Procedural and clinical outcomes of patients undergoing a TAVI in TAVI procedure: Rationale and design of the multicentre, prospective, observational ReTAVI registry.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is increasingly being used in younger patients and those with lower peri-procedural risk, meaning more patients will live long enough to experience structural valve deterioration (SVD) of the bioprosthesis, indicating repeated TAVI. Experience of repeated TAVI-transcatheter heart valve (THV) implantation into an index THV is limited. This registry aims to assess the peri-procedural and short-term safety, efficacy and durability of repeated TAVI. METHODS: The ReTAVI Prospective observational registry is an investigator-initiated, multicentre, international, prospective registry of patients undergoing repeated TAVI using balloon-expandable SAPIEN prosthesis to evaluate procedural and short-term safety, efficacy and durability as well as anatomical and procedural factors associated with optimal results. The registry will enrol at least 150 patients across 60 high-volume centres. Patients must be ≥18 years old, have had procedural success with their first TAVI, have index THV device failure, intend to undergo repeated TAVI and be considered suitable candidates by their local Heart Team. All patients will undergo a 30-day and 12-month follow-up. The estimated study completion is 2025. CONCLUSIONS: The registry will collect pre-, peri-, postoperative and 12-months data on patients undergoing repeated TAVI procedures with THVs for failure of the index THV and determine VARC-3-defined efficacy and safety at 30 days and functional outcome at 12 months. The registry will expand existing data sets and identify patient characteristics/indicators related to complications and clinical benefits for patients with symptomatic severe calcific degenerative aortic stenosis.

Pressure-Controlled Intermittent Coronary Sinus Occlusion (PiCSO) in Acute Myocardial Infarction: The PiCSO-AMI-I Trial.

BACKGROUND: Primary percutaneous coronary intervention (pPCI) has improved clinical outcomes in patients with ST-segment-elevation myocardial infarction. However, as many as 50% of patients still have suboptimal myocardial reperfusion and experience extensive myocardial necrosis. The PiCSO-AMI-I trial (Pressure-Controlled Intermittent Coronary Sinus Occlusion-Acute Myocardial Infarction-I) evaluated whether PiCSO therapy can further reduce myocardial infarct size (IS) in patients undergoing pPCI. METHODS: Patients with anterior ST-segment-elevation myocardial infarction and Thrombolysis in Myocardial Infarction flow 0-1 were randomized at 16 European centers to PiCSO-assisted pPCI or conventional pPCI. The PiCSO Impulse Catheter (8Fr balloon-tipped catheter) was inserted via femoral venous access after antegrade flow restoration of the culprit vessel and before proceeding with stenting. The primary end point was the difference in IS (expressed as a percentage of left ventricular mass) at 5 days by cardiac magnetic resonance. Secondary end points were the extent of microvascular obstruction and intramyocardial hemorrhage at 5 days and IS at 6 months. RESULTS: Among 145 randomized patients, 72 received PiCSO-assisted pPCI and 73 conventional pPCI. No differences were observed in IS at 5 days (27.2%±12.4% versus 28.3%±11.45%; P=0.59) and 6 months (19.2%±10.1% versus 18.8%±7.7%; P=0.83), nor were differences between PiCSO-treated and control patients noted in terms of the occurrence of microvascular obstruction (67.2% versus 64.6%; P=0.85) or intramyocardial hemorrhage (55.7% versus 60%; P=0.72). The study was prematurely discontinued by the sponsor with no further clinical follow-up beyond 6 months. However, up to 6 months of PiCSO use appeared safe with no device-related adverse events. CONCLUSIONS: In this prematurely discontinued randomized trial, PiCSO therapy as an adjunct to pPCI did not reduce IS when compared with conventional pPCI in patients with anterior ST-segment-elevation myocardial infarction. PiCSO use was associated with increased procedural time and contrast but no increase in adverse events up to 6 months. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03625869.

V stenting technique with covered stents for the management of ostial circumflex perforation: Good or bad idea?

We report the case of a redo Ross surgery complicated by an ostial left circumflex occlusion requiring emergent percutaneous coronary intervention. The latter was complicated by coronary perforation treated by two covered stents with V-stenting technique. After immediate success, the clinical course was marked by acute stent thrombosis requiring emergent coronary bypass. Learning objectives: Ostial left circumflex perforation is a rare and potentially fatal complication that is challenging to manage. V stenting technique with two covered stents could be used as a life-saving procedure, but is associated with a high thrombotic risk.

TransCatheter aortic valve implantation and fractional flow reserve-guided percutaneous coronary intervention versus conventional surgical aortic valve replacement and coronary bypass grafting for treatment of patients with aortic valve stenosis and multivessel or advanced coronary disease: The transcatheter valve and vessels trial (TCW trial): Design and rationale.

BACKGROUND: Patients with severe aortic stenosis (AS) frequently present with concomitant obstructive coronary artery disease (CAD). In those, current guidelines recommend combined coronary artery bypass grafting (CABG) and surgical aortic valve replacement (SAVR) as the preferred treatment option, although this surgical approach is associated with a high rate of clinical events. Combined transcatheter aortic valve implantation (TAVI) and percutaneous coronary intervention (PCI) with or without FFR have evolved as a valid alternative for cardiac surgery in patients with AS and multivessel or advanced CAD. To date, no dedicated trial has prospectively evaluated the outcomes of a percutaneous versus surgical treatment for patients with both severe AS and CAD. AIMS: To investigate whether fractional-flow reserve (FFR)-guided PCI and TAVI is noninferior to combined CABG and SAVR for the treatment of severe AS and multivessel or advanced CAD. METHODS: The Transcatheter Valve and Vessels (TCW) trial (clinicaltrial.gov: NCT03424941) is a prospective, randomized, controlled, open label, international trial. Patients ≥ 70 years with severe AS and multivessel (≥ 2 vessels) or advanced CAD, deemed feasible by the heart team for both; a full percutaneous or surgical treatment, will be randomised in a 1:1 fashion to either FFR-guided PCI followed by TAVI (intervention arm) vs. CABG and SAVR (control arm). The primary endpoint is a patient-oriented composite of all-cause mortality, myocardial infarction, disabling stroke, unscheduled clinically-driven target vessel revascularization, valve reintervention, and life threatening or disabling bleeding at 1 year. The TCW trial is powered for noninferiority, and if met, superiority will be tested. Assuming a primary endpoint rate of 30% in the CABG-SAVR arm, with a significance level α of 5%, a noninferiority limit delta of 15% and a loss to follow-up of 2%, a total of 328 patients are needed to obtain a power of 90%. The primary endpoint analysis is performed on an intention-to-treat basis. SUMMARY: The TCW Trial is the first prospective randomized trial that will study if a less invasive percutaneous treatment for severe AS and concomitant advanced CAD (i.e., FFR-guided PCI-TAVI) is noninferior to the guidelines recommended approach (CABG-SAVR).

Impact of transcatheter heart valve type on outcomes of surgical explantation after failed transcatheter aortic valve replacement: the EXPLANT-TAVR international registry.

BACKGROUND: There are limited data on the impact of transcatheter heart valve (THV) type on the outcomes of surgical explantation after THV failure. AIMS: We sought to determine the outcomes of transcatheter aortic valve replacement (TAVR) explantation for failed balloon-expandable valves (BEV) versus self-expanding valves (SEV). METHODS: From November 2009 to February 2022, 401 patients across 42 centres in the EXPLANT-TAVR registry underwent TAVR explantation during a separate admission from the initial TAVR. Mechanically expandable valves (N=10, 2.5%) were excluded. The outcomes of TAVR explantation were compared for 202 (51.7%) failed BEV and 189 (48.3%) failed SEV. RESULTS: Among 391 patients analysed (mean age: 73.0±9.8 years; 33.8% female), the median time from index TAVR to TAVR explantation was 13.3 months (interquartile range 5.1-34.8), with no differences between groups. Indications for TAVR explantation included endocarditis (36.0% failed SEV vs 55.4% failed BEV; p<0.001), paravalvular leak (21.2% vs 11.9%; p=0.014), structural valve deterioration (30.2% vs 21.8%; p=0.065) and prosthesis-patient mismatch (8.5% vs 10.4%; p=0.61). The SEV group trended fewer urgent/emergency surgeries (52.0% vs 62.3%; p=0.057) and more root replacement (15.3% vs 7.4%; p=0.016). Concomitant cardiac procedures were performed in 57.8% of patients, including coronary artery bypass graft (24.8%), and mitral (38.9%) and tricuspid (14.6%) valve surgery, with no differences between groups. In-hospital, 30-day, and 1-year mortality and stroke rates were similar between groups (allp>0.05), with no differences in cumulative mortality at 3 years (log-rank p=0.95). On multivariable analysis, concomitant mitral surgery was an independent predictor of 1-year mortality after BEV explant (hazard ratio [HR] 2.00, 95% confidence interval [CI]: 1.07-3.72) and SEV explant (HR 2.00, 95% CI: 1.08-3.69). CONCLUSIONS: In the EXPLANT-TAVR global registry, BEV and SEV groups had different indications for surgical explantation, with more root replacements in SEV failure, but no differences in midterm mortality and morbidities. Further refinement of TAVR explantation techniques are important to improving outcomes.

OPTImized coronary interventions eXplaIn the bEst cliNical outcomEs (OPTI-XIENCE) study. Rationale and study design.

INTRODUCTION: Clinical events may occur after percutaneous coronary intervention (PCI), particularly in complex lesions and complex patients. The optimization of PCI result, using pressure guidewire and intracoronary imaging techniques, may reduce the risk of these events. The hypothesis of the present study is that the clinical outcome of patients with indication of PCI and coronary stent implantation that are at high risk of events can be improved with an unrestricted use of intracoronary tools that allow PCI optimization. METHODS AND ANALYSIS: Observational prospective multicenter international study, with a follow-up of 12 months, including 1064 patients treated with a cobalt­chromium everolimus-eluting stent. Inclusion criteria include any of the following: Lesion length > 28 mm; Reference vessel diameter < 2.5 mm or > 4.25 mm; Chronic total occlusion; Bifurcation with side branch ≥2.0 mm;Ostial lesion; Left main lesion; In-stent restenosis; >2 lesions stented in the same vessel; Treatment of >2 vessels; Acute myocardial infarction; Renal insufficiency; Left ventricular ejection fraction <30 %; Staged procedure. The control group will be comprised by a similar number of matched patients included in the "extended risk" cohort of the XIENCE V USA study. The primary endpoint will be the 1-year rate of target lesion failure (TLF) (composite of ischemia-driven TLR, myocardial infarction (MI) related to the target vessel, or cardiac death related to the target vessel). Secondary endpoints will include overall mortality, cardiovascular mortality, acute myocardial infarction, TVR, TLR, target vessel failure, and definitive or probable stent thrombosis at 1 year. IMPLICATIONS: The ongoing OPTI-XIENCE study will contribute to the growing evidence supporting the use of intra-coronary imaging techniques for stent optimization in patients with complex coronary lesions.

P2Y12 Inhibitor Loading Time Before Elective PCI and the Prevention of Myocardial Necrosis.

BACKGROUND: There are dated and conflicting data about the optimal timing of initiation of P2Y12 inhibitors in elective percutaneous coronary intervention (PCI). Peri-PCI myocardial necrosis is associated with poor outcomes. We aimed to assess the impact of the P2Y12 inhibitor loading time on periprocedural myocardial necrosis in the population of the randomized Assessment of Loading With the P2Y12 Inhibitor Ticagrelor or Clopidogrel to Halt Ischemic Events in Patients Undergoing Elective Coronary Stenting (ALPHEUS) trial, which compared ticagrelor with clopidogrel in high-risk patients who received elective PCI. METHODS: The ALPHEUS trial divided 1809 patients into quartiles of loading time. The ALPHEUS primary outcome was used (type 4 [a or b] myocardial infarction or major myocardial injury) as well as the main secondary outcome (type 4 [a or b] myocardial infarction or any type of myocardial injury). RESULTS: Patients in the first quartile group (Q1) presented higher rates of the primary outcome (P = 0.01). When compared with Q1, incidences of the primary outcome decreased in patients with longer loading times (adjusted odds ratio [adjOR], 0.70 [0.52.-0.95]; P = 0.02 for Q2; adjOR 0.65 [0.48-0.88]; P < 0.01 for Q3; adjOR 0.66 [0.49-0.89]; P < 0.01 for Q4). Concordant results were found for the main secondary outcome. There was no interaction with the study drug allocated by randomization (clopidogrel or ticagrelor). Bleeding complications (any bleeding ranging between 4.9% and 7.3% and only 1 major bleeding at 48 hours) and clinical ischemic events were rare and did not differ among groups. CONCLUSIONS: In elective PCI, administration of the oral P2Y12 inhibitor at the time of PCI could be associated with more frequent periprocedural myocardial necrosis than an earlier administration. The long-term clinical consequences remain unknown.

Negative Impact of TET2 Mutations on Long-Term Survival After Transcatheter Aortic Valve Replacement.

Clonal hematopoiesis of indeterminate potential (CHIP) is considered as being a novel age-related risk factor for cardiovascular diseases. By capture-sequencing of a 67-gene panel, we established a large spectrum of CHIP in 258 patients with aortic valve stenosis undergoing transcatheter aortic valve replacement (TAVR) and assessed their association with long-term survival after TAVR. One or several CHIP variants in 35 genes were identified in 68% of the cohort, DNMT3A and TET2 being the 2 most frequently mutated genes. Patients carrying a TET2-CHIP-driver variant with low variant allele frequency (2%-10%) had a significant decrease in overall survival 5 years after TAVR.

The France PCI registry: Design, methodology and key findings.

BACKGROUND: Obstructive coronary artery disease is the main cause of death worldwide. By tracking events and gaining feedback on patient management, the most relevant information is provided to public health services to further improve prognosis. AIMS: To create an inclusive and accurate registry of all percutaneous coronary intervention (PCI) procedures performed in France, to assess and improve the quality of care and create research incentives. Also, to describe the methodology of this French national registry of interventional cardiology, and present early key findings. METHODS: The France PCI registry is a multicentre observational registry that includes consecutive patients undergoing coronary angiography and/or PCI. The registry was set up to provide online data analysis and structured reports of PCI activity, including process of care measures and assessment of risk-adjusted outcomes in all French PCI centres that are willing to participate. More than 150 baseline data items, describing demographic status, PCI indications and techniques, and in-hospital and 1-year outcomes, are captured into local reporting software by medical doctors and local research technicians, with subsequent encryption and internet transfer to central data servers. Annual activity reports and scoring tools available on the France PCI website enable users to benchmark and improve clinical practices. External validation and consistency assessments are performed, with feedback of data completeness to centres. RESULTS: Between 01 January 2014 and 31 December 2022, participating centres increased from six to 47, and collected 364,770 invasive coronary angiograms and 176,030 PCIs, including 54,049 non-ST-segment elevation myocardial infarction cases and 31,631 ST-segment elevation myocardial infarction cases. Fifteen studies stemming from the France PCI registry have already been published. CONCLUSIONS: This fully electronic, daily updated, high-quality, low-cost, national registry is sustainable, and is now expanding. Merging with medicoeconomic databases and nested randomized scientific studies are ongoing steps to expand its scientific potential.

Pharmacological coronary spasm provocative testing in clinical practice: A French Coronary Atheroma and Interventional Cardiology Group (GACI) position paper.

Vasospastic angina, also described as Prinzmetal angina, was first described as a variant form of angina at rest with transient ST-segment elevation; it is common and present in many clinical scenarios, including chronic and acute coronary syndromes, sudden cardiac death, arrhythmia and syncope. However, vasospastic angina remains underdiagnosed, and provocative tests are rarely performed. The gold-standard diagnostic approach uses invasive coronary angiography to induce coronary spasm using ergonovine, methylergonovine or acetylcholine as provocative stimuli. The lack of uniform protocol decreases the use and performance of these tests, accounting for vasospastic angina underestimation. This position paper from the French Coronary Atheroma and Interventional Cardiology Group (GACI) aims to review the indications for provocative tests, the testing conditions, drug protocols and positivity criteria.

Shear Forces Induced Platelet Clearance Is a New Mechanism of Thrombocytopenia.

BACKGROUND: Thrombocytopenia has been consistently described in patients with extracorporeal membrane oxygenation (ECMO) and associated with poor outcome. However, the prevalence and underlying mechanisms remain largely unknown, and a device-related role of ECMO in thrombocytopenia has been hypothesized. This study aims to investigate the mechanisms underlying thrombocytopenia in ECMO patients. METHODS: In a prospective cohort of 107 ECMO patients, we investigated platelet count, functions, and glycoprotein shedding. In an ex vivo mock circulatory ECMO loop, we assessed platelet responses and VWF (von Willebrand factor)-GP Ibα (glycoprotein Ibα) interactions at low- and high-flow rates, in the presence or absence of red blood cells. The clearance of human platelets subjected or not to ex vivo perfusion was studied using an in vivo transfusion model in NOD/SCID (nonobese diabetic/severe combined Immunodeficient) mice. RESULTS: In ECMO patients, we observed a time-dependent decrease in platelet count starting 1 hour after device onset, with a mean drop of 7%, 35%, and 41% at 1, 24, and 48 hours post-ECMO initiation (P=0.00013, P<0.0001, and P<0.0001, respectively), regardless of the type of ECMO. This drop in platelet count was associated with a decrease in platelet GP Ibα expression (before: 47.8±9.1 versus 24 hours post-ECMO: 42.3±8.9 mean fluorescence intensity; P=0.002) and an increase in soluble GP Ibα plasma levels (before: 5.6±3.3 versus 24 hours post-ECMO: 10.8±4.1 µg/mL; P<0.0001). GP Ibα shedding was also observed ex vivo and was unaffected by (1) red blood cells, (2) the coagulation potential, (3) an antibody blocking VWF-GP Ibα interaction, (4) an antibody limiting VWF degradation, and (5) supraphysiological VWF plasma concentrations. In contrast, GP Ibα shedding was dependent on rheological conditions, with a 2.8-fold increase at high- versus low-flow rates. Platelets perfused at high-flow rates before being transfused to immunodeficient mice were eliminated faster in vivo with an accelerated clearance of GP Ibα-negative versus GP Ibα-positive platelets. CONCLUSIONS: ECMO-associated shear forces induce GP Ibα shedding and thrombocytopenia due to faster clearance of GP Ibα-negative platelets. Inhibiting GP Ibα shedding could represent an approach to reduce thrombocytopenia during ECMO.

Contemporary European practice in transcatheter aortic valve implantation: results from the 2022 European TAVI Pathway Registry.

Background: A steep rise in the use of transcatheter aortic valve implantation (TAVI) for the management of symptomatic severe aortic stenosis occurred. Minimalist TAVI procedures and streamlined patient pathways within experienced Heart Valve Centres are designed to overcome the challenges of ever-increasing procedural volume. Aims: The 2022 European TAVI Pathway Survey aims to describe contemporary TAVI practice across Europe. Materials and methods: Between October and December 2022, TAVI operators from 32 European countries were invited to complete an online questionnaire regarding their current practice. Results: Responses were available from 147 TAVI centres in 26 countries. In 2021, the participating centres performed a total number of 27,223 TAVI procedures, with a mean of 185 TAVI cases per centre (median 138; IQR 77-194). Treatment strategies are usually (87%) discussed at a dedicated Heart Team meeting. Transfemoral TAVI is performed with local anaesthesia only (33%), with associated conscious sedation (60%), or under general anaesthesia (7%). Primary vascular access is percutaneous transfemoral (99%) with secondary radial access (52%). After uncomplicated TAVI, patients are transferred to a high-, medium-, or low-care unit in 28%, 52%, and 20% of cases, respectively. Time to discharge is day 1 (12%), day 2 (31%), day 3 (29%), or day 4 or more (28%). Conclusion: Reported adoption of minimalist TAVI techniques is common among European TAVI centres, but rates of next-day discharge remain low. This survey highlights the significant progress made in refining TAVI treatment and pathways in recent years and identifies possible areas for further improvement.

Applied coronary physiology for planning and guidance of percutaneous coronary interventions. A clinical consensus statement from the European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the European Society of Cardiology.

The clinical value of fractional flow reserve and non-hyperaemic pressure ratios are well established in determining an indication for percutaneous coronary intervention (PCI) in patients with coronary artery disease (CAD). In addition, over the last 5 years we have witnessed a shift towards the use of physiology to enhance procedural planning, assess post-PCI functional results, and guide PCI optimisation. In this regard, clinical studies have reported compelling data supporting the use of longitudinal vessel analysis, obtained with pressure guidewire pullbacks, to better understand how obstructive CAD contributes to myocardial ischaemia, to establish the likelihood of functionally successful PCI, to identify the presence and location of residual flow-limiting stenoses and to predict long-term outcomes. The introduction of new functional coronary angiography tools, which merge angiographic information with fluid dynamic equations to deliver information equivalent to intracoronary pressure measurements, are now available and potentially also applicable to these endeavours. Furthermore, the ability of longitudinal vessel analysis to predict the functional results of stenting has played an integral role in the evolving field of simulated PCI. Nevertheless, it is important to have an awareness of the value and challenges of physiology-guided PCI in specific clinical and anatomical contexts. The main aim of this European Association of Percutaneous Cardiovascular Interventions clinical consensus statement is to offer up-to-date evidence and expert opinion on the use of applied coronary physiology for procedural PCI planning, disease pattern recognition and post-PCI optimisation.

Impact of Mitral Regurgitation Etiology on Mitral Surgery After Transcatheter Edge-to-Edge Repair: From the CUTTING-EDGE Registry.

BACKGROUND: Although >150,000 mitral TEER procedures have been performed worldwide, the impact of MR etiology on MV surgery after TEER remains unknown. OBJECTIVES: The authors sought to compare outcomes of mitral valve (MV) surgery after failed transcatheter edge-to-edge repair (TEER) stratified by mitral regurgitation (MR) etiology. METHODS: Data from the CUTTING-EDGE registry were retrospectively analyzed. Surgeries were stratified by MR etiology: primary (PMR) and secondary (SMR). MVARC (Mitral Valve Academic Research Consortium) outcomes at 30 days and 1 year were evaluated. Median follow-up was 9.1 months (IQR: 1.1-25.8 months) after surgery. RESULTS: From July 2009 to July 2020, 330 patients underwent MV surgery after TEER, of which 47% had PMR and 53.0% had SMR. Mean age was 73.8 ± 10.1 years, median STS risk at initial TEER was 4.0% (IQR: 2.2%-7.3%). Compared with PMR, SMR had a higher EuroSCORE, more comorbidities, lower LVEF pre-TEER and presurgery (all P < 0.05). SMR patients had more aborted TEER (25.7% vs 16.3%; P = 0.043), more surgery for mitral stenosis after TEER (19.4% vs 9.0%; P = 0.008), and fewer MV repairs (4.0% vs 11.0%; P = 0.019). Thirty-day mortality was numerically higher in SMR (20.4% vs 12.7%; P = 0.072), with an observed-to-expected ratio of 3.6 (95% CI: 1.9-5.3) overall, 2.6 (95% CI: 1.2-4.0) in PMR, and 4.6 (95% CI: 2.6-6.6) in SMR. SMR had significantly higher 1-year mortality (38.3% vs 23.2%; P = 0.019). On Kaplan-Meier analysis, the actuarial estimates of cumulative survival were significantly lower in SMR at 1 and 3 years. CONCLUSIONS: The risk of MV surgery after TEER is nontrivial, with higher mortality after surgery, especially in SMR patients. These findings provide valuable data for further research to improve these outcomes.

Fractional flow reserve or 3D-quantitative-coronary-angiography based vessel-FFR guided revascularization. Rationale and study design of the prospective randomized fast III trial.

BACKGROUND: Physiological assessment of intermediate coronary lesions to guide coronary revascularization is currently recommended by international guidelines. Vessel fractional flow reserve (vFFR) has emerged as a new approach to derive fractional flow reserve (FFR) from 3D-quantitative coronary angiography (3D-QCA) without the need for hyperemic agents or pressure wires. STUDY DESIGN AND OBJECTIVES: The FAST III is an investigator-initiated, open label, multicenter randomized trial comparing vFFR guided versus FFR guided coronary revascularization in approximately 2228 patients with intermediate coronary lesions (defined as 30%-80% stenosis by visual assessment or QCA). Intermediate lesions are physiologically assessed using on-line vFFR or FFR and treated if vFFR or FFR ≤0.80. The primary end point is a composite of all-cause death, any myocardial infarction, or any revascularization at 1-year post-randomization. Secondary end points include the individual components of the primary end point and cost-effectiveness will be investigated. CONCLUSIONS: FAST III is the first randomized trial to explore whether a vFFR guided revascularization strategy is non-inferior to an FFR guided strategy in terms of clinical outcomes at 1-year follow-up in patients with intermediate coronary artery lesions.

Transcatheter aortic valve implantation using the SAPIEN 3 valve to treat aortic regurgitation: The French multicentre S3AR study.

BACKGROUND: Transcatheter aortic valve implantation now has a major role in the treatment of patients with severe aortic stenosis. However, evidence is scarce on its feasibility and safety to treat patients with pure aortic regurgitation. AIMS: We sought to evaluate the results of transcatheter aortic valve implantation using the balloon-expandable SAPIEN 3 transcatheter heart valve (Edwards Lifesciences, Irvine, CA, USA) in patients with pure aortic regurgitation on native non-calcified valves. METHODS: We conducted a retrospective and prospective French multicentre observational study. We included all patients with symptomatic severe pure aortic regurgitation on native non-calcified valves, contraindicated to or at high risk for surgical valve replacement, who underwent transcatheter aortic valve implantation using the SAPIEN 3 transcatheter heart valve. RESULTS: A total of 37 patients (male sex, 73%) with a median age of 81years (interquartile range 69-85years) were screened using transthoracic echocardiography and computed tomography and were included at eight French centres. At baseline, 83.8% of patients (n=31) had dyspnoea New York Heart Association class≥III. The device success rate was 94.6% (n=35). At 30days, the all-cause mortality rate was 8.1% (n=3) and valve migration occurred in 10.8% of cases (n=4). Dyspnoea New York Heart Association class≤II was seen in 86.5% of patients (n=32), and all survivors had aortic regurgitation grade≤1. At 1-year follow-up, all-cause mortality was 16.2% (n=6), 89.7% (n=26/29) of survivors were in New York Heart Association class≤II and all had aortic regurgitation grade≤2. CONCLUSION: Transcatheter aortic valve implantation using the SAPIEN 3 transcatheter heart valve seems promising to treat selected high-risk patients with pure aortic regurgitation on non-calcified native valves, contraindicated to surgical aortic valve replacement.

BAlloon expandable vs. SElf expanding transcatheter vaLve for degenerated bioprosthesIs: design and rationale of the BASELINE trial.

BACKGROUND: Surgical aortic valve bioprostheses may degenerate over time and require redo intervention. Transcatheter aortic valve replacement (TAVR) is a less invasive alternative to redo surgery. The BAlloon Expandable vs. SElf Expanding Transcatheter VaLve for Degenerated BioprosthesIs (BASELINE) trial was designed to compare the performance of the balloon-expandable SAPIEN-3 Ultra and the self-expanding EVOLUT PRO+ valve systems in symptomatic patients with a failing surgical bioprosthesis. METHODS: The BASELINE trial is an investigator-initiated, non-funded, prospective, randomized, open-label, superiority trial enrolling a total of 440 patients in up to 50 sites in 12 countries in Europe and North-America. The primary endpoint is device success at 30-days defined by the Valve Academic Research Consortium-3 Criteria as the composite of technical success, freedom from mortality, freedom for surgery or intervention related to the device or to a major vascular or access-related or cardiac structural complication with an intended performance of the valve (mean gradient <20 mmHg and less than moderate aortic regurgitation). The co-primary endpoint at 1 year is defined as the composite of all-cause death, disabling stroke, rehospitalization for heart failure or valve related problems. Independent Core Laboratories will conduct uniform analyses of echocardiography (pre-, post-, 1-year post-procedure), multi-sliced computed tomography (pre-, and if available post-procedure) and cine-fluoroscopy studies. CONCLUSIONS: The BASELINE trial is a head-to-head comparative trial investigating the 2 most used contemporary transcatheter heart valves for the treatment of a failing surgical aortic bioprosthesis. (ClinicalTrials.gov number NCT04843072).

A nanobody against the VWF A3 domain detects ADAMTS13-induced proteolysis in congenital and acquired VWD.

von Willebrand factor (VWF) is a multimeric protein, the size of which is regulated via ADAMTS13-mediated proteolysis within the A2 domain. We aimed to isolate nanobodies distinguishing between proteolyzed and non-proteolyzed VWF, leading to the identification of a nanobody (designated KB-VWF-D3.1) targeting the A3 domain, the epitope of which overlaps the collagen-binding site. Although KB-VWF-D3.1 binds with similar efficiency to dimeric and multimeric derivatives of VWF, binding to VWF was lost upon proteolysis by ADAMTS13, suggesting that proteolysis in the A2 domain modulates exposure of its epitope in the A3 domain. We therefore used KB-VWF-D3.1 to monitor VWF degradation in plasma samples. Spiking experiments showed that a loss of 10% intact VWF could be detected using this nanobody. By comparing plasma from volunteers to that from congenital von Willebrand disease (VWD) patients, intact-VWF levels were significantly reduced for all VWD types, and most severely in VWD type 2A-group 2, in which mutations promote ADAMTS13-mediated proteolysis. Unexpectedly, we also observed increased proteolysis in some patients with VWD type 1 and VWD type 2M. A significant correlation (r = 0.51, P < .0001) between the relative amount of high-molecular weight multimers and levels of intact VWF was observed. Reduced levels of intact VWF were further found in plasmas from patients with severe aortic stenosis and patients receiving mechanical circulatory support. KB-VWF-D3.1 is thus a nanobody that detects changes in the exposure of its epitope within the collagen-binding site of the A3 domain. In view of its unique characteristics, it has the potential to be used as a diagnostic tool to investigate whether a loss of larger multimers is due to ADAMTS13-mediated proteolysis.

Permanent pacemaker implantation and left bundle branch block with self-expanding valves - a SCOPE 2 subanalysis.

BACKGROUND: No detailed data on left bundle branch block (LBBB) and permanent pacemaker implantation (PPI) exist from randomised clinical trials comparing the ACURATE neo and CoreValve Evolut devices. AIMS: Our aim was to assess the incidence and impact of new LBBB and PPI with self-expanding prostheses from a powered randomised comparison. METHODS: From the SCOPE 2 trial, 648 patients with no previous pacemaker were analysed for PPI at 30 days, and 426 patients without previous LBBB were adopted for analysis of LBBB at 30 days.  Results: At 30 days, 16.5% of patients required PPI; rates were higher in CoreValve Evolut compared to ACURATE neo recipients (21.0% vs 12.3%; p=0.004). Previous right bundle branch block (odds ratio [OR] 6.11, 95% confidence interval [CI]: 3.19-11.73; p<0.001) was associated with an increased risk of PPI at 30 days, whereas the use of the ACURATE neo (OR 0.50, 95% CI: 0.31-0.81; p=0.005) was associated with a decreased risk. One-year mortality was similar in patients with and without new PPI. A total of 9.4% of patients developed persistent LBBB at 30 days, with higher incidences in CoreValve Evolut recipients (13.4% vs 5.5%; p=0.007). New LBBB at 30 days was associated with lower ejection fraction at 1 year (65.7%±11.0 vs 69.1%±7.6; p=0.041). CONCLUSIONS: New LBBB and PPI rates were lower in ACURATE neo compared to CoreValve Evolut recipients. The ACURATE neo valve was associated with a lower risk of PPI at 30 days. No effect on 1-year mortality was determined for PPI at 30 days, while LBBB at 30 days was associated with reduced ejection fraction at 1 year.