Investigation of target genes and potential mechanisms related to compound Xiao-ai-fei honey ointment based on network pharmacology and bioinformatics analysis.

BACKGROUND: Compound Xiao-ai-fei honey ointment (CXHO) is an anticancer preparation with a long history in Uyghur folk medicine in China and has been used for the treatment of gastric cancer (GC) in Xinjiang, China. Nevertheless, the mechanism of its anticancer effect remains to be investigated. METHODS: Bioactive ingredients of CXHO were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database. Target genes of ingredients were acquired via the PubChem and Swiss target prediction database. Gene expression profiling of GC was obtained from GSE54129 in the GEO database and analyzed using the limma package in R. The hub genes associated with CXHO in GC were validated using the TIMER2.0 database, GEPIA2 database and Auto Dock tools. The effect of CXHO on migration of GC cells was detected by Transwell chamber assay and Wound healing assay. The effect of CXHO on expression levels of MMP2/MMP9 and NF-κb, PI3K/AKT signaling pathway was detected by Western blot assay. RESULTS: Forty-five bioactive ingredients and their 819 related genes were found. A total of 462 differentially expressed genes were identified between GC patients and healthy controls. Seventeen common target genes were identified as hub genes CXHO against GC. Among them, MMP2 and MMP9 were significantly associated with tumor immune infiltrates and had good binding affinity with effective ingredients. Moreover, we validated the mRNA and protein expression levels and prognostic value of MMP2 and MMP9 by different databases. In addition, Kyoto encyclopedia of genes and genomes and gene ontology analyses showed that the 17 common target genes were mainly involved in steroid hormone biosynthesis and cancer-related pathways. Experimental results showed that CXHO inhibited migration of GC cells and down regulated the expression levels of MMP2/MMP9, NF-κb. In addition, CXHO can inhibited PI3K/AKT signaling pathway. CONCLUSION: We identified and experimental validated 2 pivotal target genes of CXHO against GC and preliminarily analyzed the potential mechanisms by which CXHO inhibits the development of GC. All these findings support CXHO as a promising drug for the treatment of GC.

Mixed aortic stenosis and regurgitation: a clinical conundrum.

Mixed aortic stenosis (AS) and aortic regurgitation (AR) is the most frequent concomitant valve disease worldwide and represents a heterogeneous population ranging from mild AS with severe AR to mild AR with severe AS. About 6.8% of patients with at least moderate AS will also have moderate or greater AR, and 17.9% of patients with at least moderate AR will suffer from moderate or greater AS. Interest in mixed AS/AR has increased, with studies demonstrating that patients with moderate mixed AS/AR have similar outcomes to those with isolated severe AS. The diagnosis and quantification of mixed AS/AR severity are predominantly echocardiography-based, but the combined lesions lead to significant limitations in the assessment. Aortic valve peak velocity is the best parameter to evaluate the combined haemodynamic impact of both lesions, with a peak velocity greater than 4.0 m/s suggesting severe mixed AS/AR. Moreover, symptoms, increased left ventricular wall thickness and filling pressures, and abnormal left ventricular global longitudinal strain likely identify high-risk patients who may benefit from closer follow-up. Although guidelines recommend interventions based on the predominant lesion, some patients could potentially benefit from earlier intervention. Once a patient is deemed to require intervention, for patients receiving transcatheter valves, the presence of mixed AS/AR could confer benefit to those at high risk of paravalvular leak. Overall, the current approach of managing patients based on the dominant lesion might be too reductionist and a more holistic approach including biomarkers and multimodality imaging cardiac remodelling and inflammation data might be more appropriate.

A bioenergetics assessment of aortic regurgitation: A new tool to assess severity?

Aortic regurgitation is frequently classified as mild, moderate or severe based on echocardiography. Patients with mild aortic regurgitation are usually managed medically. Decisions with regard to moderate aortic regurgitation can be difficult. We hypothesise that mild aortic regurgitation as assessed volumetrically can in fact be moderate to severe when analysed from a bioenergetics point of view. The conservation of energy predicts that any regurgitant volume will require the heart to provide more work energy to support the circulation. Aortic regurgitation involves the left ventricle imparting potential energy, via blood pressure, and kinetic energy, via increased ejected volume and velocity respectively. This implies that regurgitant volume, ejection velocity, diastolic and systolic blood pressure, heart rate, and regurgitant orifice area are all important factors. We present limited data to demonstrate our hypothesis. A bioenergetic analysis of aortic regurgitation, reveals that correlation between regurgitant volume and effective regurgitant orifice can be poor in certain physiological circumstances. In addition we identify the importance of systolic and diastolic blood pressure, and heart rate control in patients with aortic regurgitation. The concept that mild aortic regurgitation can be ignored is from an engineering point fundamentally flawed in some cases.

Transcatheter aortic valve-in-valve implantation for failed surgical bioprosthetic valves. A minimalist approach without contrast aortography or echocardiographic guidance.

OBJECTIVES: To demonstrate safety, feasibility and short-term clinical outcomes after transcatheter aortic valve-in-valve (ViV) implantation under local anesthesia without contrast aortography or echocardiographic guidance. BACKGROUND: Transcatheter ViV implantation is an emerging treatment modality for patients with degenerative surgical bioprostheses. Given the radiopaque properties of the surgical aortic valve (SAV) frame, ViV procedures can often be performed with fluoroscopic guidance alone. METHODS: ViV implantation was performed in 37 patients with SAV failure under local anesthesia without contrast aortography. Clinical and echocardiographic data were obtained at baseline, discharge, and 30 days. RESULTS: Mean age was 74 ± 10 years and STS predicted risk of mortality was 5.6 ± 2.4%. Mean transaortic gradient decreased from 39.4 ± 15.5 mmHg to 13 ± 6.3 mmHg at discharge (p < .001), and 20 ± 7.5 mmHg at 30 days (p < .001 compared to baseline), aortic valve area increased from 0.9 ± 0.3 cm2 to 1.2 ± 0.4 cm2 at 30 days (p = .007). No patient had more than mild aortic regurgitation. Hospital discharge occurred at a median of 2.6 ± 4.4 days. At 30-day follow-up there were no deaths, myocardial infarctions, strokes, repeat hospital admissions for heart failure, or renal failure. One patient (2.7%) required a new pacemaker. 93% of the patients were in New York Heart Association functional class I or II. CONCLUSIONS: Transcatheter aortic ViV implantation for selected patients with degenerative surgical bioprostheses under local anesthesia without aortography or echocardiographic guidance is feasible and safe.

Identifying patients likely to be readmitted after transcatheter aortic valve replacement.

Hospital readmission following transcatheter aortic valve replacement (TAVR) contributes considerably to the costs of care. Readmission rates following TAVR have been reported to be as high as 17.4% at 30 days and 53.2% at 1 year. Patient and procedural factors predict an increased likelihood of readmission including non-transfemoral access, acute and chronic kidney impairment, chronic lung disease, left ventricular systolic dysfunction, atrial fibrillation, major bleeding and prolonged index hospitalisation. Recent studies have also found the requirement for new pacemaker implantation and the severity of paravalvular aortic regurgitation and tricuspid regurgitation to be novel predictors of readmission. Post-TAVR readmission within 30 days of discharge is more likely to occur for non-cardiac than cardiac pathology, although readmission for cardiac causes, especially heart failure, predicts higher mortality than readmission for non-cardiac causes. To combat the risk of readmission and associated mortality, the routine practice of calculating and considering readmission risk should be adopted by the heart team. Furthermore, because most readmissions following TAVR occur for non-cardiac reasons, more holistic approaches to readmission prevention are necessary. Familiarity with the most common predictors and causes of readmission should guide the development of initiatives to address these conditions proactively.

Carditis in Acute Rheumatic Fever in a High-Income and Moderate-Risk Country.

OBJECTIVE: To describe clinical presentation, electrocardiographic, and echocardiographic characteristics of carditis at the time of diagnosis of acute rheumatic fever (ARF) over a 13-year period. STUDY DESIGN: A single-center retrospective chart analysis was conducted involving all consecutive patients diagnosed with ARF between 2003 and 2015. Patient age, sex, clinical characteristics, recent medical history for group A streptococcal pharyngotonsillitis and antibiotic treatment, and laboratory, echocardiographic, and electrocardiographic findings were recorded. RESULTS: Of 98 patients (62 boys, mean age 8.81 ± 3.04 years), 59 (60.2%) reported a positive history of pharyngotonsillitis; 48 (49%) had received antibiotic (mean duration of treatment of 5.9 ± 3.1 days), and, among these, 28 (58.3%) had carditis. Carditis was the second most frequent finding, subclinical in 27% of patients. Mitral regurgitation was present in 49 of 56 patients (87.5%) and aortic regurgitation in 36/56 (64.3%) no stenosis was documented. CONCLUSIONS: ARF is still present in high-income countries and can develop despite primary prophylaxis, especially when given for a short course. Our findings highlight the need for 10 days of antistreptococcal treatment to prevent ARF. Echocardiography is important because 27% of cases with carditis were subclinical.

Acute and chronic effects of mokuboito in a patient with heart failure due to severe aortic regurgitation.

Medical treatment for heart failure is still limited in patients with symptomatic aortic regurgitation (AR). Here we report the effects of mokuboito used in combination with standard medical therapy for heart failure in an inoperable patient with symptomatic severe AR. We observed acute effects of mokuboito in decreasing systemic vascular resistance and increasing cardiac output, as well as its chronic effects in improving New York Heart Association class, plasma brain natriuretic peptide levels, and left ventricular diastolic function. Given its efficacy, the use of mokuboito might be an additional treatment for patients with heart failure.

Iatrogenic aortic regurgitation after radiofrequency ablation of idiopathic ventricular arrhythmias originating from the aortic valvular region.

BACKGROUND: Radiofrequency ablation at the aortic root has the potential risk of aortic regurgitation (AR). OBJECTIVE: This study investigated the incidence and clinical features of iatrogenic AR after catheter ablation of idiopathic ventricular arrhythmias originating from the aortic root. METHODS: We studied 45 consecutive patients with idiopathic ventricular arrhythmias originating from the aortic cusps (ACs; AC group; n = 32 [71%]) and papillary muscles (control group; n = 13 [29%]) who underwent ablation via a retrograde aortic approach and serial echocardiography before and within 24 hours after the ablation procedure. No patients had preexisting AR. RESULTS: After ablation, mild AR occurred in 5 AC group patients and 1 control group patient. Regurgitant flow was observed at the center of the aortic leaflets in 3 patients, the left coronary cusp-noncoronary cusp commissure in 2 patients, and both in 1 patient. No patients undergoing ablation only above the aortic valve developed AR. In AC group patients, the occurrence of AR was associated with a longer ablation time (24 ± 14 minutes vs 10 ± 5 minutes; P < .01) and higher average output (36.6 ± 4.2 W vs 32.0 ± 3.2 W; P = .01). The same severity of AR still existed after 16.2 ± 3.6 months of follow-up. No patients required any additional medical management or surgical intervention. CONCLUSION: Iatrogenic mild AR after ablation in the aortic root occurred with a noticeable prevalence, which was associated with extensive ablation both above and below the ACs as well as catheter-related mechanical factors. Although it did not appear to aggravate the hemodynamic status during the mid-term follow-up, careful monitoring of AR progression should be considered.

Bailout surgical explantation of a transcatheter valve-in-valve for subacute thrombosis: When there is no time for anticoagulation: Case report and literature review.

Trancatheter heart valve (THV) thrombosis is effectively treated with anticoagulation but alternative therapies are required when a faster gradient reduction is needed. Open heart surgery has been rarely performed due to the high perioperative mortality and only five cases have been described so far. Here we describe a case of emergent surgical explantation for THV thrombosis after a valve-in-valve. A 67years old man underwent transcatheter aortic valve implantation for a failed surgical bioprosthesis Epic 21mm (St. Jude Medical; St. Paul, Minnesota, US). A CoreValve 23mm (Medtronic, Minneapolis, Minnesota, US) was implanted through femoral access under conscious sedation without complications. Mean transvalvular gradient was effectively reduced (33mmHg vs 16mmHg) with no more than mild residual aortic regurgitation. After 8days the patient was discharged on dual antiplatelet therapy but was readmitted to the intensive care unit for pulmonary oedema 13days later. Echocardiography showed a raised transvalvular mean gradient (mean gradient change from discharge=15mmHg) without aortic regurgitation. Heart Team decided for emergent open heart surgery for the hemodynamic instability. On direct inspection THV was well positioned inside the surgical bioprosthesis but two cusps were covered by thrombus which markedly restricted their mobility. The THV and the former surgical valve were explanted and a new larger stented bioprosthesis was implanted. Thrombosis of the THV was confirmed on microscopic examination which showed no signs of inflammation or degeneration. The patient was discharged after 1month and the 3month follow up showed stable transvalvular gradients.

Local Versus General Anesthesia in Transcatheter Aortic Valve Replacement.

Transcatheter aortic valve replacement (TAVR) is conventionally performed under general anesthesia (GA) allowing intraoperative transoesophageal echocardiogram imaging. We present our experience in patients having the procedure under local anesthesia (LA), who were subsequently transferred to a low dependency unit postprocedure, to assess safety and length of hospital stay. We retrospectively assessed all the transfemoral TAVR procedures conducted at our center from January 03, 2011. Of 216 patients, 145 had the procedure under GA and 71 under LA. Both groups were similar with respect to age, co-morbidities, Euro Score, and the severity of the aortic stenosis. The procedure time was significantly shorter in the LA group measured from time in room to skin closure (108 vs 143 minutes, p <0.001). Skin open to skin closure time were the same in both groups (78 vs 79.4 minutes, p = 0.57). There was no difference in 30 days: aortic regurgitation > mild (2.1% in GA and 2.8% in LA, p = 0.67), need for permanent pacing (3.4% in GA and 1.4% in LA, p = 0.32), and disabling cerebrovascular accidents (1.4% and 1.4%, p = 1.0). The 30-day survival was not significantly different (95.9% in GA and 100% in LA, p = 0.17), whereas the median number of days in hospital was shorter in the LA group (4 in GA and 2 in LA, p <0.001). No emergency conversions to GA were performed in the LA group and only 1 patient needed admission to a high dependency (HD) unit. In conclusion, performing a TAVR under LA is at least as safe as GA. In addition, there is a reduced procedural time and length of hospital stay. LA is a safe and cost-effective alternative to GA and patients can be safely transferred to a low dependency unit.

Outcomes in Moderate Mixed Aortic Valve Disease: Is it Time for a Paradigm Shift?

BACKGROUND: A direct comparison of outcomes between moderate mixed aortic valve disease (MAVD) and isolated aortic stenosis (AS) or aortic regurgitation (AR) has not been performed, making evidence-based recommendations difficult in patients with MAVD. OBJECTIVES: This study sought to determine adverse event (AE) occurrence (the primary endpoint), defined as New York Heart Association functional class III/IV symptoms, aortic valve replacement, or cardiac death, and to compare AE rates between MAVD and isolated AS or AR. METHODS: Asymptomatic patients were identified with moderate MAVD and an ejection fraction ≥50% and were followed at Mayo Clinic from 1994 to 2013. Moderate MAVD was defined as a combination of moderate AS and moderate AR. Age- and sex-matched control groups were selected with isolated moderate AR (n = 117), moderate AS (n = 117), or severe AS (n = 117). RESULTS: At 9.1 ± 4.2 years of follow-up, patients with moderate MAVD (n = 251) had a mean age of 63 ± 11 years, 73% were male, and 38% had bicuspid valve. AE occurred in 193 (77%) patients in this group, including symptom development (69%), aortic valve replacement (67%), and cardiac death (4%). Predictors of AE were older age (hazard ratio [HR]: 1.71 per decade; 95% confidence interval [CI]: 1.38 to 1.97 per decade; p = 0.001), and relative wall thickness >0.42 (HR: 2.01; 95% CI: 1.86 to 2.33; p = 0.002). AE rates were similar in the MAVD and severe AS group (71% vs. 68% at 5 years; p = 0.49), but were significantly higher compared with the moderate AS and AR groups. CONCLUSIONS: MAVD patients had outcomes comparable to those with severe AS, and preserved ejection fraction and should be monitored closely for symptoms.

Native valve disease in patients with non-valvular atrial fibrillation on warfarin or rivaroxaban.

OBJECTIVE: To compare the characteristics and outcomes of patients with atrial fibrillation (AF) and aortic stenosis (AS) with patients with AF with mitral regurgitation (MR) or aortic regurgitation (AR) and patients without significant valve disease (no SVD). METHODS: Using Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) data, we analysed efficacy and safety outcomes, adjusting hazard ratios (HRs) for potential confounders using Cox regression analysis. RESULTS: Among 14 119 intention-to-treat ROCKET AF trial patients, a trial that excluded patients with mitral stenosis or artificial valve prosthesis, 214 had AS with or without other valve abnormalities, 1726 had MR or AR and 12 179 had no SVD. After adjusting for prognostic factors, the composite of stroke, systemic embolism or vascular death increased approximately twofold in patients with AS (AS 10.84, MR or AR 4.54 and no SVD 4.31 events per 100 patient-years, p=0.0001). All-cause death also significantly increased (AS 11.22, MR or AR 4.90 and no SVD 4.39 events per 100 patient-years, p=0.0003). Major bleeding occurred more frequently in AS (adjusted HR 1.61, confidence intervals (CI) 1.03 to 2.49, p<0.05) and MR or AR (HR 1.30, 1.07 to 1.57, p<0.01) than in no SVD, but there was no difference between AS and MR or AR (HR 1.24, 0.78 to 1.97). The relative efficacy of rivaroxaban versus warfarin was consistent among patients with and without valvular disease. Rivaroxaban was associated with higher rates of major bleeding than warfarin in patients with MR or AR (HR 1.63, 1.15 to 2.31). CONCLUSIONS: We found that patients with AF and AS on oral anticoagulants may have distinctly different efficacy and safety outcomes than patients with MR or AR or no SVD. TRIAL REGISTRATION NUMBER: NCT00403767; Post-results.

Clinical characteristics and outcomes with rivaroxaban vs. warfarin in patients with non-valvular atrial fibrillation but underlying native mitral and aortic valve disease participating in the ROCKET AF trial.

AIMS: We investigated clinical characteristics and outcomes of patients with significant valvular disease (SVD) in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial. METHODS AND RESULTS: ROCKET AF excluded patients with mitral stenosis or artificial valve prostheses. We used Cox regression to adjust comparisons for potential confounders. Among 14 171 patients, 2003 (14.1%) had SVD; they were older and had more comorbidities than patients without SVD. The rate of stroke or systemic embolism with rivaroxaban vs. warfarin was consistent among patients with SVD [2.01 vs. 2.43%; hazard ratio (HR) 0.83, 95% confidence interval (CI) 0.55-1.27] and without SVD (1.96 vs. 2.22%; HR 0.89, 95% CI 0.75-1.07; interaction P = 0.76). However, rates of major and non-major clinically relevant bleeding with rivaroxaban vs. warfarin were higher in patients with SVD (19.8% rivaroxaban vs. 16.8% warfarin; HR 1.25, 95% CI 1.05-1.49) vs. those without (14.2% rivaroxaban vs. 14.1% warfarin; HR 1.01, 95% CI 0.94-1.10; interaction P = 0.034), even when controlling for risk factors and potential confounders. In intracranial haemorrhage, there was no interaction between patients with and without SVD where the overall rate was lower among those randomized to rivaroxaban. CONCLUSIONS: Many patients with 'non-valvular atrial fibrillation' have significant valve lesions. Their risk of stroke is similar to that of patients without SVD after controlling for stroke risk factors. Efficacy of rivaroxaban vs. warfarin was similar in patients with and without SVD; however, the observed risk of bleeding was higher with rivaroxaban in patients with SVD but was the same among those without SVD. Atrial fibrillation patients with and without SVD experience the same stroke-preventive benefit of oral anticoagulants.

Clinical outcomes and safety of transfemoral aortic valve implantation under general versus local anesthesia: subanalysis of the French Aortic National CoreValve and Edwards 2 registry.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) performed under local anesthesia (LA) is becoming increasingly common. We aimed to compare the clinical outcomes in patients who underwent transfemoral-TAVI under general anesthesia (GA) and LA. METHODS AND RESULTS: Data from 2326 patients in the French Aortic National CoreValve and Edwards 2 (FRANCE 2) registry who underwent transfemoral-TAVI were analyzed. During the study period, the percentage of LA procedures increased gradually from 14% in January 2010 to 59% in October 2011. The clinical outcomes for GA (n=1377) and LA (n=949) were compared. Numerous baseline characteristics differed between the 2 groups, and the use of transesophageal echocardiographic guidance was more common in GA than in LA (76.3% versus 16.9%; P<0.001). Device success and cumulative 30-day survival rates were similar in the 2 groups (97.6% versus 97.0%; P=0.41 and 91.6% versus 91.3%; P=0.69, respectively), whereas the incidence of postprocedural aortic regurgitation≥mild was significantly lower in GA than in LA (15.0% versus 19.1%; P=0.015). The groups were also analyzed using a propensity-matching model, including transesophageal echocardiographic usage (GA [n=401] versus LA [n=401]). This model indicated that there were no significant differences between the 2 groups in the rates of 30-day survival (GA [91.4%] versus LA [89.3%]; P=0.27] and postprocedural aortic regurgitation≥mild (GA [12.7%] versus LA [16.2%]; P=0.19). CONCLUSIONS: The less invasive transfemoral-TAVI under LA is preferred in clinical settings and seems to be acceptable; however, the higher incidence of postprocedural aortic regurgitation is emphasized. Therapeutic efforts should be made to reduce such complications during transfemoral-TAVI under LA.

Traveling for care: inter-regional mobility for aortic valve substitution in Italy.

Patient flows across the regions of the Italian National Health Service can shed light on patient mobility, including cross-border flows within the European Union. We used 2009 data on 11,531 NHS admissions for aortic valve replacement operations to measure the extent of inter-regional patient mobility and to determine whether resident and non-resident patients differ. We also investigated whether public and private hospitals behave differently in terms of attracting patients. For this major cardio-surgical intervention, patient mobility in Italy is substantial (13.6% of total admissions). Such mobility mainly involves patients moving from southern to northern regions, which often requires several hundred kilometers of travel and a transfer of financial resources from poorer to richer regions. Patients admitted in the regions where they reside are older than those admitted outside their regions (69.2 versus 65.6, p<0.0001), and stay in hospital approximately 0.7 days longer (14.7 versus 14.0, p=0.017). Compared to public hospitals, private hospitals are more likely to admit non-resident patients (OR between 2.1 and 4.4). The extent and direction of patients' mobility raise equity concerns, as receiving care in locations that are distant from home requires substantial financial and relational resources.

Retrograde cardioplegia revisited: open technique for long aortic cross clamping.

BACKGROUND: The efficacy of retrograde cardioplegia for myocardial protection is still controversial. In our institution, we exclusively use intermittent administration of tepid, undiluted blood supplemented with potassium and magnesium for the cases with aortic insufficiency, requiring aortotomy, or undergoing mitral valve repair. In using this retrograde technique, we make a point of cannulating a retrograde perfusion catheter under direct vision following right atriotomy. The purpose of this retrospective study is to evaluate the clinical outcome of using this technique. METHODS: This study comprises 49 patients who underwent elective valve surgery using direct-vision retrograde cardioplegia exclusively, requiring more than 3h aortic cross-clamping. Their clinical outcome was reviewed retrospectively. RESULTS: There was no hospital mortality in this study. No patient was noted to have evidence of mediastinitis, myocardial infarction, or cerebral complications in the postoperative period. The case requiring the longest aortic cross-clamping time (380 min) survived the operation without the use of intra-aortic balloon pumping or percutaneous cardiopulmonary support, and the postoperative course was uneventful. CONCLUSIONS: Our result suggests that direct-vision retrograde cardioplegia is a safe and effective method of cardioplegia delivery, and provides a longer period of myocardial protection than previously thought.

Transcatheter Edwards Sapien XT valve in valve implantation in degenerated aortic bioprostheses via transfemoral access.

OBJECTIVES: Surgical treatment of degenerated aortic bioprostheses is associated with an increased risk of morbidity and mortality, especially in elderly patients with significant co-morbidities. Therefore, transcatheter aortic valve implantation (TAVI) performed as valve in valve technique appears as an attractive alternative treatment option. We report of a case series of seven patients with dysfunctional bioprosthetic aortic heart valves who have been treated with TAVI via transfemoral access. METHODS AND RESULTS: Valve in valve implantation using the Edwards Sapien XT bioprostheses (Edwards Lifesciences LLC, Irvine, CA, USA) was performed in eight patients (3 men, 5 women, mean age 85.3 ± 6.1 years) with a high operative risk (logistic euroSCORE 27.2 ± 7.3). Six patients underwent TAVI because of high grade stenosis of the aortic bioprostheses, whereas two patients presented with high grade regurgitation. All patients suffered at least from NYHA class III dyspnea during admission. TAVI was successfully performed via transfemoral access under local anesthesia with mild analgesic medication in all cases. Mild aortic regurgitation occurred in three patients while no permanent pacemaker implantation was required. Major cardiac events or cerebrovascular events did not occur. One aneurysm spurium, with the need of one blood transfusion, occurred. All patients improved at least one NYHA class within 30 days. CONCLUSION: TAVI for degenerated aortic bioprostheses, using the Edwards Sapien XT valve via transfemoral access is a feasible option for patients at high surgical risk.

Characterisation and potential diagnostic value of circulating matrix Gla protein (MGP) species.

Matrix γ-carboxyglutamate (Gla) protein (MGP) is an important local inhibitor of vascular calcification, which can undergo two post-translational modifications: vitamin K-dependent γ-glutamate carboxylation and serine phosphorylation. While carboxylation is thought to have effects upon binding of calcium-ions, phosphorylation is supposed to affect the cellular release of MGP. Since both modifications can be exerted incompletely, various MGP species can be detected in the circulation. MGP levels were measured with two commercially available competitive and two novel sandwich assays in healthy controls, in patients with rheumatic disease, aortic valve disease, and end-stage renal disease, as well as in volunteers after vitamin K supplementation (VKS) and treatment with vitamin K antagonists (VKA). Major differences were found between the MGP assays, including significantly different behaviour with regard to vascular disease and the response to VKA and VKS. The dual-antibody assay measuring non-phosphorylated, non-carboxylated MGP (dp-ucMGP) was particularly sensitive for these changes and would be suited to assess the vascular vitamin K status. We conclude that the different assays for particular circulating MGP species allows the assessment of various aspects of the MGP system.