Y. von Kodolitsch

Universität Hamburg

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Christian Detter

Universität Hamburg

J. Olfe

University Medical Center Hamburg-Eppendorf

V. Stark

Universität Hamburg

R. Kozlik‐Feldmann

University Medical Center Hamburg-Eppendorf

Thomas S. Mir

University Medical Center Hamburg-Eppendorf

Tilo Kölbel

Universität Hamburg

H. Reichenspurner

Universität Hamburg

T. Mir

University Medical Center Hamburg-Eppendorf

Christoph Nienaber

Imperial College London

Georg Rosenberger

University Medical Center Hamburg-Eppendorf

Cooperative Institutions

Universität Hamburg

135

University Medical Center Hamburg-Eppendorf

131

Charité - Universitätsmedizin Berlin

German Centre for Cardiovascular Research

Universitätsmedizin Rostock

Eppendorf (Germany)

Ludwig-Maximilians-Universität München

Deutsches Herzzentrum der Charité

University Cancer Center Hamburg

Martini-Klinik

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Antagonism of GxxPG fragments ameliorates manifestations of aortic disease in Marfan syndrome mice

Human Molecular Genetics (2012)

Gao Guo Begoña Muñoz‐García Claus‐Eric Ott Johannes Grünhagen Shaker A. Mousa

Marfan syndrome (MFS) is an inherited disorder of connective tissue caused by mutations in the gene for fibrillin-1 (FBN1). The complex pathogenesis of MFS involves changes in transforming growth factor beta (TGF-β) signaling and increased matrix metalloproteinase (MMP) expression. Fibrillin-1 and elastin have repeated Gly-x-x- Pro-Gly (GxxPG) motifs that can induce a number of effects including macrophage chemotaxis and increased MMP activity by induction of signaling through the elastin-binding protein (EBP). In this work, we test the hypothesis that antagonism of GxxPG fragments can suppress disease progression in the Marfan aorta. Fibrillin-1 underexpressing mgR/mgR Marfan mice were treated with weekly intraperitoneal (i.p.) injections of an antibody directed against GxxPG fragments. The treatment was started at 3 weeks of age and continued for 8 weeks. The treatment significantly reduced MMP-2, MMP-9 and pSmad2 activity, as well as fragmentation and macrophage infiltration in the aorta of the mgR/mgR mice. Additionally, airspace enlargement and increased pSmad2 activity in the lungs of mgR/mgR animals were prevented by the treatment. Our findings demonstrate the important role of secondary cellular events caused by GxxPG-containing fragments and matrix-induced inflammatory activity in the pathogenesis of thoracic aortic aneurysm (TAA) in mgR/mgR mice. Moreover, the results of the current study suggest that antagonism of the effects of GxxPG fragments may be a fruitful therapeutic strategy in MFS.

Pathogenesis

Fibrillin

10.1093/hmg/dds439

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Citations (35)

The spectrum of syndromes and manifestations in individuals screened for suspected Marfan Syndrome

The Thoracic and Cardiovascular Surgeon (2009)

Amj Bernhardt M Rybczynski Christian R. Habermann Christian Detter Mine Arslan‐Kirchner

Objectives: The diagnosis of Marfan syndrome (MFS) is based on evaluating a large battery of clinical criteria. There is mounting evidence that many persons presenting in specialized centers for „Marfan-like“ features do not have MFS, but exhibit a large spectrum of other syndromes. The spectrum of these syndromes and the distribution of „Marfan-like“ features remain to be characterized.

Broad spectrum

10.1055/s-0029-1191445

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Thoracic Aortic Disease in Patients with Heterozygous Variants in FBN2

The Thoracic and Cardiovascular Surgeon (2022)

Till Demal Marco Sachse H. Gregg Schuler H. Reichenspurner Michael Kutsche

Background: Inherited thoracic aortic disease defines a group of disorders characterized by aortic aneurysm or dissection and high mortality. The most common genetic causes of thoracic aortic disease are heterozygous pathogenic variants in the FBN1 and ACTA2 genes. Heterozygous FBN2 variants have rarely been associated with aortic disease. Pathogenic variants in the central region (exons 24–35) of FBN2 cause a hereditary connective tissue disorder named congenital contractual arachnodactyly (CCA).

Arachnodactyly

Thoracic aortic aneurysm

Genetic disorder

Heterozygote advantage

10.1055/s-0042-1742951

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Coronary artery anomalies

Zeitschrift für Kardiologie (2005)

Y. von Kodolitsch Oscar Franzén Gunnar Lund Dietmar Koschyk W. Ito

Coronary arteries

Coronary flow reserve

Intravascular Ultrasound

Sudden Death

Clinical Significance

10.1007/s00392-005-0153-1

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Citations (34)

Endovascular Repair of Postdissection Thoracoabdominal Aortic Aneurysm in Patients With Vascular Ehlers-Danlos Syndrome

Journal of Endovascular Therapy (2021)

Ahmed Eleshra Giuseppe Panuccio Κωνσταντίνος Σπανός Fiona Rohlffs Y. von Kodolitsch

Purpose To report endovascular repair of postdissection thoracoabdominal aortic aneurysm (TAAA) in 2 patients with vascular Ehlers-Danlos syndrome (vEDS). Case Reports Case 1. A 56-year-old vEDS male patient with a 50-mm type III TAAA [history of aortic root repair, hemiarch replacement, and thoracic endovascular aortic repair (TEVAR) for acute type A aortic dissection (TAAD) 7 years ago] was treated by a 2-stage procedure; first, cervical debranching of the left subclavian artery and second TEVAR and t-branch. The postoperative course was uneventful. Follow-up computed tomography angiography (CTA) 3.5 years postoperatively demonstrated aortic remodeling with patency of targeted visceral vessels and no endoleak. Case 2. A 47-year-old vEDS male patient presented with a TAAA (diameter of 67 mm). The patient had a history of aortic valve and arch replacement with elephant trunk for acute TAAD, and consequently a TEVAR and candy-plug procedure after a ruptured false lumen (FL) aneurysm of the descending thoracic aorta. He also had a surgical repair by an aorto-bi-iliac graft. Two years later, CTA demonstrated aneurysmal FL dilatation distally to the candy-plug and he was treated with fenestrated EVAR (F-EVAR). Conclusion Endovascular repair of postdissection TAAA was feasible and safe with good short-term outcome in 2 patients with vEDS.

Endovascular aneurysm repair

Thoracic aorta

Ehlers–Danlos syndrome

Thoracic aortic aneurysm

10.1177/15266028211025038

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Thoracic Aortic Disease in Patients with Heterozygous Variants Outside the Central Region of FBN2

The Thoracic and Cardiovascular Surgeon (2025)

Till Demal Martin Sachse C. Metzlaff H. Gregg Schuler Katalin Szöcs

10.1055/s-0045-1804108

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A standardized education protocol significantly reduces traumatic injuries and syncope recurrence: an observational study in 316 patients with vasovagal syncope

EP Europace (2011)

Muhammet Ali Aydin K. Mortensen Tushar V. Salukhe I. Wilke Michelle Ortak

The aim of this study was to assess the role of a non-pharmacological approach on the frequency of traumatic injuries and syncope recurrence in patients with vasovagal syncope and normal hearts. We report the experience in our syncope centre with a standardized education and teaching protocol for patients with vasovagal syncope. The treatment of vasovagal syncope is often complex and discouraging. Besides medical options, behaviour modification is a main component of therapy but has no statistical evidence to support its use.Between January 1999 and September 2006, we prospectively enrolled all patients with vasovagal syncope. The patients were counselled about the benign nature of their disease. Specific recommendations were made according to a standardized education protocol established at our syncope centre. A pre-/post-study was conducted to investigate the effectiveness of our approach on syncope recurrence and frequency of injury as the study endpoints. Complete follow-up data were available from 85% of the study population (316 of 371) after a mean time of 710 ± 286 days (mean age 50 years; standard deviation ± 18 years, 160 female). Eighty-seven patients (27.5%) had a syncope recurrence with 22 suffering an injury during syncope. During the follow-up period, the syncope burden per month was significantly reduced from 0.35 ± 0.03 at initial presentation to 0.08 ± 0.02 (P< 0.001). The frequency of traumatic syncope was significantly lower at the time of recurrence compared with the initial presentation (25 vs. 42%; McNemar's test P= 0.02).A standardized education protocol significantly reduces traumatic injuries and syncope recurrence in patients with vasovagal syncope.

Vasovagal Syncope

10.1093/europace/eur341

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Citations (36)

Intramurale Hämorrhagie der thorakalen Aorta

RöFo - Fortschritte auf dem Gebiet der Röntgenstrahlen und der bildgebenden Verfahren (1998)

C Dieckmann Y. von Kodolitsch Christian R. Habermann Susanne K. Csösz R. Loose

Intramural hemorrhage (IMH) of the aorta is considered to be a possible preliminary stage to dissection. We report on our experience with MRI, CT, and TEE in the diagnosis as well as in the correct evaluation of the extent of an IMH.Between 1983 and 1997 a total of 26 patients were examined using MRI (n = 13) and/or contrast enhanced CT (n = 18) or TEE. The validation was effected in 17 cases through intraoperative or postmortem inspection and in the remaining cases either through continuous clinical or radiological monitoring (n = 6) or through the depiction of the results in 2 different imaging procedures (n = 3).The correct diagnosis of an IMH was made on all examined patients with all imaging modalities. In all cases, MRI enabled the correct identification of the affected aortic segments. Using CT the affected descending aorta was overlooked in one out of 15 cases; TEE failed in one out of two cases of intramural hemorrhage in the aortic arch. A false positive diagnosis was made with CT in one out of 9 cases in the ascending aorta, and using sonography, this occurred in two out of 3 cases in the area of the aortic arch.According to our experience, magnetic resonance imaging is the most accurate method for the diagnosis of an IMH.

Descending aorta

10.1055/s-2007-1015302

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Citations (10)

Single-Center Experience with Endovascular Therapy of the Ascending Aorta with Endografts - a New Option for High-Risk Patients

The Thoracic and Cardiovascular Surgeon (2017)

Nikolaos Tsilimparis Christian Detter Stefan Drewitz Y. von Kodolitsch J. Brickwedel

Objective: Open repair is the gold-standard for ascending aorta pathologies with exceptional results and excellent durability in good-risk patients. However open surgery is less favorable in high-risk patients with advanced age or prior cardiothoracic surgery. Thoracic endovascular aortic repair of the ascending aorta (ascend-TEVAR) is a potential alternative for patients unsuitable for open repair.

Aortic repair

Single Center

Cardiothoracic surgery

Open surgery

Thoracic aorta

Gold standard (test)

Aortic surgery

10.1055/s-0037-1598821

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Predictor Analysis for Acute Type A Aortic Dissection in Small Aortic Diameters

The Thoracic and Cardiovascular Surgeon (2023)

T. J. Demal C. Detter Y. von Kodolitsch Giovanni Mariscalco Giuseppe Gatti

Background: The risk for acute aortic dissection (AAD) increases with ascending aortic diameter especially above a cut-off of 60 mm. Therefore, ESC/EACTS guidelines recommend prophylactic replacement of the ascending aorta from a diameter of 55 mm. However, 60% of AAD occur at small aortic diameters (defined as maximum diameter of ascending aorta / aortic root < 55 mm). To identify patients at risk, we sought to evaluate predictors for AAD in patients with aortic diameters < 55 mm.

10.1055/s-0043-1761650

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