspected DCM. Left ventricular collagen volume fraction (LV-CVF) was quantified using automated image processing of high-resolution scans of LV-EMB. 13 major circulating fibrosis biomarkers were measured using Human Magnetic Luminex Screening Assays. The extent of LGE was estimated as a percentage of LV-mass using the software IntelliSpace Portal with application of the "Full-Width-Half-Maximum" (FWHM) protocol. Univariate as well as multivariate analyses between histopathological and clinical findings of patients were carried out. End-points were all-cause mortality and heart failure associated events: a composite of cardiovascular death, cardiopulmonary resuscitation, heart transplantation, sustained ventricular tachycardia, and adequate ICD treatment. ROC analyses were performed to evaluate the accuracy of different circulating fibrosis biomarkers in outcome prediction compared to LV-CVF.
Results: Using machine learning techniques, we established an automated method for quantification of LV-CVF in patients’ LV-EMBs. We could show that LV-EMB is a safe procedure with a total complication rate of 2.3 in 100 patients in our center with no case of procedure-related death. Kaplan Meier survival curves showed that the extent of LV-CVF is an independent predictor of all-cause mortality (p=0.009) and heart failure associated events (p<0.0001). In a subgroup of 150 patients with available cMRI at time point of LV-EMB taking, no significant correlation could be observed between the absence and presence of mid-wall fibrosis or the extent of LGE. ROC analyses showed that histopathological evaluation of LV-CVF offers higher specificity and sensitivity in outcome prediction compared to circulating fibrosis biomarkers.
Conclusions: Our results suggest that EMB is a reliable and precise tool to characterize DCM tissue properties and strengthen the role of LV-EMB in evaluation of clinical course and outcome of patients with cardiomyopathy.
Key words: dilated cardiomyopathy, pathological remodeling, left ventricular endomyocardial biopsy
11:54 Uhr
PS68:
Improvement of Impaired Diastolic Left Ventricular Function after Diet-induced Weight Reduction in Severe Obesity
J. Stein (Frankfurt/Main, DE)
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Autor:innen:
S. Karimian (Frankfurt/Main, DE)
J. Stein (Frankfurt/Main, DE)
B. Bauer (Frankfurt/Main, DE)
C. Teupe (Frankfurt/Main, DE)
Background/Objectives: Obesity is independently associated with left ventricular diastolic dysfunction and altered cardiac morphology. Morbidity and mortality in patients with diastolic dysfunction are similar to values observed in patients with systolic heart failure. We hypothesised that dysfunctional cardiac response in obese individuals is reversible after weight loss. Thus, we studied the effect of dietary weight reduction on left ventricular diastolic function as well as on cardiac structure, using transthoracic echocardiography and tissue Doppler imaging.
Subjects/Methods: Thirty-two subjects with obesity underwent a 12-week low calorie fasting phase of a formula diet (OPTIFAST®52). Echocardiographic tissue Doppler indices of diastolic function and measurements of cardiac size were obtained prior to and after the fasting phase.
Results: A 12-week diet significantly reduced body mass index, from 40.3 ±6.6 to 33.2 ±6.1 kg/m² (p<0.01). Weight loss was associated with a significant reduction in blood pressure and heart rate. Echocardiography revealed diastolic dysfunction in subjects with obesity, which was improved by dieting. After weight loss, transmitral Doppler echocardiography showed a significant reduction in A-wave velocity, from 65.8 ±19.2 cm/s to 57.0 ±16.8 cm/s, and an increase in E/A-ratio, from 1.2 ±0.4 to 1.4 ±0.5 (p<0.01). Tissue Doppler imaging displayed a significantly lower a´-wave velocity (10.3 ±2.3 cm/s and 8.9 ±1.7 cm/s; p<0.01). Left atrial and ventricular dimensions were normal and remained unchanged after dieting.
Conclusion: Obesity is associated with diastolic dysfunction. A 12-week low calorie diet with successful weight loss can reduce blood pressure and heart rate and partially normalise diastolic dysfunction.
12:00 Uhr
PS69:
TOPP-ABI - Tissue Optical Perfusion Pressure-Ankle Brachial Index: A new and improved method for diagnosis of PAOD
G. Horstick (Neustadt a.d. Weinstrasse, DE)
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Autor:innen:
G. Horstick (Neustadt a.d. Weinstrasse, DE)
L. Messner (Mainz, DE)
B. Betsch (Neustadt a.d. Weinstrasse, DE)
C. Georg (Neustadt a.d. Weinstrasse, DE)
C. Espinola-Klein (Mainz, DE)
The routine diagnostic for classification of PAOD is the measurement of the ABI either by doppler pressure or automated oscillometric determination (AOD). AOD shortens time of analysis and reduces measuring errors. In the past interventions of the foot arteries increased with improvement of the techniques and therefore it is of utmost interest to measure tissue perfusion pressure at the level of the toe. Performing TBI (toe brachial index) a second examination after the routine ABI measurement is needed. However, TBI is not always credible and toe pressure measurement (TPM) would afford a third examination inducing ischemia reperfusion pathology affecting the results.. Therefore, we added optical infrared sensors on the first toe of each foot measuring the pulsation of the arteries in the tissue for determination of TOPP simultaneous to the AOD of the ABI.
Methods: AngE system was used to determine ABI with AOD between ranges of 160 to 40mmHg . TOPP at the first toe was documented simultaneously in 10mmHg increments while deflating the pressure cuffs. To compare TOPP versus the Doppler signal and TPM 20 healthy people were examined with the method of optical pulsation (TOPP) detected at the measuring point of the Doppler probe at the ADP and compared to the TOPP and TPM at the toe. For clinical examination 100 patients with PAOD Fontaine class IIa, IIb and III were examined by TOPP-ABI at rest and after defined walking exercise, extensive ultrasound examination including ankle peak systolic velocity (APSV) and either MRA or CTA. 20 patients w/wo PAOD and normal TOPP-ABI and ultrasound examination without MRA or CTA served as controls. Additionally, puls wave analysis was performed to measure puls wave index (PWI) and central puls wave velocity (cPWV).
Results: TOPP in healthy subjects is 30 to 60mmHg higher versus TMP. The first optical pulsation at the measuring point of the Doppler pressure at the ADP correlates with the TOPP at the toe. There was no correlation to the PWV. TOPP correlates to the free of pain walking distance and the severity of PAOD in the MRA/CTA. TOPP presented a very good correlation to the APSV, ABI and PWI.
Conclusion: TOPP-ABI improves automated oszillometric ABI determination by measurement of the systolic tissue optical perfusion pressure at the far end of microperfusion at the toe simultaneously in one examination. This standardized technique prevents human measurement errors and ischemia reperfusion effects by multiple measurements and provides new insights into foot artery hemodynamics on top of routine ABI measurements.
12:06 Uhr
PS70:
Kardiomyopathie mit reduzierter EF als Risikofaktor für die Entstehung einer Sekundär sklerosierenden Cholangitis – Präsentation von 3 Fällen
F. Müller (Dipperz, DE)
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Autor:in:
F. Müller (Dipperz, DE)
Die sekundär sklerosierende Cholangitis bei kritisch kranken Patienten (secondary sclerosing cholangitis in critically ill patients (SSC-CIP)) ist charakterisiert durch eine progrediente Cholestase und führt mit unterschiedlicher Latenz zu einer biliären Zirrhose und Leberversagen. Ischämische Läsionen der Gallenwege, z.B. im Rahmen eines prolongierten hämodynamischen Schocks, stellen eine plausible Erklärung der Entstehung dar. Da nur ein kleiner Teil dieser Patienten eine sekundär sklerosierende Cholangitis entwickelt, scheinen weitere Trigger notwendig. Vorliegend präsentieren wir 3 Patienten mit Sekundär Sklerosierender Cholangitis mit sehr unterschiedlichem Verlauf, die eine bekannte oder neu diagnostizierte Kardiomyopathie mit reduzierter Ejektionsfraktion aufwiesen.
Fall 1:
71-jähriger Patient mit bekannter ischämischer Kardiomyopathie und Z.n. ACVB-Operation, der posttraumatisch eine fulminante Lungenembolie entwickelte.3 Monate später stellte er sich erneut mit dem Bild einer Cholangitis vor. In der Bildgebung mittels ERCP und MRCP bestand das Bild einer Sekundär sklerosierenden Cholangitis mit biliary cast.
Fall 2:
Es stellte sich eine 88-jährige, mobile Patientin bei uns zur Abklärung einer cholestatischen Hepatopatie vor. Bei ischämischer Kardiomyopathie erfolgte bereits 6 Jahre zuvor eine ACVB-Operation mit Rekonstruktion der Mitralklappe. Postoperativ kam es zu wiederholt zu hypotonenen und asystolen Phasen. Im Verlauf bestanden erhöhte Cholestasewerte bei asymptomatischem Verlauf. Bei akutem Anstieg der Werte im Rahmen einer Darm-Operation zeigte sich in der ERCP das typische Bild einer Sekundär Sklerosierenden Cholangitis.
Fall 3:
Eine 47-jährige Patientin mit schwerem Asthma bronchiale wurde bei Exazerbation auf der Intensivstation intubiert. Nachfolgend invasive Beatmung sowie 1-malige Phase eines Druckabfalls mit Reanimationsbehandlung. Echokardiographisch bestand eine deutlich reduzierte Ejektionsfraktion von ca. 25% unklarer Genese. Knapp 2 Wochen nach Aufnahme entwickelte die Patientin eine Cholangiosepsis. Im Verlauf kam es zu rapide steigenden Cholestasewerten, in der ERCP bestand das Bild einer Sekundär Sklerosierenden Cholangitis mit biliary cast. Bei fulminantem Verlauf verstarb die Patientin an Komplikationen eines Leberversagens 10 Wochen nach Aufnahme.
Diskussion:
Die Fälle zeigen den äußerst unterschiedlichen Verlauf einer Sekundär Sklerosierenden Cholangitis (SSC-CIP), vom langjährig asymptomatischen Verlauf bis hin zum akuten Leberversagen.
Bei Patienten mit reduzierter Ejektionsfraktion besteht ein reduziertes Herzminutenvolumen/Herzindex. Bei schwerer, intensivmedizinisch therapierter Erkrankung besteht bei diesen Patienten ein erhöhtes Risiko für eine prolongierte Gewebsminderperfusion. Somit könnte eine Kardiomyopathie mit reduzierter Ejektionsfraktion einen Triggerfaktor für die Entstehung einer Sekundär Sklerosierenden Cholangitis darstellen.