Self-Expanding or Balloon-Expandable TAVR in Patients with a Small Aortic Annulus.

BACKGROUND: Patients with severe aortic stenosis and a small aortic annulus are at risk for impaired valvular hemodynamic performance and associated adverse cardiovascular clinical outcomes after transcatheter aortic-valve replacement (TAVR). METHODS: We randomly assigned patients with symptomatic severe aortic stenosis and an aortic-valve annulus area of 430 mm2 or less in a 1:1 ratio to undergo TAVR with either a self-expanding supraannular valve or a balloon-expandable valve. The coprimary end points, each assessed through 12 months, were a composite of death, disabling stroke, or rehospitalization for heart failure (tested for noninferiority) and a composite end point measuring bioprosthetic-valve dysfunction (tested for superiority). RESULTS: A total of 716 patients were treated at 83 sites in 13 countries (mean age, 80 years; 87% women; mean Society of Thoracic Surgeons Predicted Risk of Mortality, 3.3%). The Kaplan-Meier estimate of the percentage of patients who died, had a disabling stroke, or were rehospitalized for heart failure through 12 months was 9.4% with the self-expanding valve and 10.6% with the balloon-expandable valve (difference, -1.2 percentage points; 90% confidence interval [CI], -4.9 to 2.5; P<0.001 for noninferiority). The Kaplan-Meier estimate of the percentage of patients with bioprosthetic-valve dysfunction through 12 months was 9.4% with the self-expanding valve and 41.6% with the balloon-expandable valve (difference, -32.2 percentage points; 95% CI, -38.7 to -25.6; P<0.001 for superiority). The aortic-valve mean gradient at 12 months was 7.7 mm Hg with the self-expanding valve and 15.7 mm Hg with the balloon-expandable valve, and the corresponding values for additional secondary end points through 12 months were as follows: mean effective orifice area, 1.99 cm2 and 1.50 cm2; percentage of patients with hemodynamic structural valve dysfunction, 3.5% and 32.8%; and percentage of women with bioprosthetic-valve dysfunction, 10.2% and 43.3% (all P<0.001). Moderate or severe prosthesis-patient mismatch at 30 days was found in 11.2% of the patients in the self-expanding valve group and 35.3% of those in the balloon-expandable valve group (P<0.001). Major safety end points appeared to be similar in the two groups. CONCLUSIONS: Among patients with severe aortic stenosis and a small aortic annulus who underwent TAVR, a self-expanding supraannular valve was noninferior to a balloon-expandable valve with respect to clinical outcomes and was superior with respect to bioprosthetic-valve dysfunction through 12 months. (Funded by Medtronic; SMART ClinicalTrials.gov number, NCT04722250.).

Transcatheter or Surgical Treatment of Aortic-Valve Stenosis.

BACKGROUND: Among low-risk patients with severe, symptomatic aortic stenosis who are eligible for both transcatheter aortic-valve implantation (TAVI) and surgical aortic-valve replacement (SAVR), data are lacking on the appropriate treatment strategy in routine clinical practice. METHODS: In this randomized noninferiority trial conducted at 38 sites in Germany, we assigned patients with severe aortic stenosis who were at low or intermediate surgical risk to undergo either TAVI or SAVR. Percutaneous- and surgical-valve prostheses were selected according to operator discretion. The primary outcome was a composite of death from any cause or fatal or nonfatal stroke at 1 year. RESULTS: A total of 1414 patients underwent randomization (701 to the TAVI group and 713 to the SAVR group). The mean (±SD) age of the patients was 74±4 years; 57% were men, and the median Society of Thoracic Surgeons risk score was 1.8% (low surgical risk). The Kaplan-Meier estimate of the primary outcome at 1 year was 5.4% in the TAVI group and 10.0% in the SAVR group (hazard ratio for death or stroke, 0.53; 95% confidence interval [CI], 0.35 to 0.79; P<0.001 for noninferiority). The incidence of death from any cause was 2.6% in the TAVI group and 6.2% in the SAVR group (hazard ratio, 0.43; 95% CI, 0.24 to 0.73); the incidence of stroke was 2.9% and 4.7%, respectively (hazard ratio, 0.61; 95% CI, 0.35 to 1.06). Procedural complications occurred in 1.5% and 1.0% of patients in the TAVI and SAVR groups, respectively. CONCLUSIONS: Among patients with severe aortic stenosis at low or intermediate surgical risk, TAVI was noninferior to SAVR with respect to death from any cause or stroke at 1 year. (Funded by the German Center for Cardiovascular Research and the German Heart Foundation; DEDICATE-DZHK6 ClinicalTrials.gov number, NCT03112980.).

Transcatheter Aortic-Valve Replacement in Low-Risk Patients at Five Years.

BACKGROUND: A previous analysis in this trial showed that among patients with severe, symptomatic aortic stenosis who were at low surgical risk, the rate of the composite end point of death, stroke, or rehospitalization at 1 year was significantly lower with transcatheter aortic-valve replacement (TAVR) than with surgical aortic-valve replacement. Longer-term outcomes are unknown. METHODS: We randomly assigned patients with severe, symptomatic aortic stenosis and low surgical risk to undergo either TAVR or surgery. The first primary end point was a composite of death, stroke, or rehospitalization related to the valve, the procedure, or heart failure. The second primary end point was a hierarchical composite that included death, disabling stroke, nondisabling stroke, and the number of rehospitalization days, analyzed with the use of a win ratio analysis. Clinical, echocardiographic, and health-status outcomes were assessed through 5 years. RESULTS: A total of 1000 patients underwent randomization: 503 patients were assigned to undergo TAVR, and 497 to undergo surgery. A component of the first primary end point occurred in 111 of 496 patients in the TAVR group and in 117 of 454 patients in the surgery group (Kaplan-Meier estimates, 22.8% in the TAVR group and 27.2% in the surgery group; difference, -4.3 percentage points; 95% confidence interval [CI], -9.9 to 1.3; P = 0.07). The win ratio for the second primary end point was 1.17 (95% CI, 0.90 to 1.51; P = 0.25). The Kaplan-Meier estimates for the components of the first primary end point were as follows: death, 10.0% in the TAVR group and 8.2% in the surgery group; stroke, 5.8% and 6.4%, respectively; and rehospitalization, 13.7% and 17.4%. The hemodynamic performance of the valve, assessed according to the mean (±SD) valve gradient, was 12.8±6.5 mm Hg in the TAVR group and 11.7±5.6 mm Hg in the surgery group. Bioprosthetic-valve failure occurred in 3.3% of the patients in the TAVR group and in 3.8% of those in the surgery group. CONCLUSIONS: Among low-risk patients with severe, symptomatic aortic stenosis who underwent TAVR or surgery, there was no significant between-group difference in the two primary composite outcomes. (Funded by Edwards Lifesciences; PARTNER 3 ClinicalTrials.gov number, NCT02675114.).

Bioprosthetic heart valve structural degeneration associated with metabolic syndrome: Mitigation with polyoxazoline modification.

Bioprosthetic heart valves (BHV), made from glutaraldehyde-fixed xenografts, are widely used for surgical and transcatheter valve interventions but suffer from limited durability due to structural valve degeneration (SVD). We focused on metabolic syndrome (MetS), a risk factor for SVD and a highly prevalent phenotype in patients affected by valvular heart disease with a well-recognized cluster of comorbidities. Multicenter patient data (N = 251) revealed that patients with MetS were at significantly higher risk of accelerated SVD and required BHV replacement sooner. Using a next-generation proteomics approach, we identified significantly differential proteomes from leaflets of explanted BHV from MetS and non-MetS patients (N = 24). Given the significance of protein infiltration in MetS-induced SVD, we then demonstrated the protective effects of polyoxazoline modification of BHV leaflets to mitigate MetS-induced BHV biomaterial degeneration (calcification, tissue cross-linking, and microstructural changes) in an ex vivo serum model and an in vivo with MetS rat subcutaneous implants.

Transcatheter or Surgical Aortic Valve Replacement in Patients With Severe Aortic Stenosis and Small Aortic Annulus: A Randomized Clinical Trial.

BACKGROUND: The optimal treatment in patients with severe aortic stenosis and small aortic annulus (SAA) remains to be determined. This study aimed to compare the hemodynamic and clinical outcomes between transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) in patients with a SAA. METHODS: This prospective multicenter international randomized trial was performed in 15 university hospitals. Participants were 151 patients with severe aortic stenosis and SAA (mean diameter <23 mm) randomized (1:1) to TAVR (n=77) versus SAVR (n=74). The primary outcome was impaired valve hemodynamics (ie, severe prosthesis patient mismatch or moderate-severe aortic regurgitation) at 60 days as evaluated by Doppler echocardiography and analyzed in a central echocardiography core laboratory. Clinical events were secondary outcomes. RESULTS: The mean age of the participants was 75.5±5.1 years, with 140 (93%) women, a median Society of Thoracic Surgeons predicted risk of mortality of 2.50% (interquartile range, 1.67%-3.28%), and a median annulus diameter of 21.1 mm (interquartile range, 20.4-22.0 mm). There were no differences between groups in the rate of severe prosthesis patient mismatch (TAVR, 4 [5.6%]; SAVR, 7 [10.3%]; P=0.30) and moderate-severe aortic regurgitation (none in both groups). No differences were found between groups in mortality rate (TAVR, 1 [1.3%]; SAVR, 1 [1.4%]; P=1.00) and stroke (TAVR, 0; SAVR, 2 [2.7%]; P=0.24) at 30 days. After a median follow-up of 2 (interquartile range, 1-4) years, there were no differences between groups in mortality rate (TAVR, 7 [9.1%]; SAVR, 6 [8.1%]; P=0.89), stroke (TAVR, 3 [3.9%]; SAVR, 3 [4.1%]; P=0.95), and cardiac hospitalization (TAVR, 15 [19.5%]; SAVR, 15 [20.3%]; P=0.80). CONCLUSIONS: In patients with severe aortic stenosis and SAA (women in the majority), there was no evidence of superiority of contemporary TAVR versus SAVR in valve hemodynamic results. After a median follow-up of 2 years, there were no differences in clinical outcomes between groups. These findings suggest that the 2 therapies represent a valid alternative for treating patients with severe aortic stenosis and SAA, and treatment selection should likely be individualized according to baseline characteristics, additional anatomical risk factors, and patient preference. However, the results of this study should be interpreted with caution because of the limited sample size leading to an underpowered study, and need to be confirmed in future larger studies. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03383445.

LANDMARK comparison of early outcomes of newer-generation Myval transcatheter heart valve series with contemporary valves (Sapien and Evolut) in real-world individuals with severe symptomatic native aortic stenosis: a randomised non-inferiority trial.

BACKGROUND: Transcatheter aortic valve implantation is an established, guideline-endorsed treatment for severe aortic stenosis. Precise sizing of the balloon-expandable Myval transcatheter heart valve (THV) series with the aortic annulus is facilitated by increasing its diameter in 1·5 mm increments, compared with the usual 3 mm increments in valve size. The LANDMARK trial aimed to show non-inferiority of the Myval THV series compared with the contemporary THVs Sapien Series (Edwards Lifesciences, Irvine, CA, USA) or Evolut Series (Medtronic, Minneapolis, MN, USA). METHODS: In this prospective, multinational, randomised, open-label, non-inferiority trial across 31 hospitals in 16 countries (Germany, France, Sweden, the Netherlands, Italy, Spain, New Zealand, Portugal, Greece, Hungary, Poland, Slovakia, Slovenia, Croatia, Estonia, and Brazil), 768 participants with severe symptomatic native aortic stenosis were randomly assigned (1:1) to the Myval THV or a contemporary THV. Eligibility was primarily decided by the heart team in accordance with 2021 European Society of Cardiology guidelines. As per the criteria of the third Valve Academic Research Consortium, the primary endpoint at 30 days was a composite of all-cause mortality, all stroke, bleeding (types 3 and 4), acute kidney injury (stages 2-4), major vascular complications, moderate or severe prosthetic valve regurgitation, and conduction system disturbances resulting in a permanent pacemaker implantation. Non-inferiority of the study device was tested in the intention-to-treat population using a non-inferiority margin of 10·44% and assuming an event rate of 26·10%. This trial is registered with ClinicalTrials.gov, NCT04275726, and EudraCT, 2020-000137-40, and is closed to new participants. FINDINGS: Between Jan 6, 2021, and Dec 5, 2023, 768 participants with severe symptomatic native aortic stenosis were randomly assigned, 384 to the Myval THV and 384 to a contemporary THV. 369 (48%) participants had their sex recorded as female, and 399 (52%) as male. The mean age of participants was 80·0 years (SD 5·7) for those treated with the Myval THV and 80·4 years (5·4) for those treated with a contemporary THV. Median Society of Thoracic Surgeons scores were the same in both groups (Myval 2·6% [IQR 1·7-4·0] vs contemporary 2·6% [1·7-4·0]). The primary endpoint showed non-inferiority of the Myval (25%) compared with contemporary THV (27%), with a risk difference of -2·3% (one-sided upper 95% CI 3·8, pnon-inferiority<0·0001). No significant difference was seen in individual components of the primary composite endpoint. INTERPRETATION: In individuals with severe symptomatic native aortic stenosis, the Myval THV met its primary endpoint at 30 days. FUNDING: Meril Life Sciences.

Transcatheter aortic valve implantation in patients with high-risk symptomatic native aortic regurgitation (ALIGN-AR): a prospective, multicentre, single-arm study.

BACKGROUND: Surgery remains the only recommended intervention for patients with native aortic regurgitation. A transcatheter therapy to treat patients at high risk for mortality and complications with surgical aortic valve replacement represents an unmet need. Commercial transcatheter heart valves in pure aortic regurgitation are hampered by unacceptable rates of embolisation and paravalvular regurgitation. The Trilogy transcatheter heart valve (JenaValve Technology, Irvine, CA, USA) provides a treatment option for these patients. We report outcomes with transfemoral transcatheter aortic valve implantation (TAVI) in patients with pure aortic regurgitation using this dedicated transcatheter heart valve. METHODS: The ALIGN-AR trial is a prospective, multicentre, single-arm study. We recruited symptomatic patients (aged ≥18 years) with moderate-to-severe or severe aortic regurgitation at high risk for mortality and complications after surgical aortic valve replacement at 20 US sites for treatment with the Trilogy transcatheter heart valve. The 30-day composite primary safety endpoint was compared for non-inferiority with a prespecified performance goal of 40·5%. The primary efficacy endpoint was 1-year all-cause mortality compared for non-inferiority with a performance goal of 25%. This trial is registered with ClinicalTrials.gov, NCT04415047, and is ongoing. FINDINGS: Between June 8, 2018, and Aug 29, 2022, we screened 346 patients. We excluded 166 (48%) patients and enrolled 180 (52%) patients with symptomatic aortic regurgitation deemed high risk by the heart team and independent screening committee assessments. The mean age of the study population was 75·5 years (SD 10·8), and 85 (47%) were female, 95 (53%) were male, and 131 (73%) were White. Technical success was achieved in 171 (95%) patients. At 30 days, four (2%) deaths, two (1%) disabling strokes, and two (1%) non-disabling strokes occurred. Using standard Valve Academic Research Consortium-2 definitions, the primary safety endpoint was achieved, with events occurring in 48 (27% [97·5% CI 19·2-34·0]) patients (pnon-inferiority<0·0001), with new pacemaker implantation in 36 (24%) patients. The primary efficacy endpoint was achieved, with mortality in 14 (7·8% [3·3-12·3]) patients at 1 year (pnon-inferiority<0·0001). INTERPRETATION: This study shows the safety and effectiveness of treating native aortic regurgitation using a dedicated transcatheter heart valve to treat patients with symptomatic moderate-to-severe or severe aortic regurgitation who are at high risk for mortality or complications after surgical aortic valve replacement. The observed short-term clinical and haemodynamic outcomes are promising as are signs of left ventricular remodelling, but long-term follow-up is necessary. FUNDING: JenaValve Technology.

Poly-2-methyl-2-oxazoline-modified bioprosthetic heart valve leaflets have enhanced biocompatibility and resist structural degeneration.

Bioprosthetic heart valves (BHV) fabricated from glutaraldehyde-fixed heterograft tissue, such as bovine pericardium (BP), are widely used for treating heart valve disease, a group of disorders that affects millions. Structural valve degeneration (SVD) of BHV due to both calcification and the accumulation of advanced glycation end products (AGE) with associated serum proteins limits durability. We hypothesized that BP modified with poly-2-methyl-2-oxazoline (POZ) to inhibit protein entry would demonstrate reduced accumulation of AGE and serum proteins, mitigating SVD. In vitro studies of POZ-modified BP demonstrated reduced accumulation of serum albumin and AGE. BP-POZ in vitro maintained collagen microarchitecture per two-photon microscopy despite AGE incubation, and in cell culture studies was associated with no change in tumor necrosis factor-α after exposure to AGE and activated macrophages. Comparing POZ and polyethylene glycol (PEG)-modified BP in vitro, BP-POZ was minimally affected by oxidative conditions, whereas BP-PEG was susceptible to oxidative deterioration. In juvenile rat subdermal implants, BP-POZ demonstrated reduced AGE formation and serum albumin infiltration, while calcification was not inhibited. However, BP-POZ rat subdermal implants with ethanol pretreatment demonstrated inhibition of both AGE accumulation and calcification. Ex vivo laminar flow studies with human blood demonstrated BP-POZ enhanced thromboresistance with reduced white blood cell accumulation. We conclude that SVD associated with AGE and serum protein accumulation can be mitigated through POZ functionalization that both enhances biocompatibility and facilitates ethanol pretreatment inhibition of BP calcification.

Outcomes of transcatheter pulmonary SAPIEN 3 valve implantation: an international registry.

BACKGROUND AND AIMS: Transcatheter pulmonary valve implantation (TPVI) is indicated to treat right-ventricular outflow tract (RVOT) dysfunction related to congenital heart disease (CHD). Outcomes of TPVI with the SAPIEN 3 valve that are insufficiently documented were investigated in the EUROPULMS3 registry of SAPIEN 3-TPVI. METHODS: Patient-related, procedural, and follow-up outcome data were retrospectively assessed in this observational cohort from 35 centres in 15 countries. RESULTS: Data for 840 consecutive patients treated in 2014-2021 at a median age of 29.2 (19.0-41.6) years were obtained. The most common diagnosis was conotruncal defect (70.5%), with a native or patched RVOT in 50.7% of all patients. Valve sizes were 20, 23, 26, and 29 mm in 0.4%, 25.5%, 32.1%, and 42.0% of patients, respectively. Valve implantation was successful in 98.5% [95% confidence interval (CI), 97.4%-99.2%] of patients. Median follow-up was 20.3 (7.1-38.4) months. Eight patients experienced infective endocarditis; 11 required pulmonary valve replacement, with a lower incidence for larger valves (P = .009), and four experienced pulmonary valve thrombosis, including one who died and three who recovered with anticoagulation. Cumulative incidences (95%CI) 1, 3, and 6 years after TPVI were as follows: infective endocarditis, 0.5% (0.0%-1.0%), 0.9% (0.2%-1.6%), and 3.8% (0.0%-8.4%); pulmonary valve replacement, 0.4% (0.0%-0.8%), 1.3% (0.2%-2.4%), and 8.0% (1.2%-14.8%); and pulmonary valve thrombosis, 0.4% (0.0%-0.9%), 0.7% (0.0%-1.3%), and 0.7% (0.0%-1.3%), respectively. CONCLUSIONS: Outcomes of SAPIEN 3 TPVI were favourable in patients with CHD, half of whom had native or patched RVOTs.

Leaflet modification before transcatheter aortic valve implantation in patients at risk for coronary obstruction: the ShortCut study.

BACKGROUND AND AIMS: This trial sought to assess the safety and efficacy of ShortCut, the first dedicated leaflet modification device, prior to transcatheter aortic valve implantation (TAVI) in patients at risk for coronary artery obstruction. METHODS: This pivotal prospective study enrolled patients with failed bioprosthetic aortic valves scheduled to undergo TAVI and were at risk for coronary artery obstruction. The primary safety endpoint was procedure-related mortality or stroke at discharge or 7 days, and the primary efficacy endpoint was per-patient leaflet splitting success. Independent angiographic, echocardiographic, and computed tomography core laboratories assessed all images. Safety events were adjudicated by a clinical events committee and data safety monitoring board. RESULTS: Sixty eligible patients were treated (77.0 ± 9.6 years, 70% female, 96.7% failed surgical bioprosthetic valves, 63.3% single splitting and 36.7% dual splitting) at 22 clinical sites. Successful leaflet splitting was achieved in all [100%; 95% confidence interval (CI) 94%-100.0%, P < .001] patients. Procedure time, including imaging confirmation of leaflet splitting, was 30.6 ± 17.9 min. Freedom from the primary safety endpoint was achieved in 59 [98.3%; 95% CI (91.1%-100%)] patients, with no mortality and one (1.7%) disabling stroke. At 30 days, freedom from coronary obstruction was 95% (95% CI 86.1%-99.0%). Within 90 days, freedom from mortality was 95% [95% CI (86.1%-99.0%)], without any cardiovascular deaths. CONCLUSIONS: Modification of failed bioprosthetic aortic valve leaflets using ShortCut was safe, achieved successful leaflet splitting in all patients, and was associated with favourable clinical outcomes in patients at risk for coronary obstruction undergoing TAVI.

Transcatheter heart valve explant with infective endocarditis-associated prosthesis failure and outcomes: the EXPLANT-TAVR international registry.

BACKGROUND AND AIMS: Surgical explantation of transcatheter heart valves (THVs) is rapidly increasing, but there are limited data on patients with THV-associated infective endocarditis (IE). This study aims to assess the outcomes of patients undergoing THV explant for IE. METHODS: All patients who underwent THV explant between 2011 and 2022 from 44 sites in the EXPLANT-TAVR registry were identified. Patients with IE as the reason for THV explant were compared to those with other mechanisms of bioprosthetic valve dysfunction (BVD). RESULTS: A total of 372 patients from the EXPLANT-TAVR registry were included. Among them, 184 (49.5%) patients underwent THV explant due to IE and 188 (50.5%) patients due to BVD. At the index transcatheter aortic valve replacement, patients undergoing THV explant for IE were older (74.3 ± 8.6 vs. 71 ± 10.6 years) and had a lower Society of Thoracic Surgeons risk score [2.6% (1.8-5.0) vs. 3.3% (2.1-5.6), P = .029] compared to patients with BVD. Compared to BVD, IE patients had longer intensive care unit and hospital stays (P < .05) and higher stroke rates at 30 days (8.6% vs. 2.9%, P = .032) and 1 year (16.2% vs. 5.2%, P = .010). Adjusted in-hospital, 30-day, and 1-year mortality was 12.1%, 16.1%, and 33.8%, respectively, for the entire cohort, with no significant differences between groups. Although mortality was numerically higher in IE patients 3 years postsurgery (29.6% for BVD vs. 43.9% for IE), Kaplan-Meier analysis showed no significant differences between groups (P = .16). CONCLUSIONS: In the EXPLANT-TAVR registry, patients undergoing THV explant for IE had higher 30-day and 1-year stroke rates and longer intensive care unit and hospital stays. Moreover, patients undergoing THV explant for IE had a higher 3-year mortality rate, which did not reach statistical significance given the relatively small sample size of this unique cohort and the reduced number of events.

Transcatheter or surgical aortic valve implantation: 10-year outcomes of the NOTION trial.

BACKGROUND AND AIMS: Transcatheter aortic valve implantation (TAVI) has become a viable treatment option for patients with severe aortic valve stenosis across a broad range of surgical risk. The Nordic Aortic Valve Intervention (NOTION) trial was the first to randomize patients at lower surgical risk to TAVI or surgical aortic valve replacement (SAVR). The aim of the present study was to report clinical and bioprosthesis outcomes after 10 years. METHODS: The NOTION trial randomized 280 patients to TAVI with the self-expanding CoreValve (Medtronic Inc.) bioprosthesis (n = 145) or SAVR with a bioprosthesis (n = 135). The primary composite outcome was the risk of all-cause mortality, stroke, or myocardial infarction. Bioprosthetic valve dysfunction (BVD) was classified as structural valve deterioration (SVD), non-structural valve dysfunction (NSVD), clinical valve thrombosis, or endocarditis according to Valve Academic Research Consortium-3 criteria. Severe SVD was defined as (i) a transprosthetic gradient of 30 mmHg or more and an increase in transprosthetic gradient of 20 mmHg or more or (ii) severe new intraprosthetic regurgitation. Bioprosthetic valve failure (BVF) was defined as the composite rate of death from a valve-related cause or an unexplained death following the diagnosis of BVD, aortic valve re-intervention, or severe SVD. RESULTS: Baseline characteristics were similar between TAVI and SAVR: age 79.2 ± 4.9 years and 79.0 ± 4.7 years (P = .7), male 52.6% and 53.8% (P = .8), and Society of Thoracic Surgeons score < 4% of 83.4% and 80.0% (P = .5), respectively. After 10 years, the risk of the composite outcome all-cause mortality, stroke, or myocardial infarction was 65.5% after TAVI and 65.5% after SAVR [hazard ratio (HR) 1.0; 95% confidence interval (CI) 0.7-1.3; P = .9], with no difference for each individual outcome. Severe SVD had occurred in 1.5% and 10.0% (HR 0.2; 95% CI 0.04-0.7; P = .02) after TAVI and SAVR, respectively. The cumulative incidence for severe NSVD was 20.5% and 43.0% (P < .001) and for endocarditis 7.2% and 7.4% (P = 1.0) after TAVI and SAVR, respectively. No patients had clinical valve thrombosis. Bioprosthetic valve failure occurred in 9.7% of TAVI and 13.8% of SAVR patients (HR 0.7; 95% CI 0.4-1.5; P = .4). CONCLUSIONS: In patients with severe AS and lower surgical risk randomized to TAVI or SAVR, the risk of major clinical outcomes was not different 10 years after treatment. The risk of severe bioprosthesis SVD was lower after TAVR compared with SAVR, while the risk of BVF was similar.

Cardiac Magnetic Resonance Imaging Versus Computed Tomography to Guide Transcatheter Aortic Valve Replacement: A Randomized, Open-Label, Noninferiority Trial.

BACKGROUND: Computed tomography (CT) is recommended for guiding transcatheter aortic valve replacement (TAVR). However, a sizable proportion of TAVR candidates have chronic kidney disease, in whom the use of iodinated contrast media is a limitation. Cardiac magnetic resonance imaging (CMR) is a promising alternative, but randomized data comparing the effectiveness of CMR-guided versus CT-guided TAVR are lacking. METHODS: An investigator-initiated, prospective, randomized, open-label, noninferiority trial was conducted at 2 Austrian heart centers. Patients evaluated for TAVR according to the inclusion criteria (severe symptomatic aortic stenosis) and exclusion criteria (contraindication to CMR, CT, or TAVR, a life expectancy <1 year, or chronic kidney disease level 4 or 5) were randomized (1:1) to undergo CMR or CT guiding. The primary outcome was defined according to the Valve Academic Research Consortium-2 definition of implantation success at discharge, including absence of procedural mortality, correct positioning of a single prosthetic valve, and proper prosthetic valve performance. Noninferiority was assessed using a hybrid modified intention-to-treat/per-protocol approach on the basis of an absolute risk difference margin of 9%. RESULTS: Between September 11, 2017, and December 16, 2022, 380 candidates for TAVR were randomized to CMR-guided (191 patients) or CT-guided (189 patients) TAVR planning. Of these, 138 patients (72.3%) in the CMR-guided group and 129 patients (68.3%) in the CT-guided group eventually underwent TAVR (modified intention-to-treat cohort). Of these 267, 19 patients had protocol deviations, resulting in a per-protocol cohort of 248 patients (121 CMR-guided, 127 CT-guided). In the modified intention-to-treat cohort, implantation success was achieved in 129 patients (93.5%) in the CMR group and in 117 patients (90.7%) in the CT group (between-group difference, 2.8% [90% CI, -2.7% to 8.2%]; P<0.01 for noninferiority). In the per-protocol cohort (n=248), the between-group difference was 2.0% (90% CI, -3.8% to 7.8%; P<0.01 for noninferiority). CONCLUSIONS: CMR-guided TAVR was noninferior to CT-guided TAVR in terms of device implantation success. CMR can therefore be considered as an alternative for TAVR planning. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03831087.

Evaluation of the 2023 Duke-International Society of Cardiovascular Infectious Diseases Criteria in a Multicenter Cohort of Patients With Suspected Infective Endocarditis.

BACKGROUND: Since publication of Duke criteria for infective endocarditis (IE) diagnosis, several modifications have been proposed. We aimed to evaluate the diagnostic performance of the Duke-ISCVID (International Society of Cardiovascular Infectious Diseases) 2023 criteria compared to prior versions from 2000 (Duke-Li 2000) and 2015 (Duke-ESC [European Society for Cardiology] 2015). METHODS: This study was conducted at 2 university hospitals between 2014 and 2022 among patients with suspected IE. A case was classified as IE (final IE diagnosis) by the Endocarditis Team. Sensitivity for each version of the Duke criteria was calculated among patients with confirmed IE based on pathological, surgical, and microbiological data. Specificity for each version of the Duke criteria was calculated among patients with suspected IE for whom IE diagnosis was ruled out. RESULTS: In total, 2132 episodes with suspected IE were included, of which 1101 (52%) had final IE diagnosis. Definite IE by pathologic criteria was found in 285 (13%), 285 (13%), and 345 (16%) patients using the Duke-Li 2000, Duke-ESC 2015, or the Duke-ISCVID 2023 criteria, respectively. IE was excluded by histopathology in 25 (1%) patients. The Duke-ISCVID 2023 clinical criteria showed a higher sensitivity (84%) compared to previous versions (70%). However, specificity of the new clinical criteria was lower (60%) compared to previous versions (74%). CONCLUSIONS: The Duke-ISCVID 2023 criteria led to an increase in sensitivity compared to previous versions. Further studies are needed to evaluate items that could increase sensitivity by reducing the number of IE patients misclassified as possible, but without having detrimental effect on specificity of Duke criteria.

Infective Endocarditis After Transcatheter Versus Surgical Aortic Valve Replacement.

BACKGROUND: Scarce data are available comparing infective endocarditis (IE) following surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR). This study aimed to compare the clinical presentation, microbiological profile, management, and outcomes of IE after SAVR versus TAVR. METHODS: Data were collected from the "Infectious Endocarditis after TAVR International" (enrollment from 2005 to 2020) and the "International Collaboration on Endocarditis" (enrollment from 2000 to 2012) registries. Only patients with an IE affecting the aortic valve prosthesis were included. A 1:1 paired matching approach was used to compare patients with TAVR and SAVR. RESULTS: A total of 1688 patients were included. Of them, 602 (35.7%) had a surgical bioprosthesis (SB), 666 (39.5%) a mechanical prosthesis, 70 (4.2%) a homograft, and 350 (20.7%) a transcatheter heart valve. In the SAVR versus TAVR matched population, the rate of new moderate or severe aortic regurgitation was higher in the SB group (43.4% vs 13.5%; P < .001), and fewer vegetations were diagnosed in the SB group (62.5% vs 82%; P < .001). Patients with an SB had a higher rate of perivalvular extension (47.9% vs 27%; P < .001) and Staphylococcus aureus was less common in this group (13.4% vs 22%; P = .033). Despite a higher rate of surgery in patients with SB (44.4% vs 27.3%; P < .001), 1-year mortality was similar (SB: 46.5%; TAVR: 44.8%; log-rank P = .697). CONCLUSIONS: Clinical presentation, type of causative microorganism, and treatment differed between patients with an IE located on SB compared with TAVR. Despite these differences, both groups exhibited high and similar mortality at 1-year follow-up.

Cutibacterium Species Valvular and Cardiac Device-Related Infective Endocarditis: Contemporary Data From the GAMES Prospective Cohort (2008-2023).

BACKGROUND: Information on infective endocarditis (IE) caused by Cutibacterium spp. is limited and new Duke-International Society for Cardiovascular Infectious Diseases (ISCVID) criteria have not yet been properly assessed. We examined clinical characteristics, outcomes, and performance of diagnostic tests for Cutibacterium valvular and cardiac implantable electronic device-related IE (CIED-IE). METHODS: Data corresponding to all episodes of Cutibacterium IE recorded from 2008 to 2023 in a prospective national cohort including 46 Spanish hospitals were examined. Possible IE cases were reassessed using the new criteria. The sensitivity of blood cultures, valvular and CIED cultures, and polymerase chain reaction of the 16S rRNA gene and sequencing (16SPCR) was evaluated. RESULTS: Of 6692 episodes of IE, 67 (1%) were caused by Cutibacterium spp. with 85% affecting men. Of these, 50 were valve-related (45 prosthetic, 5 native) and 17 CIED-related. The new criteria identified 8 additional cases and reclassified 15 as definite IE. Intracardiac complications (abscess, pseudoaneurysm, perforation, or intracardiac fistula) occurred in 23 of 50 (46%) valvular IE episodes, leading to 18% mortality, and up to 40% mortality if surgery was indicated but could not be performed. All CIED-IE cases underwent device removal and no deaths were recorded. Positive diagnosis rates for blood cultures, valve/device cultures, and 16SPCR were 52%, 70%, and 82%, respectively. CONCLUSIONS: Cutibacterium IE is a rare yet potentially life-threatening condition that warrants a high index of suspicion in men with endovascular prosthetic material. The new Duke-ISCVID criteria and molecular techniques are useful for its diagnosis. Considering a significant complication rate, cardiac surgery and removal of CIEDs play a key role in reducing mortality.

Prosthetic Valve Endocarditis Caused by Pasteurella dagmatis, Germany.

An 81-year-old male patient in Germany had prosthetic valve endocarditis caused by Pasteurella dagmatis after a domestic cat bite. We surgically treated a paravalvular abscess and administered definitive antibiotic therapy consisting of penicillin G and levofloxacin. The patient was discharged from the intensive care unit in good condition 21 days after the surgery.

Outcomes of repeat transcatheter aortic valve replacement with balloon-expandable valves: a registry study.

BACKGROUND: With increasing numbers of patients undergoing transcatheter aortic valve replacement (TAVR), data on management of failed TAVR, including repeat TAVR procedure, are needed. The aim of this study was to assess the safety and efficacy of redo-TAVR in a national registry. METHODS: This study included all consecutive patients in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry from Nov 9, 2011, to Dec 30, 2022 who underwent TAVR with balloon-expandable valves in failed transcatheter heart valves (redo-TAVR) or native aortic valves (native-TAVR). Procedural, echocardiographic, and clinical outcomes were compared between redo-TAVR and native-TAVR cohorts using propensity score matching. FINDINGS: Among 350 591 patients (1320 redo-TAVR; 349 271 native-TAVR), 1320 propensity-matched pairs of patients undergoing redo-TAVR and native-TAVR were analysed (redo-TAVR cohort: mean age 78 years [SD 9]; 559 [42·3%] of 1320 female, 761 [57·7%] male; mean predicted surgical risk of 30-day mortality 8·1%). The rates of procedural complications of redo-TAVR were low (coronary compression or obstruction: four [0·3%] of 1320; intraprocedural death: eight [0·6%] of 1320; conversion to open heart surgery: six [0·5%] of 1319) and similar to native-TAVR. There was no significant difference between redo-TAVR and native-TAVR populations in death at 30 days (4·7% vs 4·0%, p=0·36) or 1 year (17·5% vs 19·0%, p=0·57), and stroke at 30 days (2·0% vs 1·9%, p=0·84) or 1 year (3·2% vs 3·5%, p=0·80). Redo-TAVR reduced aortic valve gradients at 1 year, although they were higher in the redo-TAVR group compared with the native-TAVR group (15 mm Hg vs 12 mm Hg; p<0·0001). Moderate or severe aortic regurgitation rates were similar between redo-TAVR and native-TAVR groups at 1 year (1·8% vs 3·3%, p=0·18). Death or stroke after redo-TAVR were not significantly affected by the timing of redo-TAVR (before or after 1 year of index TAVR), or by index transcatheter valve type (balloon-expandable or non-balloon-expandable). INTERPRETATION: Redo-TAVR with balloon-expandable valves effectively treated dysfunction of the index TAVR procedure with low procedural complication rates, and death and stroke rates similar to those in patients with a similar clinical profile and predicted risk undergoing TAVR for native aortic valve stenosis. Redo-TAVR with balloon-expandable valves might be a reasonable treatment for failed TAVR in selected patients. FUNDING: Edwards Lifesciences.

Treatment of severe symptomatic aortic valve stenosis using non-invasive ultrasound therapy: a cohort study.

BACKGROUND: Calcific aortic stenosis is commonly treated using surgical or transcatheter aortic valve replacement; however, many patients are not considered suitable candidates for these interventions due to severe comorbidities and limited life expectancy. As such, non-invasive therapies might offer alternative therapeutic possibilities in these patients. This study aimed to assess the safety of non-invasive ultrasound therapy and its ability to improve valvular function by softening calcified valve tissue. METHODS: This prospective, multicentre, single-arm series enrolled 40 adult patients with severe symptomatic aortic valve stenosis at three hospitals in France, the Netherlands, and Serbia between March 13, 2019, and May 8, 2022. Patients were treated with transthoracically delivered non-invasive ultrasound therapy. Follow-ups were scheduled at 1, 3, 6, 12, and 24 months. The primary endpoints were procedure-related deaths within 30 days and improved valve function. We report the 6-month data. This study is registered at ClinicalTrials.gov, NCT03779620 and NCT04665596. FINDINGS: 40 high-risk patients with a mean Society of Thoracic Surgeons score of 5·6% (SD 4·4) and multiple severe comorbidities were included. The primary endpoint, procedure-related mortality, did not occur; furthermore, no life-threatening or cerebrovascular events were reported. Improved valve function was confirmed up to 6 months, reflected by a 10% increase in mean aortic valve area from 0·58 cm2 (SD 0·19) at baseline to 0·64 cm2 (0·21) at follow-up (p=0·0088), and a 7% decrease in mean pressure gradient from 41·9 mm Hg (20·1) to 38·8 mm Hg (17·8; p=0·024). At 6 months, the New York Heart Association score had improved or stabilised in 24 (96%) of 25 patients, and the mean Kansas City Cardiomyopathy Questionnaire score had improved by 33%, from 48·5 (SD 22·6) to 64·5 (21·0). One serious procedure-related adverse event occurred in a patient who presented with a transient decrease in peripheral oxygen saturation. Non-serious adverse events included pain, discomfort during treatment, and transient arrhythmias. INTERPRETATION: This novel, non-invasive ultrasound therapy for calcified aortic stenosis proved to be safe and feasible. FUNDING: Cardiawave.

Healthcare exposures and associated risk of endocarditis after open-heart cardiac valve surgery.

BACKGROUND: Infective endocarditis (IE) following cardiac valve surgery is associated with high morbidity and mortality. Data on the impact of iatrogenic healthcare exposures on this risk are sparse. This study aimed to investigate risk factors including healthcare exposures for post open-heart cardiac valve surgery endocarditis (PVE). METHODS: In this population-linkage cohort study, 23,720 patients who had their first cardiac valve surgery between 2001 and 2017 were identified from an Australian state-wide hospital-admission database and followed-up to 31 December 2018. Risk factors for PVE were identified from multivariable Cox regression analysis and verified using a case-crossover design sensitivity analysis. RESULTS: In 23,720 study participants (median age 73, 63% male), the cumulative incidence of PVE 15 years after cardiac valve surgery was 7.8% (95% CI 7.3-8.3%). Thirty-seven percent of PVE was healthcare-associated, which included red cell transfusions (16% of healthcare exposures) and coronary angiograms (7%). The risk of PVE was elevated for 90 days after red cell transfusion (HR = 3.4, 95% CI 2.1-5.4), coronary angiogram (HR = 4.0, 95% CI 2.3-7.0), and healthcare exposures in general (HR = 4.0, 95% CI 3.3-4.8) (all p < 0.001). Sensitivity analysis confirmed red cell transfusion (odds ratio [OR] = 3.9, 95% CI 1.8-8.1) and coronary angiogram (OR = 2.6, 95% CI 1.5-4.6) (both p < 0.001) were associated with PVE. Six-month mortality after PVE was 24% and was higher for healthcare-associated PVE than for non-healthcare-associated PVE (HR = 1.3, 95% CI 1.1-1.5, p = 0.002). CONCLUSIONS: The risk of PVE is significantly higher for 90 days after healthcare exposures and associated with high mortality.