The emerging challenge of Enterococcus faecalis endocarditis after transcatheter aortic valve implantation: time for innovative treatment approaches.

SUMMARYInfective endocarditis (IE) is a life-threatening infection that has nearly doubled in prevalence over the last two decades due to the increase in implantable cardiac devices. Transcatheter aortic valve implantation (TAVI) is currently one of the most common cardiac procedures. TAVI usage continues to exponentially rise, inevitability increasing TAVI-IE. Patients with TAVI are frequently nonsurgical candidates, and TAVI-IE 1-year mortality rates can be as high as 74% without valve or bacterial biofilm removal. Enterococcus faecalis, a historically less common IE pathogen, is the primary cause of TAVI-IE. Treatment options are limited due to enterococcal intrinsic resistance and biofilm formation. Novel approaches are warranted to tackle current therapeutic gaps. We describe the existing challenges in treating TAVI-IE and how available treatment discovery approaches can be combined with an in silico "Living Heart" model to create solutions for the future.

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.

Concomitant Left Atrial Appendage Occlusion and Transcatheter Aortic Valve Replacement Among Patients With Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) is common in patients undergoing transcatheter aortic valve replacement (TAVR) and is associated with increased risk of bleeding and stroke. While left atrial appendage occlusion (LAAO) is approved as an alternative to anticoagulants for stroke prevention in patients with AF, placement of these devices in patients with severe aortic stenosis, or when performed at the same time as TAVR, has not been extensively studied. METHODS: WATCH-TAVR (WATCHMAN for Patients with AF Undergoing TAVR) was a multicenter, randomized trial evaluating the safety and effectiveness of concomitant TAVR and LAAO with WATCHMAN in AF patients. Patients were randomized 1:1 to TAVR + LAAO or TAVR + medical therapy. WATCHMAN patients received anticoagulation for 45 days followed by dual antiplatelet therapy until 6 months. Anticoagulation was per treating physician preference for patients randomized to TAVR + medical therapy. The primary noninferiority end point was all-cause mortality, stroke, and major bleeding at 2 years between the 2 strategies. RESULTS: The study enrolled 349 patients (177 TAVR + LAAO and 172 TAVR + medical therapy) between December 2017 and November 2020 at 34 US centers. The mean age of patients was 81 years, and the mean scores for CHA2DS2-VASc and HAS-BLED (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile INR, Elderly, Drugs/alcohol concomitantly) were 4.9 and 3.0, respectively. At baseline, 85.4% of patients were taking anticoagulants and 71.3% patients were on antiplatelet therapy. The cohorts were well-balanced for baseline characteristics. The incremental LAAO procedure time was 38 minutes, and the median contrast volume used for combined procedures was 119 mL versus 70 mL with TAVR alone. At the 24-month follow-up, 82.5% compared with 50.8% of patients were on any antiplatelet therapy, and 13.9% compared with 66.7% of patients were on any anticoagulation therapy in TAVR + LAAO compared with TAVR + medical therapy group, respectively. For the composite primary end point, TAVR + LAAO was noninferior to TAVR + medical therapy (22.7 versus 27.3 events per 100 patient-years for TAVR + LAAO and TAVR + medical therapy, respectively; hazard ratio, 0.86 [95% CI, 0.60-1.22]; Pnoninferiority<0.001). CONCLUSIONS: Concomitant WATCHMAN LAAO and TAVR is noninferior to TAVR with medical therapy in severe aortic stenosis patients with AF. The increased complexity and risks of the combined procedure should be considered when concomitant LAAO is viewed as an alternative to medical therapy for patients with AF undergoing TAVR. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03173534.

Aortic Valve Stenosis Causes Accumulation of Extracellular Hemoglobin and Systemic Endothelial Dysfunction.

BACKGROUND: Whether aortic valve stenosis (AS) can adversely affect systemic endothelial function independently of standard modifiable cardiovascular risk factors is unknown. METHODS: We therefore investigated endothelial and cardiac function in an experimental model of AS mice devoid of standard modifiable cardiovascular risk factors and human cohorts with AS scheduled for transcatheter aortic valve replacement. Endothelial function was determined by flow-mediated dilation using ultrasound. Extracellular hemoglobin (eHb) concentrations and nitric oxide (NO) consumption were determined in blood plasma of mice and humans by ELISA and chemiluminescence. This was complemented by measurements of aortic blood flow using 4-dimensional flow acquisition by magnetic resonance imaging and computational fluid dynamics simulations. The effects of plasma and red blood cell (RBC) suspensions on vascular function were determined in transfer experiments in a murine vasorelaxation bioassay system. RESULTS: In mice, the induction of AS caused systemic endothelial dysfunction. In the presence of normal systolic left ventricular function and mild hypertrophy, the increase in the transvalvular gradient was associated with elevated eryptosis, increased eHb, and increased plasma NO consumption; eHb sequestration by haptoglobin restored endothelial function. Because the aortic valve orifice area in patients with AS decreased, postvalvular mechanical stress in the central ascending aorta increased. This was associated with elevated eHb, circulating RBC-derived microvesicles, eryptotic cells, lower haptoglobin levels without clinically relevant anemia, and consecutive endothelial dysfunction. Transfer experiments demonstrated that reduction of eHb by treatment with haptoglobin or elimination of fluid dynamic stress by transcatheter aortic valve replacement restored endothelial function. In patients with AS and subclinical RBC fragmentation, the remaining circulating RBCs before and after transcatheter aortic valve replacement exhibited intact membrane function, deformability, and resistance to osmotic and hypoxic stress. CONCLUSIONS: AS increases postvalvular swirling blood flow in the central ascending aorta, triggering RBC fragmentation with the accumulation of hemoglobin in the plasma. This increases NO consumption in blood, thereby limiting vascular NO bioavailability. Thus, AS itself promotes systemic endothelial dysfunction independent of other established risk factors. Transcatheter aortic valve replacement is capable of limiting NO scavenging and rescuing endothelial function by realigning postvalvular blood flow to near physiological patterns. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT05603520 and NCT01805739.

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.

TRI-SCORE and benefit of intervention in patients with severe tricuspid regurgitation.

BACKGROUND AND AIMS: Benefit of tricuspid regurgitation (TR) correction and timing of intervention are unclear. This study aimed to compare survival rates after surgical or transcatheter intervention to conservative management according to a TR clinical stage as assessed using the TRI-SCORE. METHODS: A total of 2,413 patients with severe isolated functional TR were enrolled in TRIGISTRY (1217 conservatively managed, 551 isolated tricuspid valve surgery, and 645 transcatheter valve repair). The primary endpoint was survival at 2 years. RESULTS: The TRI-SCORE was low (≤3) in 32%, intermediate (4-5) in 33%, and high (≥6) in 35%. A successful correction was achieved in 97% and 65% of patients in the surgical and transcatheter groups, respectively. Survival rates decreased with the TRI-SCORE in the three treatment groups (all P < .0001). In the low TRI-SCORE category, survival rates were higher in the surgical and transcatheter groups than in the conservative management group (93%, 87%, and 79%, respectively, P = .0002). In the intermediate category, no significant difference between groups was observed overall (80%, 71%, and 71%, respectively, P = .13) but benefit of the intervention became significant when the analysis was restricted to patients with successful correction (80%, 81%, and 71%, respectively, P = .009). In the high TRI-SCORE category, survival was not different to conservative management in the surgical and successful repair group (61% and 68% vs 58%, P = .26 and P = .18 respectively). CONCLUSIONS: Survival progressively decreased with the TRI-SCORE irrespective of treatment modality. Compared to conservative management, an early and successful surgical or transcatheter intervention improved 2-year survival in patients at low and, to a lower extent, intermediate TRI-SCORE, while no benefit was observed in the high TRI-SCORE category.

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.

Impact of untreated chronic obstructive coronary artery disease on outcomes after transcatheter aortic valve replacement.

BACKGROUND AND AIMS: In transcatheter aortic valve replacement (TAVR) recipients, the optimal management of concomitant chronic obstructive coronary artery disease (CAD) remains unknown. Some advocate for pre-TAVR percutaneous coronary intervention, while others manage it expectantly. The aim of this study was to assess the impact of varying degrees and extent of untreated chronic obstructive CAD on TAVR and longer-term outcomes. METHODS: The authors conducted a retrospective cohort study of TAVR recipients from January 2015 to November 2021, separating patients into stable non-obstructive or varying degrees of obstructive CAD. The major outcomes of interest were procedural all-cause mortality and complications, major adverse cardiovascular events, and post-TAVR unplanned coronary revascularization. RESULTS: Of the 1911 patients meeting inclusion, 75%, 6%, 10%, and 9% had non-obstructive, intermediate-risk, high-risk, and extreme-risk CAD, respectively. Procedural complication rates overall were low (death 0.4%, shock 0.1%, extracorporeal membrane oxygenation 0.1%), with no difference across groups. At a median follow-up of 21 months, rates of acute coronary syndrome and unplanned coronary revascularization were 0.7% and 0.5%, respectively, in the non-obstructive population, rising in incidence with increasing severity of CAD (P < .001 for acute coronary syndrome/unplanned coronary revascularization). Multivariable analysis did not yield a significantly greater risk of all-cause mortality or major adverse cardiovascular events across groups. One-year acute coronary syndrome and unplanned coronary revascularization rates in time-to-event analyses were significantly greater in the non-obstructive (98%) vs. obstructive (94%) subsets (Plog-rank< .001). CONCLUSIONS: Transcatheter aortic valve replacement can be performed safely in patients with untreated chronic obstructive CAD, without portending higher procedural complication rates and with relatively low rates of unplanned coronary revascularization and acute coronary syndrome at 1 year.

Transcatheter treatment of the tricuspid valve: current status and perspectives.

Transcatheter tricuspid valve interventions (TTVI) are emerging as alternatives to surgery in high-risk patients with isolated or concomitant tricuspid regurgitation. The development of new minimally invasive solutions potentially more adapted to this largely undertreated population of patients, has fuelled the interest for the tricuspid valve. Growing evidence and new concepts have contributed to revise obsolete and misleading perceptions around the right side of the heart. New definitions, classifications, and a better understanding of the disease pathophysiology and phenotypes, as well as their associated patient journeys have profoundly and durably changed the landscape of tricuspid disease. A number of registries and a recent randomized controlled pivotal trial provide preliminary guidance for decision-making. TTVI seem to be very safe and effective in selected patients, although clinical benefits beyond improved quality of life remain to be demonstrated. Even if more efforts are needed, increased disease awareness is gaining momentum in the community and supports the establishment of dedicated expert valve centres. This review is summarizing the achievements in the field and provides perspectives for a less invasive management of a no-more-forgotten disease.

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.

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.

Atrial secondary tricuspid regurgitation: pathophysiology, definition, diagnosis, and treatment.

Atrial secondary tricuspid regurgitation (A-STR) is a distinct phenotype of secondary tricuspid regurgitation with predominant dilation of the right atrium and normal right and left ventricular function. Atrial secondary tricuspid regurgitation occurs most commonly in elderly women with atrial fibrillation and in heart failure with preserved ejection fraction in sinus rhythm. In A-STR, the main mechanism of leaflet malcoaptation is related to the presence of a significant dilation of the tricuspid annulus secondary to right atrial enlargement. In addition, there is an insufficient adaptive growth of tricuspid valve leaflets that become unable to cover the enlarged annular area. As opposed to the ventricular phenotype, in A-STR, the tricuspid valve leaflet tethering is typically trivial. The A-STR phenotype accounts for 10%-15% of clinically relevant tricuspid regurgitation and has better outcomes compared with the more prevalent ventricular phenotype. Recent data suggest that patients with A-STR may benefit from more aggressive rhythm control and timely valve interventions. However, little is mentioned in current guidelines on how to identify, evaluate, and manage these patients due to the lack of consistent evidence and variable definitions of this entity in recent investigations. This interdisciplinary expert opinion document focusing on A-STR is intended to help physicians understand this complex and rapidly evolving topic by reviewing its distinct pathophysiology, diagnosis, and multi-modality imaging characteristics. It first defines A-STR by proposing specific quantitative criteria for defining the atrial phenotype and for discriminating it from the ventricular phenotype, in order to facilitate standardization and consistency in research.

A streamlined pathway for transcatheter aortic valve implantation: the BENCHMARK study.

BACKGROUND AND AIMS: There is significant potential to streamline the clinical pathway for patients undergoing transcatheter aortic valve implantation (TAVI). The purpose of this study was to evaluate the effect of implementing BENCHMARK best practices on the efficiency and safety of TAVI in 28 sites in 7 European countries. METHODS: This was a study of patients with severe symptomatic aortic stenosis (AS) undergoing TAVI with balloon-expandable valves before and after implementation of BENCHMARK best practices. Principal objectives were to reduce hospital length of stay (LoS) and duration of intensive care stay. Secondary objective was to document patient safety. RESULTS: Between January 2020 and March 2023, 897 patients were documented prior to and 1491 patients after the implementation of BENCHMARK practices. Patient characteristics were consistent with a known older TAVI population and only minor differences. Mean LoS was reduced from 7.7 ± 7.0 to 5.8 ± 5.6 days (median 6 vs. 4 days; P < .001). Duration of intensive care was reduced from 1.8 to 1.3 days (median 1.1 vs. 0.9 days; P < .001). Adoption of peri-procedure best practices led to increased use of local anaesthesia (96.1% vs. 84.3%; P < .001) and decreased procedure (median 47 vs. 60 min; P < .001) and intervention times (85 vs. 95 min; P < .001). Thirty-day patient safety did not appear to be compromised with no differences in all-cause mortality (0.6% in both groups combined), stroke/transient ischaemic attack (1.4%), life-threatening bleeding (1.3%), stage 2/3 acute kidney injury (0.7%), and valve-related readmission (1.2%). CONCLUSIONS: Broad implementation of BENCHMARK practices contributes to improving efficiency of TAVI pathway reducing LoS and costs without compromising patient safety.

Transcatheter aortic valve implantation in low-risk tricuspid or bicuspid aortic stenosis: the NOTION-2 trial.

BACKGROUND AND AIMS: Transcatheter aortic valve implantation (TAVI) has become the first choice to treat older patients with severe symptomatic aortic stenosis (AS). This study aimed to compare TAVI with surgery in low-risk patients ≤75 years of age, including both tricuspid and bicuspid AS. METHODS: The Nordic Aortic Valve Intervention (NOTION)-2 trial enrolled and 1:1 randomized low-risk patients aged ≤75 years with severe symptomatic AS to TAVI or surgery. The primary endpoint was a composite of all-cause mortality, stroke, or rehospitalization (related to the procedure, valve, or heart failure) at 12 months. RESULTS: A total of 370 patients were enrolled with a mean age of 71.1 years and a median Society of Thoracic Surgeons risk score of 1.1%. A total of 100 patients had bicuspid AS. The 1-year incidence of the primary endpoint was 10.2% in the TAVI group and 7.1% in the surgery group [absolute risk difference 3.1%; 95% confidence interval (CI), -2.7% to 8.8%; hazard ratio (HR) 1.4; 95% CI, 0.7-2.9; P = .3]. Patients with TAVI, when compared to surgery, had lower risk of major bleeding and new-onset atrial fibrillation and higher risk of non-disabling stroke, permanent pacemaker implantation, and moderate or greater paravalvular regurgitation. The risk of the primary composite endpoint was 8.7% and 8.3% in patients with tricuspid AS (HR 1.0; 95% CI, 0.5-2.3) and 14.3% and 3.9% in patients with bicuspid AS (HR 3.8; 95% CI, 0.8-18.5) treated with TAVI or surgery, respectively (P for interaction = .1). CONCLUSIONS: Among low-risk patients aged ≤75 years with severe symptomatic AS, the rate of the composite of death, stroke, or rehospitalization at 1 year was similar between TAVI and surgery. Transcatheter aortic valve implantation outcomes in young bicuspid AS patients warrant caution and should be further investigated. (NOTION-2, ClinicalTrials.gov, NCT02825134). TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT02825134.

Device innovation in cardiovascular medicine: a report from the European Society of Cardiology Cardiovascular Round Table.

Research performed in Europe has driven cardiovascular device innovation. This includes, but is not limited to, percutaneous coronary intervention, cardiac imaging, transcatheter heart valve implantation, and device therapy of cardiac arrhythmias and heart failure. An important part of future medical progress involves the evolution of medical technology and the ongoing development of artificial intelligence and machine learning. There is a need to foster an environment conducive to medical technology development and validation so that Europe can continue to play a major role in device innovation while providing high standards of safety. This paper summarizes viewpoints on the topic of device innovation in cardiovascular medicine at the European Society of Cardiology Cardiovascular Round Table, a strategic forum for high-level dialogue to discuss issues related to the future of cardiovascular health in Europe. Devices are developed and improved through an iterative process throughout their lifecycle. Early feasibility studies demonstrate proof of concept and help to optimize the design of a device. If successful, this should ideally be followed by randomized clinical trials comparing novel devices vs. accepted standards of care when available and the collection of post-market real-world evidence through registries. Unfortunately, standardized procedures for feasibility studies across various device categories have not yet been implemented in Europe. Cardiovascular imaging can be used to diagnose and characterize patients for interventions to improve procedural results and to monitor devices long term after implantation. Randomized clinical trials often use cardiac imaging-based inclusion criteria, while less frequently trials randomize patients to compare the diagnostic or prognostic value of different modalities. Applications using machine learning are increasingly important, but specific regulatory standards and pathways remain in development in both Europe and the USA. Standards are also needed for smart devices and digital technologies that support device-driven biomonitoring. Changes in device regulation introduced by the European Union aim to improve clinical evidence, transparency, and safety, but they may impact the speed of innovation, access, and availability. Device development programmes including dialogue on unmet needs and advice on study designs must be driven by a community of physicians, trialists, patients, regulators, payers, and industry to ensure that patients have access to innovative care.

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.

Economic Outcomes of Transcatheter Versus Surgical Aortic Valve Replacement in Patients with Severe Aortic Stenosis and Low Surgical Risk: Results from the PARTNER 3 Trial.

BACKGROUND: In patients with severe symptomatic aortic stenosis at low surgical risk, transfemoral transcatheter aortic valve replacement (TAVR) with the SAPIEN 3 valve has been shown to reduce the composite of death, stroke, or rehospitalization at 2-year follow-up compared with surgical aortic valve replacement (SAVR). Whether TAVR is cost-effective compared with SAVR for low-risk patients remains uncertain. METHODS: Between 2016 and 2017, 1000 low-risk patients with aortic stenosis were randomly assigned to TAVR with the SAPIEN 3 valve or SAVR in the PARTNER 3 trial (Placement of Aortic Transcatheter Valves). Of these patients, 929 underwent valve replacement, were enrolled in the United States, and were included in the economic substudy. Procedural costs were estimated using measured resource use. Other costs were determined by linkage with Medicare claims or by regression models when linkage was not feasible. Health utilities were estimated using the EuroQOL 5-item questionnaire. With the use of a Markov model informed by in-trial data, lifetime cost-effectiveness from the perspective of the US health care system was estimated in terms of cost per quality-adjusted life-year gained. RESULTS: Although procedural costs were nearly $19 000 higher with TAVR, total index hospitalization costs were only $591 more with TAVR compared with SAVR. Follow-up costs were lower with TAVR such that TAVR led to 2-year cost savings of $2030/patient compared with SAVR (95% CI, -$6222 to $1816) and a gain of 0.05 quality-adjusted life-years (95% CI, -0.003 to 0.102). In our base-case analysis, TAVR was projected to be an economically dominant strategy with a 95% probability that the incremental cost-effectiveness ratio for TAVR would be <$50 000/quality-adjusted life-year gained (consistent with high economic value from a US health care perspective). These findings were sensitive to differences in long-term survival, however, such that a modest long-term survival advantage with SAVR would render SAVR cost-effective (although not cost saving) compared with TAVR. CONCLUSIONS: For patients with severe aortic stenosis and low surgical risk similar to those enrolled in the PARTNER 3 trial, transfemoral TAVR with the SAPIEN 3 valve is cost saving compared with SAVR at 2 years and is projected to be economically attractive in the long run as long as there are no substantial differences in late death between the 2 strategies. Long-term follow-up will be critical to ultimately determine the preferred treatment strategy for low-risk patients from both a clinical and economic perspective.

Cerebrovascular Events in Patients Undergoing Transcatheter Aortic Valve Replacement: A Review.

Cerebrovascular events (CVEs) are a dreaded complication of transcatheter aortic valve replacement (TAVR). They are associated with significant mortality, morbidity, and reduced quality of life and impose a significant burden to health care systems. Although the rates of clinical stroke have reduced since the advent of TAVR, it remains an important complication, particularly as TAVR is increasingly utilized. CVE may occur at the time of the TAVR, as a direct consequence of the procedure, or may occur later, related to thrombosis of the prosthetic valve, atrial fibrillation, and other comorbidities. Imaging of the brain has revealed a high prevalence of subclinical cerebral infarcts (68%-98%) associated with the TAVR procedure. Although their clinical significance has not been fully established, clinically evident CVE ranges between 3% and 5% in patients considered at high operative risk to between 1% and 3% in low operative risk patients. Periprocedural CVEs are largely the result of embolization of the thrombus and tissue derived from the valve, vasculature, or myocardium. Cerebral embolic protection devices have been studied in multiple trials, with some evidence supporting a reduction in new cerebral lesion volume, number, and potentially disabling strokes. However, thus far, there is no robust evidence that they reduce the overall stroke rate. The number and severity of comorbidities, in particular, new-onset atrial fibrillation, are associated with CVEs. Valve thrombosis diagnosed using computed tomography as areas of hypoattenuated leaflet thickening has been identified in 10% to 15% of patients. This is a dynamic process associated with an increase in CVEs, but that resolves with anticoagulation or sometimes without it. Routine use of anticoagulation compared with a single antiplatelet agent is associated with an increased risk of bleeding, without any additional alleviation in risk of thromboembolism. Future studies to improve risk stratification could facilitate the tailoring of preventive therapies to patients at high risk of CVE, who stand to gain the most benefit.

Cardiorespiratory Instability after Percutaneous Patent Ductus Arteriosus Closure: A Multicenter Cohort Study.

OBJECTIVE: To evaluate postprocedural clinical characteristics of preterm infants undergoing transcatheter patent ductus arteriosus (PDA) closure, including oxygenation/ventilation failure and cardiovascular compromise. STUDY DESIGN: Multicenter retrospective cohort study of preterm infants who were ≤2 kg at the time of percutaneous PDA closure between August 2018 and July 2021. Indices of cardiorespiratory stability were collected pre-closure, immediately post-closure, and subsequently averaged every 4 hours for the first 24 hours post-procedure. The primary outcome was incidence of post-transcatheter cardiorespiratory syndrome: composite of hemodynamic instability (defined by systemic hypotension, systemic hypertension, or use of new inotropes/vasopressors in the first 24 hours after catheterization) and at least one of the following: (i) ventilation failure or (ii) oxygenation failure. RESULTS: A total of 197 patients were included with a median [IQR] age and weight at catheterization of 34 [25, 43] days and 1090 [900, 1367] grams, respectively. The primary composite outcome of post-transcatheter cardiorespiratory syndrome was reported in 46 (23.3%). CONCLUSION: Post-transcatheter cardiorespiratory syndrome is characterized primarily by systemic hypertension and oxygenation failure, with a very low incidence of hypotension and need for inotropes.

A Case of Autosomal Dominant Polycystic Kidney Disease With Resolution of Massive Pericardial Effusion After Renal Transcatheter Artery Embolization.

A 68-year-old woman being treated with hemodialysis for autosomal dominant polycystic kidney disease was admitted for progressive dyspnea over 6 months. On chest radiography, her cardiothoracic ratio had increased from 52.2% 6 months prior, to 71%, and echocardiography revealed diffuse pericardial effusion and right ventricular diastolic insufficiency. A resultant pericardial tamponade was thought to be the cause of the patient's dyspnea, and therefore a pericardiocentesis was performed, with a total of 2,000mL of fluid removed. However, 21 days later the same amount of pericardial fluid had reaccumulated. The second pericardiocentesis was performed, followed by transcatheter renal artery embolization (TAE). The kidneys, which were hard on palpation before TAE, softened immediately after TAE. After resolution of the pericardial effusion was confirmed, the patient was discharged after 24 days in hospital. Twelve months later, the patient was asymptomatic, the cardiothoracic ratio decreased to 48% on chest radiography and computed tomography revealed no reaccumulation of pericardial effusion. This case illustrates a potential relationship between enlarged kidneys in autosomal dominant polycystic kidney disease and pericardial effusion.