Screening for Peripheral Vascular Stiffness in Lipedema Patients by Automatic Electrocardiogram-Based Oscillometric Detection.

Body mass index (BMI) is seen as a predictor of cardiovascular disease (CVD) in lipedema patients. A valid predictor of CVD is increased aortic stiffness (IAS), and previous research described IAS in lipedema. However, it is not known if this applies to all patients. In this cross-sectional single-center cohort study, peripheral pulse wave velocity (PWV) as a non-invasive indicator of aortic stiffness was measured in 41 patients with lipedema, irrespective of stage and without pre-existing cardiovascular conditions or a history of smoking and a maximum body mass index (BMI) of 35 kg/m2. Automatically electrocardiogram-triggered oscillometric sensor technology by the Gesenius-Keller method was used. Regardless of the stage of lipedema disease, there was no significant difference in PWV compared to published standard values adjusted to age and blood pressure. BMI alone is not a predictor of cardiovascular risk in lipedema patients. Measuring other anthropometric factors, such as the waist-hip ratio or waist-height ratio, should be included, and the existing cardiovascular risk factors, comorbidities, and adipose tissue distribution for accurate risk stratification should be taken into account. Automated sensor technology recording the PWV represents a valid and reliable method for health monitoring and early detection of cardiovascular risks.

Effect of Prenatal Yoga versus Moderate-Intensity Walking on Cardiorespiratory Adaptation to Acute Psychological Stress: Insights from Non-Invasive Beat-to-Beat Monitoring.

We recently reported enhanced parasympathetic activation at rest throughout pregnancy associated with regular yoga practice. The present study presents a secondary analysis of data collected within a prospective cohort study of 33 pregnant women practicing yoga once weekly throughout pregnancy and 36 controls not involved in formal pregnancy exercise programs. The objective was to assess the impact of prenatal yoga on the autonomic nervous system stress response. Healthy pregnant women with singleton pregnancies were recruited in the first trimester. There was no significant difference in the maternal body mass index (BMI) between the yoga group and the controls (24.06 ± 3.55 vs. 23.74 ± 3.43 kg/m2, p = 0.693). Women practicing yoga were older (28.6 ± 3.9 vs. 31.3 ± 3.5 years, p = 0.005) and more often nulliparous (26 (79%) vs. 18 (50%), p = 0.001). We studied heart rate variability (HRV) parameters in the time domain (SDNN, standard deviation of regular R-R intervals, and RMSSD, square root of mean squared differences of successive R-R intervals) and frequency domain (ln(LF/HF), natural logarithm of low-frequency to high-frequency power), as well as synchronization indices of heart rate, blood pressure and respiration during and immediately following acute psychological stress of a standardized mental challenge test. Measurements were performed once per trimester before and after yoga or a 30 min moderate-intensity walk. Statistical comparison was performed using three-way analyses of variance (p < 0.05 significant). Time domain HRV parameters during and following mental challenge in the yoga group were significantly higher compared to the controls regardless of the trimester (F = 7.22, p = 0.009 for SDNN and F = 9.57, p = 0.003 for RMSSD, respectively). We observed no significant differences in the yoga group vs. the controls in terms of ln(LF/HF) and synchronization indices. Regular prenatal yoga practice was associated with a significantly reduced sympathetic response to mental challenge and quicker recovery after acute psychological stress. These effects persisted throughout pregnancy with regular practice.

MRI detects increased aortic stiffening and myocardial dysfunction after TEVAR of blunt injury in young patients.

Background: Thoracic endovascular aortic repair (TEVAR) is a well-established technique for the management of blunt thoracic aortic injury (BTAI). Despite improvements in vascular imaging, graft material properties, and implant techniques, stent-graft deployment artificially induces aortic stiffening. This study aimed to evaluate the midterm effect of thoracic endovascular aortic repair after blunt thoracic aortic injury on aortic stiffness and cardiac function in young patients using cardiovascular magnetic resonance (CMR) imaging. Patients and methods: From all patients who underwent TEVAR for BTAI between 2009 and 2019 in a single institution, 10 patients with no other comorbidities affecting arterial stiffness were sex-, age-, height-, and body surface area-matched to 10 healthy controls. Comprehensive CMR examination was performed in all controls and patients. The mean follow-up period was 5.4±1.8 years; the mean age at the time of TEVAR was 30.3±8.7 years. Results: Four patients who underwent TEVAR developed arterial hypertension. 4D flow CMR-based analysis demonstrated higher global pulse wave velocity (PWV) in TEVAR patients than in controls (p=0.012). Segmental analysis showed a higher PWV in the descending and abdominal aorta. The indexed diameter of the ascending aorta was larger in TEVAR patients than in controls (p=0.007). The CINE acquisitions demonstrated increased left ventricular myocardial thickness (p<0.001). The 3D global diastolic strain rate and diastolic longitudinal velocity (e') decreased, and the A-wave velocity increased. Native myocardial T1 values were significantly higher in TEVAR patients (p=0.037). Conclusions: Young patients with TEVAR after BTAI are at an increased risk of developing vascular and myocardial dysfunction due to increased aortic stiffness. CMR follow-up allows for a comprehensive and radiation-free evaluation of vascular stiffness and associated myocardial changes, especially at the early and subclinical stages.

Aortic stiffness and related complications after endovascular repair of blunt thoracic aortic injury in young patients.

Background: This study aimed to evaluate the changes in aortic stiffness in young patients undergoing thoracic endovascular aortic repair (TEVAR) after blunt thoracic aortic injury (TBAI) and to examine the associated cardiovascular complications during follow-up. Patients and methods: We included survivors of TBAI who underwent stent graft placement between November 2009 and November 2019 and gave their consent to participate. Patients with relevant cardiovascular risk factors, comorbidities with potential impact on arterial stiffness, and prior aortic surgical or endovascular interventions were excluded. Fourteen TEVAR patients prospectively underwent clinical and noninvasive examinations and morphological imaging (mean time of follow-up and duration of implanted stent graft: 5.3 ± 1.8 years; mean age: 35.1 ± 8.7 years) and were compared to 14 healthy controls (matched for sex, age, height, and body mass index) in order to evaluate aortic stiffness. During the follow-up examinations, we assessed the pulse wave velocity (PWV; m/s) and development of arterial hypertension or heart failure, as indicated by N-terminal pro-brain natriuretic peptide (NT-proBNP; pg/mL) levels and performed echocardiography. Results: A significant increase in PWV values was recorded in the TEVAR group (median = 10.1; interquartile range [IQR] = 8.9-11.6) compared to the healthy controls (median = 7.3; IQR = 6.7-8.4), with an increase in the rank mean PWV (+ 3.8; Mann-Whitney U test p < .001). NT-proBNP levels of patients after TEVAR did not vary significantly compared to those of healthy controls (Mann-Whitney U test, p = .154). After TEVAR, five patients developed arterial hypertension during the follow-up, and three of them exhibited diastolic dysfunction. Conclusions: In young patients, TEVAR after TBAI may cause adverse cardiovascular complications due to increased aortic stiffness; therefore, screening for arterial hypertension during follow-up is recommended.

Next-generation sequencing of 32 genes associated with hereditary aortopathies and related disorders of connective tissue in a cohort of 199 patients.

PURPOSE: Heritable factors play an important etiologic role in connective tissue disorders (CTD) with vascular involvement, and a genetic diagnosis is getting increasingly important for gene-tailored, personalized patient management. METHODS: We analyzed 32 disease-associated genes by using targeted next-generation sequencing and exome sequencing in a clinically relevant cohort of 199 individuals. We classified and refined sequence variants according to their likelihood for pathogenicity. RESULTS: We identified 1 pathogenic variant (PV; in FBN1 or SMAD3) in 15 patients (7.5%) and ≥1 likely pathogenic variant (LPV; in COL3A1, FBN1, FBN2, LOX, MYH11, SMAD3, TGFBR1, or TGFBR2) in 19 individuals (9.6%), together resulting in 17.1% diagnostic yield. Thirteen PV/LPV were novel. Of PV/LPV-negative patients 47 (23.6%) showed ≥1 variant of uncertain significance (VUS). Twenty-five patients had concomitant variants. In-depth evaluation of reported/calculated variant classes resulted in reclassification of 19.8% of variants. CONCLUSION: Variant classification and refinement are essential for shaping mutational spectra of disease genes, thereby improving clinical sensitivity. Obligate stringent multigene analysis is a powerful tool for identifying genetic causes of clinically related CTDs. Nonetheless, the relatively high rate of PV/LPV/VUS-negative patients underscores the existence of yet unknown disease loci and/or oligogenic/polygenic inheritance.

Microarray analysis for delineating the gene expression in biopsies of gastrocnemius muscle of patients with chronic critical limb ischaemia compared with non-ischaemic controls.

BACKGROUND: Microarray analysis has been carried out in this pilot study to compare delineated gene expression profiles in the biopsies of skeletal muscle taken from patients with chronic critical limb ischaemia (CLI) and non-ischaemic control subjects. PATIENTS AND METHODS: Biopsy of gastrocnemius muscle was obtained from six patients with unreconstructed CLI referred for surgical major amputation. As control, biopsies of six patients undergoing elective knee arthroplasty without evidence of peripheral arterial occlusive disease were taken. The differences in gene expression associated with angiogenic processes in specimens obtained from ischaemic and non-ischaemic skeletal muscle were confirmed by quantitative real-time polymerase chain reaction (PCR) analysis. RESULTS: Compared with non-ischaemic skeletal muscle biopsy of chronic-ischaemic skeletal muscle contained 55 significantly up-regulated and 45 down-regulated genes, out of which 64 genes had a known genetic product. Tissue samples of ischaemic muscle were characterized by increased expression of cell survival factors (e. g. tissue factor pathway inhibitor 2) in combination with reduced expression of cell proliferation effectors (e. g. microfibrillar-associated protein 5 and transferrin receptor). The expression of growth factors (e. g. early growth response 3 and chemokine receptor chemokine C-X-C motif ligand 4) which play a central role in arterial and angiogenic processes and anti-angiogenetic factors (e. g. pentraxin 3) were increased in chronic ischaemic skeletal muscle. An increased expression of extracellular matrix proteins (e. g. cysteine-rich angiogenic inducer 61) was also observed. CONCLUSIONS: Gene expression profiles in biopsies of gastrocnemius muscle in patients with chronic critical limb ischaemia showed an increase in pro-survival factors, extracellular matrix protein deposition, and impaired proliferation, compared with non-ischaemic controls. Further studies are required to analyse the endogenous repair mechanism.

Management of the left subclavian artery during TEVAR - complications and mid-term follow-up.

BACKGROUND: Numerous conditions that affect the boundary between the aortic arch and descending aorta are treated with thoracic endovascular aortic repair (TEVAR). In 40 % of cases, coverage of the left subclavian artery (LSA) cannot be prevented. Subsequently, neurological complications such as stroke or ischemia of the left upper extremity may develop. However, the actual risk of these complications is subject to considerable controversy. The optimal treatment approach, specifically the question whether primary revascularization of the LSA should be performed in all cases, is unclear. PATIENTS AND METHODS: The present retrospective study analyzed the short- and mid-term results of patients treated with TEVAR with complete coverage of the LSA. The postoperative protocol consisted of clinical and noninvasive examinations as well as morphological imaging. Survival, complication, and reintervention rates were recorded. RESULTS: A total of 40 patients, undergoing TEVAR with complete coverage of the LSA between January 2010 and December 2014 were analyzed retrospectively. The 30-day survival rate was 95 %, the survival one year after performed TEVAR was 67.5 %. The average follow-up was 1.5 years. After TEVAR procedure with complete coverage of the LSA, only one patient (2.5 %) developed critical ischemia of the left arm immediately after aortic stent implantation, requiring revascularization by transposition of the LSA. Anterior spinal artery syndrome occurred in another patient (2.5 %) immediately following TEVAR. During follow-up examinations, all patients showed a compensated arterial arm status. None of the patients developed new neurological deficits during the follow-up period. CONCLUSIONS: The study shows that performing TEVAR without primary revascularization of the LSA was justifiable in our cohort. An important risk factor of developing cerebral ischemia seems to be insufficient collateralization through the circle of Willis.

Experts' Results in Blunt Thoracic Aortic Injury are Reproducible in Lower Volume Tertiary Institutions. Early and Mid-term Results of an Observational Study.

OBJECTIVES: The aim of this study was to evaluate the early and mid-term clinical results, the device performance, and the mid-term re-intervention rates of patients suffering blunt thoracic aortic injury (BTAI) managed by a multidisciplinary team in a low-volume BTAI centre. METHODS: This was a retrospective observational study in a tertiary hospital setting. From December 2005 to March 2016, all patients over 18 years old admitted with BTAI were included in the study. No exclusion criteria were applied. The study data were collected and analysed retrospectively. Follow-up of survivors included computed tomography imaging 3 and 9 months post-procedure, then annually. RESULTS: Twenty-eight patients were included in the study. Their mean age was 42 ± 16 years and 89% were male. A contained aortic rupture was diagnosed in 20 patients, a Stanford type B dissection in six, and intramural haematoma in two patients. Multidisciplinary evaluations were performed and an intervention was indicated in 25 patients (89%), four of whom died before the intervention. Nineteen patients underwent thoracic endovascular aortic repair of the descending thoracic aorta and two patients underwent a frozen elephant trunk procedure. The procedures were performed 0.7 ± 1.2 days after injury. All procedures were successful. There were no device related complications. The post-operative 30 day mortality was 5%, with one patient dying on the day of operation from other vascular injuries. The 30 day mortality of all patients was 18%. The median mid-term follow-up period was 786 days. All 30 day survivors survived the follow-up period. The mid-term imaging showed stable results in 19 patients. Two patients required frozen elephant trunk procedures after 240 and 681 days and both procedures were successful. CONCLUSIONS: In a low volume centre, a multidisciplinary team using a standardised protocol with the endovascular first approach demonstrated excellent outcomes, similar to those of large centres. If the aortic trauma is adequately managed, the patient's outcome is closely related to the additional trauma.

Quality of Life after Surgery for Stanford Type A Aortic Dissection: Influences of Different Operative Strategies.

BACKGROUND: Outcome of surgery for acute Stanford type A aortic dissection extends beyond mortality and morbidity. More than one operative strategy is available but little is known regarding their influence on quality of life. This study analyzes the influence of defensive and aggressive operative strategies on the patients' midterm quality of life (QoL). METHODS: From July 2007 to July 2010, 95 patients underwent surgery for acute Stanford type A aortic dissection in our institution. Patients who survived the procedure, gave consent to inclusion in the institution prospective registry, completed at least 2-years of follow-up protocol, and answered two quality of life questionnaires (SF-36 and WHO-QOL-BREF) were included in the study. Patients were divided into two groups according to operative strategy: defensive (DS) with replacement of the ascending aorta only, and aggressive (AS) with replacement of the ascending aorta, aortic arch with/out a frozen elephant trunk procedure. The preoperative, operative, postoperative and the midterm QoL were analyzed and compared. RESULTS: 39 patients were included in the study. The DS group had a shorter operative time (184 ± 54 versus 276 ± 110 minutes respectively, P = .001). The AS group had higher incidence of dialysis (31% versus 4% respectively, P = .038). The midterm QoL analysis showed a collective lower value than the normal population. In the SF-36, DS performed better in all categories but with no statistical significance. In the WHO-QOL-BREF, DS performed significantly better in the global life quality and psychological health categories (P = .038 and .049 respectively). CONCLUSION: In Stanford type A aortic dissection, adopting an aggressive surgical strategy does not improve the quality of life in midterm follow-up compared to a defensive strategy. Unless the clinical setting dictates an aggressive management strategy, a defensive strategy can be safely adopted.

Legitimacy of Entry-Oriented Strategy in DeBakey I Dissection in the Era of Endovascular Therapy.

BACKGROUND: Legitimacy of entry-oriented therapy for DeBakey I aortic dissection is of eminent importance in the era of emerging ascending aorta endovascular therapy. This study aims to evaluate early, midterm, and reintervention results of entry-oriented operative strategy compared to more aggressive strategies for treatment of DeBakey type I aortic dissection with an isolated intimal tear in the ascending aorta. METHODS: This study prospectively followed 98 consecutive patients who received an operation for DeBakey type I aortic dissection with the intimal tear in the ascending aorta between 2007 and 2013 for up to 6 years. Follow-up included survival, medical therapy, CT-imaging results, and reinterventions. Patients were grouped into entry-oriented (group I) receiving an isolated replacement of the ascending aorta and/or hemiarch (65 patients); and aggressive therapy (group II) receiving a replacement of the ascending aorta and complete aortic arch (33 patients). Results: The in-hospital mortality was 19% and 23% respectively. The 3-year survival was 52% and 47% respectively (P = .193). Group II showed no advantage regarding persistence or progression of the dissection, thrombosis of false lumen, increase in aortic diameter, peripheral organ malperfusion (as assessed by follow-up computed tomography imaging) or freedom from reintervention. Conclusion: In treating DeBakey I aortic dissection with an entry tear in the ascending aorta, it might be legitimate to adopt an entry-oriented operative strategy. Further research is also needed to clearly describe the indication of extending the operative strategy in such cases.

Anastomotic leak after surgical repair of type A aortic dissection - prevalence and consequences in midterm follow-up.

BACKGROUND: This study reports the mid-term prevalence and therapeutic consequences of anastomotic leaks after surgery for Stanford type A aortic dissections. PATIENTS AND METHODS: From July 2007 to July 2013, 93 patients survived surgery for acute type A dissections at our center and underwent a standardized follow-up. The pre-, peri-, and postoperative as well as the midterm results were collected prospectively. Follow-up computed tomography (CT) imaging was performed 7 days, 3, and 12 months after surgery, and yearly thereafter, to assess the presence or progression of anastomotic leaks at the aorto-prosthesis anastomotic sites. RESULTS: The mean follow-up was 4 years (1534 ± 724 days). Follow-up CT revealed anastomotic leaks in 4 patients (4.3 %). All leaks developed during midterm follow-up and half of them did not increase with time. Two patients required redo surgery for an increase in periaortic extravasation and compression of neighboring structures. Further analysis was not able to reveal independent risk factors for development or deterioration of leaks. CONCLUSIONS: Anastomotic leaks after surgery for Stanford Type A aortic dissection can develop in midterm follow-up, even after initially excellent results. Meticulous follow-up is mandatory to detect possible deterioration and a need for redo surgery.

S100A1 deficiency impairs postischemic angiogenesis via compromised proangiogenic endothelial cell function and nitric oxide synthase regulation.

RATIONALE: Mice lacking the EF-hand Ca2+ sensor S100A1 display endothelial dysfunction because of distorted Ca2+ -activated nitric oxide (NO) generation. OBJECTIVE: To determine the pathophysiological role of S100A1 in endothelial cell (EC) function in experimental ischemic revascularization. METHODS AND RESULTS: Patients with chronic critical limb ischemia showed almost complete loss of S100A1 expression in hypoxic tissue. Ensuing studies in S100A1 knockout (SKO) mice subjected to femoral artery resection unveiled insufficient perfusion recovery and high rates of autoamputation. Defective in vivo angiogenesis prompted cellular studies in SKO ECs and human ECs, with small interfering RNA-mediated S100A1 knockdown demonstrating impaired in vitro and in vivo proangiogenic properties (proliferation, migration, tube formation) and attenuated vascular endothelial growth factor (VEGF)-stimulated and hypoxia-stimulated endothelial NO synthase (eNOS) activity. Mechanistically, S100A1 deficiency compromised eNOS activity in ECs by interrupted stimulatory S100A1/eNOS interaction and protein kinase C hyperactivation that resulted in inhibitory eNOS phosphorylation and enhanced VEGF receptor-2 degradation with attenuated VEGF signaling. Ischemic SKO tissue recapitulated the same molecular abnormalities with insufficient in vivo NO generation. Unresolved ischemia entailed excessive VEGF accumulation in SKO mice with aggravated VEGF receptor-2 degradation and blunted in vivo signaling through the proangiogenic phosphoinositide-3-kinase/Akt/eNOS cascade. The NO supplementation strategies rescued defective angiogenesis and salvaged limbs in SKO mice after femoral artery resection. CONCLUSIONS: Our study shows for the first time downregulation of S100A1 expression in patients with critical limb ischemia and identifies S100A1 as critical for EC function in postnatal ischemic angiogenesis. These findings link its pathological plasticity in critical limb ischemia to impaired neovascularization, prompting further studies to probe the microvascular therapeutic potential of S100A1.

Medical management of abdominal aortic aneurysms.

Abdominal aortic aneurysms (AAA) are the most common arterial aneurysms. Endovascular or open surgical aneurysm repair is indicated in patients with large AAA ≥ 5.5 cm in diameter as this prevents aneurysm rupture. The presence even of small AAAs not in need of immediate repair is associated with a very high cardiovascular risk including myocardial infarction, stroke or cardiovascular death. This risk by far exceeds the risk of aneurysm rupture. These patients therefore should be considered as high-risk patients and receive optimal medical treatment and life-style modification of their cardiovascular risk factors to improve their prognosis. In addition, these patients should be followed-up for aneurysm growth and receive medical treatment to decrease aneurym progression and rupture rate. Treatment with statins has been shown to reduce cardiovascular mortality in these patients, and also slows the rate of AAA growth. Use of beta-blockers, ACE inhibitors and AT1-receptor antagonists does not affect AAA growth but may be indicated for comorbidities. Antibiotic therapy with roxithromycin has a small effect on AAA growth, but this effect must be critically weighed against the potential risk of wide-spread use of antibiotics.

Evaluation of the Value of Histological Examination for the Prediction of Genetic Thoracic Proximal Aortopathies.

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.

Prevalence of Genetic Variants and Deep Phenotyping in Patients with Thoracic Aortic Aneurysm and Dissection: A Cross-Sectional Single-Centre Cohort Study.

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.

Pharmacokinetics of rivaroxaban after bariatric surgery: a case report.

Rivaroxaban is a direct factor Xa inhibitor, which is rapidly absorbed in the upper gastrointestinal (GI) tract. In large trials, it has been shown to be effective and safe in VTE treatment. However, in these trials patients with morbid obesity were not reported and it is unknown if the standard dosage of 20 mg rivaroxaban is sufficient for bariatric patients, especially after bariatric surgery, which may impact the resorption of rivaroxaban. We report the case of a bariatric patient with high venous thromboembolism risk and instable INR after recent bariatric surgery, who was switched from Vitamin-K antagonists to rivaroxaban. After intake of 20 mg rivaroxaban, plasma concentration were repeatedly measured until 3 h after the second dose using a commercially available chromogenic aXa-assay. Furthermore, INR and aPTT were measured. Peak concentrations of 224.22 ng/ml were observed. After 6 h, plasma concentration decreased to 86.9 ng/ml and remained stable until 12 h (86.32 ng/ml). After 24 h, a trough level of 35.54 ng/ml was observed. The patients INR did immediately increase and remained significantly elevated throughout the day with a slow decrease. Since peak values of rivaroxaban plasma concentrations were in the expected range of published data, we conclude that resorption of rivaroxaban was immediate and not significantly impaired by bariatric surgery of the upper GI tract. Consequently, no dose adjustments seem to be necessary in this high-risk population.

How to asses and improve cardiopulmonary risk prior to vascular surgery?

Patients with peripheral arterial disease have a high rate of cardiac, cerebrovascular, or pulmonary comorbidities. Peripheral arterial surgical interventions are associated with a moderate to high perioperative cardiac risk. Simple clinical scoring systems for preoperative risk stratification can be used to identify high-risk patients. In these patients further diagnostic and therapeutic measures are required to reduce perioperative morbidity and mortality. In contrast, a group of patients can be identifed that do not require additional cardiopulmonary diagnostics and can immediately proceed to the intervention. According to evidence-based recommendations in patients at risk beta blocker should be uptitrated and statin therapy should be initiated preoperatively. Quitting smoking preoperatively also reduces perioperative complications and should be encouraged in all patients.

The Role of Anticoagulants and Platelet Aggregation Inhibitors in the Treatment of Pseudoaneurysms and Risk of Venous Thrombosis.

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.

Concomitant cardiovascular malformations in isolated bicuspid aortic valve disease: a retrospective cross-sectional study and meta-analysis.

Background: Congenital bicuspid aortic valve affects up to 2% of the general population. It occurs in complex congenital heart defects or in syndromes such as Turner, Marfan, or Loeys-Dietz. However, the majority of bicuspid aortic valves are considered to manifest as isolated malformations. Methods: We aimed to assess retrospectively associated cardiovascular malformations in 200 individuals with bicuspid aortic valve considered to occur as an isolated manifestation. All individuals underwent transthoracic echocardiography, 164 thoracoabdominal tomographic imaging, and 84 coronary artery imaging. In addition, we also performed a meta-analysis of data from the literature to assess the occurrence of associate malformations. Results: In our retrospective cross-sectional study collective, the mean age was 45±15 years, 154 (77%) individuals were male. Anatomy of bicuspid aortic valve according to Schaefer was type 1 in 142 (71%), type 2 in 35 (18%), type 3 in 2 (1%), unicuspid in 6 (3%), and unclassified in 15 (8%) individuals. Coarctation of the aorta had 4.2% of individuals, 3.6% had coronary anomalies. No individual had a patent ductus arteriosus, 0.5% had atrial and ventricular septal defect each, 1.5% mitral valve prolapse. No individual had a tricuspid valve prolapse. Our meta-analysis identified in cohorts with isolated bicuspid aortic valve 11.8% (95% CI: 7.7-16.0%) individuals with aortic coarctation, 3.7% (95% CI: 1.2-6.1%) with coronary anomalies, 3.3% (95% CI: 0.0-6.7%) with patent ductus arteriosus, 5.9% (95% CI: 1.3-10.5%) with ventricular septal defect and 1.6% (95% CI: 1.1-2.1%) with mitral valve prolapse. Conclusions: Individuals with isolated bicuspid aortic valve may exhibit a variety of associated cardiovascular malformations and therefore screening for associated malformations may be warranted.

Use of MALDI Mass Spectrometry Imaging to Identify Proteomic Signatures in Aortic Aneurysms after Endovascular Repair.

Endovascular repair (EVAR) has become the standard procedure in treating thoracic (TAA) or abdominal aortic aneurysms (AAA). Not entirely free of complications, a persisting perfusion of the aneurysm after EVAR, called Endoleak (EL), leads to reintervention and risk of secondary rupture. How the aortic wall responds to the implantation of a stentgraft and EL is mostly uncertain. We present a pilot study to identify peptide signatures and gain new insights in pathophysiological alterations of the aortic wall after EVAR using matrix-assisted laser desorption or ionization mass spectrometry imaging (MALDI-MSI). In course of or accompanying an open aortic repair, tissue sections from 15 patients (TAA = 5, AAA = 5, EVAR = 5) were collected. Regions of interest (tunica media and tunica adventitia) were defined and univariate (receiver operating characteristic analysis) statistical analysis for subgroup comparison was used. This proof-of-concept study demonstrates that MALDI-MSI is feasible to identify discriminatory peptide signatures separating TAA, AAA and EVAR. Decreased intensity distributions for actin, tropomyosin, and troponin after EVAR suggest impaired contractility in vascular smooth muscle cells. Furthermore, inability to provide energy caused by impaired respiratory chain function and continuous degradation of extracellular matrix components (collagen) might support aortic wall destabilization. In case of EL after EVAR, this mechanism may result in a weakened aortic wall with lacking ability to react on reinstating pulsatile blood flow.