A randomized comparison of the treatment sequence of percutaneous coronary intervention and transcatheter aortic valve implantation: Rationale and design of the TAVI PCI trial.

BACKGROUND: About half of patients with severe aortic stenosis present with concomitant coronary artery disease. The optimal timing of percutaneous coronary intervention (PCI) and transcatheter aortic valve implantation (TAVI) in patients with severe aortic stenosis and concomitant coronary artery disease remains unknown. STUDY DESIGN: The TAVI PCI trial is a prospective, international, multicenter, randomized, 2-arm, open-label study planning to enroll a total of 986 patients. It is designed to investigate whether the strategy "angiography-guided complete revascularization after (within 1-45 days) TAVI" is noninferior to the strategy "angiography-guided complete revascularization before (within 1-45 days) TAVI" using the Edwards SAPIEN 3 or 3 Ultra Transcatheter Heart Valve in patients with severe aortic stenosis and concomitant coronary artery disease. Patients are randomized in a 1:1 ratio to one of the 2 treatment strategies. The primary end point is a composite of all-cause death, nonfatal myocardial infarction, ischemia-driven revascularization, rehospitalization (valve- or procedure-related including heart failure), or life-threatening/disabling or major bleeding at 1 year. CONCLUSIONS: The TAVI PCI trial tests the hypothesis that the strategy "PCI after TAVI" is noninferior to the strategy "PCI before TAVI" in patients with severe aortic stenosis and concomitant coronary artery disease.

Quality of Life Measures in Aortic Stenosis Research: A Narrative Review.

BACKGROUND: Elderly patients with aortic stenosis (AS) not only have a reduced life expectancy but also a reduced quality of life (QoL). The benefits of an AS intervention may be considered a balance between a good QoL and a reasonably extended life. However, the different questionnaires being used to determine the QoL were generally not developed for the specific situation of patients with AS and come with strengths and considerable weaknesses. The objective of this article was to provide an overview of the available QoL instruments in AS research, describe their strengths and weaknesses, and provide our assessment of the utility of the available scoring instruments for QoL measurements in AS. SUMMARY: We identified and reviewed the following instruments that are used in AS research: Short Form Health Survey (SF-36/SF-12), EuroQol-5D (EQ-5D), the Illness Intrusiveness Rating Scale (IIRS), the HeartQoL, the Kansas City Cardiomyopathy Questionnaire (KCCQ), the Minnesota Living with Heart Failure Questionnaire (MLHF), the MacNew Questionnaire, and the Toronto Aortic Stenosis Quality of Life Questionnaire (TASQ). KEY MESSAGES: There is no standardized assessment of QoL in patients with AS. Many different questionnaires are being used, but they are rarely specific for AS. There is a need for AS-specific research into the QoL of patients as life prolongation may compete for an improved QoL in this elderly patient group.

Association of N-terminal pro-B-type natriuretic peptide with mortality in elderly (≥80 years) patients undergoing percutaneous coronary intervention.

OBJECTIVES: The aim of this study was to determine the role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in the prognostication of patients ≥80 years of age undergoing percutaneous coronary intervention (PCI). BACKGROUND: Elderly patients with coronary artery disease in need of PCI represent a growing patient population. Advanced risk prediction in this frail and comorbid patient population is important. METHODS: A total of 460 consecutive patients ≥80 years of age undergoing PCI for acute (ACS) or chronic coronary syndromes (CCS) at the University Hospital Zurich, Switzerland, between January 2016 and December 2018 and with available baseline NT-proBNP levels were included in the analysis. Patients were stratified according to baseline NT-proBNP levels. The primary endpoint was all-cause mortality at a median follow-up of 33 (interquartile range: 3-392) days. RESULTS: Median baseline NT-proBNP levels were 1411 (457-3984) ng/L. All-cause mortality was 7.8% in the lowest and 27.8% in the highest NT-proBNP quartile group (p < 0.001). In patients with ACS, all-cause mortality was 4.8% and 30.4% in the lowest and the highest NT-proBNP quartile (p < 0.001), and corresponding rates in patients with CCS were 11.1% and 22.2% (p = 0.38). In multivariable Cox regression analysis, baseline NT-proBNP levels were independently associated with an increased risk of all-cause mortality (adjusted hazard ratio: 1.00, 95% confidence interval: 1.00-1.00, p = 0.04). CONCLUSIONS: Baseline NT-proBNP levels were identified as independent predictor of mortality in elderly (≥80 years) patients undergoing PCI. Hence, baseline NT-proBNP allows for the identification of a high-risk elderly patient subset.

Multiparametric PET and MRI of myocardial damage after myocardial infarction: correlation of integrin αvß3 expression and myocardial blood flow.

PURPOSE: Increased angiogenesis after myocardial infarction is considered an important favorable prognostic parameter. The αvß3 integrin is a key mediator of cell-cell and cell-matrix interactions and an important molecular target for imaging of neovasculature and repair processes after MI. Thus, imaging of αvß3 expression might provide a novel biomarker for assessment of myocardial angiogenesis as a prognostic marker of left ventricular remodeling after MI. Currently, there is limited data available regarding the association of myocardial blood flow and αvß3 integrin expression after myocardial infarction in humans. METHODS: Twelve patients were examined 31 ± 14 days after MI with PET/CT using [18F]Galacto-RGD and [13N]NH3 and with cardiac MRI including late enhancement on the same day. Normal myocardium (remote) and areas of infarction (lesion) were identified on the [18F]Galacto-RGD PET/CT images by correlation with [13N]NH3 PET and cardiac MRI. Lesion/liver-, lesion/blood-, and lesion/remote ratios were calculated. Blood flow and [18F]Galacto-RGD uptake were quantified and correlated for each myocardial segment (AHA 17-segment model). RESULTS: In 5 patients, increased [18F]Galacto-RGD uptake was notable within or adjacent to the infarction areas with a lesion/remote ratio of 46% (26-83%; lesion/blood 1.15 ± 0.06; lesion/liver 0.61 ± 0.18). [18F]Galacto-RGD uptake correlated significantly with infarct size (R = 0.73; p = 0.016). Moreover, it correlated significantly with restricted blood flow for all myocardial segments (R = - 0.39; p < 0.0001) and even stronger in severely hypoperfused areas (R = - 0.75; p < 0.0001). CONCLUSION: [18F]Galacto-RGD PET/CT allows the visualization and quantification of myocardial αvß3 expression as a key player in angiogenesis in a subset of patients after MI. αvß3 expression was more pronounced in patients with larger infarcts and was generally more intense but not restricted to areas with more impaired blood flow, proving that tracer uptake was largely independent of unspecific perfusion effects. Based on these promising results, larger prospective studies are warranted to evaluate the potential of αvß3 imaging for assessment of myocardial angiogenesis and prediction of ventricular remodeling.

[TAVI - New Frontiers]. / TAVI ­ Neue Grenzen.

TAVI - New Frontiers Abstract. In this overview, the current major challenges in the field of TAVI are discussed with available supporting data. Valve-in-valve procedures have become routine with reliable evidence to optimise outcomes and minimise the risk of patient prosthesis mismatch. Treating bicuspid aortic valve anatomy remains a challenge with no imminent sign of randomised data to assist treatment decisions; however, it seems clear that improving transcatheter technology and operator experience can lead to excellent results in selected patients. Despite the lingering risk of valve leaflet thrombosis, dual-antiplatelet therapy after TAVI appears to do more harm than good in comparison to single antiplatelet therapy. Whether oral anticoagulation may yet tip the scales toward net clinical benefit remains to be determined. Finally, with TAVI firmly established as the preferred treatment for patients with high and intermediate surgical risk, and as a suitable alternative to surgery in some low risk patients, increasing attention is being turned to the timing of valve intervention. In particular, there is a clear trend away from the traditional symptomatology and strict haemodynamic parameter-driven strategies that have dictated treatment algorithms until now, toward investigating and treating aortic stenosis before the occurrence of deleterious extra-valvular effects.

Failing bioprosthesis in systemic tricuspid position after a Senning procedure-Successful percutaneous tricuspid valve implantation.

We report on successful transvenous and transbaffle implantation of a 26-mm Sapien 3 valve into a failing tricuspid ("systemic") biological prosthesis in a patient after a Senning-Brom operation for transposition of the great arteries. © 2016 Wiley Periodicals, Inc.

[Personalized Therapeutic Concepts in Chronic Coronary Syndromes]. / Personalisierte Therapie des chronischen Koronarsyndroms.

Personalized Therapeutic Concepts in Chronic Coronary Syndromes Abstract. Chronic coronary syndromes (CCS) are related to substantial morbidity and mortality. Myocardial ischemia in CCS is caused by either obstructive or non-obstructive alterations of the coronary arteries, including both morphological and functional changes of epicardial vessels and the coronary microvasculature. Diagnostic algorithms of patients with suspected CCS include non-invasive and invasive imaging and functional testing. Therapeutic management comprises lifestyle changes, optimal medical therapy, and coronary revascularization when indicated. This review summarizes the contemporary management of patients with CCS, focusing on the role of invasive assessment and treatment.

Extracellular Volume Quantification With Cardiac Late Enhancement Scanning Using Dual-Source Photon-Counting Detector CT.

OBJECTIVES: The aim of this study was to evaluate the feasibility and accuracy of cardiac late enhancement (LE) scanning for extracellular volume (ECV) quantification with dual-source photon-counting detector computed tomography (PCD-CT). MATERIALS AND METHODS: In this institutional review board-approved study, 30 patients (mean age, 79 years; 12 women; mean body mass index, 28 kg/m2) with severe aortic stenosis undergoing PCD-CT as part of their preprocedural workup for transcatheter aortic valve replacement were included. The scan protocol consisted of a nonenhanced calcium-scoring scan, coronary CT angiography (CTA) followed by CTA of the thoracoabdominal aorta, and a low-dose LE scan 5 minutes after the administration of 100 mL contrast media (all scans electrocardiogram-gated). Virtual monoenergetic (65 keV) and dual-energy (DE) iodine images were reconstructed from the LE scan. Extracellular volume was calculated using the iodine ratios of myocardium and blood-pool of the LE scan, and additionally based on single-energy (SE) subtraction of the nonenhanced scan from the LE scan. Three-dimensional analysis was performed automatically for the whole-heart myocardial volume by matching a heart model generated from the respective coronary CTA data. Bland-Altman and correlation analysis were used to compare the ECV values determined by both methods. RESULTS: The median dose length product for the LE scan was 84 mGy·cm (interquartile range, 69; 125 mGy·cm). Extracellular volume quantification was feasible in all patients. The median ECV value was 30.5% (interquartile range, 28.4%-33.6%). Two focal ECV elevations matched known prior myocardial infarction. The DE- and SE-based ECV quantification correlated well (r = 0.87, P < 0.001). Bland-Altman analysis showed small mean errors between DE- and SE-based ECV quantification (0.9%; 95% confidence interval, 0.1%-1.6%) with narrow limits of agreement (-3.3% to 5.0%). CONCLUSIONS: Dual-source PCD-CT enables accurate ECV quantification using an LE cardiac DE scan at low radiation dose. Extracellular volume calculation from iodine ratios of the LE scan obviates the need for acquisition of a true nonenhanced scan and is not affected by potential misregistration between 2 separate scans.

Prediction of risk for bleeding, myocardial infarction and mortality after percutaneous coronary intervention in patients with acute coronary syndromes.

BACKGROUND: Whether bleeding and myocardial infarction (MI) improve the performance of risk prediction models for mortality in patients with acute coronary syndromes (ACS) treated with percutaneous coronary intervention (PCI) remains unknown. METHODS: This study included 3377 patients with ACS who underwent PCI in the setting of the ISAR-REACT 5 trial. Patients with bleeding, MI or those dying at 1 year after PCI were characterized in terms of baseline characteristics, risk estimates and C-statistic of the risk prediction models for these outcomes. RESULTS: Major bleeding (Bleeding Academic Research Consortium types 3-5), MI and mortality occurred in 195 patients (5.8%), 143 patients (4.3%) and 143 patients (4.3%), respectively. After adjustment, bleeding [hazard ratio = 5.08; 95% confidence interval (CI), 3.03-8.53; P < 0.001] and MI [hazard ratio = 5.90; 95% CI, (3.00-11.65); P < 0.001) remained independently associated with the risk for 1-year mortality. The C-statistic (with 95% CI) of the model for bleeding, MI and mortality was, 0.755 (0.722-0.786), 0.752 (0.717-0.789) and 0.868 (0.837-0.896), respectively. The inclusion of bleeding [C-statistic: 0.892 (0.867-0.913); delta C-statistic 0.024 (-0.014 to 0.065); P = 0.200] or MI [C-statistic: 0.878 (0.851-0.903); delta C-statistic 0.011 (-0.030 to 0.053); P = 0.635] in the risk prediction models for mortality alongside baseline demographical and clinical variables did not improve prediction for mortality. CONCLUSIONS: In patients with ACS treated with PCI, mortality is the most accurately predicted outcome. Bleeding and MI did not improve risk discrimination for mortality when added in the risk prediction models for mortality suggesting that these outcomes do not provide incremental prognostic information on top of baseline demographical and clinical data.

[The Role of Percutaneous Coronary Revascularization in Chronic Coronary Syndromes]. / Perkutane koronare Revaskularisation beim chronischen Koronarsyndrom: wann sinnvoll, wann nicht?

The Role of Percutaneous Coronary Revascularization in Chronic Coronary Syndromes Abstract. Coronary heart disease represents the leading cause of morbidity and mortality worldwide. Optimal management of these patients is therefore crucial and includes lifestyle changes, optimal medical therapy, and coronary revascularization. This review summarizes diagnostic and therapeutic strategies of patients with chronic coronary syndromes, focusing on the 2019 European Society of Cardiology (ESC) guidelines for the diagnosis and management of chronic coronary syndromes. In particular, the role of invasive assessment and coronary revascularization in chronic coronary syndromes is discussed.

Postprocedural Troponin Elevation and Mortality After Transcatheter Aortic Valve Implantation.

Background This study sought to investigate the role of postprocedural troponin elevations in mortality prediction after transcatheter aortic valve implantation and to define the threshold at which clinically relevant postprocedure myocardial injury determines mortality. Methods and Results A total of 1333 consecutive patients with transcatheter aortic valve implantation with available postprocedural high-sensitivity cardiac troponin T measurements were included in the analysis. The threshold at which postprocedure myocardial injury determines long-term mortality was identified using restricted cubic spline analysis. A >18.3-fold increase of troponin above the upper reference limit was identified as threshold for relevant postprocedure myocardial injury. Associations remained significant in a landmark analysis between 30 days and 2 years (hazard ratio [HR], 1.61, [95% CI, 1.13-2.28]; P=0.01), after adjusting for known confounders (adjusted HR, 1.90 [95% CI, 1.40-2.57]; P<0001), and in subgroups of patients with coronary artery disease (adjusted HR, 2.17 [95% CI, 1.44-3.29]; P<0.001), renal dysfunction (adjusted HR, 1.88 [95% CI, 1.35-2.62]; P<0.001), and intermediate/high surgical risk (adjusted HR, 2.70 [95% CI, 1.40-5.22]; P=0.003). Conclusions This study determined a troponin threshold for the identification of patients at increased mortality risk after transcatheter aortic valve implantation. The proposed definition of postprocedure myocardial injury advances risk stratification in patients with transcatheter aortic valve implantation and may assist in postprocedural patient management.

Feasibility and safety of transcaval transcatheter aortic valve implantation: a multicentre European registry.

AIMS: A transfemoral transarterial approach is considered the preferable access route for transcatheter aortic valve implantation (TAVI), followed by a transaxillary/subclavian TAVI approach. However, these approaches may not be an option in all patients. This study aimed to report the initial European experience with transfemoral transcaval TAVI. METHODS AND RESULTS: Data on 50 patients treated by transcaval TAVI in five European centres were collected and analysed according to the Valve Academic Research Consortium (VARC)-2 definitions. The study population had a mean age of 78.7±8.0 years and a high surgical risk profile (median STS risk score 6.1%, interquartile range 3.0-11.2%). Transcaval access was successful in 49 out of 50 patients and device success was obtained in 94% of cases. Closure of the caval-aortic puncture site with a nitinol cardiac occluder was successful in all cases without need for emergent surgery. One patient received additional sealing of the aortic puncture site with a covered stent one day post TAVI due to a gradual haemoglobin drop of 3 g/dL. VARC-2-defined life-threatening bleeding and major vascular complications possibly related to transcaval access were 4% and 10%, respectively. There were no bleeding or vascular complications after discharge. At 30 days, the clinical efficacy endpoint was reached in 88% of patients. CONCLUSIONS: Transfemoral transcaval access proved to be a feasible and safe TAVI approach for high-risk patients with severe aortic stenosis not suitable for transfemoral or transaxillary/subclavian transarterial access.

Comparison of latest generation supra-annular and intra-annular self-expanding transcatheter heart valves.

BACKGROUND: This study compares two latest-generation self-expanding transcatheter heart valves (THV), the supra-annular ACURATE neo (Boston Scientific) and the intra-annular Centera THV (Edwards Lifesciences). METHODS: In this single center observational cohort trial 317 patients treated with the ACURATE neo and 78 patients treated with the Centera TVH were included. The main endpoints were device success and the early safety endpoint at 30 days. RESULTS: Besides higher incidence of diabetes mellitus and higher body mass index in patients treated with the ACURATE neo THV, there were no baseline differences between the groups. Device success was similar in both groups (neo: 91.8% vs. Centera: 93.6%; P=0.598), with numerically higher rates of moderate to severe paravalvular leakage in the ACURATE neo group (4.7% vs. 1.3%; P=0.214). At 30 days all-cause mortality rates were low in both groups (0.3% vs. 0%; P=0.620) and no difference occurred in the early safety at 30 days (19.3% vs. 16.7%; P=0.599). However, all-cause stroke rates were significantly higher in patients treated with the Centera THV (6.4 vs. 1.6%; P=0.015). CONCLUSIONS: The ACURATE neo and the Centera THV show low mortality rates as well as comparable, favorable hemodynamics. The finding of higher stroke rates at 30 days with the repositionable Centera SE-THV needs further assessment.

Transcatheter Aortic Valve Replacement With Balloon-Expandable Valves: Comparison of SAPIEN 3 Ultra Versus SAPIEN 3.

OBJECTIVES: The aim of this study was to compare outcomes after transcatheter aortic valve replacement (TAVR) with the SAPIEN 3 Ultra (Ultra) and SAPIEN 3 (S3) transcatheter heart valves (THVs). BACKGROUND: The latest generation balloon-expandable Ultra THV incorporates new technical features and might improve outcomes following TAVR. METHODS: This registry included all consecutive patients who underwent TAVR with either the Ultra or S3 between January 2014 and January 2020. One-to-one propensity score matching was performed to account for differences in baseline characteristics. In-hospital and 30-day Valve Academic Research Consortium-2-defined outcomes were investigated. RESULTS: A total of 310 patients (n = 155 Ultra, n = 155 S3) were included. There were no significant differences in baseline characteristics after propensity score matching. Procedures were significantly more often performed under conscious sedation with Ultra compared with S3 (97.4% vs. 71.6%; p < 0.001). Pre-dilatation was more frequent with S3 compared with Ultra (85.2% vs. 42.6%; p < 0.001). In-hospital outcomes, including device success (91.6% vs. 95.5%; p = 0.165), major vascular complications (12.3% vs. 11.0%; p = 0.723), and new pacemaker implantation (5.8% vs. 4.5%; p = 0.608), were comparable between S3 and Ultra patients, respectively. Post-procedural mean transprosthetic gradients (13.2 ± 5.7 mm Hg vs. 13.1 ± 4.7 mm Hg; p = 0.829) and rate of moderate or greater paravalvular leakage (PVL) (1.3% vs. 2.7%; p = 0.414) were comparable, whereas mild PVL was more frequent with S3 compared with Ultra (43.0% vs. 18.7%; p < 0.001). CONCLUSIONS: Device success rates were high with both balloon-expandable THVs, with overall low rates of adverse events up to 30 days after TAVR. Despite a lower frequency of pre-dilatation, significant reduction of mild PVL confirms improved annular sealing properties of the novel Ultra THV.

Multimodality imaging derived energy loss index and outcome after transcatheter aortic valve replacement.

AIMS: To assess whether the combination of transthoracic echocardiography (TTE) and multidetector computed tomography (MDCT) data affects the grading of aortic stenosis (AS) severity under consideration of the energy loss index (ELI) in patients undergoing transcatheter aortic valve replacement (TAVR). METHODS AND RESULTS: Multimodality imaging was performed in 197 patients with symptomatic severe AS undergoing TAVR at the University Hospital Zurich, Switzerland. Fusion aortic valve area index (fusion AVAi) assessed by integrating MDCT derived planimetric left ventricular outflow tract area into the continuity equation was significantly larger as compared to conventional AVAi (0.41 ± 0.1 vs. 0.51 ± 0.1 cm2/m2; P < 0.01). A total of 62 patients (31.4%) were reclassified from severe to moderate AS with fusion AVAi being >0.6 cm2/m2. ELI was obtained for conventional AVAi and fusion AVAi based on sinotubular junction area determined by TTE (ELILTL 0.47 ± 0.1 cm2/m2; fusion ELILTL 0.60 ± 0.1 cm2/m2) and MDCT (ELIMDCT 0.48 ± 0.1 cm2/m2; fusion ELIMDCT 0.61 ± 0.05 cm2/m2). When ELI was calculated with fusion AVAi the effective orifice area was >0.6 cm2/m2 in 85 patients (43.1%). Survival rate 3 years after TAVR was higher in patients reclassified to moderate AS according to multimodality imaging derived ELI (78.8% vs. 67%; P = 0.01). CONCLUSION: Multimodality imaging derived ELI reclassifies AS severity in 43% undergoing TAVR and predicts mid-term outcome.

Patient screening for early detection of aortic stenosis (AS)-review of current practice and future perspectives.

In Europe, approximately one million people over 75 years suffer from severe aortic stenosis (AS), one of the most serious and most common valve diseases, and this disease burden is increasing with the aging population. A diagnosis of severe symptomatic AS is associated with an average life expectancy of 2-3 years and necessitates a timely valve intervention. Guidelines for valve replacement therapy have been established but only a proportion of patients with symptomatic AS actually receive this life-saving treatment. The decision for valve intervention in asymptomatic patients with severe AS is often more challenging and likely results in fewer patients receiving treatment in comparison to their symptomatic counterparts. This article reviews the epidemiology and clinical manifestations of AS, the associated economic burden of AS to the healthcare system, the diagnosis of AS and the possible mechanisms for the introduction of routine screening in elderly patients. Elderly patients typically visit healthcare providers more frequently than younger patients, thereby providing increased opportunities for ad hoc AS screening and this, along with raising patient awareness of the symptoms of AS, has the potential to result in the earlier diagnosis and treatment of AS and increased patient survival.

Transcatheter versus Surgical Aortic Valve Replacement after Previous Cardiac Surgery: A Systematic Review and Meta-Analysis.

AIM: Aortic valve replacement (AVR) in patients with prior cardiac surgery might be challenging. Transcatheter aortic valve replacement (TAVR) offers a promising alternative in such patients. We therefore aimed at comparing the outcomes of patients with aortic valve diseases undergoing TAVR versus those undergoing surgical AVR (SAVR) after previous cardiac surgery. METHODS AND RESULTS: MEDLINE, EMBASE, and the Cochrane Central Register were searched. Seven relevant studies were identified, published between 01/2011 and 12/2015, enrolling a total of 1148 patients with prior cardiac surgery (97.6% prior CABG): 49.2% underwent TAVR, whereas 50.8% underwent SAVR. Incidence of stroke (3.8 versus 7.9%, p=0.04) and major bleeding (8.3 versus 15.3%, p=0.04) was significantly lower in the TAVR group. Incidence of mild/severe paravalvular leakage (14.4/10.9 versus 0%, p < 0.0001) and pacemaker implantation (11.3 versus 3.9%, p=0.01) was significantly higher in the TAVR group. There were no significant differences in the incidence of acute kidney injury (9.7 versus 8.7%, p=0.99), major adverse cardiovascular events (8.7 versus 12.3%, p=0.21), 30-day mortality (5.1 versus 5.5%, p=0.7), or 1-year mortality (11.6 versus 11.8%, p=0.97) between the TAVR and SAVR group. CONCLUSIONS: TAVR as a redo procedure offers a safe alternative for patients presenting with aortic valve diseases after previous cardiac surgery especially those with prior CABG.

Self-Expanding Transcatheter Aortic Valve System for Symptomatic High-Risk Patients With Severe Aortic Stenosis.

BACKGROUND: The CENTERA transcatheter heart valve (THV) is a low-profile, self-expanding nitinol valve made from bovine pericardial tissue that is 14-F compatible with a motorized delivery system allowing for repositionability. OBJECTIVES: The pivotal study evaluated safety and efficacy of this THV in high-surgical-risk study patients with severe symptomatic aortic stenosis. METHODS: Implantations were completed in 23 centers. Clinical and echocardiographic outcomes were assessed at baseline, discharge, and 30 days. Major events were adjudicated by an independent clinical events committee. Echocardiograms and computed tomography scans were reviewed by core laboratories. The primary endpoint was all-cause mortality at 30 days. RESULTS: Between March 25, 2015 and July 5, 2016, 203 patients with severe symptomatic aortic stenosis and increased surgical risk, as determined by the heart team, were treated by transfemoral THV implantation (age 82.7 ± 5.5 years, 67.5% female, 68.0% New York Heart Association functional class III/IV). At 30 days, mortality was 1%, disabling stroke occurred in 2.5% of patients, and New York Heart Association functional class I/II was observed in 93.0% of patients. Effective orifice area increased from 0.71 ± 0.20 cm2 to 1.88 ± 0.43 cm2 (p < 0.001). Mean aortic transvalvular gradient decreased from 40.5 ± 13.2 mm Hg to 7.2 ± 2.8 mm Hg at 30 days post-procedure (p < 0.001). Paravalvular aortic regurgitation at 30 days was moderate or higher in 0.6% of patients. A new permanent pacemaker was implanted in 4.5% of patients receiving the THV (4.9% for patients at risk). CONCLUSIONS: The herein described THV is safe and effective at 30 days with low mortality, significant improvements in hemodynamic outcomes, and low incidence of adverse events. Of particular interest is the low incidence of permanent pacemaker implantations. (Safety and Performance Study of the Edwards CENTERA-EU Self-Expanding Transcatheter Heart Valve [CENTERA-2]; NCT02458560).