Cost-utility of transcatheter aortic valve implantation for inoperable patients with severe aortic stenosis treated by medical management: a UK cost-utility analysis based on patient-level data from the ADVANCE study.

OBJECTIVE: To use patient-level data from the ADVANCE study to evaluate the cost-effectiveness of transcatheter aortic valve implantation (TAVI) compared to medical management (MM) in patients with severe aortic stenosis from the perspective of the UK NHS. METHODS: A published decision-analytic model was adapted to include information on TAVI from the ADVANCE study. Patient-level data informed the choice as well as the form of mathematical functions that were used to model all-cause mortality, health-related quality of life and hospitalisations. TAVI-related resource use protocols were based on the ADVANCE study. MM was modelled on publicly available information from the PARTNER-B study. The outcome measures were incremental cost-effectiveness ratios (ICERs) estimated at a range of time horizons with benefits expressed as quality-adjusted life-years (QALY). Extensive sensitivity/subgroup analyses were undertaken to explore the impact of uncertainty in key clinical areas. RESULTS: Using a 5-year time horizon, the ICER for the comparison of all ADVANCE to all PARTNER-B patients was £13 943 per QALY gained. For the subset of ADVANCE patients classified as high risk (Logistic EuroSCORE >20%) the ICER was £17 718 per QALY gained). The ICER was below £30 000 per QALY gained in all sensitivity analyses relating to choice of MM data source and alternative modelling approaches for key parameters. When the time horizon was extended to 10 years, all ICERs generated in all analyses were below £20 000 per QALY gained. CONCLUSION: TAVI is highly likely to be a cost-effective treatment for patients with severe aortic stenosis

Predictors of mortality following corevalve transcatheter aortic valve implantation: results from the ADVANCE study

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Impact of Anesthesia Type on Outcomes of Transcatheter Aortic Valve Implantation (from the Multicenter ADVANCE Study).

Transcatheter aortic valve implantation (TAVI) has become the standard of care for many patients with symptomatic severe aortic stenosis who are at increased risk of morbidity and mortality during surgical aortic valve replacement. However, there is still no general consensus regarding the use of general anesthesia (GA) versus local anesthesia with sedation (non-GA) during the TAVI procedure. Using propensity score-matching analysis, we analyzed the characteristics and outcomes of patients who underwent TAVI with either GA (n = 245) or non-GA (n = 245) in the fully monitored, international, CoreValve ADVANCE Study. No statistically significant differences existed between the non-GA and GA groups in all-cause mortality (25.4% vs 23.9%, p = 0.78), cardiovascular mortality (16.4% vs 16.6%, p = 0.92), or stroke (5.2% vs 6.9%, p = 0.57) through 2-year follow-up. Major vascular complications were more common in the non-GA group. Total hospital stay was similar between the 2 groups. Conversion from non-GA to GA occurred in 13 patients (5.3%) because of procedural complications in 9 patients and discomfort or restlessness in 4 patients. Most procedural complications were related to valve positioning or vascular issues. Two of the 13 converted patients died during the procedure. Both GA and non-GA are widely used in real-world TAVI practice, and the decision appears to be guided by only a few patient-related factors and dominated by local and national practice. The outcomes of both anesthesia modes are equally good. When conversion from non-GA did occur, the complication requiring GA affected outcomes

Five-year outcome in 18 010 patients from the German Aortic Valve Registry

OBJECTIVES: To determine the 5-year outcome in patients treated by isolated transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (sAVR)—a prospective observational cohort study. METHODS: A total of 18 010 patients were included (n = 8942 TAVI and n = 9068 sAVR) in the German Aortic Valve Registry (GARY) who were treated in 2011 and 2012 at 92 sites in central Germany. Eligible patients with TAVI and sAVR were matched using propensity scores in a nearest-neighbour approach. Patients with repeat procedures or unequivocal indication for one treatment option (e.g. frailty) were excluded (n = 4785 for TAVI and n = 2 for sAVR). This led to 13 223 patients (4157 TAVI and 9066 sAVR) as an unmatched subcohort. The main outcome measure was the 5-year all-cause mortality. RESULTS: TAVI patients were significantly older (80.9 ± 6.1 vs 68.5 ± 11.1 years, P < 0.001), had a higher Society of Thoracic Surgeons (STS) score (6.3 ± 4.9 vs 2.6 ± 3.0, P < 0.001) and a higher 5-year all-cause mortality (49.8% vs 16.5%, P < 0.0001). There was no major difference in in-hospital stroke, in-hospital myocardial infarction, or temporary and chronic dialysis. In the propensity score-matched group (n = 3640), there were 763 deaths (41.9%) among 1820 TAVI patients compared with 552 (30.3%) among 1820 treated with sAVR during the 5-year follow-up (hazard ratio 1.51, 95% confidence interval 1.35–1.68; P < 0.0001). New pacemaker implantation was performed in 448 patients (24.6%) after TAVI and in 201 (11.0%) after sAVR (P < 0.0001). CONCLUSIONS: The 5-year follow-up data show that TAVI patients were significantly older and had a higher STS score than sAVR patients. After propensity score matching, TAVI with early-generation prosthesis was associated with significantly higher 5-year all-cause mortality than sAVR

The right vertical infra-axillary incision for mitral valve replacement

<p>Abstract</p> <p>Background</p> <p>As the physiologic results of valve surgery have improved dramatically in recent years, the cosmetic effect of the procedure gains increased attention, and various alternatives to the standard median sternotomy have been developed for mitral valve surgery. We report a new minimally invasive and cosmetic approach for mitral valve replacement.</p> <p>Methods</p> <p>From December 2003 to December 2009, the right vertical infra-axillary incision (RVIAI) was employed to perform mitral valve replacement in 256 patients. 62.9% patients had replaced mechanical valve, others were bioprosthetic valve, at the same time 28.1% patients received tricuspid valvuloplasty.</p> <p>Results</p> <p>There were one hospital death in this series due to multiple organ failure, one reoperation for bleeding and one incision infection. Mean follow-up duration was 42.8 months (range, 3 to 72), and follow-up rate was 94%. There were no paravalvular leaks or late death during the follow up.</p> <p>Conclusions</p> <p>The RVIAI can be performed with favorable cosmetic and clinical results. It provides a good alternative to standard median sternotomy for MVR in selected patients.</p

Assessment of mitral bioprostheses using cardiovascular magnetic resonance

<p>Abstract</p> <p>Background</p> <p>The orifice area of mitral bioprostheses provides important information regarding their hemodynamic performance. It is usually calculated by transthoracic echocardiography (TTE), however, accurate and reproducible determination may be challenging. Cardiovascular magnetic resonance (CMR) has been proven as an accurate alternative for assessing aortic bioprostheses. However, whether CMR can be similarly applied for bioprostheses in the mitral position, particularly in the presence of frequently coincident arrhythmias, is unclear. The aim of the study is to test the feasibility of CMR to evaluate the orifice area of mitral bioprostheses.</p> <p>Methods</p> <p>CMR planimetry was performed in 18 consecutive patients with mitral bioprostheses (n = 13 Hancock^®, n = 4 Labcore^®, n = 1 Perimount^®; mean time since implantation 4.5 ± 3.9 years) in an imaging plane perpendicular to the transprosthetic flow using steady-state free-precession cine imaging under breath-hold conditions on a 1.5T MR system. CMR results were compared with pressure half-time derived orifice areas obtained by TTE.</p> <p>Results</p> <p>Six subjects were in sinus rhythm, 11 in atrial fibrillation, and 1 exhibited frequent ventricular extrasystoles. CMR image quality was rated as good in 10, moderate in 6, and significantly impaired in 2 subjects. In one prosthetic type (Perimount^®), strong stent artifacts occurred. Orifice areas by CMR (mean 2.1 ± 0.3 cm²) and TTE (mean 2.1 ± 0.3 cm²) correlated significantly (r = 0.94; p < 0.001). Bland-Altman analysis showed a 95% confidence interval from -0.16 to 0.28 cm²(mean difference 0.06 ± 0.11 cm²; range -0.1 to 0.3 cm²). Intra- and inter-observer variabilities of CMR planimetry were 4.5 ± 2.9% and 7.9 ± 5.2%.</p> <p>Conclusions</p> <p>The assessment of mitral bioprostheses using CMR is feasible even in those with arrhythmias, providing orifice areas with close agreement to echocardiography and low observer dependency. Larger samples with a greater variety of prosthetic types and more cases of prosthetic dysfunction are required to confirm these preliminary results.</p

Transcatheter aortic valve implantation in failed bioprosthetic surgical valves.

IMPORTANCE: Owing to a considerable shift toward bioprosthesis implantation rather than mechanical valves, it is expected that patients will increasingly present with degenerated bioprostheses in the next few years. Transcatheter aortic valve-in-valve implantation is a less invasive approach for patients with structural valve deterioration; however, a comprehensive evaluation of survival after the procedure has not yet been performed. OBJECTIVE: To determine the survival of patients after transcatheter valve-in-valve implantation inside failed surgical bioprosthetic valves. DESIGN, SETTING, AND PARTICIPANTS: Correlates for survival were evaluated using a multinational valve-in-valve registry that included 459 patients with degenerated bioprosthetic valves undergoing valve-in-valve implantation between 2007 and May 2013 in 55 centers (mean age, 77.6 [SD, 9.8] years; 56% men; median Society of Thoracic Surgeons mortality prediction score, 9.8% [interquartile range, 7.7%-16%]). Surgical valves were classified as small (≤21 mm; 29.7%), intermediate (&gt;21 and &lt;25 mm; 39.3%), and large (≥25 mm; 31%). Implanted devices included both balloon- and self-expandable valves. MAIN OUTCOMES AND MEASURES: Survival, stroke, and New York Heart Association functional class. RESULTS: Modes of bioprosthesis failure were stenosis (n = 181 [39.4%]), regurgitation (n = 139 [30.3%]), and combined (n = 139 [30.3%]). The stenosis group had a higher percentage of small valves (37% vs 20.9% and 26.6% in the regurgitation and combined groups, respectively; P = .005). Within 1 month following valve-in-valve implantation, 35 (7.6%) patients died, 8 (1.7%) had major stroke, and 313 (92.6%) of surviving patients had good functional status (New York Heart Association class I/II). The overall 1-year Kaplan-Meier survival rate was 83.2% (95% CI, 80.8%-84.7%; 62 death events; 228 survivors). Patients in the stenosis group had worse 1-year survival (76.6%; 95% CI, 68.9%-83.1%; 34 deaths; 86 survivors) in comparison with the regurgitation group (91.2%; 95% CI, 85.7%-96.7%; 10 deaths; 76 survivors) and the combined group (83.9%; 95% CI, 76.8%-91%; 18 deaths; 66 survivors) (P = .01). Similarly, patients with small valves had worse 1-year survival (74.8% [95% CI, 66.2%-83.4%]; 27 deaths; 57 survivors) vs with intermediate-sized valves (81.8%; 95% CI, 75.3%-88.3%; 26 deaths; 92 survivors) and with large valves (93.3%; 95% CI, 85.7%-96.7%; 7 deaths; 73 survivors) (P = .001). Factors associated with mortality within 1 year included having small surgical bioprosthesis (≤21 mm; hazard ratio, 2.04; 95% CI, 1.14-3.67; P = .02) and baseline stenosis (vs regurgitation; hazard ratio, 3.07; 95% CI, 1.33-7.08; P = .008). CONCLUSIONS AND RELEVANCE: In this registry of patients who underwent transcatheter valve-in-valve implantation for degenerated bioprosthetic aortic valves, overall 1-year survival was 83.2%. Survival was lower among patients with small bioprostheses and those with predominant surgical valve stenosis

A molecular mechanism for the enzymatic methylation of nitrogen atoms within peptide bonds

This work was financially supported by ETH Zürich, University of Minnesota, the Swiss National Science Foundation (grant nos. 31003A_149512 and 200021–159713), Wellcome Trust (094476/Z/10/Z), ERC (NCB-TNT 339367), and BBSRC (BB/R018189/1).The peptide bond, the defining feature of proteins, governs peptide chemistry by abolishing nucleophilicity of the nitrogen. This and the planarity of the peptide bond arise from the delocalization of the lone pair of electrons on the nitrogen atom into the adjacent carbonyl. While chemical methylation of an amide bond uses a strong base to generate the imidate, OphA, the precursor protein of the fungal peptide macrocycle omphalotin A, self-hypermethylates amides at pH 7 using S-adenosyl methionine (SAM) as cofactor. The structure of OphA reveals a complex catenane-like arrangement in which the peptide substrate is clamped with its amide nitrogen aligned for nucleophilic attack on the methyl group of SAM. Biochemical data and computational modeling suggest a base-catalyzed reaction with the protein stabilizing the reaction intermediate. Backbone N-methylation of peptides enhances their protease resistance and membrane permeability, a property that holds promise for applications to medicinal chemistry.Publisher PDFPeer reviewe

Transapical mitral valve implantation for treatment of symptomatic mitral valve disease: a real-world multicentre experience.

AIMS Transcatheter mitral valve implantation (TMVI) is a new treatment option for patients with symptomatic mitral valve (MV) disease. Real-world data have not yet been reported. This study aimed to assess procedural and 30-day outcomes of TMVI in a real-world patient cohort. METHOD AND RESULTS All consecutive patients undergoing implantation of a transapically delivered self-expanding valve at 26 European centres from January 2020 to April 2021 were included in this retrospective observational registry. Among 108 surgical high-risk patients included (43% female, mean age 75 ± 7 years, mean STS-PROM 7.2 ± 5.3%), 25% was treated for an off-label indication (e.g. previous MV intervention or surgery, mitral stenosis, mitral annular calcification). Patients were highly symptomatic (New York Heart Association [NYHA] functional class III/IV in 86%) and mitral regurgitation (MR) was graded 3+/4+ in 95% (38% primary, 37% secondary, and 25% mixed aetiology). Technical success rate was 96%, and MR reduction to ≤1+ was achieved in all patients with successful implantation. There were two procedural deaths and 30-day all-cause mortality was 12%. At early clinical follow-up, MR reduction was sustained and there were significant reductions of pulmonary pressure (systolic pulmonary artery pressure 52 vs. 42 mmHg, p < 0.001), and tricuspid regurgitation severity (p = 0.013). Heart failure symptoms improved significantly (73% in NYHA class I/II, p < 0.001). Procedural success rate according to MVARC criteria was 80% and was not different in patients treated for an off-label indication (74% vs. 81% for off- vs. on-label, p = 0.41). CONCLUSION In a real-world patient population, TMVI has a high technical and procedural success rate with efficient and durable MR reduction and symptomatic improvement