A. Bernhardt

Analysis of phenotype and genotype information for the diagnosis of Marfan syndrome.

Sheikhzadeh S, Kade C, Keyser B, Stuhrmann M, Arslan‐Kirchner M, Rybczynski M, Bernhardt AM, Habermann CR, Hillebrand M, Mir T, Robinson PN, Berger J, Detter C, Blankenberg S, Schmidtke J, von Kodolitsch Y. Analysis of phenotype and genotype information for the diagnosis of Marfan syndrome.

Marfan syndrome and the evolving spectrum of heritable thoracic aortic disease: Do we need genetics for clinical decisions?

Marfan syndrome (MFS) is a disorder of the connective tissue that is inherited in an autosomal dominant fashion and that is classically caused by mutations in the gene coding for fibrillin-1, FBN1. The high mortality of untreated MFS results almost exclusively from aortic complications such as aortic dissection and rupture. However, more than half of patients with Marfan-like features do not have MFS, but have other diseases including inherited aortic aneurysms and dissections (TAAD). We elucidate the increasing spectrum of syndromes associated with Marfan-like features and discuss the clinical implications of these diseases. We performed a systematic review to tabulate all known inherited diseases and syndromes carrying a risk for thoracic aortic disease. We discuss evidence that different syndromes with different causative genes and mutations have different prognoses and profiles of cardiovascular manifestations. We conclude that future decisions for optimized management of patients with inherited TAAD require a comprehensive clinical and genetic work-up.

Dural ectasia in individuals with Marfan-like features but exclusion of mutations in the genes FBN1, TGFBR1 and TGFBR2

Sheikhzadeh S, Rybczynski M, Habermann CR, Bernhardt AMJ, Arslan‐Kirchner M, Keyser B, Kaemmerer H, Mir TS, Staebler A, Oezdal N, Robinson PN, Berger J, Meinertz T, von Kodolitsch Y. Dural ectasia in individuals with Marfan‐like features but exclusion of mutations in the genes FBN1, TGFBR1 and TGFBR2.

A simple clinical model to estimate the probability of Marfan syndrome

BACKGROUND Marfan syndrome is a heritable connective tissue disease. Definitive diagnosis is complex, and requires sequencing of a large gene, FBN1. AIM We aimed to develop a simple model to estimate the pre-test probability of Marfan syndrome. DESIGN Prospective cross-sectional study. METHODS We applied diagnostic standards for definitive diagnosis or exclusion of Marfan syndrome in 329 consecutive persons. In 208 persons with random assignment to our derivation group, we performed multivariate logistic regression to assess 14 clinical variables for inclusion in a prediction model with derivation of score points from the estimated coefficients. We created cut-offs to classify low, moderate and high probability of Marfan syndrome. For validation, we applied the model to the remaining 121 persons. RESULTS We identified seven variables for inclusion in the final model, where we assigned four score points to ectopia lentis, two points to a family history of Marfan syndrome, and one point to previous thoracic aortic surgery, to pectus excavatum, to a wrist and thumb sign, to previous pneumothorax, and to skin striae. In the derivation group 12, 42 and 92% of persons with low (≤1 point), moderate (>1-3.5 points) or high pre-test probability (>3.5 points) had Marfan syndrome, compared to 12, 57 and 91%, respectively, in the validation group. Positive likelihood ratios were 13.96 and 8.54 in the high probability group of the derivation and validation group, respectively. CONCLUSION A simple prediction model provides evidence for Marfan syndrome. This model can be used to identify patients who require definitive diagnostic work-up.

Aortic aneurysms after correction of aortic coarctation: a systematic review.

Despite advanced techniques for surgical or percutaneous therapy coarctation of the aorta continues to carry a high risk of aneurysmal formation. Mortality of these aneurysms ranges between <1 and >90%, reflecting remarkable differences in surgical strategies and the follow-up management of coarctation. We review the frequency, anatomical types, risk factors and mechanisms of aortic aneurysm forming late after surgical or percutaneous therapy of aortic coarctation. We emphasize that aneurysms do not form exclusively at the site of previous intervention, but also at remote locations such as the ascending aorta. Moreover, aneurysm formation may only in part be attributed to a specific technique of coarctation therapy, and we emphasize the role of a bicuspid aortic valve and inherent weakness of the aortic wall as significant risk factors for aneurysm after aortic coarctation. We report the presenting symptoms, follow-up protocols, and imaging criteria for local and proximal aneurysms. Finally, we discuss criteria for prophylactic intervention at the site of such aneurysms, and present therapeutic options for different types of aneurysms. With this systematic review, we wish to provide data for establishing more uniform strategies for preventing, diagnosing and treating aneurysms associated with aortic coarctation.

Aortic Arch Replacement with Frozen Elephant Technique - A Single Center Experience Evaluating the Neurological Outcome

Introduction: A modern concept for the treatment of extensive aortic disease involving the aortic arch and the proximal descending aorta is the frozen elephant trunk (FET) technique. The perioperative incidence of spinal cord ischemia and stroke is reported to be up to 24% and 16%, respectively. The results on neurological outcome with the FET technique are presented. Methods: Between July 2011 and August 2014, 33 consecutive patients underwent extensive thoracic aorta surgery using the FET technique (n = 11 E-vita hybrid open stent graft, n = 22 Thoraflex hybrid graft). Root replacement was performed in 38.7% (Bentall n = 9, David procedure n = 3) and additional bypass grafting in 6.1% (n = 2). Mean age of these high-risk patients (mean Euroscore II 13.2 ± 15.7) was 63.2 ± 10.7 years (75.8% males). Indications for surgery were as follows: extensive degenerative aneurysm (33.3%, n = 11), acute (36.4%, n = 12), and chronic (30.3%, n = 10) type A dissection. Of these, 3 patients had acute aortic rupture and 3 patients suffered from Marfan syndrome. About one quarter (24.2%, n = 8) were reoperations. Preoperative neurological pathologies were as follows: paraparesis n = 1, monoparesis n = 2, impaired consciousness n = 2. In addition, 4 patients had already been intubated at the referring clinic. For perioperative neurological protection deep hypothermia (< 25°C) and bilateral antegrade perfusion were used and cerebral oxygenation was monitored by NIRS. Results: Cardiopulmonary bypass, aortic clamping, cerebral perfusion, and circulatory arrest times were 262 ± 79, 143 ± 63, 88 ± 31 and 80 ± 28 minute, respectively. The 30-day mortality was 15.2% (n = 5). Of these, 4 patients underwent emergency surgery. Only 1 patient who underwent elective FET died (3%). Permanent and temporary neurological deficit occurred in 6.3% (n = 2) and 15.2% (n = 5), respectively. Paraplegia occurred in 1 patient (3%) who had previous complete thoracoabdominal endovascular stenting. Left recurrent nerve paralysis was observed in 22.6% (n = 7). Conclusion: The above-mentioned regime which involves bilateral antegrade cerebral perfusion in combination with deep hypothermia provides adequate protection for the spinal cord and the brain even during longer periods of circulatory arrest. Due to anatomical reasons, the left recurrent nerve is difficult to protect.