Papers by Yskert Kodolitsch
Background—Nucleotide variants in several genes for lipid and methionine metabolism influence the... more Background—Nucleotide variants in several genes for lipid and methionine metabolism influence the risk of premature atherosclerosis. Ten percent of single nucleotide substitutions in these genes involve mRNA splice sites. The effects of some of these changes on splicing and on phenotypic severity are not inherently obvious. Methods and Results—Using an information theory-based model, we measured the individual information content (R
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Zeitschrift f�r Kardiologie, 1998
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Cardiology in review
Marfan syndrome is an autosomal dominant disorder of the connective tissues, with mutation on the... more Marfan syndrome is an autosomal dominant disorder of the connective tissues, with mutation on the fibrillin-1 gene encoding for fibrillin, a major component of the extracellular microfibrils. The prevalence of the syndrome is 7 to 17 in 100,000. The mean life expectancy for untreated patients with Marfan syndrome is 32 years, with aortic dissection, aortic rupture, or cardiac failure from mitral or aortic valve regurgitation as the predominant cause of death in >90% of patients. However, with optimal clinical management of patients with Marfan syndrome, life expectancy may be improved substantially to a nearly normal life span. Cornerstones of clinical management include modern noninvasive imaging modalities, molecular analysis at the complementary deoxyribonucleic acid/deoxyribonucleic acid level of the fibrillin-1 gene, genetic counseling, lifestyle changes, and cardiovascular surveillance, the latter including regular imaging of the aorta and endocarditis prophylaxis. Prophyla...
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International journal of cardiac imaging, 1994
Thirty-five consecutive patients with clinically suspected aortic dissection were subjected to a ... more Thirty-five consecutive patients with clinically suspected aortic dissection were subjected to a dual noninvasive imaging protocol using comprehensive echocardiography and ECG-triggered MRI with multi-slice spin echo and cine sequences in random order. The purpose of this dual imaging study was to compare the diagnostic accuracy of two-dimensional and color-coded Doppler echocardiography using the conventional transthoracic (TTE) and the transesophageal approach (TEE) with magnetic resonance imaging (MRI) for the exact morphologic evaluation and anatomical mapping of the thoracic aorta. The results of each diagnostic method were validated independently against the 'gold standard' of intraoperative findings (n = 17), necropsy (n = 4) or contrast angiography (n = 22). Compared to conventional transthoracic echocardiography both TEE and MRI were more reliable in detecting aortic dissections (TTE vs TEE: p < 0.02; TTE vs MRI: p < 0.01) and associated epiphenomena. Moreover...
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Medizinische Klinik, 2010
The Marfan syndrome is a typical rare disease with multiorgan involvement and the need for specia... more The Marfan syndrome is a typical rare disease with multiorgan involvement and the need for specialized interdisciplinary medical care. A novel German legal directive according to section sign 116 b of the Social Statutes Book V (116 b SGB V) improves options for reimbursement and thus encourages specialized hospitals to provide ambulatory care for rare diseases such as Marfan syndrome. The authors provide the first economic analysis of section sign 116 b in a German Marfan center. The costs were assessed in 184 cases with Marfan syndrome receiving medical care in the Hamburg Marfan Clinic. The authors assessed the financial profit both according to payments received from invoices established according to the 116 b directive [reimbursement (116b)] and from calculations according to section sign 117 SGB V [reimbursement (117)]. A total of 117 patients traveled to the Marfan clinic (64%) &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 50 km, 27 patients (15%) between &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;or= 50 and &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;or= 100 km, and 40 patients (22%) &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 100 km. The total costs for ambulatory care were 71,606.28 Euro. The reimbursement (116b) was 55,549.87 Euro and the reimbursement (117) was 11,776.00 Euro. Many patients accept long distances of traveling to receive specialized ambulatory medical care. However, for optimal patient management specialized centers need to cooperate intensively with local health care providers. The novel legal directive according to section sign 116 b has significantly improved reimbursement for Marfan centers and allows for improving the quality of medical care.
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American Journal of Hypertension, 2009
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American Journal of Hypertension, 2010
The augmentation index at a heart rate of 75 beats/min (AIx@HR75) and central pulse pressure (CPP... more The augmentation index at a heart rate of 75 beats/min (AIx@HR75) and central pulse pressure (CPP) can be measured noninvasively with applanation tonometry (APT). In this observational study, we investigated the relationship between AIx@HR75, CPP and aortic disease in patients with Marfan-like syndromes. We performed APT in 78 consecutive patients in whom classic Marfan syndrome (MFS) had been excluded (46 men and 32 women aged 34 +/- 13 years). These patients comprised 9 persons with MFS-like habitus, 6 with a bicuspid aortic valve (BAV), 5 with MASS phenotype, 3 with vascular type of Ehlers-Danlos syndrome (EDS), 3 with familial thoracic aortic aneurysm, 2 with Loeys-Dietz syndrome (LDS), 1 with mitral valve prolapse syndrome, 1 with familial ectopia lentis, and 48 persons with Marfan-like features but no defined syndrome. During 20 +/- 18 months after APT, we observed progression of aortic diameters in 15 patients, and aortic surgery or aortic dissection in 3 individuals. All 11 patients with Marfan-like syndromes and progression of aortic disease exhibited AIx@HR75 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or =11%, including 8 individuals with aortic diameters &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; or =95th percentile of normal at baseline. Similarly, all 7 individuals without any defined syndrome but progression of aortic diameters exhibited AIx@HR75 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;11%, including 6 individuals with aortic diameters &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; or =95th percentile at the time of APT. Aortic disease did not evolve at AIx@HR75 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;11%. CPP is also related to aortic disease progression. Aortic disease evolution relates to AIx@HR75 and CPP in Marfan like syndromes. Larger studies with comprehensive clinical and echocardiographic follow-up over long time intervals will be required to establish APT for prediction of aortic disease evolution in Marfan-like syndromes.
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The Thoracic and Cardiovascular Surgeon, 2013
Mitral valve (MV) regurgitation is a common manifestation in patients with Marfan syndrome (MFS) ... more Mitral valve (MV) regurgitation is a common manifestation in patients with Marfan syndrome (MFS) and is age dependent. Valve pathology shares some features with myxomatous MV disease. Surgical treatment is still being debated and not well characterized in patients with MFS. We retrospectively evaluated the results of mitral valve repair (MVR) of symptomatic patients with MFS who underwent surgery between January 2004 and April 2011. MFS was diagnosed following the Ghent criteria. MVR was performed in 12 patients. Three patients underwent minimally invasive MVR despite severe thorax deformities. Mean follow-up was 60.1 months (95% CI: 48-72) and was complete. Thirty-day mortality was 0%. One patient died because of arrhythmia 66 months after MVR. Transthoracic echocardiography at last visit showed mild mitral regurgitation in one patient (8.3%) and no mitral regurgitation in the remaining patients (91.7%). MVR was associated with excellent survival and a low rate of complications. Transthoracic echocardiography showed good results of the repaired valves even years later. Minimally invasive repairs are feasible even in deformed thoraces, lowering the risk for future aortic surgery. Because of excellent mid-term to long-term results, MVR may also be justified in asymptomatic Marfan patients.
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Pediatric Cardiology, 2013
Cardiac pathologies are the major aspect in the treatment strategies for Marfan syndrome (MFS). I... more Cardiac pathologies are the major aspect in the treatment strategies for Marfan syndrome (MFS). In this progressive disease, less is known about manifestations and progression of cardiovascular symptoms in children. To define a certain decision regarding therapeutic options, knowledge concerning the onset of cardiovascular findings is essential. From 1998 to 2011, suspected pediatric Marfan patients were subjected to a standardized diagnostic program. Cardiovascular findings were analyzed in terms of age at first clinical manifestation, prevalence and gender differences, morbidity, mortality, and treatment. Marfan syndrome was diagnosed in 82 patients (46 boys; mean age at diagnosis, 9.0 ± 5.7 years). At first presentation, aortic root dilation was found in 56 % of patients, mitral valve prolapse in 31 %, whereas pulmonary artery dilation was detected in 22 % and tricuspid valve prolapse in only 17 % of patients. Aortic (2.5 %) and mitral valve regurgitations (22 %) are significantly correlated with aortic root dilation (p &amp;amp;amp;amp;amp;amp;lt; 0.01) and mitral valve prolapse (p &amp;amp;amp;amp;amp;amp;lt; 0.05) but without relevant progression during childhood. Prophylactic medication was initiated for 42 % of the patients (mean age, 8.0 ± 4.5 years) because of progressive aortic root dilation. Aortic dissection did not appear. Aortic root surgery was needed for 4 % of the patients. Gender-specific differences in cardiovascular findings, progression of disease, or treatment did not appear. Comparable with adults, aortic root dilation is the most frequent cardiovascular finding in children and associated with relevant morbidity, whereas aortic and mitral valve regurgitation are of minor clinical relevance. Manifestation at an early age and slow progression of cardiovascular findings underscore the necessity of repeated echocardiographic examinations for early diagnosis and start of prophylactic treatment.
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New England Journal of Medicine, 1999
The treatment of thoracic aortic dissection is guided by prognostic and anatomical information. P... more The treatment of thoracic aortic dissection is guided by prognostic and anatomical information. Proximal dissection requires surgery, but the appropriate treatment of distal thoracic aortic dissection has not been determined, because surgery has failed to improve the prognosis. We prospectively evaluated the safety and efficacy of elective transluminal endovascular stent-graft insertion in 12 consecutive patients with descending (type B) aortic dissection and compared the results with surgery in 12 matched controls. In all 24 patients, aortic dissection was diagnosed by magnetic resonance angiography. In each group, the dissection involved the aortic arch in 3 patients and the descending thoracic aorta in all 12 patients. With the patient under general anesthesia, either surgical resection was undertaken or a custom-designed endovascular stent-graft was placed by unilateral arteriotomy. Stent-graft placement resulted in no morbidity or mortality, whereas surgery for type B dissection was associated with four deaths (33 percent, P=0.09) and five serious adverse events (42 percent, P=0.04) within 12 months. Transluminal placement of the stent-graft prosthesis was successful in all patients, with no leakage; full expansion of the stents was ensured by balloon inflation at 2 to 3 atm. Sealing of the entry tear was monitored during the procedure by transesophageal ultrasonography and angiography, and thrombosis of the false lumen was confirmed in all 12 patients after a mean of three months by magnetic resonance imaging. There were no deaths or instances of paraplegia, stroke, embolization, side-branch occlusion, or infection in the stent-graft group; nine patients had postimplantation syndrome, with transient elevation of C-reactive protein levels and body temperature plus mild leukocytosis. All the patients who received stent-grafts recovered, as did seven patients who underwent surgery for type B dissection (58 percent) (P=0.04). These preliminary observations suggest that elective, nonsurgical insertion of an endovascular stent-graft is safe and efficacious in selected patients who have thoracic aortic dissection and for whom surgery is indicated. Endoluminal repair may be useful for interventional reconstruction of thoracic aortic dissection.
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The Lancet, 1999
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Journal of the American College of Cardiology, 2002
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Journal of Cardiac Surgery, 2003
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Human Mutation, 2005
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Human Mutation, 1999
Analysis of large genes for mutations of clinical relevance is complicated by intragenic heteroge... more Analysis of large genes for mutations of clinical relevance is complicated by intragenic heterogeneity, sensitivity, and cost of the methods available, and in the case of many conditions, specificity of the genetic alterations detected. We examined the FBN1 gene for mutations in people who had Marfan syndrome using three methods: single-chain polymorphism analysis (SSCP) with heteroduplex (HA) analysis, enzyme-mediated cleavage (EMC) of heteroduplexes, and direct sequencing. We also used these methods to search for mutations in the P53 gene in patients with hepatocellular carcinoma. The results showed that EMC was most efficient for detecting mutations. However, the cost favored SSCP with heteroduplex analysis, provided conditions did not need to be optimized to detect a mutation. Until more cost-effective and sensitive methods are developed to detect unknown mutations in large genes, diagnosis of many genetic disorders will depend on the willingness of an investigator who is studying a particular disorder to perform clinical molecular testing and have the laboratory accredited.
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Heart, 2007
... TAAD without systemic manifestations, and may even be present in patients fulfilling Marfan c... more ... TAAD without systemic manifestations, and may even be present in patients fulfilling Marfan criteria but exhibiting only mild ocular involvement (called Marfan syndrome type II by some authors, although the occurrence of LDS-features may ... Gott VL, Greene PS, Alejo DE, et al. ...
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Zeitschrift für Kardiologie, 1998
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Zeitschrift f�r Kardiologie, 1998
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Zeitschrift f�r Kardiologie, 2001
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Clinical Cardiology, 1998
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Papers by Yskert Kodolitsch