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Background/Objective: To investigate the prevalence and effects of genetic variants (GVs) in survivors of thoracic aortic dissection/aneurysm repair. Methods: Patients aged 18–80 years who survived follow-up after cardiosurgical or endovascular repair of thoracic aortic aneurysm or dissection at a single tertiary center between 2008 and 2019 and underwent genetic testing were enrolled. The exclusion criteria were age >60 years, no offspring, and inflammatory- or trauma-related pathogenesis. Follow-up entailed computed tomography-angiography at 3 and 9 months and annually thereafter. All patients underwent genetic analyses of nine genes using next-generation sequencing. In cases of specific suspicion, the analysis was expanded to include 32 genes. Results: The study included 95 patients. The follow-up period was 3 ± 2.5 years. GVs were detected in 40% of patients. Correlation analysis according to primary diagnosis showed no significant correlation in disease persistence, progression, or in reintervention rates in aneurysm patients and a correlation of disease persistence with genetic variants according to variant class in dissection patients (p = 0.037). Correlation analysis according to follow-up CD finding revealed that patients with detected dissection, irrespective of original pathology, showed a strong correlation with genetic variants regarding disease progression and reintervention rates (p = 0.012 and p = 0.047, respectively). Conclusions: The prevalence of VUS is high in patients with aortic pathology. In patients with dissected aorta in the follow-up, irrespective of original pathology, genetic variants correlate with higher reintervention rates, warranting extended-spectrum genetic testing. The role of VUS may be greater than is currently known. [ABSTRACT FROM AUTHOR]

Background: Heritable connective tissue disorders are often accompanied by an increased risk for thoracic aortic aneurysm and dissection (TAAD). Profound knowledge of the underlying pathology may have an impact on individual treatment, systematic follow-up, and early detection by the screening of offspring. The aim of this study, based in a single high-volume tertiary center, was an analysis of the diagnostic validity of histopathologic findings in patients with TAAD due to these findings' accuracy in diagnosing heritable connective tissue disorders. Methods: Therefore, genetic testing by next-generation sequencing (NGS) was performed to evaluate the correlations. In total, 65 patients with TAAD undergoing surgical treatment before the age of 60 years or with age up to 80 years if they had offspring at the time of the procedure were included in the analysis. Results: In our cohort, no certain correlation of histological findings to the results of genetic diagnostics in patients with clinically relevant aortic pathology could be shown. Patients with histopathologic findings for heritable connective tissue disorder and a positive gene variant were 11.6 years younger than patients without mutation and without histological evidence for connective tissue disorder. Conclusions: Genetic clarification is useful to define the specific genotype of the disease of the aortic wall in the case of non-specific histological characteristics. [ABSTRACT FROM AUTHOR]

Pseudoaneurysms (PSA) are one of the most common complications after arterial punctures. This retrospective study examined whether platelet aggregation inhibitors (APT) or anticoagulants (AC) lower the success rates of PSA treatment. A total of 468 patients with PSA were retrospectively analyzed between 2010 and 2018, and 238 were included in the study. Despite co-medication with APT or AC, thrombin injection (TI) was superior to compression bandage (CB) therapy in treating PSA (TIwAC 79 vs CBwAC 51%; P =.004 and TIwAPT 93 vs CBwAPT 54%; P =.001). There was no decrease in PSA-associated thrombosis in patients requiring anticoagulation after TI. The success rates of the TI and CB groups were compared in patients with and without AC therapy, and the latter was significantly lower. A reduced success rate was not observed in CB therapy patients requiring APT. In contrast, better results were seen in the TI group. Regarding PSA treatment, TI therapy is significantly superior to CB, including in patients requiring concomitant AC or APT therapy. PSA-associated thrombosis also occurs in patients requiring anticoagulation, and sonography should be performed. Concomitant medication use with APT does not significantly influence PSA therapy success or prevention of PSA-associated thrombosis. [ABSTRACT FROM AUTHOR]

Background: There is a paucity of evidence on people with thoracic aortic aneurysm and dissection. We aimed to determine the prevalence of genetic variants and their associations with phenotypes. Methods: In this cross-sectional single-centre cohort study of consecutive patients who underwent endovascular or open-surgical repair of thoracic aortic aneurysm and dissection, genetic analysis was performed using four-stage Next Generation Sequencing, and findings were confirmed with Sanger sequencing. We collected personal and family history on comorbidities, clinical examination, anthropometrics, skeletal deformities, joint function, and ophthalmological measures. Cardiovascular risk and phenotype scores were calculated. Results: Ninety-five patients were eligible (mean age 54 ± 9 years, 70% males, 56% aortic dissection). One-fifth had a family history of aortic disease. Furthermore, 95% and 54% had a phenotype score of ≤5 and ≤2, respectively. There were no significant differences in the distribution of phenotype characteristics according to age, sex, aortic pathology, or performed invasive procedures. Genetic variants of uncertain significance were detected in 40% of patients, with classic mutations comprising 18% of all variants. We observed no significant association with cardiovascular and phenotype scores but with higher joint function scores (p = 0.015). Conclusion: Genetic variants are highly present in clinically relevant aortic pathologies. Variants appear to play a larger role than previously described. The different variants do not correlate with specific phenotypes, age, pathology, sex, or family history. [ABSTRACT FROM AUTHOR]

Background: The use of percutaneous left ventricular assist devices in patients with acute myocardial infarction complicated by cardiogenic shock (AMICS) is evolving. The aim of the study was to assess the long-term outcome of patients with AMICS depending on early initiation of Impella CP ® support prior to a percutaneous coronary intervention (PCI)., Methods: We retrospectively reviewed all patients who underwent PCI and Impella CP ® support between 2014 and 2016 for AMICS at our institution. We compared survival to discharge between those with support initiation before (pre-PCI) and after (post-PCI) PCI., Results: A total of 73 consecutive patients (69±12 years old, 27.4% female) were supported with Impella CP ® and underwent PCI for AMICS (34 pre-PCI vs . 39 post-PCI). All patients were admitted with cardiogenic shock, and 58.9% sustained cardiac arrest. Survival at discharge was 35.6%. Compared with the post-PCI group, patients in the pre-PCI group had more lesions treated ( p =0.03), a higher device weaning rate ( p =0.005) and higher survival to discharge as well as to 30 and 90 days after device implantation, respectively (50.0% vs . 23.1%, 48.5% vs . 23.1%, 46.9 vs . 20.5%, p < 0.05). Kaplan-Meier analysis showed a higher survival at one year (31.3% vs . 17.6%, log-rank p -value=0.03) in the pre-PCI group. Impella support initiation before PCI was an independent predictor of survival up to 180 days after device implantation., Conclusions: In this small, single-centre, non-randomized study Impella CP ® initiation prior to PCI was associated with higher survival rates at discharge and up to one year in AMICS patients presenting with high risk for in-hospital mortality.

Background: Monocytes (Mo) are the most important mediators in arteriogenesis. Previous results from our group demonstrated the great potential of allogenic Mo transplantation for improving collateral vessel growth, which appeared to be due to a considerable host vs. graft reaction. To prove this hypothesis and introduce this new method in clinical practice, we performed transplantation of human Mo (HuMo) in a mouse model. Methods and results: We ligated the femoral artery of BALB/c mice and transplanted Mo via the tail vein. Perfusion was measured by laser Doppler perfusion imaging (LDPI). We also performed clinical scoring based on behavior, wound healing, signs of inflammation and mobility of the ligated extremity. Finally, arteriogenesis and angiogenesis were examined histologically and by quantitative RT-PCR of the hind limb musculature. LDPI increased within one week after ligation when HuMo were transplanted and increased further up to day 21 (0.63±0.12 (n=12) in HuMo vs. 0.50±0.12 (n=17) in the control group (P<0.01)). A histological evaluation showed significantly more collateral arteries within the adductor muscles after HuMo transplantation. The promotion of collateral vessel growth after HuMo transplantation resulted in better clinical scores (0.33±0.26 (n=12) vs. 3.3 (n=9), SEM; P<0.01). Conclusions: Transplantation of HuMo improves collateral vessel growth and clinical outcomes in mice. These results verify our hypothesis that controlled triggering of the inflammatory mechanism resulted in collateral vessel growth by a local host vs. a graft reaction in the ischemic hind limbs and could represent a further step in the development of a clinical strategy for promoting arteriogenesis., Competing Interests: None.

Serine proteases and G-protein-coupled receptors have been studied extensively as effectors of cell death. However, their roles in myocardial infarction have not been determined. In this study, we investigated the influence of the plasminogen activator system involving urokinase and urokinase receptor on necrosis after acute myocardial infarction. Myocardial infarction and reperfusion were induced in mouse hearts using the in vitro Langendorff model. DNA fragmentation and cleaved caspase-3 activity in urokinase- (uPA -/- ) and urokinase receptor-knockout mice (uPAR -/- ) were determined and compared with those in wild-type mice using in situ nick-end DNA labeling (TUNEL) and enzyme-linked immunosorbent assays, respectively. Infarct sizes were determined using propidium iodide and fluorescent microspheres. Following regional ischemia and reperfusion, a significant increase in the number of TUNEL-positive nuclei was observed in the ischemic zone in mouse hearts and to a lesser degree in regions remote from the ischemic area in wild-type, uPAR -/- , and uPA -/- groups compared with those in directly removed hearts. No significant differences were observed between uPAR -/- and wild-type mice. Conversely, a significant reduction in DNA fragmentation was observed in ischemic and nonischemic regions after acute myocardial infarction in uPA -/- mice when compared with that in wild-type and uPAR -/- groups. The resulting infarct sizes were significantly smaller in uPA -/- mice than in uPAR -/- and wild-type mice. These data demonstrated the involvement of uPA, but not uPAR, in protecting against necrosis during acute myocardial infarction., Competing Interests: None.

Stenoses of the carotid artery are associated with an increased stroke risk. Duplex ultrasound is the method of choice for screening for carotid artery stenosis. Unselected screening for carotid stenosis in unselected persons is not efficient and cannot be recommended. Screening by vascular ultrasound, however, is indicated in patients with neurologic symptoms from cerebral territories supplied by the anterior or mid cerebral artery, and in asymptomatic patients with carotid bruits, atherosclerotic disease in other vascular territories, after contralateral carotid artery revascularization, and after radiation therapy of the neck., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: This study aimed to simplify an until-now complex procedure for the treatment of proximal aortic arch pathology (zones 0 and 1), where a deep hypothermic circulatory arrest even with selective cerebral perfusion is still a high-risk procedure with accompanying splanchnic and spinal cord ischemia., Methods: From June 2012 until March 2013, 106 patients underwent aortic surgery in our institution, of whom, 20 patients underwent aortic arch surgery. Of the 20 patients, 7 with multiple comorbidities and a high operative risk and no other indication for a cardiopulmonary bypass were selected to undergo an off-pump aortic arch debranching and thoracic endovascular aortic repair: 4 patients had chronic dissections, and 3 patients had arch aneurysms. The procedure was performed through median sternotomy. The supraaortic branches were rerouted to the ascending aorta, and this process was followed by thoracic endovascular aortic repair of the aortic arch and proximal descending aorta. Transaortic antegrade stenting was performed in 5 cases. Cerebral protection and perfusion monitoring were achieved by biradial pressure monitoring, electroencephalogram, and online transcranial duplex sonography. The preoperative, operative, and postoperative data were collected and analyzed retrospectively., Results: All procedures were successful. There were no conversions to cardiopulmonary bypass support. The mean operative time was 184 ± 24 minutes. Postoperatively, there was 1 rethoracotomy for bleeding and 1 cerebrovascular insult. The 30-day mortality was 1 patient., Conclusions: Off-pump aortic debranching with arch stenting is a reproducible procedure that could be favorable in certain situations, such as in patients with a higher operative risk profile, thereby reducing the risks associated with deep hypothermic circulatory arrest and also yielding favorable outcomes, even in an older patient cohort with more comorbidities.